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EXHIBIT 10.35
LICENSE AGREEMENT
THIS LICENSE AGREEMENT ("Agreement") is made and effective this 16th
day of June, 1999, by and between AMARILLO BIOSCIENCES, INC., a Texas
corporation with its principal place of business at 000 X. 0xx, Xxxxxxxx, Xxxxx
00000 (hereinafter "ABI") and NORTH CHINA PHARMACEUTICAL GROUP CORPORATION, a
company organized under the laws of P.R. China with its principal place of
business at Heping Xxxxxx 000, Xxxxxxxxxxxx, Xxxxx (hereinafter "NCPC") (ABI
and NCPC are hereinafter collectively referred to as the "Parties"). This
agreement shall be finally effective upon approval of the Foreign Trade &
Economic Co-operation Bureau of Hebei Province, P.R. China. MITSUBISHI
CORPORATION is ABI's shipping agent with respect to product shipped to NCPC
under this Agreement.
WHEREAS, ABI and its contract suppliers have substantial expertise in
the production and use of oral interferon alpha (hereinafter, "IFN-[alpha]") and
have proprietary rights and know-how in the field of production, purification
and formulation of IFN-[alpha];
WHEREAS, ABI is willing to disclose to NCPC Technical Information
including preliminary human data for hepatitis B; and
WHEREAS, ABI has an exclusive worldwide license to market and
distribute HBL IFN-[alpha] (as defined in ARTICLE I, below), and desires to
provide HBL IFN-[alpha] to NCPC on the terms and conditions herein set forth,
and NCPC desires to obtain the right to test, formulate, distribute and market
HBL IFN-[alpha] contained in Licensed Product on the terms and conditions herein
set forth;
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NOW, THEREFORE, for and in consideration of the mutual covenants
contained herein, and for other good and adequate consideration the receipt and
sufficiency of which are evidenced by the execution hereof, ABI and NCPC agree
as follows:
ARTICLE I
DEFINITIONS
1.1. "ABI" and "NCPC" shall mean and include not only the indicated
company, but also such company's Assignees.
1.2. "Affiliate" means a corporation, company, partnership, or other
business entity which controls or is controlled by, or is under common control
with, the designated party. In the case of a corporation or company, "control"
means ownership either directly or indirectly of at least Fifty Percent (50%) of
the shares of stock entitled to vote for the election of directors.
1.3. "Agreement" means this License and Supply Agreement.
1.4. "Assignee" means any permitted assignee or sublicensee of rights
under this Agreement
1.5. "Bulk Product" means the major ingredients to be formulated by
NCPC into Licensed Product, to include the following: HBL IFN-[alpha]; diluents;
stabilizing components; and other components (if any) mutually agreed upon by
the Parties, as being required or desirable in the formulation of Licensed
Product.
1.6. "Dose" means *** International Units of IFN-[alpha].
1.7. "HBL IFN-[alpha]" means the cell culture derived human
lymphoblastoid IFN-[alpha] used for the formulation by HAYASHIBARA BIOCHEMICAL
LABORATORIES, INC. ("HBL")
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of natural IFN-[alpha]-containing formulations approved for use in the treatment
of human renal cell carcinoma, hepatitis B and C, and chronic myelogenous
leukemia in Japan, which may be produced, purified and formulated by HBL in
Japan, or under license from HBL in Japan, or elsewhere.
1.8. "Licensed Indication" means the human disease of hepatitis B.
1.9. "Licensed Product" means a formulation or composition containing
HBL IFN-[alpha] and designated, detailed, or labeled for oral use in the
treatment of any Licensed Indication.
1.10. "Technical Information" means all information, reports, results,
inventions, know-how, materials, and any other technical and scientific data,
specifications and formulae directly related to the development, regulatory
approval, manufacture, testing, use, marketing and/or sale of Licensed Product,
and any non-public information relevant to the business of the Parties which is
necessarily disclosed by one to the other during the Parties' conduct under this
Agreement. "ABI Technical Information" refers to Technical Information
originating with ABI or which ABI has obtained through its contractual
relationships with third parties. "NCPC Technical Information" refers to
Technical Information originating with NCPC or which NCPC has obtained through
its contractual relationships with third parties. "Technical Information" when
not otherwise specified herein means both ABI Technical Information and NCPC
Technical Information.
