Exhibit 10.74
CONFIDENTIAL TREATMENT HAS BEEN REQUESTED FOR PORTIONS OF THIS AGREEMENT
PURSUANT TO AN APPLICATION DATED JANUARY 27, 1997, AS SEPARATELY FILED WITH
THE SECURITIES AND EXCHANGE COMMISSION. CONFIDENTIAL PORTIONS ARE INDICATED
WITH AN ASTERISK ("*"), EXCEPTING THOSE ASTERISKS CONTAINED IN SCIENTIFIC
FORMULAS CONTAINED IN SECTION 2(A) OF EXHIBIT A.
LETTER OF INTENT
THIS LETTER OF INTENT is made on the 17th day of January 1997, by and
between Agouron Pharmaceuticals, Inc., a corporation duly organized and
existing under the laws of the state of California, having a principal place
of business at 10350 North Torrey Pines Road, La Jolla, California, United
States of America (hereinafter called "Agouron"), Japan Tobacco Inc., a
corporation duly organized and existing under the laws of Japan, having its
principal place of business at JT Building, 2-1, Toranomon 2-chome, Minato-
ku, Tokyo, Japan (hereinafter called "JT"), and F. Hoffmann-La Roche Ltd., a
corporation duly organized and existing under the laws of Switzerland,
having its principal place of business at CH-4002-Basel, Switzerland
(hereinafter called "Roche"). Agouron, JT and Roche are sometimes
hereinafter referred to as a party (collectively "parties") to this
Agreement.
Background
In December 1994, Agouron and JT entered into a Development and
License Agreement ("D&L Agreement") under which they have collaborated in
the development and commercialization of the chemical compound known as
"nelfinavir mesylate" to treat and prevent Human Immunodeficiency Virus
infections. Agouron, JT and Roche now agree to enter into a license
agreement under which Roche will be licensed to sell nelfinavir mesylate in
certain countries of the world. This Letter of Intent ("LOI") which shall
be binding on the parties sets forth the basic license terms upon which the
parties have agreed. The full terms of the license will be set forth in a
definitive agreement to be prepared as described below.
NOW THEREFORE, the parties agree as follows:
1. Terms. The parties hereby enter into this Letter of Intent to
confirm their entering into a license agreement on terms substantially in
accordance with those contained in Exhibit A attached hereto. The parties
acknowledge that Exhibit A only states the basic terms of the understanding
between the parties and is subject to the further negotiation and
preparation of an agreement containing the full terms of the license between
the parties ("Definitive Agreement"). Each party agrees to act in good
faith in an effort to negotiate, execute and deliver the Definitive
Agreement on or before * .
2. Disclosure. The parties shall jointly prepare and release a
statement about the existence of this Letter of Intent and of the license
between Agouron, JT and Roche. Except as agreed to by the parties, Agouron,
JT and Roche shall not release any further information to any third party
who is not under an obligation of confidentiality with respect thereto about
any of the terms of this Letter of Intent or of the license without the
prior written consent of the other parties, which consent shall not
unreasonably be withheld. This prohibition includes, but is not limited to,
press releases, educational and scientific conferences, promotional
materials and discussions with the media. If a party determines that it is
required by law to release information to any third party regarding the
terms of this Letter of Intent or the subject matter of the license, it
shall notify the other parties of this fact prior to releasing the
information. The notice to the other parties shall include the text of the
information proposed for release. The other parties
shall have the right to confer with the notifying party regarding the
necessity for the disclosure and the text of the information proposed for
release.
