Exhibit 4.5
LICENSING AGREEMENT
This Agreement is made this 24th of January, 2001 between CIMYM Inc., a
corporation incorporated under the laws of Barbados and located at The LIFE OF
BARBADOS BUILDING, ▇▇▇▇▇▇, St. ▇▇▇▇▇▇▇, Barbados ("CIMYM") and CIMAB S.A.. a
corporation incorporated under the laws of Cuba, located at ▇▇▇▇▇ ▇▇▇, ▇▇▇▇▇
▇▇▇▇, ▇/ ▇▇ ▇ ▇▇, ▇▇▇▇▇▇, ▇▇▇▇▇▇, ▇▇▇▇ ("CIMAB")
BACKGROUND
1. Center of Molecular Immunology (CIM) has appointed CIMAB to act as its agent
to negotiate and sign this Agreement.
2. CIM owns and has given CIMAB the right to license certain technology relating
to the Products identified in this Agreement.
3. CIMAB and CIMYM wish to establish a long term relationship to exploit the
technology and to commercialize the Products identified in this Agreement.
Therefore, in consideration of the mutual covenants and agreements contained in
this Agreement, CIMYM and CIMAB agree as follows:
1. DEFINITIONS
AFFILIATED COMPANY -means any company that is controlled directly or indirectly
by one of the parties, or any company that directly or indirectly controls one
of the parties, or any company that is directly or indirectly controlled by a
company which also directly or indirectly controls one of the parties, so that
Affiliated Company shall include any parent or subsidiary of one of the parties,
or any direct or indirectly held subsidiary of one of the parties.
BEST AVAILABLE PRICE -means 90 % of the best available price for the
Manufacture, supply and delivery of the Product (FOB Havana), to any location
designated by CIMYM in writing, until such time as there are positive Net
Revenues at which time best available price shall mean 100 % of the best
available price for the Manufacture, supply and delivery for the Product (FOB
Havana), to any location designated by CIMYM in writing.
CGMP -means Current Good Manufacturing Practices as established by the United
States Food and Drug Administration and the Canadian Health Protection Branch
from time to time.
CUBA -means the Republic of Cuba.
FINISH -means to convert bulk Product into final dosage form and to package and
label the Product.
IMPROVEMENTS -means a product or process, the use or sale of which would
infringe a valid claim of one or more of the Patents.
MARKET -means to test, register" market and sell the Product and MARKETING has a
corresponding meaning.
NET REVENUES -means the total of all money received by CIMYM from sales of the
Product, from rights to Finish or Market the Product in the Territory and for
any sublicensing revenue less operating expenses associated with the
commercialization of the Products, including the following: (i) pre-clinical and
clinical trial costs, (ii) sales, general and administrative costs, (iii) costs
of goods sold, where expenditure is applicable, (iv) research and development
costs, (v) interest expenses, if any, (vi) capital expenditures (vii) the costs
of the Product supplied by CIMAB to CIMYM for the pre-clinical and clinical
trials conducted outside of Cuba.:. Money received means money received less
trade-allowances, credit or refunds for returned or defective Product, and
allowances for doubtful debts.
PATENTS -means all patents, patent applications and other intellectual property
rights relating to the Product and includes the patents and patent applications
identified in Appendix 2.
PERSON -or any word or expression descriptive of a person, includes a
corporation, partnership, sole proprietorship, association, organization or
centre.
PRODUCT -means TGF-alpha Vaccine and HER-1 Vaccine being developed by CIM or
CIMAB and all therapeutic combinations thereof_and includes the information
contained in Appendices III and IV.
STANDARDS -means cGMP and other standards prescribed by health authorities in
the Territory from time to time during the term of this Agreement.
SUBLICENSING REVENUE: shall, unless otherwise agreed upon in writing, means all
payments, whether in cash or otherwise, whether in the form of up front
payments, milestone payments, royalties or otherwise received by CIMYM, net of
any withholding taxes imposed by sovereign governments, from sublicensees and
assignees in consideration for the rights granted to C IMYM under this
Agreement.
