1
AGREEMENT
BETWEEN
MITSUBISHI CHEMICAL CORPORATION
AND
TEXAS BIOTECHNOLOGY CORPORATION
AND
SMITHKLINE XXXXXXX PLC
2
MITSUBISHI-TBC-SB AGREEMENT
THIS MITSUBISHI-TBC-SB AGREEMENT, made as of the date of execution by
all parties hereof, between Mitsubishi Chemical Corporation, a company
organized under the laws of the country of Japan, having a principal place of
business at Tennoz Xxxxxxx Xxxxx, 0-00 Xxxxxxxxxxxxxxxx 0-xxxxx, Xxxxxxxxx-Xx,
Xxxxx 000 Xxxxx ("Mitsubishi"), Texas Biotechnology Corporation, a company
organized under the laws of the state of Delaware and having a place of
business at 0000 Xxxxxx, Xxxxxxx, Xxxxx 00000, X.X.X. ("TBC"), and SmithKline
Xxxxxxx plc, a company organized under English law and having its registered
office at New Horizons Court, Brentford, Middlesex TW8 9EP, England ("SB"),
WITNESSETH THAT:
WHEREAS, an assignment agreement ("Assignment Agreement") was entered
into on April 30, 1997 between TBC, Mitsubishi, and Genentech, Inc., a Delaware
corporation having a principal place of business at 000 Xxxxx Xxx Xxxxx Xxxx.,
Xxxxx Xxx Xxxxxxxxx, Xxxxxxxxxx 00000 ("Genentech") under which:
(a) Genentech and Mitsubishi have terminated all of Genentech's
rights and obligations under the June 30, 1987 MG Agreement between Mitsubishi
and Genentech, as amended by the parties on June 25, 1992 and May 27, 1993 ("MG
Agreement") with respect to Prior Licensed Product (as defined in the
Assignment Agreement), and
(b) Genentech has assigned to Mitsubishi all of Genentech's rights
and obligations under the May 27, 1993 Sublicense and License Agreement between
Genentech, Inc. and Texas Biotechnology Corporation, as subsequently amended by
Genentech and TBC ("GT Agreement").
WHEREAS, as a result of such Assignment Agreement, TBC has the right
to grant certain licenses or sublicenses thereunder, in the United States of
America and Canada ("Territory") relating to a composition of matter known as
argatroban; and
WHEREAS, SB desires to obtain certain licenses and sublicensees in the
Territory from TBC under the aforesaid patents and know-how, and TBC is willing
to grant to SB such licenses and sublicenses, upon terms which have been
mutually agreed by the TBC and SB ("License");
WHEREAS, SB desires to obtain the supply of argatroban, in bulk active
ingredient form, in the Territory from Mitsubishi, which SB will require to
fully exercise its rights under such License, upon terms which have been
mutually agreed by Mitsubishi and SB ("Supply Agreement");
WHEREAS, in view of the Assignment Agreement, SB has concluded that
TBC and Mitsubishi will need to agree to the following warrants,
representations, waivers and consents as a condition for SB's execution of the
License and the Supply Agreement;
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WHEREAS, TBC and Mitsubishi are willing to agree to such warrants,
representations, waivers and consents.
NOW, THEREFORE, in consideration of the covenants and obligations
expressed herein, and intending to be legally bound, and otherwise to be bound
by proper and reasonable conduct, the parties agree as follows:
SECTION 1-WARRANTS/REPRESENTATIONS/WAIVERS/CONSENTS WITH RESPECT TO THE MG
AGREEMENT
1.1 EXCLUSIVITY AND TERM OF MG AGREEMENT-Mitsubishi and TBC each expressly
waive Section 2.04 of the MG Agreement and expressly consent to the
application of the Exclusivity Period to the entirety of the term of
the MG Agreement. In addition, Mitsubishi and TBC each expressly
waive the term expiration provisions of Section 12.01 of the MG
Agreement and each expressly consent that the term of the MG Agreement
shall expire, on a per country basis, upon the later of expiration of
Patent Rights in a particular country of the Territory, or 20 years
after first commercial introduction of Licensed Product by TBC (or its
sublicensee) in such country.
