ISIS PHARMACEUTICALS, INC.

                               10B5-1 TRADING PLAN



         This 10b5-1 Trading Plan, (the "Trading Plan"), between ISIS

PHARMACEUTICALS, INC. ("Isis") and GOLDEN TRIANGLE SECURITIES LLC ("Broker"), is

entered into on February 26, 2002. Capitalized terms not otherwise defined

herein will have the meanings given to them in Exhibit A attached hereto.



         1.       RECITALS.



                  (a)      This Trading Plan is entered into between Isis and

Broker for the purpose of establishing a trading plan that complies with the

requirements of Rule 10b5-1(c) under the Exchange Act.



                  (b)      The purpose of this Trading Plan is to provide a

mechanism by which eligible Sellers can orderly dispose of a portion of each

Seller's holdings of Stock, including Stock that such Seller has the right to

acquire under the Options.



                  (c)      Isis and Broker hereby agree as follows:



         2.       APPOINTMENT. Isis hereby appoints and authorizes Broker to

sell shares of Stock pursuant to the terms and conditions set forth below and in

the applicable Sellers Plan. Subject to the terms and conditions set forth

below, Broker hereby accepts such appointment.



         3.       SELLERS PLANS. Each Seller may establish up to three

individual Sellers Plans with Broker in any Sales Period. In connection with

such Sellers Plans, each Seller will establish an account at Broker in the name

of and for the benefit of Seller (the "Plan Account"). Sales under each Sellers

Plan cannot begin until the Broker receives (i) the Plan Shares, to the extent

such Plan Shares are currently owned by Seller, (ii) a properly executed Seller

Representation Letter and (iii) a properly completed and executed Sellers Plan,

including an acknowledgment by Isis.



         4.       OBLIGATIONS OF BROKER. With respect to each Sellers Plan,

Broker will have the following obligations:



                  (a)      Broker will sell the Plans Shares for the account of

each Seller according to the terms of the Seller's Sellers Plan.



                  (b)      Broker will not sell any Stock when broker is in

possession of any material nonpublic information concerning Isis or its

securities.



                  (c)      Once a Sellers Plan becomes effective, Broker will

not allow Seller to exercise, any influence over how, when or whether to effect

sales of Stock pursuant to the Sellers Plan.





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                  (d)      Broker will withdraw Stock from Seller's Plan Account

in order to effect sales of Stock under Seller's Sellers Plan. Broker will

exercise Options to effect such sales according to the Seller's Option Priority

Guidelines.



                  (e)      Broker will deliver the proceeds from each sale of

unrestricted Stock effected under a Sellers Plan to Seller's Account on a normal

three-day settlement basis less any commission, commission equivalent, mark-up

or differential and other expenses of sale to be paid to Broker. With respect to

each sale of restricted Stock, Broker will deliver the net proceeds from such

sales as soon as reasonably practicable.



                  (f)      Broker will, in connection with the exercise of

Options, remit to Isis the exercise price thereof along with such amounts as may

be necessary to satisfy withholding obligations. These amounts will be deducted

from the proceeds of the sale of the Stock.



                  (g)      To the extent that any Stock remains in the Plan

Account upon termination of the Sellers Plan, Broker agrees to return such Stock

promptly to the Seller.



                  (h)      Broker agrees to conduct all sales pursuant to each

Sales Plan in accordance with the manner of sale requirement of Rule 144 of the

Securities Act and in no event will Broker effect any sale if such sale would

exceed the then-applicable amount limitation under Rule 144 or will violate the

"short-swing profit" provisions of Section 16 of the Exchange Act. Broker will

file Forms 144 on behalf of Seller as required by applicable law.



                  (i)      Promptly after each Sale, Broker will advise Seller

in writing as to the number of shares of Stock sold, the date of each sale and

the sales price.



                  (j)      Broker will suspend or terminate a Sellers Plan and

cancel any pending sale upon notice from Isis of a Suspension Event (such notice

to specify termination or suspension of the Sellers Plan). In the event of a

suspension, Broker will cancel any open orders for sales of Plan Shares and will

cease placing orders for Sales of Plan Shares under the Sellers Plan until

Broker receives written notice from Isis stating that the relevant Suspension

Event is no longer in effect. Upon Broker's receipt of notice from Isis, Broker

may resume placing orders for sales of the Plan Shares in accordance with the

terms and conditions of this Trading Plan and the applicable Sellers Plan;

PROVIDED, HOWEVER, that Broker will not reinstate any orders cancelled due to a

suspension and will not place any orders that would have been placed during the

suspension.



                  (k)      Broker will not sell more than an aggregate of 30,000

shares on any single Trading Day for any individual Seller under all the Sellers

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