IONIS PHARMACEUTICALS INC — Director's Dealing 2012

Jan 3, 2012

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2012-01-01

Reporting Person: Monia Brett P (Director, Senior Vice President)

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2012-01-01	Common Stock	J	587	$6.1285	Disposed	5660	Direct

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2012-01-01	Employee Stock Option (right to buy)	$7.21	A	7500	Acquired	2021-12-31	Common Stock (7500)	Direct
2012-01-03	Employee Stock Option (right to buy)	$7.25	A	18993	Acquired	2022-01-02	Common Stock (18993)	Direct

Footnotes

F1: Reporting 587 shares acquired under the Isis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on January 1, 2012. Theses 587 shares may not be sold until July 2, 2012.

F2: Grant of 1/1/12 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option will vest and become exercisable on 1/1/13. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 1,875 shares per year. The option is exercisable as to 0 shares on 1/1/12.

F3: Grant of 1/3/12 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option will vest and become exercisable on 1/3/13. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 4,749 shares per year. The option is exercisable as to 0 shares on 1/3/12.