1.2 RIGHT TO GRANT SUBLICENSE TO SB-Mitsubishi expressly consents to the
grant of a sublicense to SB under TBC's rights under the MG Agreement.
TBC shall guarantee full performance by SB for all obligations under
such sublicense. Such sublicense substantially complies with the MG
Agreement, the GT Agreement and this MITSUBISHI-TBC-SB AGREEMENT.
1.3 LICENSED PRODUCT-Mitsubishi and TBC each expressly consent to the
amendment of the definition of "Licensed Product" in the MG Agreement
to mean the chemical compound known as argatroban, also known as
MCI-9038, whose more specific chemical name is
(2R,4R)-4-methyl-l-[N2-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfony
1)-L- arginyl]2-piperidinecarboxylic acid monohydrate, its prodrugs
and metabolites, and all pharmaceutically active derivatives thereof,
such as, but not limited to, esters, salts, hydrates, solvates,
polymorphs and isomers thereof, and shall include compositions
comprising such compound, prodrug or metabolites, or esters, salts,
hydrates, solvates, polymorphs and isomers.
1.4 FIELD-Mitsubishi and TBC each expressly consent that each of the terms
"Field" and "TBC Field" as used in the MG Agreement and/or any
amendment thereof encompass any use of Licensed Product, other than
the use of Licensed Product for the coating of stents, related to the
therapeutic, palliative, or prophylactic treatment of any human
condition for any cardiovascular, renal, neurological, or
immunological purpose, including, but not limited to, the indications
of anti-coagulant therapy in heparin-induced or heparin-associated
thrombocytopenia ("HIT"), anti-coagulant therapy in heparin induced or
heparin-associated thrombocytopenia and thrombosis syndrome ("XXXXX")
and anti-coagulation therapy in acute myocardial infarction ("AMI"),
[*]
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed separately
with the Securities and Exchange Commission.
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as well as cerebral ischemic stroke, provided, however, that if
Mitsubishi should terminate the GT Agreement and the MG Agreement with
respect to an indication in accordance with Paragraph 1.9 of this
MITSUBISHI-TBC-SB AGREEMENT, such indication shall automatically be
excluded from the scope of the term 'Field'.
1.5 FIRST [*] RIGHT TO LICENSE TO USE PRODUCT OUTSIDE OF THE
FIELD-Mitsubishi agrees that, during the term of the License, SB has
the first [*] right to an exclusive license, under patents and
know-how owned or controlled by Mitsubishi, to use, sell, offer for
sale and import Licensed Product in the Territory for use outside of
the Field, upon terms and conditions to be negotiated in good faith by
the parties. [*] of Licensed Product in the Territory shall be
excluded from the aforesaid first [*] right, provided that Mitsubishi
shall first provide SB with all protocols for any preclinical or
clinical trials of Licensed Product which will be carried out for [*]
for the purpose of regulatory filings in the Territory (regardless of
where in the world such trials are carried out), [*]
1.6 SUPPLY AFTER TERM-Mitsubishi expressly consents that after the term of
the MG Agreement, it shall be willing to provide supply of Licensed
Product to SB upon terms and conditions to be negotiated between
Mitsubishi and SB in good faith, which terms shall be no less
favorable to SB as the terms which exist in the Supply Agreement, and
which terms shall be agreed upon by SB and Mitsubishi within a
reasonable period of time prior to the expiration of the term of the
MG Agreement to ensure that there is no interruption in SB's
distribution of Licensed Product to the marketplace.
1.7 PATENT RIGHTS-Mitsubishi expressly warrants and represents that the
definition 'Patent Rights' as used in the MG Agreement shall mean (a)
all patents and patent applications which are or become owned by
Mitsubishi, or to which Mitsubishi otherwise has, now or in the
future, the right to grant licenses, which generically or specifically
claim Licensed Product, a process for formulating Licensed Product, an
intermediate used in such process or a use of Licensed Product in the
Field, (b) all continuations, continuations-in-part, divisions,
patents of addition, reissues, renewals or extensions thereof and all
SPCs (i.e., a right based upon a Patent Right to exclude others from
making, using or selling Licensed Product, such as a Supplementary
Protection Certificate), and (c) any patents or patent applications
which generically or specifically claim any improvements on Licensed
Product or intermediates or formulation processes required or useful
for production of Licensed Product which are developed by Mitsubishi,
or which Mitsubishi otherwise has the right to grant licenses, now or
in the future, during the term of the MG Agreement.