1.11. "Territory" means P.R. China.
ARTICLE II
GRANT OF LICENSE
2.1. ABI grants to NCPC and NCPC accepts, subject to the terms of this
Agreement, the right to use HBL IFN-[alpha] for testing, trials, development,
and formulation into
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Licensed Product, and upon proper regulatory approval, the exclusive right to
formulate, market and distribute Licensed Product to treat the Licensed
Indication in the Territory. ABI will provide NCPC technical information and
clinical trial samples for the above-mentioned purposes. ABI retains all other
rights to HBL IFN-[alpha], including without limitation, the right to test,
develop, license, sublicense, market, distribute or otherwise use HBL
IFN-[alpha] for treatment of all indications other than the Licensed Indication,
and for treatment of the Licensed Indication in all countries not included in
the Territory.
2.2. The license grant to NCPC under this Agreement shall commence on
the effective date of this Agreement and shall terminate immediately upon the
termination or expiration of this Agreement unless extended by consultation
between the parties at least one hundred and eighty (180) days prior to the
expiration date.
2.3. NCPC shall have the right to use and sell Licensed Product only in
the Territory. NCPC shall not seek customers, establish any branch or maintain
any distribution depot for Licensed Product in any country outside the
Territory. NCPC shall not sell Licensed Product to any customer in any country
outside the Territory or to any customer in the Territory if, to the knowledge
of NCPC, such customer intends to resell the Licensed Product in any country
outside the Territory. NCPC shall cause ABI's name to appear on each outer
package of the Licensed Product distributed in the Territory.
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ARTICLE III
SUPPLY OF PRODUCT
3.1. Subject to the terms and conditions of this Agreement, ABI shall
supply Bulk Product to NCPC for formulation, testing, and (upon government
approval) sale in the Territory. Bulk Product shall be supplied in response to
issuance by NCPC of written purchase orders delivered to ABI specifying the
quantity to be supplied, along with any special instructions/requests regarding
supply and/or delivery. In addition to Bulk Product, ABI shall supply other
product or ingredients reasonably requested by NCPC, subject to agreement by the
Parties regarding price and other terms and conditions, and subject to
availability. ABI shall have no responsibility for formulating or manufacturing
lozenges, nor for obtaining any required regulatory approvals, nor for
packaging, distribution, promotion, pricing, or marketing of lozenges in the
Territory, all of which shall be completed by NCPC with the assistance of ABI.
3.2. ABI agrees to allow NCPC right of reference to ABI's US FDA Drug
Master File for HBL IFN-[alpha] and to do such other acts as are reasonably
necessary, and within ABI's control, to facilitate approval of HBL
IFN-[alpha]-containing lozenges in the Territory for use in the Licensed
Indication, and ABI also hereby agrees to consult with NCPC at NCPC's request
concerning regulatory affairs, to review documents to be submitted to
governmental agencies for approval, and to take such other actions as may be
necessary from time to time to facilitate approval of Licensed Product for sale
and use in the Territory. ABI also agrees to provide clinical data from its
past, current or future studies, that would be relevant to the testing, use or
sale of Licensed Products in the Territory. ABI further agrees to provide
sufficient Bulk Product for preliminary studies and
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clinical trials as may be appropriate and necessary to support testing and
application for approval and commercialization of Licensed Products. ABI shall
reasonably provide to NCPC other support or assistance requested by NCPC and
within ABI's capabilities with respect to regulatory and clinical activities, on
a fully reimbursed basis.
ARTICLE IV
CONSIDERATION
4.1. ABI shall receive from NCPC a research reimbursement payment and a
fee for clinical study design and supplies for the Territory. The payments and
fees are set forth at Exhibit "A" hereto. The License Fee shall be due and
payable upon execution of this Agreement by the signatory parties and the
approval of the Foreign Trade & Economic Co-operation Bureau of Hebei Province,
P.R. China. ABI agrees to pay income tax on the up-front payment amount in
compliance with the Foreign Enterprise Income Tax Law of the People's Republic
of China.
