IONIS PHARMACEUTICALS INC — Director's Dealing 2014

Jul 2, 2014

SEC Form 4 — Statement of Changes in Beneficial Ownership

Issuer: ISIS PHARMACEUTICALS INC (ISIS)
CIK: 0000874015
Period of Report: 2014-07-01

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

Non-Derivative Transactions

Date	Security	Code	Shares	Price	A/D	Holdings After	Ownership
2014-07-01	Common Stock	M	15500	$14.47	Acquired	22441	Direct
2014-07-01	Common Stock	S	15500	$35.578	Disposed	6941	Direct
2014-07-01	Common Stock	M	200	$14.47	Acquired	827	Indirect
2014-07-01	Common Stock	S	200	$35.55	Disposed	627	Indirect
2014-07-01	Common Stock	M	1800	$11.27	Acquired	2427	Indirect
2014-07-01	Common Stock	S	1800	$35.55	Disposed	627	Indirect

Derivative Transactions

Date	Security	Exercise Price	Code	Shares	A/D	Expiration	Underlying	Ownership
2014-07-01	Employee Stock Option (right to buy)	$14.47	M	15500	Acquired	2016-01-02	Common Stock (15500)	Direct
2014-07-01	Employee Stock Option (right to buy)	$14.47	M	200	Disposed	2016-01-02	Common Stock (200)	Indirect
2014-07-01	Employee Stock Option (right to buy)	$11.27	M	1800	Disposed	2017-01-03	Common Stock (1800)	Indirect

Holdings (Non-Derivative)

Security	Shares	Ownership
Common Stock	725391	Indirect

Footnotes

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

F2: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $35.51 to $35.65, inclusive. The reporting person undertakes to provide to Isis Pharmaceuticals, Inc., any security holder of Isis Pharmaceuticals, Inc. or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnote (2) on this Form 4.

F3: Acquired as a result of exercising a stock option pursuant to Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to Rule 10b5-1 Trading Plan adopted by the reporting person's wife on 8/6/13.

F4: Grant of 1/2/2009 to reporting person of stock options under the Isis Pharmacueticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vested and became exercisable on 1/2/2010. Thereafter, the remaining shares subject to the option vest and become exercisable in 36 equal monthly installments, at the rate of 37,500 shares per year. Following this transaction, the option was exercisable as to 66,500 on 7/1/14.

F5: Grant of 1/4/10 to reporting person's wife of stock options under the Isis Pharmacueticals, Inc. 1989 Stock Option Plan. 25% of the shares subject to the option vested and became exercisable on 1/4/11. Thereafter, the remaining shares subject to the option vest and become exercisalbe in 36 equal monthly installments, at the rate of 1,650 shares per year. Following this transaction, the option was exercisable as to 4,800 on 7/1/2014.