X0306 4 2013-01-15 0000874015 ISIS PHARMACEUTICALS INC ISIS 0000897667 CROOKE STANLEY T C/O ISIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD CA 92010 1 1 0 0 Chairman, CEO and President Common Stock 2013-01-15 2013-01-15 4 M 0 2978 0 A 2978 D Common Stock 2013-01-16 2013-01-16 4 S 0 1317 13.9999 D 1661 D Common Stock 2013-01-15 2013-01-15 4 M 0 317 0 A 317 I by wife Common Stock 2013-01-16 2013-01-16 4 S 0 143 13.9994 D 174 I by wife Common Stock 875391 I by Trust Restricted Stock Units 2013-01-15 2013-01-15 4 M 0 2978 0 D Common Stock 2978 8932 D Restricted Stock Units 2013-01-15 2013-01-15 4 M 0 317 0 D Common Stock 317 949 I by wife Restricted Stock Units 2013-01-15 2013-01-15 4 A 0 1666 0 A Common Stock 1666 1666 I by wife Acquired pursuant to vesting and release of shares pursuant to an RSU award granted on January 15, 2012. The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice, dated January 15, 2012 Restricted Stock Unit Award granted on January 15, 2012. Restricted Stock Units vest in equal annual installments, the first installment vested on January 15, 2013. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2016. Each restricted stock unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value. Restricted Stock Units vest in four equal annual installments, the first installment vesting on January 15, 2014. Upon vesting, the restricted stock units will be paid out in whole shares of Isis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2017. The RSU is vested as to 0 shares on January 15, 2013. /s/B. Lynne Parshall, Attorney-in-Fact 2013-01-17