3. Miscellaneous. This Letter of Intent contains the entire
agreement between the parties as to the matters set forth herein and shall
be construed in accordance with the laws of the State of California, United
States of America. Exhibit A describes the parties' understanding with
respect to the development and sale of nelfinavir mesylate by Roche in
certain countries of the world. This Letter of Intent, including Exhibit A,
shall not be amended, supplemented or otherwise modified, except by an
instrument in writing signed by duly authorized officers of all of the
parties. Roche shall bear all of the expenses incurred by it in connection
with the negotiation and preparation of this Letter of Intent and the
Definitive Agreement. Agouron and JT shall bear all of the expenses
incurred by them in connection with the negotiation and preparation of this
Letter of Intent and the Definitive Agreement. Notwithstanding the
preceding, the use and disclosure of confidential and proprietary
information disclosed to Roche for the purpose of determining Roche's
interest in entering into (and for the subsequent negotiation and
performance of) a license agreement for Viracept for certain countries of
the world shall be governed by the terms of the Confidentiality Agreement
between the parties with an effective date of January 7, 1997.
IN WITNESS WHEREOF, the parties hereto have executed this Letter of
Intent by their respective officers thereunto duly authorized, the day and
year hereinabove written. This Letter of Intent may be executed in
counterparts and all of such counterparts taken together shall be deemed to
constitute one and the same instrument.
AGOURON PHARMACEUTICALS, INC. JAPAN TOBACCO INC.
By: /s/ Kent Snyder By: /s/ Masamichi Nishimoto
Name: Kent Snyder Name: Masamichi Nishimoto
Title: Vice President Title: Executive Vice President
By: /s/ Gary Friedman By: /s/ Masakazu Kakei
Name: Gary Friedman Name: Masakazu Kakei
Title: Vice President Title: Managing Director
F. HOFFMANN-LA ROCHE LTD
By: /s/ Werner Henrich
Name: Werner Henrich
Title: Director
By: /s/ Dr. Bruno Maier
Name: Dr. Bruno Maier
Title: Deputy Director
Exhibit A
1. JT and Agouron, individually and directly, under terms and conditions
specified below, hereby grant Roche the exclusive right, even as to
Agouron and JT, to sell the Product in the Field in the Licensed
Territory.
2. Definitions: Except as otherwise set forth herein, items containing
an initial capitalized letter shall have the meaning stated in the
Letter of Intent ("LOI") and/or this Exhibit A.
(a) "Product" means nelfinavir mesylate, however formulated, whose
chemical name is as follows:
[3S-(3R*, 4aR*, 8aR*, 2'S*, 3'S*)]-2-[2'-hydroxy-3'-
phenylthiomethyl-4'-aza-5'-oxo-5'-(2''-methyl-3''-
hydroxyphenyl)pentyl]-decahydroisoquinoline-3-N-t-butyl
carboxamide methanesulfonic acid salt,
and whose chemical structure is as follows:
<DIAGRAM>
(b) "Licensed Territory" means all countries of the world, except
for the United States (and its territories, possessions and
protectorates, and the District of Columbia), Canada, Mexico,
Japan, Taiwan, South Korea, North Korea, and all the countries
of Asia listed on Schedule 1 attached hereto.
(c) "Field" means the treatment and prevention of Human
Immunodeficiency Virus ("HIV") infections.
(d) "Affiliate" means any person, organization or entity which is,
directly or indirectly, controlling, controlled by, or under
common control with Roche, Agouron or JT, as the case may be.
The term "control" (including, with correlative meaning, the
terms "controlled by" and "under common control with"), as used
with respect to any person or entity, means the possession,
directly or indirectly, of the power to direct or cause the
direction of the management and
A-1
policies of such person, organization or entity, whether through the
ownership of voting securities, or by contract, or court order, or
otherwise. The ownership of voting securities of a person,
organization or entity shall not, in and of itself, constitute
"control" for purposes of this definition, unless said ownership is
of a majority of the outstanding securities entitled to vote of such
person, organization or entity. For purposes of this Agreement,
Genentech, Inc. shall be considered to be an Affiliate of Roche.
(e) "Major European Country" means the *
(f) "MAA" means Marketing Authorization Application.
(g) "EMEA" means the European Agency for the Evaluation of Medicinal
Products.
(h) "D&L Agreement" means the December 1, 1994 Development and
License Agreement between Agouron and JT.
