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  <xs:element name="NextPaymentToBeAchieved" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_NextPaymentToBeAchieved"/>
  <xs:element name="CumulativePaymentsReceived" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_CumulativePaymentsReceived"/>
  <xs:element name="MaximumAmountOfPaymentsReceivableOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfPaymentsReceivableOverTermOfCollaboration"/>
  <xs:element name="MaximumAmountOfLicenseFeesOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfLicenseFeesOverTermOfCollaboration"/>
  <xs:element name="MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfDevelopmentMilestonePaymentsOverTermOfCollaboration"/>
  <xs:element name="MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfRegulatoryMilestonePaymentsOverTermOfCollaboration"/>
  <xs:element name="MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfSalesMilestonePaymentsOverTermOfCollaboration"/>
  <xs:element name="RoyaltyPercentageReceivedOnNetSalesOfMedicine" type="dtr:percentItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicine"/>
  <xs:element name="NumberOfMajorEuropeanCountriesRequiredToReceiveReimbursementApproval" type="xbrli:integerItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfMajorEuropeanCountriesRequiredToReceiveReimbursementApproval"/>
  <xs:element name="NumberOfMajorEuropeanCountries" type="xbrli:integerItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfMajorEuropeanCountries"/>
  <xs:element name="MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfUpfrontPaymentsOverTermOfCollaboration"/>
  <xs:element name="RoyaltyPercentageReceivedOnNetSalesOfMedicineDescription" type="xbrli:stringItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_RoyaltyPercentageReceivedOnNetSalesOfMedicineDescription"/>
  <xs:element name="NumberOfCollaborationAgreements" type="xbrli:integerItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfCollaborationAgreements"/>
  <xs:element name="AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage" type="dtr:percentItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_AvailableForSaleSecuritiesDebtMaturitiesWithinTwoYearsPercentage"/>
  <xs:element name="NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment" type="xbrli:integerItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfPrivatelyHeldCompaniesInWhichEntityHasEquityInvestment"/>
  <xs:element name="NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment" type="xbrli:integerItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfPubliclyHeldCompaniesInWhichEntityHasEquityInvestment"/>
  <xs:element name="TermOfContractualSaleRestriction" type="xbrli:durationItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_TermOfContractualSaleRestriction"/>
  <xs:element name="NumberOfNewMembersAppointedToBoardOfDirectors" type="xbrli:integerItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfNewMembersAppointedToBoardOfDirectors"/>
  <xs:element name="NumberOfMembersRetiringFromBoardOfDirectors" type="xbrli:integerItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_NumberOfMembersRetiringFromBoardOfDirectors"/>
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfUnitsGuaranteedToVest"/>
  <xs:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfUnitsGuaranteedToVest"/>
  <xs:element name="UpfrontRoyaltyPaymentReceived" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_UpfrontRoyaltyPaymentReceived"/>
  <xs:element name="MaximumAmountOfPaymentsReceivableForAdditionalMilestones" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="debit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfPaymentsReceivableForAdditionalMilestones"/>
  <xs:element name="PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine" type="dtr:percentItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_PercentageOfRoyaltyPaymentsPaidOnAnnualSalesOfMedicine"/>
  <xs:element name="MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumAmountOfAnnualSalesOnWhichRoyaltyPaymentsArePaid"/>
  <xs:element name="MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="ions_MaximumRoyaltyPaymentsMadeBeforeRoyaltyInterestRevertsBack"/>
  <xs:element name="PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties" type="xbrli:monetaryItemType" abstract="false" xbrli:periodType="duration" xbrli:balance="credit" nillable="true" substitutionGroup="xbrli:item" id="ions_PaymentsForTransactionCostsRelatedToSaleOfFutureRoyalties"/>
  <xs:element name="DebtInstrumentConvertibleConversionPriceIncludingCallSpread" type="dtr:perShareItemType" abstract="false" xbrli:periodType="instant" nillable="true" substitutionGroup="xbrli:item" id="ions_DebtInstrumentConvertibleConversionPriceIncludingCallSpread"/>
  <xs:element name="SharesReceivedFromExerciseOfNoteHedges" type="xbrli:sharesItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SharesReceivedFromExerciseOfNoteHedges"/>
  <xs:element name="DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange" type="dtr:percentItemType" abstract="false" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_DebtInstrumentConvertiblePercentageOfPrincipalAmountUsedAsPurchasePriceUponOccurrenceOfFundamentalChange"/>
  <xs:element name="AstraZenecaCollaborationWainuaMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_AstraZenecaCollaborationWainuaMember"/>
  <xs:element name="BiogenCollaboration2017SpinalMuscularAtrophyMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_BiogenCollaboration2017SpinalMuscularAtrophyMember"/>
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  <xs:element name="GlaxoSmithKlineCollaborationMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_GlaxoSmithKlineCollaborationMember"/>
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  <xs:element name="OnoCollaborationMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_OnoCollaborationMember"/>
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  <xs:element name="OtherRoyaltiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_OtherRoyaltiesMember"/>
  <xs:element name="OtsukaCollaborationDawnzeraMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_OtsukaCollaborationDawnzeraMember"/>
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  <xs:element name="RecordatiAgCollaborationMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_RecordatiAgCollaborationMember"/>
  <xs:element name="ResearchAndDevelopmentRevenueMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_ResearchAndDevelopmentRevenueMember"/>
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  <xs:element name="RocheCollaborationRNATargetedProgramsForADAndHDMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_RocheCollaborationRNATargetedProgramsForADAndHDMember"/>
  <xs:element name="RocheCollaborationSefaxersenForComplementMediatedDiseasesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_RocheCollaborationSefaxersenForComplementMediatedDiseasesMember"/>
  <xs:element name="RocheCollaborationsMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_RocheCollaborationsMember"/>
  <xs:element name="RoyaltyPurchaseAgreementMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_RoyaltyPurchaseAgreementMember"/>
  <xs:element name="SalanersenMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SalanersenMember"/>
  <xs:element name="SapablursenMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SapablursenMember"/>
  <xs:element name="SpinrazaMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SpinrazaMember"/>
  <xs:element name="SpinrazaRoyaltiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SpinrazaRoyaltiesMember"/>
  <xs:element name="TryngolzaMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_TryngolzaMember"/>
  <xs:element name="WainuaJointDevelopmentRevenueMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_WainuaJointDevelopmentRevenueMember"/>
  <xs:element name="WainusRoyaltiesMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_WainusRoyaltiesMember"/>
  <xs:element name="ZilganersenMember" type="dtr:domainItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_ZilganersenMember"/>
  <xs:element name="CollaborativeArrangementsAndLicensingAgreementsAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_CollaborativeArrangementsAndLicensingAgreementsAbstract"/>
  <xs:element name="ConvertibleNotesDisclosureTable" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrldt:hypercubeItem" id="ions_ConvertibleNotesDisclosureTable"/>
  <xs:element name="SupplementalFinancialDataAbstract" type="xbrli:stringItemType" abstract="true" xbrli:periodType="duration" nillable="true" substitutionGroup="xbrli:item" id="ions_SupplementalFinancialDataAbstract"/>
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