X0202 4 2007-04-17 0000874015 ISIS PHARMACEUTICALS INC ISIS 0001073385 PARSHALL B LYNNE C/O ISIS PHARMACEUTICALS, INC. 1896 RUTHERFORD ROAD CARLSBAD CA 92008 1 1 0 0 Executive Vice President Employee Stock Option (right to buy) 5.25 2007-04-17 2007-04-17 5 G 0 10000 0 D 2007-01-03 2013-01-02 Common Stock 49506 39506 D Employee Stock Option (right to buy) 5.25 2007-04-17 2007-04-17 5 G 0 5000 0 A 2007-04-17 2013-01-02 Common Stock 5000 5000 I By daughter Employee Stock Option (right to buy) 5.25 2007-04-17 2007-04-17 5 G 0 5000 0 A 2007-04-17 2013-01-02 Common Stock 5000 5000 I By daughter The reporting person transferred options to her two daughters (one is a minor) who share reporting person's household, divided equally. Stock option under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vested and became exercisable on 1-3-07. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 12,377 shares per year. The option was exercisable as to 15,471 shares on 4-17-07. /s/B. Lynne Parshall 2007-04-18