3. The term of this license will extend on a country-by-country basis
from the effective date of the signing of the LOI to which this
Exhibit A is an attachment, until the later of: (i) the last to
expire of any patents covering the Product in a country; or (ii) * years
after the date of the initial commercial launch of the Product in such
country.
4. With the consent of JT and Agouron, whose consent shall not be
unreasonably withheld, Roche shall have the right to sublicense its
rights in the Product in one or more countries of the Licensed
Territory.
5. Subject to the provisions of the D&L Agreement, Agouron may *
be agreed upon by the parties after discussions between Roche and
Agouron. Subject to the provisions of the D&L Agreement, JT may *
to
be agreed upon by the parties after discussions between Roche and JT.
The terms of the *
modified to reflect the *
6. Until * except for the countries of *
in countries where either JT or Agouron control the
exclusive rights to the Product, *
On or before *
the parties agree to further discuss the *
A-2
For purposes of this paragraph, JT and
Agouron shall not be considered independent third parties.
7. Except as otherwise agreed to by the parties, Agouron and JT will be
responsible for
completing in a reasonable manner and funding the studies *
studies include the core development program studies designed to
achieve registration of the Product in the Field in the major
countries of the Licensed Territory. The parties acknowledge that
Agouron and JT despite reasonable diligence may be unable to *
8. In collaboration with Roche, Agouron will be responsible for *
and will have
the primary responsibility for *
Roche and its Affiliates will provide assistance, as
necessary, to *
Roche
will have the primary responsibility for the *
Roche will be
responsible for *
9. Alterations to the * which are required for *
will be the
responsibility of * Except as
otherwise agreed to by the parties, Roche will be responsible for *
10. Roche will be responsible for *
(other than those * ) which involve the *
(including *
). Roche will be responsible
for the
A-3
*
11. A party conducting a study involving the Product will assist the other
parties in the incorporation of the data from such study into their
dossiers, if necessary. *
12. Roche will be responsible for the cost and implementation (possibly in
cooperation with a previously-contracted contract research
organization) of an expanded access program in Europe and Australia
which will be consistent in scope with the expanded access program
implemented by Agouron in North America.
13. Roche shall use reasonable diligence in the development and
registration of the Product in the Field in the countries of the
Licensed Territory. Reasonable diligence shall mean at least the
comparable standard of effort used by Roche in *
If, after *
days written notice of the failure by Roche to use reasonable
diligence in the development and registration of the Product in the
Field in a country located in the Licensed Territory Roche fails to
fulfill its obligations under this paragraph, such failure shall be
deemed to be an election pursuant to *
14. Roche will purchase the Product from JT or Agouron directly as
determined by JT and Agouron,*
15. Roche will make the following license issue fee payments to Agouron
and JT directly.
On January 24, 1997
To Agouron USD 9 million
To JT USD 9 million
Within thirty (30) days of first regulatory approval
in a Major European Country or upon marketing
authorization from the European Commission
To Agouron USD 11 million
To JT USD 11 million
--------------
TOTAL USD 40 million
A-4
16. *
will be consistent with the
*
will modify the *
only to the extent required to respond to *
and implement *
As
they deem appropriate, Agouron, JT and their licensees will *
17. It is the intent of the parties that a single trademark be identified
and developed for use in connection with marketing the Product in the
Field wherever possible throughout the Territory. The parties
acknowledge their intention to use the VIRACEPT (R) trademark in
connection with the marketing of the Product in the Field wherever
possible. Unless otherwise agreed and as permitted by law, Roche will
sell the Product under the VIRACEPT brand name in all countries of the
Licensed Territory. The parties also acknowledge their intention to
use, if appropriate, the same trade dress in connection with the
marketing of the Product in the Field wherever possible. In
countries where Roche is exclusively marketing the Product, unless
prohibited by law or regulation, the labeling for the Product shall
state that the Product is licensed from Agouron and JT.