TECHNOLOGY -means (i) confidential information relating to the Finishing or
Marketing of the Product, or relating to technology pertaining to the Product
(ii) the Patents including information in the Patents relating to the Product or
relating to Finishing or Marketing the Product, and (iii) Improvements.
TERRITORY -means Europe (Albania, Andorra, Austria, Belgium, Belarus, Bosnia and
Herzogovina, Bulgaria, Channel Islands, Czech Republic, Denmark, Estonia,
France, Federal Republic of Germany, Finland, Greece, Hungary, Iceland, Italy,
Latvia, ▇▇▇▇▇▇▇▇▇▇▇, Lithuania, Luxembourg, (The Former Yugoslav Republic of)
Macedonia, Republic of Moldova, Monaco, The Netherlands, Norway, Poland,
Portugal, Republic of San Marino, Rumania, Russian Federation, Serbia, Slovakia,
Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom of Great
Britain and Northern Ireland, Republic of Ireland), Canada, the United States of
America, Japan, Australia, New Zealand, Taiwan, Singapore, Thailand, Hong Kong,
South Korea, Malaysia, Indonesia, the Philippines, and any other country that
may be added to this Agreement by mutual agreement from time to time.
TRADEMARK -means a trademark of CIMAB used in association with the Product.
YMB means York Medical Biosciences Inc., its affiliated companies, and its sub-
licensees.
2. LICENSE
(1) CIMAB grants to CIMYM the exclusive right to Finish and Market the Products
in the Territory using the Technology. This exclusive license includes the right
to sub-license the rights granted under this Agreement to any other Person,
provided CIMYM obtains the written consent of CIMAB to each sublicensee, such
consent not to be withheld unreasonably. This license includes the right to use
the Trademark or any other trademarks in the Territory in association with the
Products.
3. REPRESENTATIONS AND WARRANTIES
CIMAB represents and warranties that:
o nothing in this Agreement is contrary to or unenforceable under the laws of
Cuba.
o CIMAB has the right, power and authority to represent and act as agent for
CIM and that this authority will survive the termination of this license.
o To the best of CIMAB's knowledge CIM owns the Technology absolutely, free
and clear of any liens or claims.
o CIMAB has the authority to grant the license granted to CIMYM.
o CIMAB have not granted any rights to any Persons other than CIMYM to use the
Technology in any country within the Territory.
o CIMAB is not aware of any actual or potential claim by any Person that CIM
does not own the Technology or cannot use the Technology.
o CIMAB is not aware of any challenge to CIM's ownership of, or the validity
of the Patents.
o CIMAB is not aware of any rights that could be infringed in the Territory by
the use of the Technology o~ by the Manufacture, Finishing or Marketing of
the Products in the Territory.
o CIMYM represents and warranties that:
o nothing in this Agreement is contrary to or unenforceable under the laws of
Barbados.
o CIMYM is duly incorporated under the laws of Barbados, is a corporation in
good standing and may undertake this Agreement.
o CIMYM shareholders shall not be changed unless both parties otherwise agree.
4. DISCLOSURE OF TECHNOLOGY BY CIMAB
Immediately upon the execution of this Agreement and at the end of each month
during the term, CIMAB shall disclose to CIMYM all Technology to assist CIMYM in
fulfilling its obligations under this Agreement, including (i) all manufacturing
procedures and processes, raw material lists and specifications, equipment lists
and specifications, and all quality assurance and other in vitro and in vivo
test methodologies, validations and results; (ii) reports of all stability
studies; (iii) reports of all animal and human studies; (iv) reports of all
clinical efficacy and safety studies; (v) reports of all other pre-clinical,
pharmacological and toxicological studies; (vi) all reports or other information
relating to any potential threat or risk to users of the Products, or any
contra-indications to the use of the Technology or the Products; and (vii) all
knowledge and experience in the Finishing and
Marketing of the Products. CIMAB shall grant CIMYM access to all plant master
files that are submitted to regulatory authorities in the Territory from time to
time for the plant in which the Product are made.
