0000912057-02-021915 Sample Contracts

REGISTRATION RIGHTS AGREEMENT
Registration Rights Agreement • May 24th, 2002 • Isis Pharmaceuticals Inc • Pharmaceutical preparations • New York

THIS REGISTRATION RIGHTS AGREEMENT (the “Agreement”) is made and entered into as of May 1, 2002, by and between Isis Pharmaceuticals, Inc., a Delaware corporation (the “Company”) and UBS Warburg LLC and the other Initial Purchasers named in the Purchase Agreement referred to below (collectively, the “Initial Purchasers”), for whom UBS Warburg LLC is acting as representative, pursuant to that certain Purchase Agreement, dated as of April 26, 2002 (the “Purchase Agreement”) between the Company and the Initial Purchasers.

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Isis Pharmaceuticals, Inc. due 2009 PURCHASE AGREEMENT
Purchase Agreement • May 24th, 2002 • Isis Pharmaceuticals Inc • Pharmaceutical preparations • New York

The Notes are to be issued pursuant to an indenture (the "Indenture") to be dated as of May 1, 2002, between the Company and Wells Fargo Bank Minnesota, N. A., as trustee (the "Trustee"). Copies of the Indenture, in substantially final form, have been delivered to the Initial Purchasers. The Notes will be convertible in accordance with their terms and the terms of the Indenture into shares of the common stock (the "Common Stock") of the Company, par value $0.001 per share (the "Shares").

ISIS PHARMACEUTICALS, INC.
Isis Pharmaceuticals Inc • May 24th, 2002 • Pharmaceutical preparations

THIS SECURITY HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), OR THE SECURITIES LAWS OF ANY STATE OR OTHER JURISDICTION. NEITHER THIS SECURITY NOR ANY INTEREST OR PARTICIPATION HEREIN MAY BE REOFFERED, SOLD, ASSIGNED, TRANSFERRED, PLEDGED, ENCUMBERED OR OTHERWISE DISPOSED OF IN THE ABSENCE OF SUCH REGISTRATION OR UNLESS SUCH TRANSACTION IS EXEMPT FROM, OR NOT SUBJECT TO, SUCH REGISTRATION. THE HOLDER HEREOF MAY NOT ENGAGE IN HEDGING TRANSACTIONS WITH RESPECT TO THIS SECURITY UNLESS SUCH TRANSACTIONS ARE IN COMPLIANCE WITH THE SECURITIES ACT.

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