4.2. For all Bulk Product supplied by ABI to NCPC (other than
quantities provided pursuant to Paragraph 3.2 above), ABI shall receive from
NCPC the payment per Dose specified at Exhibit "B". Payment for each shipment of
Bulk Product shall be made by NCPC by irrevocable letter of credit on a U.S.
bank. The price per Dose shall be further adjusted from time to time as may be
necessary to reflect any Change in the Producers Price Index, Drugs and
Pharmaceuticals, Subdivision Code 063, after the date of this Agreement. In
addition, both the price per Dose and the amount to be invoiced and paid for
Bulk Product shall be further adjusted to reflect any changes for (i) the
variable cost of any raw material or combination of raw materials that changes
by more than twenty percent (20%) from ABI's cost at the date of this Agreement,
and (ii) the variable cost arising
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from changes in product specifications, manufacturing, testing, or release of
the product. NCPC shall receive Bulk Product at a named port of destination in
the Territory and the shipping arrangements shall be made by ABI's nominated
shipping agent. NCPC shall pay CIF price at the named port of destination in the
Territory against the invoice containing shipping charge, freight, and
insurance, in addition to the Bulk Product price specified above. Title to Bulk
Product purchased by NCPC shall transfer to NCPC, and NCPC shall pay all freight
charges and bear the risk of loss and damage, from the time Bulk Product, in
compliance with the standards of the Drug Quality Control Bureau of the Chinese
Port Customs Administration, is placed at the disposal of NCPC at the port of
destination.
4.3. NCPC shall within three (3) months of the Effective date of this
agreement commence the clinical trial already designed to achieve government
approval of the Licensed Product for marketing and distribution. NCPC will
conduct all clinical trials at its own expense, and will contract for and
utilize the services of ************** and ************** in the design,
supervision and implementation of the clinical trial for submission of the file
for government approval. NCPC shall, within three (3) months of the conclusion
of the afore mentioned clinical study, apply for, at its own cost and expense
and without any contribution from ABI, all necessary licenses or approvals
required to be issued in the Territory, or any agency or instrumentality
thereof, as a precondition to the import, formulation, manufacture, and sale of
Licensed Product, within three (3) months of any such approval being granted.
NCPC will apply for any pricing or reimbursement approvals, will exercise
diligence to maintain all such approvals, and will diligently market the
approved Licensed Product through the term of this Agreement. NCPC will launch
product in the Territory within three (3) months of receipt of all necessary
governmental approvals, and shall
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thereafter use its best efforts to advertise, promote and sell such product
after approval. The import licenses shall be issued in the name of ABI. However,
both production license and production approval shall be issued in the name of
NCPC. If at any time during the term of this Agreement NCPC should fail to
comply in a timely way with any of the requirements set forth in this Section
4.3, or if at any time during the term of this Agreement NCPC should no longer
be actively pursuing the application for any such approval or license in the
Territory, or if, having obtained such approval or license, NCPC should no
longer be actively developing or marketing any Licensed Product under this
Agreement in the Territory, under the preconditions permitted by applicable laws
and regulations, both parties shall enter into consultation to decide the
assignment of such applications, approvals and/or licenses from NCPC.
4.4. NCPC shall provide ABI by December 31st of each year during the
term of this Agreement, a report of ongoing efforts for the development of
Licensed Products, including a report of efforts by NCPC with respect to
formulation development, pre-clinical and clinical testing, regulatory approval
efforts, marketing/sales strategy, and any other areas into which NCPC's
reasonable business efforts in accordance with this paragraph may reasonably be
categorized. Such report shall be provided in English and shall be accompanied
by labeling, instructions, promotional and other support materials developed for
NCPC's sales force, patients, physicians, or other outside parties. Such a
report shall be prepared more often if ABI so requests in writing, if ABI pays
to NCPC the expenses incurred by NCPC in generating such additional reports. It
is understood that ABI will receive a copy in English of all NCPC Technical
Information.