1.8 NO GENENTECH PATENT RIGHTS WITH RESPECT TO ARGATROBAN-Mitsubishi and
TBC expressly warrant and represent that Genentech has warranted and
represented to them that, as of April 30, 1997, Genentech had no
pending or issued patents in the Territory which would be
__________________________________
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed
separately with the Securities and Exchange Commission.
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infringed by the making, having made, use, sale, offer for sale or
importation of Licensed Product in the Territory for any purpose
contemplated by this MITSUBISHI-TBC-SB AGREEMENT.
1.9 FAILURE TO [*]
(a) In the event that TBC and SB fail to have determined
a 'go' position for proceeding to clinical trials in AMI on or before
three (3) months after TBC and SB have received all the data from
Synthelabo related to the clinical trials for AMI being conducted by
Synthelabo as of the date of last written below, in a form which is
practicable for evaluation, [*] In the event that [*] but not with
respect to [*] by written notification to TBC, and provided that [*]
(b) Within four (4) months after the execution of the
License, the Joint Development Committee (as defined in the License)
will meet to consider the development of the Licensed Product for the
indication of cerebral ischemic stroke. Mitsubishi shall be entitled
to attend all meetings of the Joint Development Committee and the
Joint Marketing Team contemplated by the License, provided that such
meetings shall be held at the convenience of only SB and TBC,
Mitsubishi shall be a non-voting observer, and such attendance shall
be at Mitsubishi's expense. Within one (1) year after the initial
meeting of the Joint Development Committee regarding development of
Licensed Product for the cerebral ischemic stroke indication, the
Joint Development Committee will [*] decision with respect to a
decision [*] unless Mitsubishi agrees to extend such one (1) year
period. In the event that the Joint Development Committee makes a [*]
(c) At any time after the [*] of the Effective Date (as
defined in the License), Mitsubishi may present to the Joint
Development Committee proposals for the development of Licensed
Product for indications, applications or formulations in the Field [*]
or for indications, applications or formulations outside the Field [*]
Such proposals shall be in the English language and shall contain
sufficient data and information reasonably supporting the clinical use
and commercial potential of Licensed Product for the proposed
indication, application or formulation to enable an appropriate
consideration of such indication, application or formulation by the
Joint Development Committee. Within [*] of a proposal Product for the
proposed indication, application or formulation to enable an
appropriate consideration of such indication, application or
formulation by the Joint Development Committee. Within [*] of a
proposal which meets all of the qualifications outlined in this
Paragraph, the Joint Development Committee will make a 'go' or 'no go'
decision [*] If the Joint Development Committee makes a [*] with
respect to an indication, application or formulation in the Field, [*]
__________________________________
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed
separately with the Securities and Exchange Commission
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(d) In the event that [*] or in the event that the Joint
Development Committee makes a 'no go' decision with respect to an
indication, application or formulation outside of the Field [*]
Mitsubishi may develop Licensed Product for the Terminated Item in the
Territory [*] provided that SB shall have the first [*] right to
commercialize Licensed Product in the Territory for the Terminated
Item [*] In the event that [*] or in the event that the parties [*]
In the event that [*] or in the event that [*] and in no event may [*]
1.10 TERMINATION OF RIGHT TO TERMINATE FOR FAILURE TO ACHIEVE MILESTONES IN
THE MG AGREEMENT AND THE GT AGREEMENT- Mitsubishi hereby waives any
and all rights to terminate the MG Agreement and the GT Agreement due
to TBC or its sublicensee's failure to comply with the milestone
timeline requirements set forth in Section 5.1 of the GT Agreement, or
the milestone timeline requirements set forth in the June 30, 1995
Extension Agreement between Mitsubishi, Genentech and TBC
("Extension") and the July 10, 1996 Understanding between Mitsubishi
and TBC ("Understanding"), or the milestone timeline requirements of
the MG Agreement as they relate to the filing for U.S. marketing
approval by January 1, 1996, provided that TBC shall diligently pursue
filing of a NDA in cooperation with SB and in accordance with SB's
business, legal, medical and scientific judgment and SB's normal
practices and procedures for compounds having similar technical and
commercial potential. Said waiver is expressly understood to include
any failure of TBC or its sublicensee to meet any of the requirements
set forth in the preceding sentence whether they occur before or after
the date of full execution of this MITSUBISHI-TBC-SB AGREEMENT.