18. *
19. * Roche using diligent
marketing efforts, agrees to provide sales and other promotional
support for the Product in each country in the Licensed Territory
which is equivalent to or greater than that which Roche, its
Affiliates and/or sublicenses are providing *
After the * Roche will provide a reasonable level of
sales and other promotional support for the Product in each country in
the Licensed Territory which, when measured as a percentage of
adjusted gross product sales in such country, is equivalent to or
greater than that which Roche, its Affiliates and/or sublicenses are
providing for *
shall be attributed to *. If, after * written
notice of the failure by Roche to
A-5
provide the agreed upon level of
sales and other promotional support for the Product in a country
located in the Licensed Territory Roche fails to fulfill its
obligation under this Paragraph, Agouron and JT shall have the right,
*
20. Roche shall keep Agouron and JT informed of its progress in the
development and registration of the Product. This shall include, at
least * the regular meetings of the parties and such
written progress reports as are agreed to by the parties summarizing
Roche's activities during each reporting period and Roche's planned
activities for the succeeding period. Agouron and JT shall keep Roche
informed of their development and registration activities to the
extent that such development and registration activities are relevant
to the development and registration of the Product by Roche in the
Licensed Territory. Each of the parties will *
each representative shall report
to his/her management on the matters discussed at each of the meetings
of the parties. Each party, prior to the implementation of *
will provide the other parties with a copy of
the * and an opportunity in a timely manner to
comment on the *
Roche agrees to use its diligent
efforts in responding in a timely manner, but not more than *
to requests from Agouron or JT for information *
21. Roche shall keep Agouron and JT informed of *
This shall include, at least *
the regular meetings of the parties and such written progress reports
as are agreed to by the parties summarizing Roche's activities during
each reporting period and Roche's planned activities for the Product
for the succeeding period. Each of the parties will *
each representative shall report
to his management on the matters discussed at each of the meetings of
the parties. The representatives of the parties at the meeting will
review and discuss *
Each
party agrees to inform the other parties, *
A-6
22. Agouron, JT and Roche each acknowledge the interests of the other
parties *
The parties also recognize their mutual interests in
obtaining *
Consequently, a party, its employees or
consultants
*
Furthermore, in acknowledgment that certain *
the parties agree that each party
shall
*
After giving reasonable consideration
to the suggestions of the objecting party, the party wishing to *
23. Roche will pay JT and Agouron directly, a royalty based on the net
sales of the Product by Roche, its Affiliates and sublicenses,
consolidated into CHF, in amounts which equal the greater of: (i) the
royalty amounts calculated according to Schedule 1 below (Product
only); or (ii) the royalty amounts calculated according to Schedule 2
below (Product and any formulations of INVIRASE which Roche markets
with royalties being calculated separately for the consolidated annual
net sales of the Product and INVIRASE). Schedule 2 shall not apply to
net sales in a country until the Product is approved and available for
sale in such country. The following royalties shall be divided
equally between JT and Agouron.
Schedule 1
Royalty Rate
Per Consolidated Consolidated Annual Net Sales Level
Annual Net Sales Level of the Product in Licensed Territory
---------------------- --------------------------------------
* <= CHF *
* > CHF * / <= CHF *
* > CHF *
A-7
Schedule 2
Consolidated Annual Net Sales Level for
the Product and INVIRASE in the Licensed
Territory (With Royalties Being
Royalty Rate Calculated Separately for the
Per Consolidated Consolidated Annual Net Sales of the
Annual Net Sales Level Product and INVIRASE)
---------------------- --------------------------------------
* <= CHF *
* > CHF * / <= CHF *
* > CHF *
24. If either: (i) regulatory approval for the Product is not obtained in
a Major European Country prior to * or (ii) marketing
authorization for the Product is not obtained from the European
Commission prior to * the royalty rate for Schedule 2
will be adjusted as follows:
Schedule 2
Consolidated Annual Net Sales Level for
the Product and INVIRASE in the
Licensed Territory (With Royalties
Royalty Rate Being Calculated Separately for the
Per Consolidated Consolidated Annual Net Sales of the
Annual Net Sales Level Product and INVIRASE)
---------------------- --------------------------------------
* <= CHF *
* > CHF * / <= CHF *
* > CHF *
25. If either: (i) regulatory approval for the Product is not obtained in
a Major European Country prior to * or (ii) marketing
authorization for the Product is not obtained from the European
Commission prior to * Schedule 2 will not apply and
Roche will be obligated to pay JT and Agouron directly, royalties
according to Schedule 1 only.
