[Confidential Treatment Requested. Confidential Portions of This Agreement have
been Redacted and have been separately filed with the Commission]
LICENSE AND COLLABORATION AGREEMENT
-----------------------------------
THIS LICENSE AND COLLABORATION AGREEMENT dated as of September 15,
1995 (the "Agreement"), is entered into between THE IMMUNE RESPONSE CORPORATION,
a Delaware corporation ("IRC"), having a place of business at 0000 Xxxxxx Xxxxx,
Xxxxxxxx, Xxxxxxxxxx 00000, U.S.A., and TRINITY MEDICAL GROUP, CO., LTD., a Thai
limited company ("Trinity"), having a place of business at 000/0 Xxxxx Xx. 0,
Xxxxx Xxxx, Xxxxxxx 00000, Xxxxxxxx.
W I T N E S S E T H :
WHEREAS, IRC owns or has rights in certain technology relating to a
certain immunotherapeutic product which uses inactivated human immunodeficiency
virus ("HIV") depleted of its gp120 envelope administered in Incomplete Xxxxxx'x
Adjuvant.
WHEREAS, IRC and Trinity desire to collaborate together to conduct
clinical development of, and to obtain regulatory approval to market, such
product in Thailand and certain other countries of Asia for use in treatment of
HIV infection, on the terms and subject to the conditions of the Agreement.
WHEREAS, Trinity desires to fund such clinical development and
regulatory activities, and to obtain the rights to commercialize such product in
such countries for use in the treatment of HIV infection, on the terms and
subject to the conditions of the Agreement.
NOW, THEREFORE, in consideration of the foregoing premises and the
mutual covenants herein contained, the parties hereby agree as follows:
ARTICLE 1
DEFINITIONS
-----------
For purposes of the Agreement, the terms defined in this Article 1
shall have the respective meanings set forth below;
1.1 "Affiliate" shall mean, with respect to any Person, any other
Person which directly or indirectly controls, is controlled by, or is under
common control with, such Person. A Person shall be regarded as in control of
another Person if it owns, or directly or indirectly controls, at least forty
percent (40%) of the voting stock or other ownership interest of the other
Person, or if it directly or indirectly possesses the power to direct or cause
the direction of the management and policies of the other Person by any means
whatsoever.
1.2 "Development Program" shall mean the program to conduct the
clinical development of the Product in the Territory, and to conduct the related
activities to obtain
regulatory approval to market the Product in the Territory for use in the Field,
as described generally in the Development Workplans.
1.3 "Development Workplan" shall mean, with respect to each country in
the Territory, the written workplan to conduct the clinical development of the
Product, and to conduct the related activities to obtain regulatory approval to
market the Product in such country for use in the Field, as set forth in Exhibit
A with respect to Thailand, and as prepared pursuant to the provisions of
Section 3.1.1 below with respect to each other country in the Territory, in each
case as the same may be revised from time to time pursuant to the provisions of
Section 3.1.3 below.
1.4 "FDA" shall mean the United States Food and Drug Administration, or
the successor thereto.
1.5 "Field" shall mean the treatment of HIV infection.
1.6 "First Commercial Sale" shall mean, with respect to any country,
the first sale or distribution for use or consumption by the general public of
the Product in such country after the required marketing approval has been
granted by the governing health authority of such country.
1.7 "GMP" shall mean current Good Manufacturing Practices promulgated
by the FDA in the United States.
1.8 "Manufacturing Cost" shall mean the fully-burdened cost, expressed
on a per unit manufactured basis, of manufacturing the Product, together with
the packaging thereof, including the cost of materials, direct labor and
benefits, and overhead, all as determined in accordance with generally accepted
accounting principles and consistently with the manufacturer's accounting
practices for other products manufactured. Materials, direct labor and benefits
and overhead shall be further defined as follows:
1.8.1 "Materials" shall include those items which form an integral
and direct part of the bulk form of the Product and are necessary for its
production, as well as cartons, labels, package inserts and shippers.
1.8.2 "Direct Labor and Benefits" shall include that portion of
basic wages, labor and related payroll taxes and employee benefits spent in
actual production of the particular Product which can be identified with or
charged to the Product.
1.8.3 "Overhead" shall include all operating expenses incurred by
and in support of the particular manufacturing cost centers, purchasing
department and quality assurance operations, with respect to the Product,
including the following:
- Indirect labor, related payroll taxes and employee benefits
- Depreciation
- Taxes
- Insurance
- Rent
- Repairs and maintenance
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- Supplies
- Utilities
- Factory administrative expenses
1.9 "Manufacturing Know-How" shall mean all information and data,
including, but not limited to, formulae, procedures, protocols, techniques and
results of experimentation and testing; which are necessary or useful to make,
or to seek regulatory approval to make, the Product in Thailand for use in the
Field, in which IRC has an ownership or other licensable interest and which is
in the possession of IRC on the date of the Agreement or thereafter during the
term of the Agreement.
1.10 "Person" shall mean an individual, corporation, partnership,
trust, business trust, association, joint stock company, joint venture, pool,
syndicate, sole proprietorship, unincorporated organization, governmental
authority or any other form of entity not specifically listed herein.
1.11 "Product" shall mean a certain immunotherapeutic product which
uses inactivated HIV depleted of its gp120 envelope administered in Incomplete
Xxxxxx'x Adjuvant.
1.12 "Product Know-How" shall mean all information and data,
including, but not limited to, formulae, procedures, protocols, techniques and
results of experimentation and testing, which are necessary or useful to use,
develop, sell, distribute or seek regulatory approval in any country in the
Territory to market the Product for use in the Field, in which IRC has an
ownership or other licensable interest and which is in the possession of IRC on
the date of the Agreement or thereafter during the term of the Agreement.
1.13 "Product Specifications" shall mean the specifications for the
manufacture of the Product as established by IRC, as the same may be modified by
IRC from time to time.
1.14 "Royalty Term" shall mean, with respect to each country in the
Territory, the period of fifteen (15) years commencing on the date of the First
Commercial Sale of the Product in such country.
1.15 "Stock Purchase Agreement" shall mean the Stock Purchase
Agreement dated as of the date hereof, between IRC and Trinity (as the same may
be amended or restated from time to time).
1.16 "Territory" shall mean Thailand, Cambodia, Burma, Singapore,
Vietnam, Sri Lanka, Indonesia, Malaysia, the Philippines and Laos.
1.17 "Third Party" shall mean any Person other than IRC, Trinity and
their respective Affiliates.
ARTICLE 2
REPRESENTATIONS AND WARRANTIES
Each party hereby represents and warrants to the other party as
follows:
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2.1 Existence and Power. Such party (a) is a corporation or limited
company (as the case may be) duly organized, validly existing and in good
standing under the laws of the jurisdiction in which it is organized; (b) has
the requisite power and authority and the legal right to own and operate its
property and assets, to lease the property and assets it operates under lease,
and to carry on its business as it is now being conducted and (c) is in
compliance with all requirements of applicable law, except to the extent that
any noncompliance would not have a material adverse effect on the properties,
business, financial or other condition of such party and would not materially
adversely affect such party's ability to perform its obligations under the
Agreement.
2.2 Authorization and Enforcement of Obligations. Such party (a) has
the requisite power and authority and the legal right to-enter into the
Agreement and to perform its obligations hereunder and (b) has taken all
necessary action on its part to authorize the execution and delivery of the
Agreement and the performance of its obligations hereunder. The Agreement has
been duly executed and delivered on behalf of such party, and constitutes a
legal, valid, binding obligation, enforceable against such party in accordance
with its terms.
2.3 Consents. All necessary consents, approvals and authorizations
of all governmental authorities and other Persons required to be obtained by
such party in connection with the Agreement have been obtained.
