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: PARSHALL B LYNNE (Director, Director, COO)

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2011-12-16	Common Stock	M	2000	$5.80	Acquired	3985	Direct
2011-12-16	Common Stock	S	2000	$6.79	Disposed	1985	Direct
2011-12-19	Common Stock	M	2000	$5.80	Acquired	2000	Indirect
2011-12-16	Common Stock	S	2000	$6.79	Disposed	0	Indirect
2011-12-16	Common Stock	M	2000	$5.80	Acquired	2000	Indirect
2011-12-16	Common Stock	S	2000	$6.79	Disposed	0	Indirect
2011-12-19	Common Stock	M	2054	$5.80	Acquired	4039	Direct
2011-12-19	Common Stock	S	2054	$6.82	Disposed	1985	Direct
2011-12-19	Common Stock	M	246	$5.80	Acquired	2231	Direct
2011-12-19	Common Stock	S	246	$6.90	Disposed	1985	Direct
2011-12-19	Common Stock	M	2054	$5.80	Acquired	2054	Indirect
2011-12-19	Common Stock	S	2054	$6.82	Disposed	0	Indirect
2011-12-19	Common Stock	M	246	$5.80	Acquired	246	Indirect
2011-12-19	Common Stock	S	246	$6.90	Disposed	0	Indirect
2011-12-20	Common Stock	M	2900	$5.80	Acquired	4885	Direct
2011-12-20	Common Stock	S	2900	$6.82	Disposed	1985	Direct
2011-12-20	Common Stock	M	700	$5.80	Acquired	2685	Direct
2011-12-20	Common Stock	S	700	$6.92	Disposed	1985	Direct
2011-12-20	Common Stock	M	700	$5.80	Acquired	700	Indirect
2011-12-20	Common Stock	S	700	$6.92	Disposed	0	Indirect
2011-12-20	Common Stock	M	2800	$5.80	Acquired	2800	Indirect
2011-12-20	Common Stock	S	2800	$6.82	Disposed	0	Indirect
2011-12-20	Common Stock	M	700	$5.80	Acquired	700	Indirect
2011-12-20	Common Stock	S	700	$6.92	Disposed	0	Indirect
2011-12-20	Common Stock	M	2800	$5.80	Acquired	2800	Indirect
2011-12-20	Common Stock	S	2800	$6.82	Disposed	0	Indirect
2011-12-19	Common Stock	M	246	$5.80	Acquired	246	Indirect
2011-12-19	Common Stock	S	246	$6.90	Disposed	0	Indirect
2011-12-19	Common Stock	M	2054	$580.00	Acquired	2054	Indirect
2011-12-19	Common Stock	S	2054	$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	2000	Disposed	2012-01-02	Common Stock (2000)	Direct
2011-12-16	Employee Stock Option (right to buy)	$5.80	M	2000	Disposed	2012-01-02	Common Stock (2000)	Indirect
2011-12-16	Employee Stock Option (right to buy)	$5.80	M	2000	Disposed	2012-01-02	Common Stock (2000)	Indirect
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	2300	Disposed	2012-01-02	Common Stock (2300)	Direct
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	2300	Disposed	2012-01-02	Common Stock (2300)	Indirect
2011-12-19	Employee Stock Option (right to buy)	$5.80	M	2300	Disposed	2012-01-02	Common Stock (2300)	Indirect
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	3600	Disposed	2012-01-02	Common Stock (3600)	Direct
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	3500	Disposed	2012-01-02	Common Stock (3500)	Indirect
2011-12-20	Employee Stock Option (right to buy)	$5.80	M	3500	Disposed	2012-01-02	Common Stock (3500)	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 10/21/11.

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 reporting person's daughter on 10/21/11.