Exhibit 10.47
*** TEXT OMITTED AND FILED SEPARATELY
CONFIDENTIAL TREATMENT REQUESTED
UNDER 17 C.F.R. SECTIONS 200.80(b)(4),
200.83 AND 240.24b-2
PATENT RIGHTS PURCHASE AGREEMENT
This Patent Rights Purchase Agreement (this "Agreement") is
made and entered into as of December 18, 1998 (the "Effective Date") between
Isis Pharmaceuticals, Inc. ("Isis"), and Gilead Sciences, Inc. ("Gilead").
1. DEFINITIONS.
1.1 "Cationic Lipid" means those compounds
described in United States Patent Nos. 5,777,153 and 5,705,693; United States
Patent Application Serial No. 08/672,206; and European Patent Application No.
97931462.2, to the extent such compounds are not Codeblocker Compounds.
1.2 "Codeblocker Compound" means an oligonucleotide
that binds directly to DNA or RNA within a cell on a selective basis
determined by the nucleotide sequence of the target DNA or RNA and exerts its
biological activity predominantly through binding to DNA or RNA to inhibit
the transcription or replication of the target DNA or RNA or binding to RNA
to inhibit the translation, processing, packaging or regulatory activity of
the target RNA. A Codeblocker Compound may also have a mechanism of action
or biological activity other than one conferred through direct binding to RNA
or DNA provided that (i) the compound originally was designed to bind a
target DNA or RNA and (ii) the final compound or any compounds used to derive
the final compound were not identified using selective purification and
polymerase amplification in any fashion. An oligonucleotide, is any oligomer
or polymer made up [***] An oligonucleotide includes RNA or DNA fragments,
and may be composed of naturally occurring or non-naturally occurring bases,
sugars or intersugar linkages. An oligonucleotide may have the bases, sugars
or intersugar linkages partially or completely absent. Oligonucleotides may
be made such that adjacent nucleoside or nucleoside fragments are linked
together by phosphate groups or modified or non-naturally occurring
internucleoside linkages to form the internucleoside backbone of the
oligomer, whether or not such linkages retain a phosphorous atom in the
linkage.
1.3 "Oligonucleotide Delivery System" means any
carrier, targeting entity, excipient, formulation, device, prodrug, covalent
or noncovalent conjugate, encapsulating vesicle, microcapsule, micro- or
nanosphere, emulsion, or microemulsion, lipid, liposome, virosome, or
artificial vial envelope which was developed by Gilead on or prior to the
Effective Date, and which (i) enhances the cellular penetration or
circulating half-life of a Codeblocker Compound, (ii) selectively delivers a
Codeblocker compound to the intended target tissue, cell or subcellular
compartment, (iii) provides sustained release of a Codeblocker Compound from
a depot formulation, or (iv) otherwise favorably alters the absorption,
distribution, metabolism or excretion of a Codeblocker Compound so as to
enhance its pharmacological activity of clinical value. "Oligonucleotide
Delivery System" includes cationic lipids.
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[***]=CONFIDENTIAL TREATMENT REQUESTED
1.
1.4 "Patent Rights" means the patents and patent
applications listed in Exhibit A attached hereto.
2. ASSIGNMENTS AND LICENSES.
2.1 Gilead hereby sells and assigns to Isis all of
Gilead's right, title and interest in Patent Rights, subject to the rights of
Glaxo Wellcome Inc. ("Glaxo") under the Collaborative Research Agreement
between Glaxo and Gilead dated March 25, 1996 (the "Glaxo Agreement"),
provided however, that the assignment of U.S. Patent Number 5,256,775 shall
be subject to the condition precedent that Gilead settle the interference
involving this patent on conditions of Gilead's choosing (including conceding
priority). Gilead hereby grants Isis an exclusive, royalty-free, worldwide,
assignable license (with the right to grant sublicenses) to U.S. Patent
Number 5,256,775 beginning on the Effective Date and continuing until such
time that Gilead settles the interference and the assignment to Isis becomes
effective.