2.4 No Conflict. The execution and delivery of the Agreement and the
performance of such party's obligations hereunder (a) do not conflict with or
violate any requirement of applicable laws or regulations and (b) do not
conflict with, or constitute a default under, any contractual obligation of such
party
2.5 DISCLAIMER OF WARRANTIES. NOTHING IN THE AGREEMENT SHALL BE
CONSTRUED AS A REPRESENTATION MADE, OR WARRANTY GIVEN, BY IRC THAT THE USE OF
ANY LICENSE GRANTED HEREUNDER WILL NOT INFRINGE THE PATENT OR PROPRIETARY RIGHTS
OF ANY OTHER PERSON. FURTHERMORE, IRC MAKES NO REPRESENTATIONS OR WARRANTIES,
EXPRESS OR IMPLIED, WITH RESPECT TO THE LICENSED RIGHTS HEREUNDER, INCLUDING
WITHOUT LIMITATION, ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR
PURPOSE.
ARTICLE 3
DEVELOPMENT PROGRAM
-------------------
3.1 Development Workplans.
3.1.1 Preparation of the Workplans. The Development Workplan for
Thailand is set forth in Exhibit A hereto. Not less than ninety (90) days prior
to the anticipated filing of the first Investigational New Drug application
("IND") for the Product, or its equivalent, with the governing health authority
in any other country in the Territory, or not less than ninety (90) days prior
to the commencement of human clinical trials of the Product in any such country
if no such
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filing or application is required in such country, IRC and Trinity jointly shall
prepare a mutually acceptable Development Workplan for such country.
3.1.2 Content of the Workplans. In accordance with the provisions of
Sections 3.2 below, the Development Workplan for each country in the Territory
(a) shall specify generally the activities necessary to obtain all applicable
marketing approvals required for the commercial sale, distribution or use of the
Product in such country for use in the Field, (b) shall set forth generally the
structure of all human clinical trials to be conducted in such country for the
Product, (c) shall identify the principal investigators for such clinical
trials, and (d) shall establish the required resources and efforts of IRC and
Trinity, and the required funding by Trinity, necessary to conduct such clinical
trials and to obtain the required marketing approval to commercially sell,
distribute and use the Product in such country as soon as commercially
practicable, consistent with prudent drug development practices.
3.1.3 Modifications to the Workplans. Prior to July 1 of each year
during the term of the Development Program, the Project Leaders (as defined in
Section 4.1 below) shall recommend to the parties any modifications to the
Development Workplan for each country which they determine to be necessary or
desirable. Such modifications shall be effective only upon the mutual written
agreement of IRC and Trinity. The parties additionally may revise the
Development Workplan for each country upon the completion of each phase of human
clinical trials of the Product in such country and otherwise from time to time,
upon the mutual written agreement of IRC and Trinity.
3.2 Clinical Development. On the terms and subject to the conditions of
the Agreement, Trinity diligently shall cause to be conducted such human
clinical trials as the parties mutually determine are necessary or desirable to
obtain all required approvals to market the Product in each country in the
Territory for use in the Field, all in accordance with the applicable
Development Workplan.
3.2.1 Trinity shall engage one or more clinical research
organizations (each, a "CRO") of internationally-recognized standing, subject to
the approval of IRC which shall not be unreasonably withheld or delayed, to
manage such human clinical trials.
3.2.2 Trinity shall consult generally with IRC with respect to each
such clinical trial.
3.2.3 Each such clinical trial shall be conducted in accordance with
a protocol jointly prepared by, and in form and substance mutually agreed to in
writing by IRC and Trinity.
3.2.4 Trinity shall select the clinical sites and principal
investigators for each such clinical trial, subject to the approval of IRC which
shall not be unreasonably withheld or delayed. Each clinical site shall enter
into a clinical trials site agreement with IRC and Trinity in the form of
Exhibit B hereto with only such modifications as necessary to reflect the name
of the clinical site, the name of the principal investigator and the country in
which the clinical trial is conducted, and as otherwise expressly agreed to in
writing by IRC and Trinity. Trinity shall cause its CRO to collect from each
clinical Site, and to provide IRC with, fully-executed drug disposition forms,
in the form provided by IRC.
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3.2.5 Trinity shall cause its CRO to oversee the conduct of each
such clinical trial. With respect to each clinical site, Trinity shall cause its
CRO to conduct a site initiation visit, subsequent monthly monitoring visits and
a site closing visit to ensure such site's compliance in all material respects
with all requirements of laws and regulations of the United States and the
applicable countries of the Territory, internal institutional procedures and
guidelines, the applicable protocol, and good laboratory and clinical practices
of the United States and the applicable countries of the Territory.
3.2.6 IRC, at its sole expense, shall provide each clinical site
with the Product and placebo as identified in the applicable protocol for use in
the clinical trial to be conducted at such site.
3.2.7 Trinity promptly shall cause its CRO to collect, review and
evaluate all case record forms, laboratory report forms and related documents
from each clinical site for legibility, completeness and safety information.
Trinity and its CRO shall immediately notify IRC of any serious or unexpected
side effect, toxicity or sensitivity reaction, or any unexpected incidence, and
the severity thereof, associated with any clinical trial. Trinity and its CRO
shall work with each clinical site to collect any missing information and to
clarify or correct any inconsistencies or other ambiguous information provided
by such clinical site. With respect to each clinical site, on the first day of
each month, Trinity shall cause its CRO to complete and provide IRC with a
monthly site monitoring report, in a form reasonably acceptable to IRC,
regarding all patient visits completed during the immediately preceding month at
such clinical site.
3.2.8 Each clinical site shall be required to use case record and other forms
provided by IRC in connection with such clinical trial. Not later than thirty
(30) days following the completion of each such clinical trial, Trinity shall
cause its CRO to provide IRC with a copy of all case record forms from such
clinical trial.
3.2.9 IRC shall have the right, but not the obligation, to monitor
the conduct of, and data gathering under, each such clinical trial for
compliance with all requirements of laws and regulations of the United States
and the applicable countries of the Territory, internal institutional procedures
and guidelines, the applicable protocol, and good laboratory and clinical
practices of the United States and the applicable countries of the Territory.
IRC also shall have the right, but not the obligation, to enter, upon reasonable
notice during normal business hours, the business facilities of Trinity where
the clinical trial records are maintained and during such time to review such
records and to consult with Trinity's staff with respect thereto.
3.2.10 IRC, at its sole expense, shall provide Trinity with such
technical assistance regarding the Product Know-How as the parties mutually
determine is reasonably necessary or desirable to enable Trinity to conduct its
obligations under the Development Program. Such technical assistance shall
include certain training of Trinity employees, from time to time, at the
facilities of IRC in Carlsbad, California.
3.3 Regulatory Filings and Applications. IRC and Trinity jointly shall
prepare, file and prosecute all filings and applications necessary to obtain all
required marketing approvals to commercially sell, distribute and use (but not
to manufacture) the Product in the Territory for use
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in the Field. Each such filing and application shall be in Trinity's name, and
shall be in form and substance mutually acceptable to IRC and Trinity. Trinity
shall be the owner and party of record for all such filings and applications.
IRC shall be entitled to cross reference all such filings and applications by
Trinity in connection with the filing and prosecution of any filings and
applications by IRC regarding the Product. Trinity shall be entitled to review
and cross reference all filings and applications by IRC regarding the Product
solely in connection with the filing and prosecution of all such filings and
applications by Trinity.
3.4 Subcontracts. Trinity may subcontract (including by the engagement
of one or more CRO's as required under Section 3.2.1 above) portions of the
Development Program to be performed by it in the normal course of its business
without the prior consent of IRC; provided, however, that (a) such
subcontracting shall not involve the transfer of Product Know-How to Third
Parties without the prior express written consent of IRC; (b) the subcontracted
party shall enter into a confidentiality agreement with Trinity in accordance
with Section 10.2 below; (c) Trinity shall supervise such subcontract work; and
(d) the subcontracted party shall be in compliance in all material respects with
all requirements of laws and regulations of the United States and the countries
of the Territory, together with all good laboratory practices and good clinical
practices of the United States and the applicable countries of the Territory.