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4.5. During the term of this Agreement, both Parties shall provide to
the other all data relating to the testing and development of the Licensed
Product in the Licensed Indication.
4.6. Unless specifically authorized in writing by ABI, NCPC shall not
sell, or offer for sale, or act as sales agent for the solicitation of orders
for any oral products (other than Licensed Products) that contain any
IFN-[alpha] derived from any species and designated, detailed, or labeled for
oral use for the Licensed Indication. ABI shall not authorize any third parties,
directly or indirectly, to market or sell any IFN-[alpha] in the Territory for
oral use in the treatment of the Licensed Indication.
4.7. NCPC shall provide medical, pharmacovigilance and other
appropriate customer support services in connection with sale of Licensed
Products, and will report to ABI on a timely basis all material adverse
reactions, product complaints and other relevant customer feedback. NCPC agrees
to advise ABI fully with respect to all health, safety, environmental, and other
standards, specifications, and other requirements imposed by law, regulation, or
order in the Territory and applicable to Licensed Product. NCPC shall also
advise ABI of all instructions, warnings, and labels applicable to Licensed
Product that are necessary or desirable under laws, regulations, or practices in
the Territory. ABI shall meet such safety standards or specifications. ABI shall
not increase the price charged to NCPC for the Bulk Product unless changes to
the specification are required.
ARTICLE V
ORDERS AND SHIPMENTS
5.1. Within thirty (30) days of the date hereof, and at least ninety
(90) days prior to the commencement of each calendar year during the term of
this Agreement, NCPC will furnish
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ABI with its projected requirements for Bulk Product during the next succeeding
calendar year. NCPC may amend its projected requirements from time-to-time,
provided, however, that ABI shall be obligated only to make its best effort to
comply with any requests in excess of annual projections received by it at least
ninety (90) days prior to the commencement of the calendar year in question.
Under no circumstances shall ABI be required to deliver to NCPC hereunder, an
amount of Bulk Product which exceeds the amount ABI is able, in good faith, to
acquire from HBL, or from HBL's contract manufacturers. The exact composition of
Bulk Product shall be disclosed in writing by ABI to NCPC. Subject to the
foregoing, ABI shall use its best efforts to deliver Bulk Product in accordance
with NCPC's projected requirements and product specifications.
5.2. ABI shall ship product within thirty (30) days of request by NCPC,
against an irrevocable letter of credit on a U.S. bank (or other financial
surety acceptable to ABI or to the agent nominated by ABI) in an amount
sufficient to cover the CIF price payable to ABI or the agent nominated by ABI
under Paragraph 4.2 above. The letter of credit shall be issued by a financial
institution acceptable to ABI or to the agent nominated by ABI, shall be in U.S.
dollars and shall not expire until the final payment for the respective shipment
has been made to ABI or to the agent nominated by ABI.
5.3. Orders of Bulk Product for commercial sales shall be made for
"full lot" quantities of *** Doses. A minimum of *** Doses of Bulk Product shall
be purchased by NCPC for the Territory during each year during the term of this
Agreement, commencing with the first full calendar year after all necessary
approvals for marketing and reimbursement have been obtained.
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ARTICLE VI
TERM AND TERMINATION
6.1. This Agreement and all rights granted hereunder by each Party
shall terminate upon December 31, 2009, unless extended on a yearly basis by
request of NCPC at least one hundred and eighty (180) days prior to the
expiration date provided, however, that if NCPC does not commence application
for government approval, as may be required or advisable, within three (3)
months after NCPC receives all supporting documentation required for application
for approval of commencement of the pivotal clinical trial; and after approval
of the Licensed Product, place orders for minimum annual shipments as provided
in Paragraph 5.3, above; then ABI shall have the right to terminate this
Agreement upon three (3) months prior written notice to NCPC. NCPC will proceed
diligently to obtain market approval for the Territory according to the
timetable set forth in paragraph 4.3 of this Agreement.
6.2. Termination of this Agreement for any reason shall not relieve the
Parties of any obligation accruing prior to such termination. In addition,
ARTICLE VIII ("Confidentiality") shall survive termination of this Agreement.