Mitsubishi further expressly consents that TBC has completely
fulfilled the requirements set forth in the Understanding within the
timelines set forth therein. Once the New Drug Application ("NDA")
for HIT has been filed, TBC shall thereafter provide Mitsubishi with
quarterly written updates on the progress of the NDA and all clinical
studies in the Field.
1.11 TRADEMARK-Mitsubishi expressly warrants and represents that it owns
the trademark NOVASTAN in the U.S. and Canada, and their respective
territories and possessions, and that it will promptly apply for the
trademark NOVASTAN in Puerto Rico.
1.12 RIGHT TO GRANT LICENSE TO TRADEMARK-Mitsubishi expressly warrants and
represents that it has the right to license the trademark NOVASTAN
exclusively to TBC, and that it has not licensed NOVASTAN to any other
party, in the U.S., Canada, and their respective territories and
possessions.
1.13 NO TRADEMARK INFRINGEMENT-Mitsubishi expressly warrants and represents
that, to the best of its knowledge, the trademark NOVASTAN does not
infringe any trademark rights, and is available for use and
registration in the U.S., Canada and their respective territories and
possessions.
__________________________________
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed
separately with the Securities and Exchange Commission
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1.14 IDENTITY OF LICENSOR OF TRADEMARK-Mitsubishi expressly warrants and
represents that it is the Licensor in the Trademark License Agreement
("Trademark Agreement") between Mitsubishi Kasei Corporation and Texas
Biotechnology Corporation ("TBC"), in that Mitsubishi Kasei
Corporation changed its name to Mitsubishi Chemical Corporation.
1.15 RIGHT TO EXCLUSIVE USE OF TRADEMARK-Mitsubishi expressly consents to
the amendment of the April 20, 1994 Trademark License Agreement
between Mitsubishi Kasei Corporation and TBC ("Trademark Agreement")
such that TBC's right to use the trademark NOVASTAN is exclusive in
the Territory.
1.16 FIELD OF USE FOR TRADEMARK-Mitsubishi expressly consents that (i) the
term "Field" as used in the Trademark Agreement is the same as
outlined in Paragraph 1.4 of this MITSUBISHI-TBC-SB AGREEMENT, and
(ii) the definition of the chemical compound set forth in Exhibit B of
the Trademark Agreement will conform to the definition set forth in
Section 1.3 of this MITSUBISHI-TBC-SB AGREEMENT.
1.17 RIGHT TO LICENSE TO USE TRADEMARK OUTSIDE OF THE FIELD-Mitsubishi
agrees that, in the event that SB has obtained a license to use
Licensed Product outside of the Field as a result of SB's exercise of
its first [*] right, SB, at its election, shall have a royalty-free
exclusive license to use Trademark with respect to Licensed Product in
the Territory for such uses outside of the Field for which SB has
exercised such rights.
1.18 USE OF TRADEMARK AFTER TERM-Mitsubishi expressly consents that after
the term of the MG Agreement, SB shall have an exclusive license to
use Trademark with respect to Licensed Product in the Field (and with
respect to areas outside of the Field for which SB has exercised its
first [*] right), provided that such license shall be [*] for so long
as Mitsubishi is providing supply of Licensed Product to SB in the
Territory, and in the event that [*] such license shall be [*]
1.19 NO RIGHTS OUTSIDE FIELD IN THE TERRITORY-Mitsubishi expressly consents
that it shall not use the trademark NOVASTAN for any use outside of
the Field in the Territory, either on its own, or through any
arrangement with any Third Party, including, but not limited to, any
licensing, distribution or comarketing arrangement.