3.5 Conduct of Development Program. Trinity shall conduct its
obligations under the Development Program in good scientific manner, and in
compliance in all material respects with all requirements of laws and
regulations of the United States and the countries of the Territory and all
applicable good laboratory practices and good clinical practices of the United
States and the applicable countries of the Territory.
3.6 Funding the Development Program. Except as otherwise set forth
below in this Section 3.6 Trinity shall be solely responsible for funding all
the costs of conducting the clinical development of the Product in the
Territory, and the related activities necessary to obtain the required approvals
to market the Product in the Territory for use in the Field. IRC shall be solely
responsible for funding (a) the costs of supplying each clinical site with
certain materials as identified in the applicable protocol for use in the
clinical trial to be conducted at such site, and (b) its internal and
out-of-pocket costs of conducting its obligations under the Development Program.
3.7 Development Reports and Results.
3.7.1 Each party shall keep the other informed regarding the
progress of such party's responsibilities regarding the clinical development of
each Product and the preparing, filing and obtaining of the required approvals
to market the Product in the Territory for use in the Field.
3.7.2 Within thirty (30) days following the end of each calendar
quarter following the commencement of human clinical trials of the Product in
the Territory, each party shall prepare, and provide to the other, a reasonably
detailed written report which shall describe the progress of such party's
responsibilities regarding the clinical development and testing of the Product,
all regulatory filings and submissions made, and all approvals obtained.
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3.7.3 Each party shall make its employees and relevant reports of
nonemployee consultants available, upon reasonable notice during normal business
hours, at their respective places of employment to consult with the other party
on issues arising during the Development Program and in connection with any
request from any regulatory agency, including regulatory, scientific, technical
and clinical testing issues.
3.7.4 Representatives of IRC and Trinity may, upon reasonable notice
during normal business hours, visit the facilities where the Development Program
is being conducted, and consult informally, during such visits and by telephone,
with personnel of the other party performing work on the Development Program. If
requested by the-other party, IRC and Trinity shall cause appropriate
individuals working on the Development Program to be available for meetings at
the location of the facilities where such individuals are employed at times
reasonably convenient to the party responding to such request.
3.7.5 Trinity shall be the sole owner of all data, information and
other results (including, without limitation, data forms and protocols)
resulting from or relating to the clinical trials of the Product, excluding
subject and patient records. IRC shall have the right to use and disclose all
such data, information and results for any purpose.
3.8 Election Not to Develop. If Trinity elects at any time not to
develop and commercialize, or abandons the development and commercialization of
the Product in any country in the Territory, then (a) all rights and obligations
of Trinity to develop and commercialize the Product in such country shall
terminate, and (b) thereafter IRC shall have the exclusive right, in its Sole
discretion and at its sole expense, to develop and commercialize the Product in
such country.
3.9 Excused Performance. In addition to the provisions of Article 14
below, the obligations of Trinity under the Development Program are expressly
conditioned upon the continuing absence of any adverse conditions relating to
the safety or efficacy of the Product, and the obligations of Trinity to develop
the Product shall be delayed or suspended so long as any such condition or event
exists. If Trinity delays or suspends development of the Product in Thailand for
a period which exceeds eighteen (18) months in duration (except for delays or
suspensions due solely to regulatory delays beyond Trinity's reasonable
control), then all Trinity's rights and obligations to develop and commercialize
the Product in the Territory shall terminate and thereafter IRC shall have the
exclusive right, in its sole discretion and at its sole expense, to develop and
commercialize the Product in the Territory.
ARTICLE 4
MANAGEMENT OF THE DEVELOPMENT PROGRAM
-------------------------------------
4.1 Project Leaders. IRC and Trinity each shall appoint a person (a
"Project Leader") to coordinate its part of the Development Program. The Project
Leaders shall be the primary contacts between the parties with respect to the
Development Program. Each party shall notify the other within thirty (30) days
of the date of the Agreement of the appointment of its Project Leader and shall
notify the other party as soon as practicable upon changing this appointment.
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4.2 Disagreements. All disagreements between the Project Leaders shall
be resolved in the following manner:
4.2.1 The Project Leaders promptly shall present the disagreement to
the executive of each of IRC and Trinity who has the principal responsibility
for such party's work under the Agreement.
4.2.2 Such executives shall meet to discuss each party's view and to
explain the basis for their respective positions, and in good faith shall
attempt to resolve such disagreement among themselves.
4.2.3 If such executive officers cannot resolve such disagreement
within thirty (30) days after the meeting described in Section 4.2.2 above, then
such disagreements shall be resolved in any manner which such executives
mutually agree or by any available legal or equitable means.
4.2.4 Notwithstanding the foregoing, the parties do not waive any
rights which they may have under the Agreement or otherwise as a result of one
party's settlement of a disagreement under Section 4.2.3 above.
ARTICLE 5
LICENSES
--------
5.1 License Grant. Except as otherwise provided in the Agreement, IRC
hereby grants to Trinity an exclusive license in the Territory under the Product
Know-How to conduct its obligations under the Development Program in the
Territory and to sell, distribute and use the Product in the Territory for use
in the Field. Trinity shall not sell or distribute the Product in any country in
the Territory, other than Thailand, unless Trinity has previously received the
required marketing approval from the governing health authority in Thailand for
the Product and Trinity has commenced marketing and is diligently marketing the
Product in Thailand for use in the Field.
5.2 Sublicense Rights. Trinity may not grant sublicenses under such
license to any Affiliate or Third Party without the prior written consent of
IRC, except. for sublicense solely for the purpose of marketing, promoting,
selling and distributing the Product. Trinity shall provide to IRC a copy of any
permitted sublicense promptly upon execution of the same. Any permitted
sublicense shall be subject to the provisions of the Agreement.
5.3 Reversion of Rights to IRC. With respect to (a) each country in
which Trinity abandons or elects not to develop or commercialize the Product,
and (b) the Territory, if Trinity delays or suspends the development of the
Product in Thailand for more than eighteen (18) months under Section 3.10 above,
the license granted to Trinity with respect to each such country (or the
Territory under clause (b) above) shall automatically revert to IRC, and Trinity
shall have no further rights under the Agreement with respect thereto.
5.4 Option to License Manufacturing Technology. Subject to the
provisions of this Section 5.4, IRC shall have the exclusive right to make and
have made the Product for sale,
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distribution and use in the Territory. For a period of three years commencing on
the date of the First Commercial Sale of the Product in Thailand, Trinity shall
have the exclusive option, in its sole discretion, to obtain an exclusive
license (except as to IRC and its Affiliates) under the Manufacturing Know-How
to make the Product in Thailand solely for sale, distribution and use in the
Territory. If Trinity gives timely written notice to IRC of its exercise of such
option, the parties promptly shall negotiate in good faith and attempt to reach
a mutually acceptable agreement which would include, without limitation, the
following material provisions: (a) grant of a license (without the right to
sublicense) under the Manufacturing Know-How to such licensee as the parties
mutually agree (which shall be either Trinity, an Affiliate of Trinity, a joint
venture entity owned by IRC, Trinity or their respective Affiliates, or such
other entity as the parties mutually agree) to make the Product in Thailand
solely for sale, distribution and use in the Territory; (b) transfer of the
Manufacturing Know-How, reasonable technical assistance regarding the
Manufacturing Know-How and adequate protection to prevent the unauthorized use
or disclosure of the Manufacturing Know-How; (c) control of the construction,
validation and licensing of the manufacturing facility in accordance with GMP
and all applicable laws, regulations and good manufacturing practices
promulgated by the governing health authority of Thailand; (d) control of the
employees and operations of the manufacturing facilities and processes; (e)
quality control and quality assurance of the Product in accordance with GMP and
all applicable laws, regulations and good manufacturing practices promulgated by
the governing health authority of Thailand; (f) terms and conditions of a
manufacturing royalty payable to IRC; (g) performance criteria and maximum
output limitations; (h) insurance and indemnification provisions; (i)
termination provisions; and (j) such other terms and conditions as are customary
or appropriate in such agreements. If Trinity fails to timely give such notice
to IRC or, if after good faith negotiations, the parties are unable to reach a
mutually acceptable agreement prior to the expiration of such three-year period,
then Trinity shall have no further option to obtain a license to make the
Product in Thailand for sale, distribution and use in the Territory.