5. VISITS
(1) Technical personnel of CIMYM shall have the right to visit the facilities of
CIM to review the Technology. Technical personnel of CIM shall have the right to
visit the facilities of CIMYM to review the application of the Technology. Each
party shall give reasonable notices to the other of the proposed visit.
(2) At the request of CIMYM, representatives of CIM skilled in the Technology
shall visit CIMYM's facility to assist CIMYM's personnel in using the
Technology. CIMYM shall pay all expenses to CIMAB in sending such
representatives to CIMYM's facility.
6. IMPROVEMENTS
All Improvements to the Technology by CIM shall be the property of CIM, shall be
disclosed to CIMYM and shall be included within the license granted under this.
Agreement.
7. CONFIDENTIALITY OF INFORMATION
CIMYM, CIM and CIMAB shall maintain the confidentiality of information, other
than its own, that is not publicly available, including (i) the Technology, and
(ii) information about the businesses of the other relating to the Technology,
the Products or the Agreement. CIMYM, CIM and CIMAB shall not disclose any such
information other than its own, to Persons other than their officers, employees,
agents, consultants and advisers, except where the disclosure of such
information by CIMYM, CIM or CIMAB is to a Person who has agreed to maintain the
confidentiality of such information, or except where CIMYM, CIM and CIMAB agree
to disclose such information. YMB shall have the right to disclose confidential
information for the purpose of raising investment capital.
8. PRODUCT DEVELOPMENT -SUPPLY, PRE-CLINICAL, CLINICAL, COMMERCIAL
(1) In consideration of the payments from CIMYM to CIMAB under this agreement,
CIMAB will develop the product according to the plan described in Appendix I or
as it may be amended by mutual written agreement from time to time. CIMAB will
provide updates of its progress at least every 90 days or as otherwise agreed
upon by CIMYM.
(2) CIMAB shall make its staff, facilities and equipment available to assist
CIMYM in performing its obligations under this Agreement and in commercializing
the Product.
(3) CIMYM shall source the Product from CIMAB. If CIMAB cannot supply the
Product in accordance with the Standards or if Product meeting the Standards
cannot be supplied in time to meet the Product development timelines reasonably
set from time to time by CIMYM and CIMAB, then the parties agree that CIMAB
shall, with the consent of CIMYM which shall not be unreasonably withheld,
contract with another site for the Manufacture of Product. CIMAB shall keep
CIMYM informed of all progress with arranging such other supply of Product.
(4) CIMYM shall use its best efforts to obtain a sub-license agreement in which
CIMAB retains the right to manufacture the Product. However, if the sublicensee
insists on manufacturing the Product itself, through its contractors or
sub-contractors, CIMAB shall waive its manufacturing rights, if both parties
consider that sub-license agreement offers mutual favorable commercial terms.
(5) CIMAB or its licensed manufacturer shall Manufacture and supply the Product
to CIMYM for pre-clinical and clinical trials at its expense and shall be
entitled to recoup this expense as described in Article (11) (6). Before
supplying the Product, CIMAB, or its licensed manufacturer, shall perform
quality control tests requested by CIMYM and provide samples of the Product to
CIMYM for review within ten (10) days after the tests are completed. CIMYM shall
notify CIMAB whether the samples meet the Standards. Provided that CIMAB has
Manufactured Product that meets the Standards, CIMYM shall, at its own expense,
and within time frames to be agreed upon with CIMAB, conduct or cause to be
conducted all further tests and clinical studies necessary to enable CIMYM to
file applications for regulatory approval with the appropriate regulatory
authorities in the Territory for the Marketing of the Product. If CIMYM fails to
conduct such tests or fails to cause such tests to be conducted within the time
frames agreed upon by CIMYM and CIMAB, CIMAB shall have the right to convert the
exclusive license granted under this Agreement to a non-exclusive license to
CIMYM to Finish and Market the Product in the Territory using the Technology by
providing notice in writing to CIMYM, except in those countries in the Territory
in which the Product has already been submitted for registration.
