IONIS PHARMACEUTICALS INC — Director's Dealing 2011

Dec 20, 2011

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2011-12-16

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

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2011-12-16	Common Stock	M	15000	$5.80	Acquired	15000	Direct
2011-12-16	Common Stock	S	15000	$6.79	Disposed	0	Direct
2011-12-16	Common Stock	M	1500	$5.80	Acquired	1500	Indirect
2011-12-16	Common Stock	S	1500	$6.79	Disposed	0	Indirect
2011-12-19	Common Stock	M	1822	$5.80	Acquired	1822	Direct
2011-12-19	Common Stock	S	1822	$6.90	Disposed	0	Direct
2011-12-19	Common Stock	M	15178	$5.80	Acquired	15178	Direct
2011-12-19	Common Stock	S	15178	$6.82	Disposed	0	Direct
2011-12-19	Common Stock	M	118	$5.80	Acquired	118	Indirect
2011-12-19	Common Stock	S	118	$6.90	Disposed	0	Indirect
2011-12-19	Common Stock	M	982	$5.80	Acquired	982	Indirect
2011-12-19	Common Stock	S	982	$6.82	Disposed	0	Indirect
2011-12-20	Common Stock	M	22000	$5.80	Acquired	22000	Direct
2011-12-20	Common Stock	S	22000	$6.82	Disposed	0	Direct
2011-12-20	Common Stock	M	5000	$5.80	Acquired	5000	Direct
2011-12-20	Common Stock	S	5000	$6.92	Disposed	0	Direct
2011-12-20	Common Stock	M	300	$5.80	Acquired	300	Indirect
2011-12-20	Common Stock	S	300	$6.92	Disposed	0	Indirect
2011-12-20	Common Stock	M	1400	$5.80	Acquired	1400	Indirect
2011-12-20	Common Stock	S	1400	$6.82	Disposed	0	Indirect

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2011-12-16	Employee Stock Option (right to buy)	$5.80	M	15000	Disposed	2012-01-02	Common Stock (15000)	Direct
2011-12-16	Employee Stock Option (right to buy)	$5.80	M	1500	Disposed	2012-01-02	Common Stock (1500)	Indirect
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	17000	Disposed	2012-01-02	Common Stock (17000)	Direct
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	1100	Disposed	2012-01-02	Common Stock (1100)	Indirect
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	27000	Disposed	2012-01-02	Common Stock (27000)	Direct
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	1700	Disposed	2012-01-02	Common Stock (1700)	Indirect

Holdings (Non-Derivative)

Security	Shares	Ownership
Common Stock	875391	Indirect

Footnotes

F1: Acquired as a result of exercising a stock option that was scheduled to expire on 1/2/12. The purchase and sale reported on this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the reporting person on 10/3/11.

F2: Acquired as a result of exercising a stock option that was scheduled to expire on 1/2/12. The purchase and sale reported on this Form 4 was effected pursuant to a Rule 10b5-1 trading plan adopted by the wife of the reporting person on 10/3/11.