5.5 Right to Negotiate License to Gene Therapy Products. For a period
of fifteen (15) years after the date of the Agreement, Trinity shall have
the-right, in its sole discretion, to negotiate with IRC to obtain an exclusive
license (except as to IRC and its Affiliates) in the Territory under IRC's
patent rights and know-how, existing as of the date of the Agreement, to develop
and commercialize gene therapy products in the Territory for use in the Field.
If Trinity gives timely written notice to IRC of its desire to so negotiate for
such a license, the parties shall negotiate in good faith and attempt to reach a
mutually acceptable agreement which shall include, without limitation, the
following material provisions: (a) grant of a license under the IRC's patent
rights and know-how to develop and commercialize such gene therapy products in
the Territory solely for use in the Field; (b) transfer of any necessary
technology to Trinity, reasonable technical assistance and adequate protection
to prevent the unauthorized use or disclosure of such technology; (c) research
and development rights and obligations; (d) promotion, marketing, sales and
distribution rights and obligations; (e) manufacturing and supply rights and
obligations; (f) license fee, royalty and milestone payment terms and
conditions; (g) performance criteria and diligence obligations; (h) insurance
and indemnification provisions; (i) termination provisions; and (j) such other
terms and conditions as are customary or appropriate in such agreements. If
Trinity fails to timely give such notice to IRC or, if after good faith
negotiations, the parties are unable to reach a mutually acceptable agreement
prior to the expiration of such fifteen (15) year period, then Trinity shall
have no further right to negotiate to obtain a license to develop and
commercialize such gene therapy products in the Territory for use in the Field.
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5.6 Diligence. Trinity diligently shall take all actions reasonably
necessary to obtain the required approval to market the Product in each country
in the Territory for use in the Field, as soon as commercially practicable, in
accordance with the applicable Development Workplan and consistent with prudent
drug development practices. Upon receipt of the required marketing approval for
the Product in a country in the Territory, Trinity promptly shall commence
marketing, and thereafter Trinity diligently shall market the Product in such
country for use in the Field to meet the reasonably anticipated market demand
for the Product in such country. Trinity shall not promote, market, sell,
distribute, seek customers, establish any branch or maintain any sales or
distribution network or instrumentality for the sale or distribution of the
Product outside the Territory.
ARTICLE 6
PRODUCT SUPPLY
--------------
6.1 Purchase and Sale of Products. On the terms and subject to the
conditions of the Agreement, IRC shall manufacture, sell and deliver the Product
to Trinity, and Trinity shall purchase and accept such amount of the Product as
ordered by Trinity, for sale, distribution and use in the Territory for use in
the Field. The Product shall be manufactured to conform with the Product
Specifications and in compliance with the applicable laws and regulations of the
applicable governing health authority in the Territory.
6.1.1 For Clinical Development. IRC shall manufacture, sell and
deliver to Trinity such amounts of the Product and placebo, as Trinity
reasonably requests, equal to Trinity's requirements of Products for clinical
development in the Territory under the Development Program.
6.1.2 For Commercial Sale and Distribution. IRC shall manufacture,
sell and deliver to Trinity such amounts of the Product, as Trinity reasonably
requests pursuant to the provisions of Section 6.4 below, equal to Trinity's
requirements of the Product for commercial sale and distribution in the
Territory for use in the Field.
6.2 Packaging. Upon the mutual agreement of the parties in writing, IRC
shall supply Product under the Agreement in unlabeled unit dose containers. The
specifications of such unit dose containers shall meet all requirements of
applicable laws and regulations. If IRC supplies Trinity with unlabeled unit
dose containers of the Product, Trinity, at its sole expense, shall finalize
packaging and labeling of the Product for sale and distribution in accordance
with the requirements of applicable laws and regulations.
6.3 Purchase Price and Payment Terms.
6.3.1 Purchase Price.
(a) With respect to clinical development supply under Section 6.1.1
above, after receipt of approval from the governing health authority of Thailand
to conduct the applicable human clinical trials in Thailand and approval from
the FDA to supply the Product for use therein, IRC shall supply Trinity with
such 100 microgram, 400 microgram and DTH skin testing doses of the Product and
placebo (as set forth in mutually acceptable protocols), for use in
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human clinical trials in Thailand under the Development Program for a period not
to exceed three (3) years after the commencement of human clinical trials in
Thailand. IRC shall supply such doses of Product and placebo for use in such
human clinical trials in Thailand for not more than 10,000 enrolled patients
during such period at no cost to Trinity. If additional Product and placebo is
required for use in human clinical trials in Thailand prior to the First
Commercial Sale, IRC shall supply such additional Product and placebo as the
parties mutually agree in writing; at the purchase price US$*** per 100
microgram dose, US$*** per 400 microgram dose and US$*** per DTH skin testing
dose of the Product and at such purchase price as the parties mutually agree in
writing for placebo.
(b) With respect to clinical development supply under Section 6.1.1
above, for use in human clinical trials in any other Country in the Territory
under the Development Program, Trinity shall purchase such quantity of Product
and placebo from IRC at such price as the parties mutually agree in writing.
(c) With respect to commercial supply under Section 6.1.2 above,
Trinity shall purchase Product from IRC at a price determined as follows: For a
period of three years commencing on the date of the First Commercial Sale in
Thailand, the purchase price shall equal US$*** per 100 microgram dose, US$***
per 400 microgram dose and US$*** per DTH skin testing dose of the Product;
provided, however, if the Product is commercially sold or distributed in the
Territory in other than 100 microgram, 400 microgram and DTH skin testing doses,
or if IRC's Manufacturing Cost materially increases prior to the expiration of
such three-year period, then the parties shall negotiate in good faith a
mutually acceptable adjustment to the purchase price for the balance of such
period which enables IRC, considering all the circumstances, to receive the
substantially equivalent economic benefit from the adjusted purchase price as it
reasonably expected as of the date of the Agreement to receive from the purchase
price set forth above. After the three-year period as aforesaid, the purchase
price shall be revised annually, on or before each anniversary of the date of
the First Commercial Sale of the Product in Thailand, by the mutual written
agreement of the parties.
(d) IRC shall calculate its Manufacturing Cost for the Product in
good faith in a manner which reasonably and equitably allocates the cost of
overhead, materials, direct labor and benefits (each as defined in Section 1.9
above) to the Product.
6.3.2 Invoicing. Upon shipment of Product to Trinity, IRC shall
submit invoices therefor to Trinity. For all deliveries accepted pursuant to
Section 6.6 below, Trinity shall pay each invoice in full within thirty (30)
days of receipt. Trinity shall pay interest to IRC on any unpaid invoice amount,
which remains outstanding in excess of such thirty (30) day period at a rate
equal to the three-month London Inter-Bank Offering Rate (LIBOR), as published
in The Wall Street Journal under the caption "Money Rates," increased by two
percent (2%) per annum, and adjusted on the first business day of each calendar
Quarter, for a period than an invoice remains outstanding in excess of such
thirty (30) day period.
6.3.3 Sales and Use Taxes. Any federal, state, county or municipal
sales or use tax, excise or similar charge, or other tax assessment of any
country (other than that assessed against income), assessed or charged on the
sale of Product sold pursuant to the Agreement shall be paid by Trinity.