(6) CIMAB or its licensed manufacturer, shall Manufacture and supply the Product
to CIMYM for commercial sale at the Best Available Price and shall provide all
quality control tests requested by CIMYM relating to the Product to CIMYM. CIMYM
shall indicate to CIMAB whether the Product meets the Standards. Provided that
the Product meets the Standards, and subject to the completion of the
pre-clinical and clinical trials, CIMYM shall Finish and Market the Product,
acting in a commercially reasonable manner.
(7) If CIMYM determines that any of the test results or samples of the Product
provided by CIMAB, whether for pre-clinical, clinical or commercial use, do not
meet the Standards, CIMYM may either (i) require that the Manufacture of any of
the batches of Product which do not meet the Standards be repeated within a time
specified by CIMYM, or (ii) obtain the Product from a source acceptable to CIMAB
anywhere in the world which Manufactures the Product in accordance with the
Standards as described in (8) (3) above.
(8) If CIMAB cannot supply the Product, for commercial use, at the Best
Available Price, CIMYM may obtain the Product from a source anywhere in the
world offering the Best Available Price until such time as CIMAB is able to
supply the Product at the Best Available Price as described in (8) (3) above.
(9) If CIMAB cannot supply the Product, for any reason including force majeure,
whether for pre-clinical or commercial use, within the time frames specified by
CIMYM from time to time during the term of this Agreement, CIMYM may, with the
consent of CIMAB, not to be unreasonably withheld, obtain the Product from a
source acceptable to CIMAB anywhere in the world which Manufactures the Product
in accordance with the time frames, and in accordance with 8 (3) above.
9. RIGHT OF FIRST REFUSAL
CIMAB shall give CIMYM the first right to acquire a license to Manufacture,
Finish or Market, in the Territory, all other product derived from the EGF
active immunotherapy program of CIM. If CIMYM waives this right, CIMAB may enter
into a license with another Person on the same terms as those that CIMAB offered
to CIMYM or on less favourable terms than those that CIMAB offered to CIMYM. If
CIMAB proposes to offer the right on more favourable terms than the terms that
CIMAB offered initially to CIMYM, CIMAB shall first offer those more favourable
terms to CIMYM. Should CIMYM wish to acquire a license to Manufacture, Finish or
Market that other product, CIMYM and CIMAB shall enter into a further agreement.
10. REGULATORY APPROVALS
(1) Subject to Article 8, CIMYM shall conduct or cause to be conducted pre-
clinical and clinical trials to evaluate the Products. CIMYM shall work together
with CIMAB to
o select sites in any country of the Territory for pre-clinical and clinical
trials;
o develop protocols for pre-clinical and clinical trials; and
o instruct investigators of the pre-clinical and clinical trials.
(2) Within ninety (90) days after the end of each stage of the pre-clinical and
clinical trials of each Product, CIMYM in its discretion shall determine whether
to proceed with the next stage of the trials or whether to terminate this
Agreement for that Product, in accordance with the provisions of Article 14
after an evaluation of results by both CIMYM and CIMAB experts. CIMAB shall
receive the results of the preclinical and clinical trials performed.
3) Where commercially reasonable, CIMYM shall file or shall cause to be filed
applications for regulatory approval to Market the Product in the Territory. All
applications for regulatory approval shall be filed in the name of CIMYM. The
approvals shall not affect CIM's ownership of the Patents.
11. LICENSING REMUNERATION AND COMPENSATION.
(1) In considerations of the rights granted by CIMAB to CIMYM under this
Agreement CIMYM shall pay CIMAB the remuneration set out in this Section. .
