IONIS PHARMACEUTICALS INC — Director's Dealing 2014

Jan 3, 2014

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2014-01-02

Reporting Person: CROOKE STANLEY T (Director, Chairman, President and CEO)

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2014-01-02	Common Stock	M	25000	$14.47	Acquired	26661	Direct
2014-01-02	Common Stock	S	25000	$39.253	Disposed	1661	Direct
2014-01-02	Common Stock	M	4000	$14.47	Acquired	5661	Direct
2014-01-02	Common Stock	S	4000	$40.00	Disposed	1661	Direct
2014-01-02	Common Stock	M	2500	$14.47	Acquired	2674	Indirect
2014-01-02	Common Stock	S	2500	$39.253	Disposed	174	Indirect

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2014-01-02	Employee Stock Option (right to buy)	$39.87	A	187500	Acquired	2021-01-01	Common Stock (187500)	Direct
2014-01-02	Employee Stock Option (right to buy)	$39.87	A	8500	Acquired	2021-01-01	Common Stock (8500)	Indirect

Holdings (Non-Derivative)

Security	Shares	Ownership
Common Stock	725391	Indirect

Footnotes

F1: Acquired as a result of exercising a stock option pursuant to a Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on 8/6/13.

F2: Acquired as a result of exercising a stock option pursuant to a Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person's wife on 8/6/13.

F3: Grant of 1/2/14 to reporting person of stock options under the Isis Pharmaceuticals, Inc. 2011 Equity Incentive Plan. 25% of the shares subject to the option vest and become exercisable on 1/2/15. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 46,875 shares per year. The option shall be fully vested and exercisable on 1/2/18. The option is exercisable as to 0 shares on 1/2/14.

F4: Grant of 1/2/14 to reporting person's wife of stock options under the Isis Pharmaceuticals, Inc. 2011 Equity Incentive Plan. 25% of the shares subject to the option vest and become exercisable on 1/2/15. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 2,125 shares per year. The option shall be fully vested and exercisable on 1/2/18. The option is exercisable as to 0 shares on 1/2/14.