-12-
6.4 Orders and Forecasts.
6.4.1 Prior to Regulatory Approval. Beginning upon Trinity's first
submission for regulatory approval of the Product to the governing health
authority in Thailand, and prior to approval to market the Product by the
governing health authority in Thailand, Trinity shall issue at quarterly
intervals a twelve (12) month forecast estimating Trinity's requirements of such
Product for the first twelve (12) months of supply. These forecasts may be used
by IRC for planning purposes only, unless and until such time as Trinity elects
to issue an order or purchase order for its first delivery of Product in
anticipation of Product approval. The order or purchase order (as the case may
be) shall indicate dates and delivery information requirements. Trinity shall be
obligated to accept or purchase and IRC shall supply one hundred percent (100%)
of the quantity of Product listed in this initial order or purchase order (as
the case may be) provided that such order or purchase order (as the case may be)
is received by IRC not less than six (6) months prior to the requested delivery
date in such order or purchase order (as the case may be) . If such order or
purchase order (as the case may be) contains a delivery date of less than six
(6) months, IRC shall use its commercially reasonable efforts to meet such
delivery date.
6.4.2 After Regulatory Approval. Subsequent to regulatory approval
to market the Product in Thailand, Trinity shall continue to issue at quarterly
intervals a twelve (12) month forecast estimating its requirements of the
Product during the succeeding four quarterly periods. Trinity shall be required
to accept or purchase one hundred percent (100%) of the quantity of Product
listed for the first quarterly period of each forecast and seventy-five percent
(75%) of the quantity of Product listed for the second quarterly period of such
forecast, but shall be able to increase or decrease the quantities estimated for
the remaining two quarters of such forecast in subsequent forecasts. Trinity
shall issue orders or purchase orders (as the case may be) for its Product
requirements which shall provide dates and delivery information requirements.
6.4.3 Supply Obligation. IRC shall supply one hundred percent (100%)
of Product listed for the first quarterly period of each forecast, and shall
have sufficient in-process inventory to produce one hundred twenty-five percent
(125%) of the quantity of Product listed for the second quarterly period of each
forecast. IRC shall use its commercially reasonable best efforts to accommodate
any increases in quantity of Product which Trinity shall request under new
orders or purchase orders (as the case may be). IRC shall meet Trinity's
delivery requirements specified in accordance with this Section 6.4. IRC's
obligation to supply Product, after regulatory approval to market the Product in
Thailand, shall be subject to consummation of the purchase by Trinity of the
shares of IRC common stock required to be purchased pursuant to Section 1.1.2 of
the Stock Purchase Agreement.
6.4.4 Planning Forecasts. Each September during the term of the
Agreement or any extension thereof, Trinity shall prepare for IRC a special
planning forecast for the following calendar year estimating Trinity's
requirements for each Product for such year. This forecast shall not be binding
upon the parties and shall be used for internal planning purposes only.
6.4.5 Agreement Controlling. Each firm order by Trinity under the
Agreement shall be governed by the terms of the Agreement. None of the terms or
conditions of Trinity's or IRC's orders , purchase orders, invoices or similar
instruments shall be applicable, except those specifying quantity ordered,
delivery dates, special supply instructions and invoice information.
-13-
6.5 Manufacturing Practices.
6.5.1 GMP. IRC shall manufacture Product under the Agreement in
accordance with GMP, IRC shall promptly advise Trinity of any process changes
experienced by IRC during the manufacture of Product. Trinity shall have the
right, at its sole expense, to audit IRC for compliance with GMP at reasonable
intervals. Such audits shall be scheduled at mutually agreeable times upon at
least fifteen (15) days' prior written notice to IRC.
6.5.2 Certificates of Analysis. IRC shall provide certificates of
analysis to Trinity for all Product delivered hereunder.
6.5.3 Quality Control Information. Upon the reasonable request of
either IRC or Trinity, the other party shall provide the requesting party with
such information, including analytical and manufacturing documentation,
requested by the requesting party relating to quality control of the Product;
provided, however, the requesting party shall treat all such information
disclosed pursuant to this Section 6.5.3 as confidential information subject to
the provisions of Article 10 below.
6.6 Delivery and Acceptance.
6.6.1 Delivery. IRC's obligation to deliver Products under the
Agreement shall be subject to obtaining all necessary consents, approvals and
authorizations of the applicable governmental and regulatory authorities. All
Products supplied under the Agreement shall be shipped f.o.b. place of
manufacture. Title and risk of loss and damages to the Products shall pass to
Trinity upon release to Trinity's designated carrier.
6.6.2 Rejection and Cure. If a shipment of Product or any portion
thereof is spoiled, damaged or defective, then Trinity shall have the right to
reject such shipment of the Product or the portion thereof that fails to so
conform, as the case may be. Trinity shall give written notice to IRC of its
rejection hereunder, within sixty (60) days following the date on which such
shipment was delivered, specifying the grounds for such rejection. All or any
part of any shipment may be held for IRC's disposition and at IRC's expense if
found to be not in conformance with the Product Specifications. No claims with
respect to rejected Product shall be in an amount greater than the purchase
price of such Product; provided, however, that IRC shall use its commercially
reasonable efforts to cure such rejection or replace such spoiled, damaged or
defective shipment of Product within, ninety (90) days after receipt of notice
of rejection thereof. Should cover be utilized, IRC shall be responsible for the
cost of such cover pertaining to the rejected Product in question. If no notice
of rejection is given by Trinity within such sixty (60) day period, the shipment
of the Product shall be deemed to have been accepted.
6.7 Subcontract Manufacture. IRC shall have the right to subcontract
with an Affiliate or Third Party subcontractor to manufacture, sell and deliver
Products under the Agreement.
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ARTICLE 7
ROYALTIES
---------
During the Royalty Term, Trinity shall pay to IRC royalties equal to
US$*** per each 100 microgram dose, US$ *** per 400 microgram dose and US$***
per DTH skin testing dose of the Product sold or distributed by Trinity, its
Affiliates and sublicensees in the Territory. Notwithstanding the foregoing, if
the Product is sold or distributed and used in the Territory in other than 100
microgram, 400 microgram and DTH skin testing doses, the parties shall negotiate
a mutually acceptable adjustment to the royalty rate which enables IRC,
considering all the circumstances, to receive the substantially equivalent
economic benefit from the adjusted royalty rate as it reasonably expected as of
the date of the Agreement to receive from the royalty rate set forth above.
ARTICLE 8
ROYALTY REPORTS AND ACCOUNTING
------------------------------
8.1 Reports, Exchange Rates. During the term of the Agreement following
the First Commercial Sale of the Product, Trinity shall furnish to IRC a
quarterly written report showing in reasonably specific detail, on a country by
country basis, (a) the quantity of all Product sold or .distributed by Trinity,
its Affiliates and its sublicensees in the Territory during the reporting
period; (b) the calculation of royalties payable in United States dollars, if
any, which shall have accrued based upon such sale or distribution of Product;
(c) the withholding taxes, if any, required by law with respect to such sale or
distribution; and (d) the date of the First Commercial Sale of the Product in
each country in the Territory during the reporting period. Reports shall be due
on the thirtieth (30th) day following the close of each quarter. Trinity shall
keep complete and accurate records in sufficient detail to properly reflect all
sales and distributions of the Product and to enable the royalties payable
hereunder to be determined.
8.2 Audits.
8.2.1 Upon the written request of IRC and not more than twice in
each calendar year, Trinity shall permit an independent certified public
accounting firm of internationally recognized standing, selected by IRC and
reasonably acceptable to Trinity, at IRC's expense, to have access during normal
business hours to such of the records of Trinity as may be reasonably necessary
to verify the accuracy of the royalty reports hereunder for any year ending not
more than thirty-six (36) months prior to the date of such request. The
accounting firm shall disclose to IRC only whether the records are correct or
not and the specific details concerning any discrepancies. No other information
shall be shared.
8.2.2 If such accounting firm concludes that additional royalties
were owed during such period, Trinity shall pay the additional royalties within
thirty (30) days of the date IRC delivers to Trinity such accounting firm's
written report so concluding. The fees charged by such accounting firm shall be
paid by IRC; provided, however, if the audit discloses that the royalties
payable by Trinity for the audited period are more than one hundred five percent
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(105%) of the royalties actually paid for such period, then Trinity shall pay
the reasonable fees and expenses charged by such accounting firm.