(2) CIMYM shall pay CIMAB US $125,000.00 following the signing of this Agreement
by both parties for the research and development (R&D) goals described in
Appendix I.
(3) CIMYM, upon achievement of the final goal (described in Appendix I) in each
Product shall have prepared a clinical development program for each Product. The
clinical development program shall contain timelines, milestones and research &
development payments.
(4) CIMYM shall undertake the costs of the licensing and commercial development
of the Products within the timelines contained in the development program
described in (3).
(5) CIMAB owns 20 % of the equity of CIMYM and as such will receive an ongoing
commercial interest in the product.
(6) Within ninety (90) days of the end of each calendar quarter, CIMYM shall
send to CIMAB a statement certified by a financial officer of CIMYM disclosing
the Net Revenues for the just ended calendar quarter and giving the equity
interest due to CIMAB, at the end of each year. On completion of the clinical
trials CIMAB shall be reimbursed for the cost of the Product supplied by it for
the pre clinical and clinical trials conducted outside Cuba from revenues
received by CIMYM.
(7) For as long as Net Revenues are less than or equal to the amount of advances
from York Medical to CIMYM, York Medical shall recover such advances from 30% of
Net Revenues and the remaining 70% of the Net Revenues shall be retained by
CIMYM to be distributed between the parties according to their equity interest.
(8) If CIMYM fails to make the payments by the dates set out in the plan
described in Appendix I and/or in the clinical development program described in
(3) CIMAB shall have the right to convert the exclusive license granted under
this Agreement to a non-exclusive license to CIMYM to Finish and Market the
Product in the Territory using the Technology or to terminate this agreement by
providing notice in writing to CIMYM.
(9) If obliged so to do by any applicable tax law, CIMYM may deduct any
governmental withholding tax on any payment due under this Agreement. CIMYM
shall provide reasonable assistance to CIMAB in securing any benefits available
to CIMAB with respect to governmental tax withholdings by any relevant law or
double tax treaty.
(10) CIMYM shall keep at its registered office full and accurate records of the
Net Revenues and Sublicensing Revenues. Such records shall be made available for
inspection by CIMAB or an independent certified public or chartered accountant
of CIMAB's choice during normal business hours after reasonable notice.
12. PATENTS AND INFRINGEMENT
(1) If any infringement comes to the attention of CIMYM, CIMYM shall promptly
notify CIMAB in writing. If any infringement comes to the attention of CIMAB or
CIM, CIMAB shall promptly notify CIMYM in writing. CIMYM shall take such steps,
as it may consider advisable against that infringement for the protection of
CIMAB, CIM and CIMYM rights in the Territory. CIMYM shall have exclusive
carriage and control of any action for infringement, and may settle any of such
actions without the consent of CIMAB or CIM. CIMYM shall assume the cost of any
such action in the Territory. CIMYM may delegate the carriage and control of any
such action to an Affiliated Company or to a sub-licensee, provided CIMYM
obtains the written consent of CIMAB, such consent not to be withheld
unreasonably.
(2) If any actual or potential claim against CIMAB, CIM or CIMYM relating to the
Product comes to the attention of CIMYM, CIMYM shall promptly notify CIMAB in
writing. If any actual or potential claim against CIMAB, CIM or CIMYM relating
to the Product comes to the attention of CIMAB or CIM, CIMAB shall promptly
notify CIMYM in writing. CIMYM shall have exclusive carriage and control of any
action brought against CIMAB, CIM or CIMYM arising out of CIMYM's use of the
Technology, or arising out of the Manufacturing, Finishing or Marketing, or any
sale or offer of sale of the Product in any country in the Territory, and may
settle any such action without the consent of CIMAB or CIM, CIMYM may delegate
the carriage and control of any such action to an Affiliated Company or to a
sub-licensee provided CIMYM obtains the written consent of CIMAB, such consent
not to be withheld unreasonably.
