-----BEGIN PRIVACY-ENHANCED MESSAGE-----
Proc-Type: 2001,MIC-CLEAR
Originator-Name: webmaster@www.sec.gov
Originator-Key-Asymmetric:
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 TWSM7vrzLADbmYQaionwg5sDW3P6oaM5D3tdezXMm7z1T+B+twIDAQAB
MIC-Info: RSA-MD5,RSA,
 Avyk33DLiZh5cZbtu5l+MIxxugTk3Oy1pHe3N3r/1EfbBlF4U3udNuFV3bNX+h5E
 ciR2LQBppSRHBAWpjglKfQ==

<SEC-DOCUMENT>0000874015-03-000037.txt : 20030513
<SEC-HEADER>0000874015-03-000037.hdr.sgml : 20030513
<ACCEPTANCE-DATETIME>20030513171410
ACCESSION NUMBER:		0000874015-03-000037
CONFORMED SUBMISSION TYPE:	4
PUBLIC DOCUMENT COUNT:		1
CONFORMED PERIOD OF REPORT:	20030509
FILED AS OF DATE:		20030513

REPORTING-OWNER:	

	OWNER DATA:	
		COMPANY CONFORMED NAME:			COLE DOUGLAS L
		CENTRAL INDEX KEY:			0001181550
		STATE OF INCORPORATION:			DE
		FISCAL YEAR END:			1231

	FILING VALUES:
		FORM TYPE:		4
		SEC ACT:		1934 Act
		SEC FILE NUMBER:	000-19125
		FILM NUMBER:		03696336

	BUSINESS ADDRESS:	
		STREET 1:		2292 FARADAY AVENUE
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
		BUSINESS PHONE:		7609319200

ISSUER:		

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

	BUSINESS ADDRESS:	
		STREET 1:		2292 FARADAY AVE
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
		BUSINESS PHONE:		7609319200

	MAIL ADDRESS:	
		STREET 1:		2292 FARADAY AVE
		CITY:			CARLSBAD
		STATE:			CA
		ZIP:			92008
</SEC-HEADER>
<DOCUMENT>
<TYPE>4
<SEQUENCE>1
<FILENAME>edgar.xml
<DESCRIPTION>PRIMARY DOCUMENT
<TEXT>
<XML>
<?xml version="1.0"?>
<ownershipDocument>
    <schemaVersion>X0101</schemaVersion>

<documentType>4</documentType><periodOfReport>2003-05-09</periodOfReport>
<issuer><issuerCik>0000874015</issuerCik>
        <issuerName>ISIS PHARMACEUTICALS INC</issuerName>
<issuerTradingSymbol>ISIS</issuerTradingSymbol></issuer><reportingOwner><reportingOwnerId><rptOwnerCik>0001181550</rptOwnerCik>
            <rptOwnerName>COLE DOUGLAS L</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>  </rptOwnerStreet1>
            <rptOwnerStreet2>  </rptOwnerStreet2>
            <rptOwnerCity>  </rptOwnerCity>
            <rptOwnerState>  </rptOwnerState>
            <rptOwnerZipCode>  </rptOwnerZipCode>
        </reportingOwnerAddress>
<reportingOwnerRelationship>
<isDirector>0</isDirector><isOfficer>1</isOfficer><isTenPercentOwner>0</isTenPercentOwner><isOther>0</isOther><officerTitle>Vice President</officerTitle></reportingOwnerRelationship></reportingOwner><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>5.15</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>A</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>44410</value><footnoteId id="F1"/></transactionShares><transactionValue><value>5.15</value></transactionValue><transactionAcquiredDisposedCode><value>A</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>2004-01-01</value><footnoteId id="F1"/></exerciseDate><expirationDate><value>2
008-12-31</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>44410</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>44410</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>6.625</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAm
ounts><transactionShares><value>15267</value><footnoteId id="F2"/></transactionShares><transactionValue><value>6.625</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>1996-10-01</value></exerciseDate><expirationDate><value>2003-06-16</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>15267</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>6.75</value></conversio
nOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>20000</value><footnoteId id="F2"/></transactionShares><transactionValue><value>6.75</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>1998-12-31</value></exerciseDate><expirationDate><value>2003-12-30</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>20000</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><dir
ectOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>13.125</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>15000</value><footnoteId id="F2"/></transactionShares><transactionValue><value>13.125</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>2000-01-01</value></exerciseDate><expirationDate><value>2005-12-31</value></expirationDate><underlyingSecurity><u
nderlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>15000</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>18</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>8500</value><footnoteId id="F2"
/></transactionShares><transactionValue><value>18</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>2001-01-01</value></exerciseDate><expirationDate><value>2006-12-31</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>8500</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>12.3125</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></tran
sactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>10000</value><footnoteId id="F2"/></transactionShares><transactionValue><value>12.3125</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>2002-01-01</value></exerciseDate><expirationDate><value>2007-12-31</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyingSecurityTitle><underlyingSecurityShares><value>10000</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwner
ship><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><derivativeSecurity><securityTitle><value>Employee Stock Option (right to buy)</value></securityTitle><conversionOrExercisePrice><value>12.9375</value></conversionOrExercisePrice><transactionDate><value>2003-05-09</value></transactionDate><deemedExecutionDate><value>2003-05-09</value></deemedExecutionDate><transactionCoding><transactionFormType>4</transactionFormType><transactionCode>D</transactionCode><equitySwapInvolved>0</equitySwapInvolved></transactionCoding><transactionAmounts><transactionShares><value>10000</value><footnoteId id="F2"/></transactionShares><transactionValue><value>12.9375</value></transactionValue><transactionAcquiredDisposedCode><value>D</value></transactionAcquiredDisposedCode></transactionAmounts><exerciseDate><value>2003-01-01</value></exerciseDate><expirationDate><value>2008-12-31</value></expirationDate><underlyingSecurity><underlyingSecurityTitle><value>Common Stock</value></underlyi
ngSecurityTitle><underlyingSecurityShares><value>10000</value></underlyingSecurityShares></underlyingSecurity><postTransactionAmounts><sharesOwnedFollowingTransaction><value>0</value></sharesOwnedFollowingTransaction></postTransactionAmounts><ownershipNature><directOrIndirectOwnership><value>D</value></directOrIndirectOwnership><natureOfOwnership><value></value></natureOfOwnership></ownershipNature></derivativeSecurity><footnotes><footnote id="F1">These options were issued in connection with the Company's option exchange program.  33.34% of the shares subject to the option vest and become exercisable on 01/01/2004.  Thereafter, the remaining shares subject to the option vest and become exercisable in 24 equal monthly installments, at the rate of 14,803 shares per year.  The option is exercisable as to 0 shares on 05/09/2003.</footnote><footnote id="F2">These options were cancelled in connection with the Company's option exchange program</footnote></footnotes><ownerSignature><signatureName>/s/Douglas L. Cole<
/signatureName><signatureDate>2003-05-13</signatureDate></ownerSignature></ownershipDocument>

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</SEC-DOCUMENT>
-----END PRIVACY-ENHANCED MESSAGE-----