8.2.3 Trinity shall include in each permitted sublicense granted by
it pursuant to the Agreement a provision requiring the sublicensee to make
reports to Trinity, to keep and maintain records of sales and distributions made
pursuant to such sublicense and to grant access to such records by IRC's
independent accountant to the same extent required of Trinity under the
Agreement. Upon the expiration of thirty-six (36) months following the end of
any year, the calculation of royalties payable with respect to such year shall
be binding and conclusive upon IRC and Trinity shall be released from any
liability or accountability with respect to royalties for such year.
8.3 Confidential Financial Information. IRC shall treat all financial
information subject to review under this Article 8 or under any sublicense
agreement as confidential, and shall cause its accounting firm to retain all
such financial information in confidence.
ARTICLE 9
PAYMENTS
--------
9.1 Payment Terms. Royalties shown to have accrued by each royalty
report provided for under Article 8 above shall be due and payable on the date
such royalty report is due. Payment of royalties in whole or in part may be made
in advance of such due date.
9.2 Payment Method. All payments by Trinity to IRC under the Agreement
shall be paid in United States dollars, and all such payments shall be
originated from a United States bank located in the United States and made by
bank wire transfer in immediately available funds, or by such other method of
payment as IRC and Trinity mutually agree in writing before such payment is due,
to such account as IRC shall designate before such payment is due.
9.3 Exchange Control. If at any time legal restrictions prevent the
prompt remittance of part or all royalties with respect to any country in the
Territory where the Product is sold or distributed, payment shall be made
through such lawful means or methods as IRC reasonably shall determine.
9.4 Withholding Taxes. All amounts owing from Trinity to IRC under the
Agreement are net amounts, and shall be grossed-up to account for any
withholding taxes, value-added taxes or other taxes, levies or charges with
respect to such amounts, other than (a) United States taxes and (b) taxes
imposed solely by reason of IRC having a permanent establishment in any other
country or IRC otherwise being subject to taxation by such country (except
solely by reason of the license granted under the Agreement).
9.5 Late Payments. Unless otherwise provided in the Agreement, Trinity
shall pay interest to IRC on the aggregate amount of any payments by Trinity
that are not paid on or before the date such payments are due under the
Agreement at a rate per annum equal to the prime rate of interest as reported by
Bank of America NT&SA in San Francisco, California, from time to time, plus
***, calculated on the number of days such payment is delinquent.
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ARTICLE 10
CONFIDENTIALITY
---------------
10.1 Nondisclosure Obligations. Except as otherwise provided in this
Article 10, during the term of the Agreement and for a period of five (5) years
thereafter, Trinity shall maintain in confidence and use only for purposes of
the Agreement all information and data, of any type whatsoever, (a) disclosed by
IRC and identified as, or acknowledged to be, confidential, or (b) resulting
from the Development Program or relating to the Product (the "Confidential
Information").
10.2 Permitted Disclosures. To the extent it is reasonably necessary or
appropriate to fulfill its obligations under the Agreement, Trinity may disclose
(a) Confidential Information it is otherwise obligated under this Article 10 not
to disclose to its employees on a need-to-know basis on the condition that such
persons agree in writing, or are subject to a written Institution policy, to
keep the Confidential Information confidential for the same time periods and to
the same extent as Trinity is required to keep the Confidential Information
confidential and (b) such Confidential Information to governmental or other
regulatory authorities to the extent that such disclosure is required by
applicable law, regulation or court order, provided that Trinity shall give
advance written notice to IRC thereof and sufficient opportunity to object to
such disclosure or to request confidential treatment thereof. Trinity shall
notify IRC promptly upon discovery of any unauthorized use or disclosure of the
Confidential Information.
The obligation not to disclose or use Confidential Information shall
not apply to the extent that Trinity can demonstrate that (i) the disclosed
information was public knowledge at the time of such disclosure by Trinity, or
thereafter became public knowledge, other than as a result of actions of
Trinity, its directors, officers or employees, in violation hereof; (ii) the
disclosed information was rightfully known by Trinity or its affiliates (as
shown by its written records) prior to the date of disclosure to Trinity
hereunder: or (iii) the disclosed information was disclosed to Trinity or its
affiliates on an unrestricted basis from a source unrelated to any party to the
Agreement and not under a duty of confidentiality to IRC.
10.3 Publication. Subject to the provisions of Sections 10.1 and 10.2
above, Trinity shall have the right to publish the results of the Development
Program; provided, however, that Trinity shall provide IRC the opportunity to
review any proposed manuscripts or any other proposed disclosure describing the
such results not less than sixty (60) days prior to their proposed submission
for publication or other proposed disclosure. IRC shall have the right to
require the delay of any such publication or disclosure for a period of up to
ninety (90) days to permit IRC to prepare and file such patent applications as
it believes are necessary or desirable to protect any patentable subject matter
to be disclosed in such publication or other disclosure. IRC shall also have the
right to require the delay of any such publication or disclosure until such time
as IRC has filed such results with the FDA.
10.4 Terms of the Agreement. IRC and Trinity shall not disclose any
terms or conditions of the Agreement to any Third Party without the prior
consent of the other party, except as required by applicable law or to Persons
with whom Trinity or IRC has entered into or proposes to enter into a business
relationship, provided that such Persons shall enter into the
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regutied
confidentiality agreement. Notwithstanding the foregoing, prior to execution of
the Agreement, Trinity and IRC shall agree upon the substance of information
that can be used to describe the terms of this transaction, and Trinity and IRC
may disclose such information, as modified by mutual agreement from time to
time, without the other party's consent.
ARTICLE 11
TERM AND TERMINATION
--------------------
11.1 Expiration. Unless terminated earlier pursuant to Sections 11.2 or
11.3 below, the Agreement shall expire on the expiration of Trinity's
obligations to pay royalties under the Agreement.
11.2 Termination by IRC. The Agreement shall terminate, at the option
of IRC effective upon written notice thereof to Trinity, if Trinity has not
received the required marketing approval from the governing health authority of
Thailand for the Product on or before the first to occur of (a) the date which
is eighteen (18) months after receipt of the required marketing approval from
the FDA for the Product in the United States, (b) the date which is twenty-four
(24) months after completion of the Phase 3 clinical trial of the Product in
Thailand under the applicable Development Workplan, and (c) December 31, 2000.
11.3 Termination for Cause. Either party may terminate the Agreement
upon the occurrence of any of the following:
11.3.1 Trinity shall have failed to timely deliver to IRC the letter of
credit required under Section 1.4 of the Stock Purchase Agreement; or
11.3.2 Trinity has not received, on or before April 1, 1996, the
required approval from the governing health authority of Thailand to commence
human clinical trials of the Product in Thailand under the applicable
Development Workplan; or
11.3.3 Trinity shall have failed to purchase the shares of IRC common
stock under Section 1.1.1 and/or 1.1.2 of the Stock Purchase Agreement (without
regard to Section 1.2 of the Stock Purchase Agreement) ; or
11.3.4 Any serious and unexpected side effect, injury, toxicity or
sensitivity reaction, or any unexpected incidence associated with the clinical
uses, studies, investigations, tests and marketing of the Product, as further
specified in Article 13 below; or
11.3.5 The other party shall (a) seek the liquidation, reorganization,
dissolution or winding up of itself (other than dissolution or winding up for
the purposes of reconstruction or amalgamation) or the composition or
readjustment of all or substantially all of its debts, (b) apply for or consent
to the appointment of, or the taking of possession by, a receiver, custodian,
trustee or liquidator of itself or of all or substantially all of its assets,
(c) make a general assignment for the benefit of its creditors, (d) commence a
voluntary case under the Bankruptcy Code, (e) file a petition seeking to take
advantage of any other law relating to bankruptcy, insolvency, reorganization,
winding-up or composition or readjustment of debts, or (f) adopt any resolution
of its Board of Directors or stockholders for the purpose of effecting any of
the foregoing; or
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11.3.6 A proceeding or case shall be commenced without the application
or consent of the other party and such proceeding or case shall continue
undismissed, or an order, judgment or decree approving or ordering any of the
following shall be entered and continue unstayed in effect, for a period of
ninety (90) days from and after the date service of process is effected upon the
other party, seeking (a) its liquidation, reorganization, dissolution or winding
up, or the composition or readjustment of all or substantially all of its debts,
(b) the appointment of a trustee, receiver, custodian, liquidator or the like of
itself or of all or substantially all of its assets, or (c) similar relief under
any law relating to bankruptcy, insolvency, reorganization, winding up or
composition or readjustment of debts; or
11.3.7 Upon or after the breach of any material provision of the
Agreement or any material provision (other than Sections 1.1.1 and 1.4) of the
Stock Purchase Agreement, if the breaching party has not cured such breach
within ninety (90) days, or such longer period as the other party in its sole
discretion agrees, after notice thereof from the other party, the Agreement
shall terminate, at the option of the other party, upon the expiration of such
cure period.
