IONIS PHARMACEUTICALS INC — Director's Dealing 2012

May 22, 2012

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2012-05-21

Reporting Person: BERTHELSEN SPENCER R (Director)

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2012-05-21	Common Stock	M	2731	$9.40	Acquired	32031	Direct
2012-05-21	Common Stock	S	2731	$9.42	Disposed	29300	Direct
2012-05-22	Common Stock	M	17269	$9.40	Acquired	46569	Direct
2012-05-22	Common Stock	S	17269	$9.56	Disposed	29300	Direct

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2012-05-21	Director Stock Option (right to buy)	$9.40	M	2731	Disposed	2012-05-30	Common Stock (2731)	Direct
2012-05-22	Director Stock Option (right to buy)	$9.40	M	17269	Disposed	2012-05-30	Common Stock (17269)	Direct

Holdings (Non-Derivative)

Security	Shares	Ownership
Common Stock	70	Indirect

Footnotes

F1: Acquired as a result of exercising a stock option that was scheduled to expire on 5/30/12. 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 3/1/12.