X0202 4 2007-11-28 0000874015 ISIS PHARMACEUTICALS INC ISIS 0000897667 CROOKE STANLEY T C/O ISIS PHARMACEUTICALS, INC. 1896 RUTHERFORD ROAD CARLSBAD CA 92008 1 1 0 0 Chairman, President, CEO Common Stock 2007-11-28 2007-11-28 4 M 0 30000 5.15 A 903291 D Common Stock 2007-11-28 2007-11-28 4 S 0 30000 18.011 D 872241 D Common Stock 2007-11-30 2007-11-30 4 M 0 29851 5.15 A 903142 D Common Stock 2007-11-30 2007-11-30 4 S 0 29851 18.028 D 872241 D Common Stock 1050 I By wife Employee Stock Option (right to buy) 5.15 2007-11-28 2007-11-28 4 M 0 30000 0 D 2006-01-01 2008-12-31 Common Stock 30000 37333 D Employee Stock Option (right to buy) 5.15 2007-11-30 2007-11-30 4 M 0 29851 0 D 2006-01-01 2008-12-31 Common Stock 29851 7482 D The purchase reported on this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the reporting person on 10/5/05. The sale reported on this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the reporting person on 10/5/05. /s/Stanley T. Crooke 2007-11-30