<SUBMISSION>
<PAPER>
<ACCESSION-NUMBER>9999999997-15-010058
<TYPE>ARS
<PUBLIC-DOCUMENT-COUNT>1
<PERIOD>20141231
<FILING-DATE>20150519
<DATE-OF-FILING-DATE-CHANGE>20150521
<EFFECTIVENESS-DATE>20150519
<FILER>
<COMPANY-DATA>
<CONFORMED-NAME>ISIS PHARMACEUTICALS INC
<CIK>0000874015
<ASSIGNED-SIC>2834
<IRS-NUMBER>330336973
<STATE-OF-INCORPORATION>DE
<FISCAL-YEAR-END>1231
</COMPANY-DATA>
<FILING-VALUES>
<FORM-TYPE>ARS
<ACT>34
<FILE-NUMBER>000-19125
<FILM-NUMBER>15007471
</FILING-VALUES>
<BUSINESS-ADDRESS>
<STREET1>2855 GAZELLE COURT
<CITY>CARLSBAD
<STATE>CA
<ZIP>92010
<PHONE>7609319200
</BUSINESS-ADDRESS>
<MAIL-ADDRESS>
<STREET1>2855 GAZELLE COURT
<CITY>CARLSBAD
<STATE>CA
<ZIP>92010
</MAIL-ADDRESS>
</FILER>
<DOCUMENT>
<TYPE>ARS
<SEQUENCE>1
<FILENAME>9999999997-15-010058.paper
<DESCRIPTION>AUTO-GENERATED PAPER DOCUMENT
<TEXT>
This document was generated as part of a paper submission.
Please reference the Document Control Number 15007471 for access to the original document.
</TEXT>
</DOCUMENT>
</SUBMISSION>
