X0101 42003-05-09 0000874015 ISIS PHARMACEUTICALS INC ISIS0000897667 CROOKE STANLEY T 1100Chairman, President, CEOEmployee Stock Option (right to buy)5.152003-05-092003-05-094A0673335.15A2004-01-012008-12-31Common Stock6733367333DEmployee Stock Option (right to buy)6.752003-05-092003-05-094D0300006.75D1998-12-312003-12-30Common Stock300000DEmployee Stock Option (right to buy)13.1252003-05-092003-05-094D04000013.125D2000-01-012005-12-31Common Stock400000DEmployee Stock Option (right to buy)182003-05-092003-05-094D02250018D2001-01-012006-12-31Common Stock225000DEmployee Stock Option (right to buy)21.052003-05-092003-05-094D05500021.05D2006-01-022012-01-01Common Stock550000DEmployee Stock Option (right to buy)5.152003-05-092003-05-094A046915.15A2004-01-012008-12-31Common Stock46914691IBy WifeEmployee Stock Option (right to buy)6.752003-05-092003-05-094D022506.75D1998-12-312003-12-30Common Stock22500IBy WifeEmployee Stock Option (right to buy)13.1252003-05-092003-05-094D0225013.125D2000-01-012005-12-31Common Stock22500IBy WifeEmployee Stock Option (right to buy)16.1252003-05-092003-05-024D0225016.125D2001-02-012007-01-31Common Stock22500IBy WifeEmployee Stock Option (right to buy)182003-05-092003-05-094D0100018D2001-01-012006-12-31Common Stock10000IBy WifeEmployee Stock Option (right to buy)21.052003-05-092003-05-094D0230021.05D2006-01-022012-01-01Common Stock23000IBy WifeThese 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 22,444 shares per year. The option is exercisable as to 0 shares on 05/09/2003.These options were cancelled in connection with the Company's option exchange program. 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 1,564 and 1,564, respectively, shares per year. The option is exercisable as to 0 shares on 05/09/2003. Dr. Crooke disclaims beneficial ownership of the shares of Common Stock owned and issuable upon exercise of options held by his wife./s/Stanley T. Crooke2003-05-13