2.2 Gilead hereby assigns and delegates to Isis
(and Isis accepts and agrees to perform) all of Gilead's rights and
obligations under the License Agreement between ▇▇▇▇ Research Corporation
("▇▇▇▇ Research") and Gilead dated January 1, 1994 and amended on November
19, 1996. A copy of the written consent to such assignment and delegation
signed by ▇▇▇▇ Research is attached hereto as Exhibit B. In the event that
Isis, by reason of this Agreement, is required to indemnify ▇▇▇▇ Research
under Section 8.1 (b) of the ▇▇▇▇ Research License Agreement, Gilead will
indemnify Isis up to a maximum amount equal to one hundred percent (100%) of
total royalties received by Gilead from ▇▇▇▇ Research; thereafter, Gilead
will not have any indemnity obligations to Isis related to such Agreement.
Gilead will continue to honor its obligations to ▇▇▇▇ Research for activities
preceding the Effective Date of this Agreement.
2.3 Subject to the rights of ▇▇▇▇ Research above,
Isis hereby grants to Gilead an exclusive, perpetual, irrevocable,
royalty-free, worldwide, assignable license (with the right to grant
sublicenses) to directly or indirectly make, have made, use, import, export
or sell compounds and other subject matter falling within the scope of Patent
Rights which are [***]
2.4 Gilead hereby grants to Isis a nonexclusive,
perpetual, royalty-free, worldwide, assignable license (with the right to
grant sublicenses) to compounds and other subject matter which are within the
scope of Patent Rights, solely for use as intermediates in the manufacture of
Codeblocker Compounds or oligomers [***]
2.5 Isis hereby grants to Gilead a non-exclusive,
non-sublicensable, non-assignable, perpetual, irrevocable, royalty-free,
worldwide license under Patent Rights to make and use Codeblocker Compounds
and Oligonucleotide Delivery Systems for internal research purposes, but not
for any commercial purpose.
2.6 Isis will not have any obligations to Gilead
relating to Codeblocker Compounds or this Agreement to the extent arising
prior to the Effective Date.
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[***]=CONFIDENTIAL TREATMENT REQUESTED
2.
2.7 Each party hereby agrees to execute such
documents and to take such other actions as shall be necessary or appropriate
to effectuate the assignments and licenses set forth in this Section 2.
3. REPRESENTATIONS AND WARRANTIES BY GILEAD.
Gilead makes the following representations and warranties to Isis, each of
which will survive the Effective Date:
3.1 To the best of Gilead's knowledge, the Patent
Rights include all of the patents and patent applications owned or controlled
by Gilead on or prior to the Effective Date that cover Codeblocker Compounds
and Oligonucleotide Delivery Systems, their manufacture or use. There are no
other US or unpublished foreign filings owned or controlled by Gilead filed
prior to the Effective Date which claim Codeblocker Compounds or
Oligonucleotide Delivery Systems other than as set forth in Exhibit A, nor
does Gilead have any present intention to make such filings. If Gilead
becomes aware of any patents or patent applications that (i) are owned or
controlled by Gilead, (ii) claim inventions made prior to the Effective Date,
(iii) cover Codeblocker Compounds or Oligonucleotide Delivery Systems, and
(iv) are not included in Exhibit A, Gilead will promptly notify Isis in
writing and execute appropriate documents to transfer such patents and patent
applications to Isis.
3.2 Gilead represents and Isis acknowledges that
(i) the Glaxo Agreement remains in effect and Gilead and Glaxo have ongoing
rights and obligations thereunder, modified to the extent specifically set
forth in this Agreement and (ii) this Agreement is not an assignment of
Gilead's rights or obligations under the Glaxo Agreement and that Isis
assumes no rights or obligations to Glaxo under this Agreement. Gilead
represents that the Research Term and all rights, obligations and funding
relating thereto under the Glaxo Agreement have been terminated. Gilead will
not enter into any future amendments to the Glaxo Agreement which in any way
affect the rights of Isis hereunder.
3.3 The Glaxo Agreement and the license to ▇▇▇▇
Research referenced in Section 2.2 above are the only licenses and Gilead is
not aware of any other third party rights of any kind affecting the Patent
Rights. Except with respect to U.S. Patent Number 5,256,775, which is subject
to an interference proceeding, the Patent Rights are not the subject of any
pending interference, cancellation or other protest proceeding not otherwise
known to Isis, or otherwise subject to rights or obligations to any third
party other than Glaxo and ▇▇▇▇ Research. The complete terms and conditions
of such rights and obligations relating to Glaxo and ▇▇▇▇ Research have been
disclosed to Isis.