1.20 RIGHT TO GRANT SUBLICENSE TO TRADEMARK-Mitsubishi expressly consents
to the grant of an exclusive, royalty free, sublicense to SB under
TBC's rights under the Trademark Agreement, subject to TBC's right to
copromote Licensed Product in the event that SB determines it wants
such a sublicense.
__________________________________
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed
separately with the Securities and Exchange Commission
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1.21 TERM OF SUBLICENSE RIGHT TO USE TRADEMARK-Mitsubishi expressly
consents that the term of SB's right to a sublicense under the
Trademark Agreement shall correspond to the term of the MG Agreement,
except as otherwise provided in Section 1. 18 of this
MITSUBISHI-TBC-SB AGREEMENT. Mitsubishi expressly states that as the
owner of the trademark NOVASTAN, it controls the nature and quality of
the product on which SB will use the trademark NOVASTAN under a
sublicense from TBC. SB agrees to provide samples of the finished
product, labels, and packaging to Mitsubishi and TBC, upon request,
for their review of the nature and quality of the product and the
proper use of the NOVASTAN trademark by SB.
1.22 USE OF TRADEMARK-All warrants, representations and agreements by
Mitsubishi with respect to the NOVASTAN trademark hereunder shall be
subject to the actual use of such trademark for Licensed Product by SB
and TBC in a given country of the Territory.
SECTION 2-WARRANTS/REPRESENTATIONS/WAIVERS/CONSENTS WITH RESPECT TO THE GT
AGREEMENT
2.1 ACKNOWLEDGMENT THAT WARRANTS/REPRESENTATIONS/WAIVERS/CONSENTS RELATED
TO MG AGREEMENT ARE EQUALLY APPLICABLE TO GT AGREEMENT-Mitsubishi and
TBC each expressly consent that all warrants, representations, waivers
and consents outlined in Section I of this letter are equally
applicable to the GT Agreement.
2.2 TRANSFER OF GENENTECH KNOW-HOW AND GENENTECH ARGATROBAN IND-Mitsubishi
and TBC each expressly warrant and represent that all Genentech
Know-How (as defined in the Assignment Agreement) and the complete
Genentech Argatroban IND (as defined in the Assignment Agreement) have
been transferred to Mitsubishi and/or TBC.
2.3 TERM OF GT AGREEMENT-Mitsubishi and TBC each expressly waive the term
expiration provisions of Section 8.1 of the GT Agreement and expressly
consent that the term of the GT Agreement shall expire, on a per
country basis, upon the later of expiration of Patent Rights in a
particular country of the Territory, or 20 years after first
commercial introduction of Licensed Product by TBC (or its
sublicensee) in such country.
2.4 ARGATROBAN DEFINITION-Mitsubishi expressly consents that the
definition of "Argatroban" in the GT Agreement shall be amended to
have the same meaning as that outlined in Paragraph 1.3 of this
MITSUBISHI-TBC-SB AGREEMENT.
2.5 WAIVER OF RIGHT TO CO-MARKET-Mitsubishi expressly waives its exclusive
right of first negotiation with regard to co-marketing Licensed
Product in the Territory under Section 2.3 of the GT Agreement.
2.6 SUBLICENSE TO SB-Mitsubishi expressly waives the requirements outlined
in Paragraph 2.4(a) of the GT Agreement, as well as the last sentence
of Paragraph 2.4 with respect to these requirements. In addition,
Mitsubishi expressly waives the requirements outlined in
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Paragraph 2.4(d) of the GT Agreement, as well as the last sentence of
Paragraph 2.4 with respect to these requirements. Mitsubishi
expressly grants its consent under Section 2.4 of the GT Agreement to
TBC's grant of a sublicense to SB with respect to SB's exclusive
marketing of Licensed Product in the Territory in the Field, subject
to TBC's retained right to co-promote Licensed Product with SB as
described in the subject agreement.