(3) CIMYM shall assume the expense for the filing, prosecution and maintenance
of all Patents in all countries in the Territory. CIMAB shall consult with
-CIMYM in making any significant decisions in the filing, prosecution and
maintenance of the Patents.
13. ASSIGNMENT
This Agreement may be assigned by CIMAB or CIMYM only with the prior written
consent of the other, which consent shall not be unreasonably withheld.
14. TERM AND TERMINATION
(1) This Agreement becomes effective on the date first above set out above and
shall remain in full force and effect until each Patent has expired, has been
abandoned, or has been declared invalid by a court of competent jurisdiction in
each Territory, or unless terminated in accordance with the provisions of this
Article.
(2) Within ninety (90) days after the end of each stage of the pre-clinical
trials, and after each stage of the clinical trials, CIMYM may, by written
notice, terminate this Agreement in relation to any Product in any country in
the Territory. The Agreement shall continue in relation to all remaining
Products and remaining countries in the Territory.
(3) If CIMAB defaults in performing its obligations under this Agreement, and if
the default has not been remedied within ninety (90) days following the date of
receipt of a notice in writing from CIMYM, CIMYM may terminate this Agreement in
relation to the country of the Territory and Product to which the defaults
relates.
(4) If CIMYM defaults in performing its obligations under this Agreement,
including but not limited to failure in any payments and if the default has not
been remedied within ninety (90) days following the date of receipt of a notice
in writing from CIMAB, CIMAB may terminate this Agreement in relation to the
country of the Territory and Product to which the defaults relates.
..(5) On termination of this Agreement pursuant to subsection (3) of this
Article, CIMAB shall transfer to CIMYM, at not cost, the Technology to allow
CIMYM to Manufacture, Finish and Market the Products in relation to the Product
and the Territory to which the defaults relates.
(6) On termination of this Agreement pursuant to subsection (4) of this article,
CIMYM shall transfer to CIMAB, at no cost, the registration held by it for the
Product in that country in the Territory to which the default relates.
15. FORCE MAJEURE
Subject to Article 8, if any Person is unable to carry out its obligations under
this Agreement, acting in good faith with due diligence, by reason of acts of
God, war, sabotage, acts of the public enemy, riot, civil or political
commotion, strikes or other labour disputes, fires, floods, or other natural
disasters, then the performance of the obligations of such Person, insofar as it
is affected by such cause, shall be excused during the continuance of any such
cause. If the cause continuances for more than one (1) year parties should
evaluate the possibility of terminate the Agreement.
16. PROPER LAW
Any action brought by CIMAB or CIMYM to enforce any provision of this Agreement
or alleging any breach thereof shall be brought before the applicable Courts of
Barbados. CIMAB attorns to the jurisdiction of the applicable Courts of
Barbados. This Agreement shall be governed by and construed in accordance with
the laws of Barbados.
17. COMPLIANCE WITH LAWS AND CHANGES IN LEGISLATION
CIMYM and CIMAB shall perform their obligations under this Agreement in
compliance with all applicable laws. If national or international legislation or
other national or international rules necessitate changes in the present
Agreement or make it illegal for a Person to apply a provision of this Agreement
the Agreement shall continue to be applied to the extent that it is legally
possible and insofar as it is not ▇▇▇▇▇▇ unfair to one of the parties. Changes
in the provisions of this Agreement that might be necessary due to the
above-mentioned conditions shall be kept to the minimum which is legally
required and to the extent possible the changes shall aim at maintaining the
contents of this Agreement as much as possible in word as well as in spirit.
18. INDEMNIFICATION BY CIMAB
(1) CIMAB shall indemnify CIMYM, its affiliates and sub-licensees against all
claims, damages, liabilities, costs and expenses, including all counsel fees,
arising from:
o any default or negligence of CIMAB, or a licensee, or
o any allegation of injury, damage or wrongdoing caused by the Manufacturing
of the Product by CIMAB, or a licensee, or any breach of this Agreement or
any covenant or warranty in it by CIMAB.