3.4 There are no Collaboration Compounds (as
defined in Section 1.7 of the Glaxo Agreement) and none were developed during
the Research Term under the Glaxo Agreement. Gilead does not owe any
royalties to Glaxo or any third party under the Glaxo Agreement nor does
Gilead have any known or pending claims against Glaxo arising out of the
Glaxo Agreement. To the best of Gilead's knowledge, (i) Glaxo does not owe
any royalties to Gilead or any third party under the Glaxo Agreement, (ii)
nor does Glaxo have any known or pending claims against Gilead arising out of
the Glaxo Agreement.
3.
4. TECHNOLOGY TRANSFER.
4.1 Gilead and Isis will cooperate in the filing
and execution of any and all documents necessary to effectuate the assignment
to Isis of the Patent Rights, including the filing of assignments or other
transfer of title covenants with the U.S. Patent and Trademark Office and
foreign patent offices as applicable to the Patent Rights. Within thirty
(30) days from the Effective Date, Gilead will notify all attorneys handling
the prosecution of the Patent Rights to contact the Isis Patent Department to
provide an immediate status update on the Patent Rights and to prepare the
documents necessary to transfer the Patent Rights to Isis. The cost of
recording assignments of the Patent Rights will be borne by Isis. Within
forty-five (45) days from the Effective Date, Gilead and its counsel will use
their reasonable best efforts to transfer all files and supporting documents
relating to the Patent Rights to Isis, including but not limited to, all
initial invention disclosure documents, all documents sent to the U.S. Patent
and Trademark Office regarding inventions and claims, all draft patent
applications, all filing or prosecution documents submitted to the patent
offices, and all file wrappers. Conception notebooks and all other documents
in the possession or under the control of Gilead or its counsel relating to
conception and/or reduction to practice, such as scientist notebooks shall be
obtained in accord with Gilead's ordinary document retention and made
available to Isis upon Isis' reasonable request. All documents to be
provided to Isis hereunder are to be sent by expedited delivery service.
4.2 Gilead will make appropriate scientific staff
available to Isis for a scientific tutorial on the subject matter of this
Agreement, such tutorial not to exceed more than [***] from Gilead's staff
and not to obligate Gilead to disclose any third party confidential
information.
5. PATENT MAINTENANCE AND PROSECUTION RESPONSIBILITIES.
5.1 On and after the Effective Date, Isis will take
responsibility for any action or proceeding involving Patent Rights. The
cost of recording the assignment of Patent Rights shall be borne solely by
Isis. If Isis elects not to take such responsibility involving Patent
Right(s) in a particular country then Isis will timely notify Gilead and
Glaxo 30 days before the time future action is due, and thereafter Gilead or
Glaxo shall undertake such responsibility. If Gilead or Glaxo elects to do
so, Isis will grant any necessary authority to Gilead. Gilead will determine
whether Gilead or Glaxo shall take such responsibility at their expense.
Isis assumes no obligation to Glaxo as a result of its agreement with Gilead
in this Section 5.1.
5.2 NOTICE OF INFRINGEMENT. Isis shall promptly
notify Gilead in writing of any infringement of any assigned Patent Right(s)
of which it becomes aware.
5.3 ENFORCEMENT OF PATENTS. Except as otherwise
set forth in this Section, Isis may, but shall not be required to, prosecute
any alleged infringement or threatened infringement of any assigned Patent
Right(s) of which it is aware or which is brought to its attention. Isis
shall act in its own name and at its own expense. If Isis has failed to
prosecute under the first sentence of this paragraph with respect to alleged
or threatened infringement
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[***]=CONFIDENTIAL TREATMENT REQUESTED
4.
relating to any Patent Right(s) (i) two months after it has been notified in
writing of such alleged infringement, or (ii) one month before the time
limit, if any, set forth in the appropriate laws and regulations for the
filing of such actions, whichever comes first, Gilead (or at its election
Glaxo) may, but shall not be required to, prosecute any such alleged
infringement or threatened infringement of a Patent within the Patent Rights.