6.3. On termination of this Agreement for any reason, NCPC shall cease
to sell Licensed Product and shall surrender to ABI all ABI Technical
Information that it may have received during the term of this Agreement, and at
the request of ABI, NCPC may conditionally assign any approval, permit, or
license it holds relating to Licensed Products to ABI. Any accrued payment
obligations shall be paid within thirty (30) days of the termination of this
Agreement.
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ARTICLE VII
WARRANTY AND INDEMNIFICATION
7.1. ABI represents and warrants that as of the date of this Agreement,
it is the exclusive owner of the right to sell and distribute HBL IFN-[alpha]
for use in treating the Licensed Indication in the Territory. ABI further
warrants that at the time of shipment, all product supplied by it (i) shall meet
all product specifications previously agreed in writing between ABI and NCPC;
(ii) shall not be adulterated or misbranded; and (iii) shall be manufactured in
accordance with good manufacturing practices in the country of manufacture. ABI
shall indemnify and hold NCPC harmless from any and all costs, expenses,
damages, judgments, and liabilities incurred by or rendered against NCPC arising
from any claim made or suit brought as a result of a breach by ABI of its
warranties under this Paragraph 7.1.
7.2. NCPC warrants that its operations and activities in the Territory shall be
in compliance with applicable laws, statutes and regulations; and NCPC shall
indemnify and hold ABI harmless from any and all costs, expenses, damages,
judgments, and liabilities incurred by or rendered against ABI or its affiliates
arising from the use, testing, recall, labelling, promotion, sale, distribution,
or use of Bulk Product or Licensed Product as a result of any breach of these
warrants by NCPC.
ARTICLE VIII
CONFIDENTIALITY
8.1. ABI owns or is licensed under confidential or secret
information relating to the Licensed Products, and NCPC intends to conduct
trials in the Territory which will generate
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confidential or secret information relating to the Licensed Products, and it is
the intention of both ABI and NCPC to maintain this confidentiality.
8.2. Each Party agrees to maintain confidential and secret all
Technical Information which may be disclosed or provided to it by the other
Party or that the Parties may together subsequently acquire.
8.3. Each Party's obligation to the other to maintain confidentiality
hereunder shall terminate with respect to any particular item and only said item
of the disclosing Party's Technical Information, when the recipient Party can
demonstrate that such item of information:
8.3.1. Is publicly known and available through some means other
than by the recipient Party's act or omission; or
8.3.2. Was in the recipient Party's possession prior to its
disclosure by the other Party, as established by written evidence; or
8.3.3. Has come into the recipient Party's possession through a
third party free of any obligation of confidentiality to the disclosing Party,
where said third party has acquired said information lawfully and not under
circumstances forbidding its disclosure.
8.4. Neither Party will permit the other Party's Technical Information
or any part thereof to be disclosed to third parties or to employees except on a
"need-to-know" basis and each will maintain such information and/or documents
with the same precautions it uses to safeguard its own confidential or secret
information.
8.5. Each Party will notify the other promptly if it has knowledge that
an unauthorized third party possesses Technical Information of the other Party.
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8.6. NCPC shall have the right to use ABI's Technical Information, and
to access ABI's US FDA Drug Master File for HBL IFN-[alpha], to the extent
reasonably necessary to accomplish the objectives of this Agreement, including
specifically the right to disclose such information to its contract consultants
and scientific investigators (from whom NCPC shall secure Confidential
Non-Disclosure Agreements) and to regulatory agencies of the Territory in
support of applications for regulatory agency approval to make, test and/or sell
Licensed Product.
8.7. With the written consent of NCPC, ABI may use NCPC's Technical
Information for the purposes of designing protocols and studies, and for
submission to regulatory authorities in any country outside the Territory in
connection with an application for drug approval of the Product.