11.4 Effect of Expiration and Termination. Expiration or termination of
the Agreement shall not relieve the parties of any obligation accruing prior to
such expiration or termination. The provisions of Articles 10 and 12 shall
survive the expiration or termination of the Agreement.
ARTICLE 12
INDEMNITY
---------
12.1 Direct Indemnity. Each party shall indemnify, defend and hold the
other party harmless, and hereby forever releases and discharges the other
party, from and against any loss, liability, cost or expense, including
attorneys' fees and costs (any "Liability"), resulting from any claim, action or
other proceeding by a Third Party, arising out of the negligence, recklessness
or intentional acts or omissions of the indemnifying party in connection with
the work performed by such party during the Development Program.
12.2 Other Indemnity. Each party shall indemnify, defend and hold the
other party harmless from and against any Liability, resulting from any claim,
action or other proceeding by a Third Party, for personal injuries or any
product recall to the extent caused by: (a) any failure of the indemnifying
party to test for or provide adequate warnings of adverse side effects to the
extent such failure arises out of acts or omissions in connection with such
party's obligations hereunder, (b) any manufacturing defect by the indemnifying
party in the Product or any other material manufactured by such party, or (c)
any other act or omission (without regard to culpable conduct) of the
indemnifying party in connection with the activities contemplated under the
Agreement; except in each case to the extent any such Liability resulted from
negligence, recklessness or intentional acts or omissions of the other party.
12.3 Procedure. A party (the "Indemnitee") that intends to claim
indemnification under this Article 12 shall promptly notify the Party (the
"Indemnitor") under obligation of indemnification hereunder of any Liability for
which the Indemnitee intends to claim such
-19-
indemnification. The Indemnitor shall have the right to participate in, and, to
the extent the Indemnitor so desires, jointly with any other indemnitor
similarly noticed, to assume the defense thereof with counsel selected by the
Indemnitor; provided, however, that an Indemnitee shall have the right to retain
its own counsel, with the fees and expenses to be paid by the Indemnitee, if
representation of such Indemnitee by, the counsel retained by the Indemnitor
would be inappropriate due to actual or potential differing interests between
such Indemnitee and any other party represented by such counsel in such
proceedings. The indemnity agreement in this Article 12 shall not apply to
amounts paid in settlement if effected without the prior express written consent
of the Indemnitor, which consent shall not be unreasonably withheld or delayed.
The failure to deliver notice to the Indemnitor within a reasonable time after
the commencement of any such action, if prejudicial to its ability to defend
such action, shall relieve the Indemnitor of any liability to the Indemnitee
under this Article 12, but the omission so to deliver notice to the Indemnitor
will not relieve it of any liability that it may have to the Indemnitee
otherwise than under this Article 12. The Indemnitor may not settle the action
or otherwise consent to an adverse judgment in such action that diminishes the
rights or interests of the Indemnitee without the express written consent of the
Indemnitee. The Indemnitee, its employees and agents, shall cooperate fully with
the Indemnitor and its legal representatives in the investigation and defense of
any Liability covered by this indemnification.
12.4 Insurance. Trinity and IRC each shall maintain, through self
insurance or otherwise, product liability insurance with respect to development,
manufacture, sale and distribution of the Product by Trinity or IRC, as the case
may be, in such amount as Trinity or IRC, respectively, customarily maintains
with respect to sales and distribution of its other products. Trinity and IRC,
as applicable, shall maintain such insurance for so long as each continues to
manufacture, sell or distribute the Product, and thereafter for so long as
Trinity and IRC, as applicable, each maintain insurance for itself covering such
manufacture, or sale distribution.
ARTICLE 13
ADVERSE EXPERIENCE REPORTING
----------------------------
During the term of the Agreement, each party shall notify the other
immediately of any information concerning any serious or unexpected side effect,
injury, toxicity or sensitivity reaction, or any unexpected incidence, and the
severity thereof, associated with the clinical uses, studies, investigations,
tests and marketing of the Product. For purposes of this Article 13, "serious"
shall mean an experience which (a) results in the death, permanent or
substantial disability, in-patient hospitalization or prolongation of
hospitalization, or (b) is a congenital anomaly, cancer, the result of an
overdose or life threatening. For purposes of this Article 13, "unexpected"
shall mean (x) for a non-marketed product, an experience that is not identified
in nature, severity or frequency in the current clinical investigator's
confidential information brochure, and (y) for a marketed product, an experience
which is not listed in the current labeling for such product, and includes an
event that may be symptomatically and pathophysiologically related to an event
listed in the labeling but differs from the event because of increased frequency
or greater severity or specificity. Each party further shall immediately notify
the other of any information received regarding any threatened or pending action
by an agency which may affect the safety and efficacy claims of any such
product. Upon receipt of any such information, the
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parties shall consult with each other in an effort to arrive at a mutually
acceptable procedure for taking appropriate action; provided, however, that
nothing contained herein shall be construed as restricting either party's right
to make a timely report of such matter to any government agency or take other
action that it deems to be appropriate or required by applicable law or
regulation.
ARTICLE 14
FORCE MAJEURE
-------------
Neither party shall be held liable or responsible to the other party
nor be deemed to have defaulted under or breached the Agreement for failure or
delay in fulfilling or performing any term of the Agreement to the extent, and
for SO long as, such failure or delay is caused by or results from causes beyond
the reasonable control of the affected party including but not limited to fire,
floods, embargoes, war, acts of war (whether war be declared or not),
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God or acts, omissions or delays in acting by any
governmental authority or the other party.
ARTICLE 15
ASSIGNMENT
----------
The Agreement may not be assigned nor, except as expressly provided or
otherwise transferred, hereunder, may any right or obligations hereunder be
assigned or transferred by either party without the consent of the other party;
provided, however, that either IRC or Trinity may, without xxx Agreement and its
rights and obligations hereunder h connection with the transfer or sale of all
or substantially all of its business, or in the event of its merger or
consolidation or change in control or similar transaction. Any permitted
assignee shall assume all obligations of its assignor under the Agreement.
ARTICLE 16
SEVERABILITY
------------
Each party hereby acknowledges that it does not intend to violate any
public policy, statutory or common laws, rules, regulations, treaty or decision
of any government agency or executive body thereof of any country or community
or association of countries. Should one or more provisions of the Agreement be
or become invalid, the parties shall substitute, by mutual consent, valid
provisions for such invalid provisions which valid provisions in their economic
effect are sufficiently similar to the invalid provisions that it can be
reasonably assumed that the parties would have entered into the Agreement with
such provisions. In case such provisions cannot be agreed upon the invalidity of
one or several provisions of the Agreement shall not affect the validity of the
Agreement as a whole, unless the invalid provisions are of such essential
importance to the Agreement that it is to be reasonably assumed that the parties
would not have entered into the Agreement without the invalid provisions.