26. Roche agrees not to market any other HIV protease inhibitors in the
Licensed Territory during the term of the agreement, unless sales for
such product(s) are included in the consolidated net sales calculation
according to Schedule 2.
27. * despite reasonable efforts to *
provided,
however, that in no case will *
The parties acknowledge that the *
that the provisions of this paragraph do not apply
to *
A-8
The parties
specifically acknowledge that *
Notwithstanding the
preceding, *
which are then being commercially used in the manufacture of the
Product, the parties will *
28. In any country where the amount of third party unlicensed sales of
drug products containing nelfinavir mesylate for a quarterly period
exceed * of the total sales of all drug products containing
nelfinavir mesylate in such country for such quarterly period,
royalties due on the net sales of the Product in such country for such
quarterly period will be *
29. Roche will purchase the Product from Agouron or JT directly, for sale
in the Licensed Territory at a price which *
30. * and
if Agouron or JT, independently or jointly, *
31. Roche will assist Agouron and JT in the identification of low-cost
manufacturing sources for the Product. Roche will also provide
without charge, to the extent available, technical and manufacturing
assistance and use of its technology and proprietary information to
Agouron and JT in an effort to decrease the production costs of the
Product. Agouron and JT agree to discuss in good faith with Roche an
arrangement under which Roche could be the contract manufacturer of
the Product to be used in the Licensed Territory, including the
prerequisite requirement that *
Notwithstanding the preceding, Agouron and JT shall be entitled to *
including the right to continue their *
32. *
A-9
Subject to the provisions of the D&L Agreement, in the event
that *
Agouron and JT, their Affiliates and
sublicensees shall be free, without any further action by Agouron, JT
or Roche and without any further obligation to Roche and its
Affiliates, to *
provided that Agouron and JT
shall not
*
For purposes of this paragraph, Roche's *
In the event of *
pursuant
to the terms of this paragraph: (i) the *
(ii) Agouron and JT, their Affiliates and
sublicensees shall
*
(iii) Roche shall *
and
(iv) Roche shall
*
Roche
shall be responsible for *
33. Roche may elect to *
In the event that Roche elects to *
, subject to the provisions of the D&L Agreement: (i)
Agouron and JT shall
*
(ii) Agouron and JT will *
(iii) Roche shall *
and (iv) Roche shall *
34. This Agreement shall be assignable by Agouron and JT, but shall not be
assignable by Roche, except to an Affiliate, without the prior written
consent of Agouron and JT, which consent may be withheld at the sole
discretion of Agouron and JT. Any such assignment without the prior
written consent of Agouron and JT shall be void. If this Agreement is
assigned to an Affiliate, Roche shall still be responsible for all of
its obligations specified in this Agreement. Notwithstanding the
preceding, in the event of: (i) a sale or transfer of all or
substantially all of Roche's assets; or (ii) the merger or
A-10
consolidation of Roche with another company, this Agreement shall be
assignable to the transferee or successor company.
35. *
A-11
SCHEDULE 1 TO EXHIBIT A
ASIAN COUNTRIES
*
*
*
*
*
*
*
*
*
*
*
*
*
*
Licenses in the above-listed countries shall be subject to compliance by
Roche with the United States laws and regulations governing exports and re-
exports of the Product and any technology developed or disclosed as a result
of this Agreement.
S1-1
SCHEDULE 2 TO EXHIBIT A
NELFINAVIR MESYLATE *
Protocol Title
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
* *
S2-1
Protocol Title
* *
* *
* *
* *
* *
* *
S2-2
Protocol Title
* *
* *
* *
* *
* *
* *
* *
* *
* *
S2-3