19. INDEMNIFICATION BY CIMYM
(1) CIMYM shall indemnify CIMAB against all claims, damages, liabilities, costs
and expenses, including all counsel fees, arising from:
o any allegation of infringement of another Person's rights other than patent
or proprietary rights which were infringed by CIMAB or CIM before the date
of execution of this Agreement, or
o any allegation of injury, damage or wrongdoing caused by the Finishing or
Marketing of the Product by CIMYM, an Affiliated Company, or a sub-
licensee, or
o any default or negligence of CIMYM, or its affiliates or its sub-licensees,
or
o any breach of this Agreement or any covenant or warranty in it by CIMYM.
20. GENERAL
(1) This Agreement is the entire Agreement of CIMYM and CIMAB with respect to
the subject of this Agreement.
(2) No amendment or other modification of this agreement shall be valid or
binding on either party to this agreement unless reduced to writing and executed
by each of CIMYM and CIMAB.
(3) Any waiver of any right under this Agreement shall be in writing. No waiver
of any breach shall be a waiver of any subsequent breach of this Agreement.
(4) All provisions of this Agreement shall be severable and no such provision
shall be affected by the invalidity of any other such provision to the extent
that such invalidity does not also render such other provision invalid.
(5) Time is of the essence in this Agreement.
(6) The use of the singular in this Agreement shall include the plural and vice
versa.
(7) Article 3, Article 7, Article 14, Article 16, Article 18, Article 19 and
Article 20 shall survive the termination of this Agreement.
(8) All information required to be provided to CIMYM by the terms of this
Agreement shall, if necessary, be translated into the English language.
21. NOTICE
Any notice required to be given pursuant to the provisions of this Agreement
shall be in writing and shall be delivered personally, sent by facsimile or sent
by registered or certified mail (return receipt requested), postage prepaid, to
the address and facsimile numbers identified on the first page of this
Agreement. Such notice shall be effective on the date that it is delivered or
sent by facsimile or, in the case where notice is sent by registered or
certified mail, on the seventh business day after the notice is so sent. Any
party may change its address for service by sending a notice in accordance with
the terms of this section of the Agreement.
SIGNED FOR
CIMYM INC.
DATE:
"▇▇▇▇▇ ▇▇ ▇▇▇▇▇"
-----------------
By: ▇▇▇▇▇ ▇.▇. ▇▇▇▇▇
Title: Director
SIGNED FOR CIMAB S.A
DATE: Jan 24/01
"▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇ Biazquez"
---------------------------
Name: ▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇ Biazquez
Title: President
APPENDIX 1.
HER-1 Vaccine
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Research Goals | Research Payment - Preceding Research |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Generate murine and human ECD HER-1 immunization constructs and express in | $ 25 000 |
|mammalian cells. | |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Determine immunogenicity and anti- tumour activity in syngeneic mouse model if | $ 25 000 |
|possible (failing which, in xenograft) | |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Long term toxicity in mouse and monkey using an appropriate vehicle such as VSSP | $ 50 000 |
+-----------------------------------------------------------------------------------+---------------------------------------------+
TGFa Vaccine
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Research Goals | Research Payment - Preceding Research |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Generate human TGFa, P64 fusion protein constructs and express in E. coli. | |
|Optimize structure of construct. | |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Determine immunogenicity and anti- tumour activity in syngeneic mouse model if | |
|possible (failing which, in xenograft) | |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Long term toxicity in mice and monkeys | $ 25 000 |
+-----------------------------------------------------------------------------------+---------------------------------------------+
| | |
|Evaluate whether EGF and TGFa vaccine have synergistic effect | |
+-----------------------------------------------------------------------------------+---------------------------------------------+