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ARTICLE 17
MISCELLANEOUS
-------------
17.1 Notices. Any consent, notice or report required or permitted to be
given or made under the Agreement by a party to the other shall be in writing,
delivered personally or by facsimile (and promptly confirmed by personal
delivery, air mail or internationally-recognized courier), air mail
internationally-recognized courier, postage prepaid (where applicable),
addressed to the other party at its address indicated below, or to such other
address as the addressee, shall have last furnished in writing to the addressor
and (except as otherwise provided in the Agreement) shall be effective upon
receipt by the addressee.
If to IRC: The Immune Response Corporation
0000 Xxxxxx Xxxxx
Xxxxxxxx, Xxxxxxxxxx 00000, X.X.X.
Attention: Xxxxxx X. Xxxxx, Ph. D.
with a copy to: Pillsbury Madison & Sutro
000 Xxxxxxxxxx Xxxxxx, 15th Floor
Xxx Xxxxxxxxx, Xxxxxxxxxx 00000, X.X.X.
Attention: Xxxxxx X. Xxxxxx, Xx.
If to Trinity: Trinity Medical Group, Co., Ltd.
000/0 Xxxxx Xx. 0
Xxxxx Xxxx
Xxxxxxx 00000, Xxxxxxxx
Attention: Xx. Xxxx Xxxxxxxxxxxxxx
17.2 Applicable Law. The Agreement shall be governed by and construed
in accordance with the laws of the State of California, without regard to the
conflicts of law principles thereof, and shall not be governed by the United
Nations Convention on Contracts for the International Sale of Goods.
17.3 U. S. Export Laws and Regulations. Each party acknowledges that
its rights and obligations under the Agreement are subject to the laws and
regulations of the United States relating to the export of products and
technical information. Without limitation, each party shall comply with all such
laws and regulations.
17.4 Legal Enforcement. If a party initiates any legal action or other
proceeding for the enforcement or interpretation of the Agreement, or because of
a dispute or an alleged default, breach or misrepresentation in connection with
the Agreement or the rights or obligations of the parties hereunder, the parties
consent to the exclusive personal jurisdiction of the appropriate state or
federal court located in San Francisco, California, U.S.A., in such action or
other proceeding.
17.5 Entire Agreement. The Agreement and the Stock Purchase Agreement
dated as of the date hereof between IRC and Trinity, together with their
respective exhibits, contain the
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entire understanding of the parties with respect to the subject matter hereof.
All express or implied agreements and understandings, either oral or written,
heretofore made are expressly superseded by the Agreement. The Agreement may be
amended, or any term hereof modified, only by a written instrument duly executed
by both parties.
17.6 Headings. The captions to the several Articles and Sections hereto
are not a part of the Agreement, but are merely guides or labels to assist in
locating and reading the several Articles and Sections hereof.
17.7 Independent Contractors. It is expressly agreed that IRC and
Trinity shall be independent contractors and that the relationship between the
two parties shall not constitute a partnership, joint venture or agency. Neither
IRC nor Trinity shall have the authority to make any statements, representations
or commitments of any kind, or to take any action, which shall be binding on the
other, without the prior consent of the party to do so.
17.8 Waiver. The waiver by either party of any right hereunder or
failure to perform or of a breach by the other party shall not be deemed a
waiver of any other right hereunder or of any other breach or failure by said
other party whether of a similar nature or otherwise.
17.9 Counterparts. The Agreement may be executed in two or more
counterparts, eat of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.
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IN WITNESS WHEREOF, the parties have executed the Agreement as of the
date first set forth above.
THE IMMUNE RESPONSE CORPORATION
By: /s/ Xxxxxx X. Xxxxx, Ph. D.
--------------------------
Title President and CEO
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TRINITY MEDICAL GROUP, CO., LTD.
By: /s/ Xxxx Xxxxxxxxxxxxxx
---------------------------
Title: President and CEO
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Exhibit A
DEVELOPMENT WORK PLAN FOR THAILAND
A. ACTIVITIES NECESSARY TO OBTAIN ALL APPLICABLE MARKETING APPROVALS
REQUIRED FOR THE COMMERCIAL SALE, DISTRIBUTION, OR USE OF THE PRODUCT
IN THAILAND.
1. Clinical trial as required by the Thai Government;
2. Apply with the Thai FDA for permission to import product;
3. Register with the Ministry of Commerce;
4. Acquire license for commercialization.
B. THE GENERAL STRUCTURE OF ALL HUMAN CLINICAL TRIALS TO BE CONDUCTED IN
THAILAND.
A Phase II (Protocol No. 2101 June 23, 1995), randomized, double blind,
two arm, placebo controlled safety and immunogenicity study in up to
300 HIV infected subjects with CD4 counts greater than or equal to 300
cells/ul.
A Phase III (Protocol No. 301 June 23, 1995) randomized, double-blind,
multicenter, two arm, placebo controlled clinical endpoint study in
2,000 HIV seropositive patients. An additional 7,700 HIV seropositive
patients may be enrolled in an open label clinical study upon mutual
agreement of the parties.
C. PRINCIPAL INVESTIGATORS (CO-CHAIRS) FOR THE HUMAN CLINICAL TRIALS.
Protocol Coordinator: Xx. Xxxx Xxxxxxxxxxxxxx, Ph. D.
Protocol Co-Chairs : Xxxxxx Xxxxxxxx, MD
Chuanchom Sakondhavat, MD
Buranaj Smutharaks, MD, Msc, Mph
Xxxxxx X. Xxxx, MD
Scientific Advisor : Xxxxxx Xxxxxxxxxxxxxxxx, MD
D. THE REQUIRED RESOURCES AND EFFORTS OF IRC AND TRINITY NECESSARY TO
CONDUCT THE CLINICAL TRIALS AND TO OBTAIN THE REQUIRED MARKETING
APPROVAL IN THAILAND.
RESPONSIBILITIES OF THE IMMUNE RESPONSE CORPORATION
1. Supply product for clinical trial use.
2. Draft protocol, statistical analysis plan, case report forms
and informed consent form.
3. Organize the data management system (Case Report Form
tracking, database setup, data entry, QA review, database
closure, and statistical analysis) in conjunction with the
contract research organization (CRO) or a Thai Government
approved committee and PI.
4. Assist with preparation of the medical and statistical
summaries in conjunction with the CRO or a Thai Government
approved committee and PI.
5. Set up the clinical supplies labeling, ordering and tracking
system in conduction with the CRO or a Thai Government
approved committee and PI.
6. Organization of a Data Safety and Efficacy Monitoring Board
(DSMB) composed of HIV clinical and statistical experts to be
administered by the CRO or a Thai Government approved
committee and PI.
7. Draft development of all study preparation materials
(instructions manuals, monitoring notebook, Q&A line, etc.) in
conjunction with the CRO or a Thai Government approved
committee and PI.
8. Preparation of regulatory submissions for exporting of Product
to Thailand and to assist with regulatory submissions to the
Thailand FDA.
9. Assistance with routine safety monitoring and development of a
central Adverse Event (AE) notification system in conjunction
with the CRO or a Thai Government approved committee and PI.
10. Assistance with site and laboratory selection and quality
assurance reviews.
11. Travel expenses and other administration and personnel cost of
IRC employees.
RESPONSIBILITIES OF TRINITY MEDICAL GROUP, CO., LTD.
1. Funding for expenses associated with conducting the clinical
trial (data management and monitoring), performance of study
procedures (such as medical histories, physical examinations,
drug administration, venipuncture), investigator payments
including study site coordinator and other study personnel and
all laboratory assays and testing (e. g., safety labs
including hematology and chemistries and lymphocyte
phenotyping -CD4).
2. Recruitment and follow-up of patients which meet protocol
inclusion and exclusion criteria.
3. Quality assurance monitoring of medical records and case
report forms which would meet worldwide Good Clinical
Practices (GCPs) requirements.
4. Preparation of Thailand regulatory submissions and translation
of all required documents.
5. Importing Product into Thailand.
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