0001047469-05-006784 Sample Contracts

AGREEMENT FOR SALE AND ASSIGNMENT OF RIGHTS
Agreement for Sale and Assignment of Rights • March 16th, 2005 • Isis Pharmaceuticals Inc • Pharmaceutical preparations • New York

THIS AGREEMENT (the "Agreement") is made and entered into as of this 21 day of December, 2004 (the "Effective Date") by and between ISIS PHARMACEUTICALS, INC., a subsisting corporation under the laws of the State of Delaware ("ISIS") and DRUG ROYALTY USA, INC., a subsisting corporation under the laws of the State of Nevada ("DRC").

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Isis Pharmaceuticals, Inc. 2000 Plan Supplemental Stock Option Agreement
Supplemental Stock Option Agreement • March 16th, 2005 • Isis Pharmaceuticals Inc • Pharmaceutical preparations

Isis Pharmaceuticals, Inc. (the "Company"), pursuant to its 2000 Broad-Based Equity Incentive Plan (the "Plan") has this day granted to the undersigned optionee, an option to purchase shares of the common stock of the Company ("Common Stock") as described herein. This option is not intended to qualify and will not be treated as an "incentive stock option" within the meaning of Section 422 of the Internal Revenue Code of 1986, as amended from time to time (the "Code"). This option is subject to all of the terms and conditions as set forth herein and on Attachment I hereto, which is incorporated herein in its entirety.

Isis Pharmaceuticals, Inc. Supplemental Stock Option Agreement
Supplemental Stock Option Agreement • March 16th, 2005 • Isis Pharmaceuticals Inc • Pharmaceutical preparations

Isis Pharmaceuticals, Inc. (the "Company"), pursuant to its 1989 Stock Option Plan (the "Plan") has this day granted to the undersigned optionee, an option to purchase shares of the common stock of the Company ("Common Stock") as described herein. This option is not intended to qualify and will not be treated as an "incentive stock option" within the meaning of Section 422 of the Internal Revenue Code of 1986, as amended from time to time (the "Code"). This option is subject to all of the terms and conditions as set forth herein and on Attachment I hereto, which is incorporated herein in its entirety.

COLLABORATION AND LICENSE AGREEMENT
Collaboration and License Agreement • March 16th, 2005 • Isis Pharmaceuticals Inc • Pharmaceutical preparations • Delaware

THIS COLLABORATION AND LICENSE AGREEMENT ("Agreement") is made and entered into effective as of February 10, 2005 (the "Effective Date"), by and among Sarissa, Inc., having principal offices at 121 Timber Drive, London, ON, N6K4A2, Canada ("Sarissa") and Isis Pharmaceuticals, Inc., having principal offices at 2292 Faraday Avenue, Carlsbad CA 92008 ("Isis"). Sarissa and Isis each may be referred to herein individually as a "Party," or collectively as the "Parties."

Amendment No. 1
Isis Pharmaceuticals Inc • March 16th, 2005 • Pharmaceutical preparations • Delaware

This AMENDMENT No. 1 (the "Amendment") is entered into as of the 21 day of December, 2004 ("the Effective Date") by and among EYETECH PHARMACEUTICALS, INC., a Delaware Corporation having its principal place of business at 3 Times Square, 12th Floor, New York, NY 10036 ("EYETECH") and ISIS PHARMACEUTICALS, INC., a Delaware Corporation having its principal place of business at 2292 Faraday Ave., Carlsbad CA ("ISIS") to amend the License Agreement effective as of December 31, 2001 ("the Agreement"), by and among EYETECH and ISIS. Capitalized terms used and not otherwise defined herein shall have the meanings given them in the Agreement.

SECURITY AGREEMENT
Security Agreement • March 16th, 2005 • Isis Pharmaceuticals Inc • Pharmaceutical preparations • New York

THIS SECURITY AGREEMENT (this "Agreement") is made and entered into as of this 21 day of December, 2004 by and between ISIS PHARMACEUTICALS, INC., a subsisting corporation under the laws of the State of Delaware ("ISIS"), and DRUG ROYALTY USA, INC., a subsisting corporation under the laws of the State of Nevada ("DRC").

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