2.7 FIELD-Mitsubishi expressly consents that the term "Field" as used in
the GT Agreement has the same scope as outlined in Paragraph 1.4 of
this MITSUBISHI-TBC-SB AGREEMENT under the heading "Field", and
expressly waives all references to the term "Genentech Field" in the
GT Agreement including any rights that Mitsubishi may have with
respect to the Genentech Field.
2.8 WAIVER OF RIGHT TO TERMINATE-Mitsubishi expressly waives Paragraph 8.3
of the GT Agreement during the term of the License, but only with
respect to [*]
2.9 PAYMENT OF ROYALTIES-Mitsubishi and TBC agree that the total royalty
owed to Mitsubishi by TBC pursuant to the GT Agreement shall be [*] of
Net Sales (as defined in the License) of Licensed Product and shall be
paid [*]
SECTION 3-MISCELLANEOUS
3.1 INCONSISTENT PROVISIONS-Mitsubishi and TBC each warrant and represent
that to the extent the Warrants/Representations/Waivers/Consents
outlined in this MITSUBISHI-TBC-SB AGREEMENT are in conflict with any
provisions of the MG Agreement and/or the GT Agreement, then the
provisions of the MG Agreement and/or the GT Agreement shall be deemed
inoperative to the extent that they may conflict therewith and shall
be deemed to be modified to conform with this MITSUBISHI-TBC-SB
AGREEMENT.
3.2 GOVERNING LAW-This MITSUBISHI-TBC-SB AGREEMENT shall be deemed to have
been made in the State of New York and its form, execution, validity,
construction and effect shall be determined in accordance with the
laws of the State of New York, U. S. A.
3.3 ENTIRE AGREEMENT-This MITSUBISHI-TBC-SB AGREEMENT, entered into as of
the date written above, constitutes the entire agreement between the
parties relating to the subject matter hereof and supersedes all
previous writings and understandings. No terms or provisions of this
MITSUBISHI-TBC-SB AGREEMENT shall be varied or modified by any prior
or subsequent statement, conduct or act of either of the parties,
except that the parties may amend this MITSUBISHI-TBC-SB AGREEMENT by
written instruments specifically referring to and executed in the same
manner as this MITSUBISHI-TBC-SBN AGREEMENT.
__________________________________
[*] This information has been omitted in reliance on Rule 24B-2 under
the Securities Exchange Act of 1934, and has been filed
separately with the Securities and Exchange Commission
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3.4 ASSIGNMENT-This MITSUBISHI-TBC-SB AGREEMENT and the license right and
licenses herein granted shall be binding upon and inure to the benefit
of the successors in interest of the respective parties. Neither this
MITSUBISHI-TBC-SB AGREEMENT nor any interest hereunder shall be
assignable by either party without the written consent of the other
parties provided, however, that any party may assign this
MITSUBISHI-TBC-SB AGREEMENT or any part of its rights and obligations
hereunder to any affiliate of such party or to any corporation with
which such party may merge or consolidate, or to which it may transfer
all or substantially all of its assets to which this MITSUBISHI-TBC-SB
AGREEMENT relates, without obtaining the consent of the other parties.
3.5 NO PARTNERSHIP OF JOINT VENTURE-This MITSUBISHI-TBC-SB AGREEMENT shall
not be deemed to establish a joint venture or partnership between SB
and TBC.
3.6 EXECUTION IN COUNTERPARTS-This MITSUBISHI-TBC-SB AGREEMENT may be
executed in any number of counterparts, each of which shall be deemed
an original but all of which together shall constitute one and the
same instrument.
IN WITNESS WHEREOF, the parties, through their authorized officers,
have executed this MITSUBISHI-TBC-SB AGREEMENT as of the date last written
below.
MITSUBISHI CHEMICAL CORPORATION
BY: /s/ Kanji Shono
---------------------------
TITLE: Kanji Shono
---------------------------
DATE: August 5, 1997
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SMITHKLINE XXXXXXX plc
BY: /s/ X. Xxxxxxxxx
---------------------------
TITLE: Executive Vice President
---------------------------
DATE: August 5, 1997
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TEXAS BIOTECHNOLOGY CORPORATION
BY: /s/ Xxxxx X. XxXxxxxxxx
---------------------------
TITLE: President
---------------------------
DATE: August 5, 1997
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