ARTICLE IX
MISCELLANEOUS
9.1. Force Majeure. The failure of NCPC, ABI, or any of their
Affiliates to take any action required by this Agreement if such failure is
occasioned by an act of God or the public enemy, fire, explosion, perils of the
sea, floods, drought, war, riot, sabotage, accident, embargo or any circumstance
of like or different character beyond the reasonable control of the Party so
failing or by the interruption or delay in transportation, inadequacy, or
shortage or failure of the supply of materials and/or equipment, equipment
breakdown, labor trouble or compliance with any order, direction, action or
request of any governmental officer, department or agency and whether in any
case such circumstances now exist or hereafter arise, shall not subject said
Party to any liability to the other.
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9.2. Communication. Any payment, notice or other communication required
or permitted to be made or given to either Party pursuant to this Agreement
shall be sufficiently made or given on the date of sending if sent to such Party
by certified or registered mail, or by courier service, postage or delivery
charge prepaid, addressed to it at its address set forth below, or to such other
address as it may have designated by written notice given to the other Party.
Fax numbers are given for convenience only, as an additional method of delivery,
and no notice or other communication transmitted by fax shall be considered to
be sufficiently made or given until such notice or communication is also sent by
one of the other means described above.
In case of NCPC:
Chairman
North China Pharmaceutical Group Corporation
Heping Xxxxxx 000
Xxxxxxxxxxxx, Xxxxx Fax: 000-00-000-0000000
In case of ABI:
President
Amarillo Biosciences, Inc.
000 X. 0xx
Xxxxxxxx, Xxxxx 00000 Fax: (000) 000-0000
And:
Xxxxxx X. Xxxxxx, Legal Counsel
Morris, Moore, Xxxx & Xxxxxxxx, P.C.
P. O. Xxx 00000
Xxxxxxxx, XX 00000 Fax: (000) 000-0000
9.3. Amendments to Agreement. This Agreement constitutes the entire
Agreement between the Parties hereto on this subject matter and supersedes all
previous arrangements whether
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written or oral. Any amendment or modification of this Agreement shall be
effective only if made in writing, and executed by both Parties.
9.4. Enforceability. To the extent permitted by law, each Party waives
any provision of law which renders any provision herein invalid, illegal or
unenforceable in any respect.
9.5. Relationship of Parties. All purchases and resales of Bulk Product
and Licensed Product by NCPC shall be for NCPC's own account as a principal and
not as an agent of ABI. NCPC shall act in all respects as an independent
contractor and not as a representative or agent of ABI. This Agreement shall not
be construed to create a relationship of partners, joint venturers, brokers,
employees, agents, master or servant between the Parties. Neither Party shall
have any right or authority to assume or create any responsibility, express or
implied, in the name of the other Party or to bind the other Party in any manner
whatsoever.
9.6. Assignment. Neither Party hereto shall assign any of its rights
under this Agreement to any person or entity not an Affiliate of the assigning
Party without the prior written consent of the other Party, which consent shall
not be unreasonably withheld.
9.7. Venue and Jurisdiction. Venue of any action brought under this
Agreement shall be as follows: Actions initiated or filed by or behalf of ABI
shall be brought in the People's Court of Hebei Province, P.R. China; and
actions initiated or filed by or on behalf of NCPC shall be brought in the
federal district court for the Northern District of Texas, Amarillo Division.
9.8. Governing Language. The English language of this Agreement shall
govern and control any translations of the Agreement into any other language.
Documents furnished by
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NCPC to ABI under the terms of this Agreement shall be furnished in English, or
alternatively, shall be accompanied by an English translation.
IN WITNESS WHEREOF, the Parties hereunto have caused this instrument to be
executed in duplicate by their duly authorized representatives as of the date
first above written.
ABI: NCPC:
AMARILLO BIOSCIENCES, INC. NORTH CHINA PHARMACEUTICAL GROUP
CORPORATION
By: By:
------------------------------------ ---------------------------------
Xxxxxx X. Xxxxxxx, Lu Weichuan,
President Chairman
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EXHIBIT "A"
This Exhibit "A" is attached to that certain License Agreement by and
between AMARILLO BIOSCIENCES, INC. and NORTH CHINA PHARMACEUTICAL GROUP
CORPORATION dated 16th, day of June, 1999, and constitutes a part of said
Agreement, as if fully set forth therein. For all purposes of said Agreement,
the "Territory" shall mean P.R. China. In addition, the License Fee referred to
in Section 4.1 of the Agreement is set forth below, for the Territory.
