Stock Option Exchange Program

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Exhibit 99.(a)(1)(B)


MEMO To: abM_1st_namebb abLast_Namebb
From:

B. Lynne Parshall
Date:

APRIL 9, 2003
Subject:

Stock Option Exchange Program


Isis is pleased to announce that its Board of Directors has approved management's proposal to allow eligible employees the opportunity to exchange outstanding stock options granted prior to January 5, 2002, under Isis' 1989 Stock Option Plan and 2000 Broad-Based Equity Incentive Plan for replacement options to purchase shares of Isis' Common Stock. This is a one-time opportunity designed to improve performance incentives for our employees and thereby maximize stockholder value. The key features of this offer are summarized below.

Please also read the distributed Offer to Exchange and Summary of Terms of Option Exchange in their entirety, because the information in this memorandum is not complete and does not contain all of the information relevant to your decision whether or not to participate in this offer. You can obtain a copy of Offer to Exchange and Summary of Terms of Option Exchange on the Isis Intranet under the heading "Stock Option Exchange Program." In addition, if you contact Linda Powell at (760) 603-2471 she will provide you a copy of these documents.

Isis is offering its employees the opportunity to exchange eligible options as follows: Option Price Exchange Ratio
(new for old) Greater than or equal to $5 but less than $10 1:1.5 Greater than or equal to $10 but less than $15 1:2 Greater than or equal to $15 but ...