In any such event, Gilead or Glaxo shall be free to act in its own name and
at its own expense. Notwithstanding the foregoing and as between the
parties, Gilead shall have the sole and exclusive right of enforcement with
respect to any alleged or threatened infringement of any right within the
scope of the license granted in Section 2.3 of this Agreement. Isis shall
cooperate fully with Gilead or Glaxo in any action by Gilead or Glaxo,
respectively, under this paragraph, including if required in order to bring
such an action, the furnishing of a power of attorney.
6. INDEMNITY AND WARRANTY.
6.1 INDEMNITY BY ISIS. Isis will indemnify, save,
defend and hold Gilead and its agents, directors and employees harmless from
and against any and all suits, claims, actions, demands, liabilities,
expenses and/or loss, including reasonable legal expense and attorneys fees,
resulting from activities under this agreement by Isis.
6.2 INDEMNITY BY GILEAD. Gilead will indemnify,
save, defend and hold Isis and its agents, directors and employees harmless
from and against any and all suits, claims, actions, demands, liabilities,
expenses and/or loss, including reasonable legal expense and attorney fees,
resulting from (i) Gilead's, Gilead's sublicensee's or Gilead's assignee's
activities under the licenses provided for in Sections 2.3 and 2.5; (ii)
Gilead's contractual obligations to third parties including Glaxo and ▇▇▇▇
Research, except to the extent resulting from Isis' activities under this
Agreement; or (iii) Gilead's exercise of the Patent Rights prior to the
Effective Date.
6.3 WARRANTY. Gilead warrants that it has
sufficient right and title to enter into and to perform its obligations under
this Agreement. EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, THE PARTIES
DISCLAIM ALL WARRANTIES OF ANY NATURE, EXPRESS OR IMPLIED, INCLUDING WITHOUT
LIMITATION WARRANTIES OF VALIDITY, MERCHANTABILITY, NONINFRINGEMENT, AND
FITNESS FOR A PARTICULAR PURPOSE.
7. CONFIDENTIALITY. Confidential Information under the
terms of this Agreement is all information relating to the Patent Rights
sold, assigned or licensed to Isis under Section 2.1 and the Technology
Transfer to Isis by Gilead under Section 4.1. Gilead agrees to treat the
Confidential Information as confidential and to protect and maintain the
confidentiality thereof. Gilead will use at least the same standard of care
as it uses to protect its own Confidential Information to ensure that its
employees, agents, and consultants do not disclose or make any unauthorized
use of such Confidential Information. Gilead will promptly notify Isis upon
discovery of any unauthorized use or disclosure of the Confidential
Information. Confidential Information will not include any information which
is generally available to the public, is otherwise part of the public domain
other than through any act or omission of Gilead in breach of this Agreement,
or which is required to be disclosed by law or contract entered into
5.
prior to this Agreement (provided that Isis shall have notice thereof in
advance so that it can act to protect its interests should it decide to do
so).
8. CONSIDERATION. Isis shall pay Gilead the following
noncontingent, non-refundable cash payments as consideration for the
assignments provided for in this Agreement: $2,000,000 on the Effective Date,
$1,000,000 on the first anniversary of the Effective Date, $1,000,000 on the
second anniversary of the Effective Date, and $2,000,000 on the third
anniversary of the Effective Date, for total payments of $6,000,000. In the
event that Isis defaults on any of these payments, after thirty (30) days
notice and an opportunity to cure, then ownership of all Patent Rights will
automatically revert to Gilead and Isis will take all actions reasonably
requested by Gilead for such purposes, including, without limitation, signing
and delivering any applicable assignments and other documents. Isis shall be
entitled to no damages exceeding the consideration set forth in this Section
8 for any uncured claim against Gilead respecting Gilead's performance or
representations hereunder.
9. NOTICES. Notices under this Agreement shall be
sufficient only if personally delivered, delivered by a major commercial
rapid delivery courier service, facsimile or mailed by certified or
registered mail, return receipt requested, to a party at its addresses set
forth as follows:
If to Isis: Isis Pharmaceuticals, Inc.
▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Attn: Executive Vice President, CFO
Facsimile: (▇▇▇) ▇▇▇-▇▇▇▇
If to Gilead: Gilead Sciences, Inc.
▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇ ▇▇▇▇, ▇▇ ▇▇▇▇▇
Attn: Vice President, Intellectual Property
Facsimile: (▇▇▇) ▇▇▇-▇▇▇▇
If to Glaxo: Glaxo Wellcome, Inc.
Five ▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇, ▇▇ ▇▇▇▇▇
Attn: Company Secretary
Facsimile: (▇▇▇) ▇▇▇-▇▇▇▇
10. MISCELLANEOUS. If any provision of this Agreement
shall be adjudged by any court of competent jurisdiction to be unenforceable
or invalid, that provision shall be limited or eliminated to the minimum
extent necessary to continue to effect the intent of the parties, and this
Agreement shall otherwise remain in full force and effect and enforceable.
Any waivers or amendments shall be effective only if made in writing and
signed by a representative of the respective parties authorized to bind the
parties. This Agreement shall be governed by the laws of the State of
Delaware, excluding conflicts-of-law principles. This Agreement is the
complete and exclusive statement of the mutual understanding of the parties
and supersedes and cancels all previous written and oral agreements and
communications relating to the subject matter of this
6.
Agreement, excluding the Confidential Disclosure Agreement between the
parties dated July 29, 1998.
7.
IN WITNESS WHEREOF, the parties have executed this Agreement as of the
day and year first indicated above.
ISIS PHARMACEUTICALS, INC. GILEAD SCIENCES, INC.
By: /s/ B. ▇▇▇▇▇ ▇▇▇▇▇▇▇▇ By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇
------------------------------ ------------------------------
Printed: B. ▇▇▇▇▇ ▇▇▇▇▇▇▇▇ Printed: ▇▇▇▇ ▇. ▇▇▇▇▇
-------------------------- --------------------------
Title: Executive Vice President, CFO Title: Sr. Vice President, Chief
Financial Officer and General Counsel
Address: ▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Address: ▇▇▇ ▇▇▇▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇ ▇▇▇▇, ▇▇ ▇▇▇▇▇
8.
12/16/98 EXHIBIT A
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[***]=CONFIDENTIAL TREATMENT REQUESTED
Page 4
12/16/98 EXHIBIT A
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[***]=CONFIDENTIAL TREATMENT REQUESTED
Page 5
EXHIBIT B
December 16, 1998
VIA FACSIMILE AND COURIER
▇▇▇▇ ▇▇▇▇▇▇, Ph.D.
▇▇▇▇ Research Corporation
▇▇▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
RE: ASSIGNMENT OF LICENSE AGREEMENT
Dear ▇▇▇▇:
As we discussed today by phone, Gilead has negotiated a Patent Rights
Purchase Agreement with Isis Pharmaceuticals, Inc. ("Isis"), a
biopharmaceutical company based in Carlsbad, California, pursuant to which
Gilead will assign all of its antisense patent rights to Isis. As part of
this Agreement, Gilead will be assigning to Isis the License Agreement
between Gilead and ▇▇▇▇ Research Corporation dated January 1, 1994, as
amended November 19, 1996 (the "License Agreement"). The purpose of this
letter is to obtain the formal consent of ▇▇▇▇ Research Corporation to the
proposed assignment of the License Agreement to Isis, as required by Section
16 of the License Agreement. Please indicate your consent to the assignment
by executing and dating this letter in the space indicated below and
returning it to my attention via facsimile at (▇▇▇) ▇▇▇-▇▇▇▇. When you
receive the original copy of the letter please execute and date it (using the
same date) and return it to me by courier.
We would be happy to discuss the proposed assignment in more detail with you,
or put you in touch with appropriate people at Isis. Please give me a call at
(▇▇▇) ▇▇▇-▇▇▇▇, or ▇▇▇▇ ▇▇▇▇▇▇▇▇ at (▇▇▇) ▇▇▇-▇▇▇▇, if you have any
questions. Thank you for your prompt response to this matter.
Very truly yours,
/s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇
▇▇▇▇▇▇▇ ▇. ▇▇▇▇, M.D., Ph.D.
Senior Vice President, Business Operations
ACCEPTED AND AGREED TO:
▇▇▇▇ Research Corporation
By /s/ ▇▇▇▇ ▇▇▇▇▇▇
Name: ▇▇▇▇ ▇▇▇▇▇▇
Title: President
Date: December 17, 1998