FEE $*** within 30 days of the signature and approval of this
Agreement.
$*** within 30 days of NCPC's acceptance of all applicable
information provided by ABI necessary for application for
approval (Exhibit "C") as well as clinical trial samples, and
ABI has transferred its clinical trial approval to NCPC.
$*** within 30 days of NCPC's receipt of production approval.
-A-1-
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EXHIBIT "B"
This Exhibit "B" is attached to that certain License Agreement by and between
AMARILLO BIOSCIENCES, INC. and NORTH CHINA PHARMACEUTICAL GROUP CORPORATION
dated 16th day of June, 1999, and constitutes a part of said Agreement, as if
fully set forth therein.
Per *** IU Dose Price (interferon and anhydrous crystalline maltose) f.o.b.
***** to ***** $*** per dose
***** to ***** $*** per dose
***** to ***** $*** per dose
Over ***** $*** per dose
Finished bulk tablets can be supplied ex Canada at prices above plus $***
tableting and packaging charge per dose up to a maximum of ****** doses per
year.
-B-1-
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EXHIBIT "C"
ABI shall provide NCPC the following information necessary to apply for clinical
trial and for production which includes:
1. New drug name (include official name, chemical name, Latin name,
foreign language name and Chinese Phonetic Alphabet etc. The evidence
of nomenclature shall be provided for new given name), aim and evidence
of topic selection, summary of current research status or manufacture,
application of the drug at home and abroad.
2. Experimental data, chromatography, explanation and analysis of
chromatography and related references to certify the drug chemical
structure or composition.
3. The drug's experimental profile, purification method,
specification/standard of chemical materials, source of biological
materials, generic name, description of formulation, evidence of
process and description, source and quality standard of excipients and
related references, etc. Evidence of revisions shall be provided if the
prescription, manufacture process, raw material and strain are
different from the main reference.
4. Quality controls such as physical/chemical constants, purity analysis
and determination of content (potency) etc.
5. Main pharmacodynamics related to treatment effects.
6. General pharmacologic research.
7. Animal acute toxicity.
8. Animal chronic toxicity.
9. Local toxicity.
10. Influence of excipients in formulation on pharmacodynamics and
toxicity.
11. Mutagenicity.
12. Toxicity in different species .
13. Carcinogenicity.
14. Dependence.
15. Pharmacokinetics.
-C-1-
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16. Preliminary stability on bulk drug and its formulation.
17. Proposed clinical trial drug quality standard and explanation of its
design. Standard samples and control samples.
18. Clinical trial samples and certificate of analysis (sample shall be at
least three times quantity necessary to do full scale analysis).
19. Protocol of proposed clinical trial and summary of preclinical
pharmacological and toxicological research for clinical physicians'
review.
20. Clinical pharmacokinetics.
21. Bioavailability or dissolution characteristics.
22. Stability study on bulk drug and its formulation. Conclusion (include
biological and chemical results) and shelf-life.
23. Proposal on drug quality standard in manufacture and explanation of
design (formulation shall include the active ingredient qualitative
test result and quantitative recovery test result).
Standard samples and control samples.
24. Samples of three to five consecutively manufactured batches and their
certificates of analysis (sample per batch shall be at least three
times the quantity needed for full-scale analysis).
25. Clinical trial summary issued by department responsible for clinical
trials and clinical trial reports.
26. Drug packaging material, label, trial-use or official instruction
leaflets designed by department responsible for clinical trials
(include new drug name, structural formula and molecular
formula)(formulation shall include active ingredient), mode of action
and indications, dosage and administration, toxic effects and side
effects, contraindications, precautions, packaging (specification and
content), storage condition and shelf life, etc.
27. Oral IFN manufacturing procedure (confidential technical data).
28. Quality standard and analytical methods on raw materials and product
(process procedures) etc. (confidential technical data).
29. GMP production requirements, etc. (confidential technical data).
-C-2-
***Indicates that a portion of the text has been omitted and filed separately
with the Commission.
