EXHIBIT 4.4
Page 1 (35)
AGREEMENT
THIS AGREEMENT, effective __November2___, 2000, is entered into
BETWEEN:
YORK MEDICAL INC.
a corporation incorporated under the
laws of Ontario, having its principal place of business at 5045 Orbitor Drive,
Building 11, Suite 400, Mississauga, Ontario, L4W 4Y4, Canada
(hereinafter referred to as "YORK")
- -AND-
UNIVERSITY OF MANITOBA
having its principal place of business at
Fort Garry Campus, Rm 631 Drake Centre, 181 Freedman Crescent,
Winnipeg, Manitoba, R3E 0W3, Canada
(hereinafter referred to as "UM")
- -AND-
THE MANITOBA CANCER TREATMENT AND RESEARCH FOUNDATION, CARRYING ON ITS
UNDERTAKING AS CANCERCARE MANITOBA
having its principal place of business at
675 McDermot Ave., Winnipeg, Manitoba, R3E 0V9, Canada
(hereinafter referred to as "CCMB")
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1 BACKGROUND OF AGREEMENT
1.1 UM and CCMB are owners, by assignment, of all right, title and interest
in and to the patents and patent applications listed in Exhibit 1
hereto which have arisen from studies by Dr. L. Brandes (the
"Inventor") in the course of research within the Manitoba Institute of
Cell Biology.
1.2 The Manitoba Institute of Cell Biology is an Institute of CCMB and UM
pursuant to their agreement dated March 2, 1989 (the "MICB Agreement)
which governs certain actions related to patents and copyrights arising
from research conducted in the institute.
1.3 By agreement (the "B-M Agreement"), UM and CCMB licensed the patent
rights to Bristol-Myers Squibb Company and pursuant to the B-M
Agreement, BristolMyers Squibb Company funded the production,
preclinical and clinical development of DPPE.
1.4 Through termination of the B-M Agreement, UM and CCMB have retrieved
the licensed rights.
1.5 UM and CCMB are interested in continuing research, development and
commercialization of DPPE, including pursuit of all related clinical
and pre-clinical results and clinical material and production methods
therefor.
1.6 YORK is a biopharmaceutical licensing and development company, with a
management group experienced in developing human pharmaceuticals in the
clinical fields of oncology and anti-infectives. In addition, York's
management group has experience in partnering with multinational
pharmaceutical companies and other related business development
activities.
1.7 UM and CCMB have revealed to YORK certain information relating to DPPE
under terms of confidentiality agreement dated April 12, 2000.
1.8 YORK, UM and CCMB now wish to set forth the terms and conditions of an
agreement through which YORK shall acquire a license to exploit the
assets of UM and CCMB related to the Patents, that are useful in the
further research, development and commercialization of DPPE.
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NOW THEREFORE, in consideration of the foregoing premises, the mutual covenants
and obligations hereinafter contained, and other good and valuable consideration
which is hereby acknowledged, UM, CCMB and YORK agree as follows:
2 DEFINITIONS
As used herein, the following terms shall have the meanings set forth below:
2.1 AFFILIATE means any COMPANY that is controlled directly or indirectly
by a party hereto or any COMPANY that directly or indirectly controls a
party hereto, so that AFFILIATE shall include any parent or subsidiary
of a party hereto, or any directly or indirectly held subsidiary of a
party hereto.
2.2 ASSETS are those existing and arising assets related to DPPE that are
or become owned or controlled by UM and CCMB and are useful to YORK for
the purpose herein licensed, and include DPPE, INFORMATION, MATERIAL
and PATENTS.
2.3 COMPANY means a corporation or other juridical entity.
2.4 CONTROL means the ownership, directly or indirectly, of more than 50 %
of voting rights attached to the issued voting shares of a COMPANY.
2.5 DPPE means N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCl, as
described in the PATENTS.
2.6 DEVELOPMENT COSTS means the third party expenses incurred by YORK in
connection with the development of LICENSED PRODUCT including but not
limited to the cost of filing, prosecuting, maintaining, defending and
enforcing the PATENTS, the direct cost of CLINICAL TRIALS and work
related thereto including quality control and assurance, regulatory
filings and preparation therefor, production and packaging of LICENSED
PRODUCT and the cost of acquiring further in-licenses as may be
necessary for the commercial exploitation of LICENSED PRODUCT.
2.7 EFFECTIVE DATE shall be the date first written above.
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2.8 IMPROVEMENTS means products or processes the manufacture, use or sale
of which would infringe a VALID CLAIM.
2.9 INFORMATION means information relating to DPPE and includes, but is not
limited to, confidential information and know-how, in the knowledge,
possession or control of a party and which the party has a right to
disclose, particulary but not exclusively including information
relating to production and to preclinical and clinical protocols,
results and approvals.
2.10 LICENSED TERRITORY means all countries of the world.
2.11 LICENSED FIELD means, and is limited to, the exploitation of the ASSETS
in respect of veterinary and human therapeutic products within the area
of cancer treatment and the manufacture, use and sale thereof.
2.12 LICENSED PRODUCT means all products and formulations thereof for DPPE,
the manufacture, use or sale of which utilizes, wholly or partially,
the ASSETS or the YORK PATENTS and would, but for the license herein
granted, infringe a VALID CLAIM.
2.13 MATERIAL means biological and chemical material that either is
incorporated in the LICENSED PRODUCT or is useful in the production,
evaluation or development thereof.
2.14 NET SALES shall mean the total NET SALES PRICE of LICENSED PRODUCT sold
by YORK and its AFFILIATES.
2.15 NET SALES PRICE shall mean the total of net invoice prices for all
LICENSED PRODUCTS sold by YORK and its AFFILIATES, for any given period
of time during the term of this Agreement, less DEVELOPMENT COSTS, less
wholesaler's or distributor's commissions, discounts, rebates, samples
and freight charges, and taxes separately listed on such invoices, and
less the amount of any credits or refunds actually given by YORK for
defective or returned LICENSED PRODUCTS. NET SALES PRICE shall not
include any consideration received by YORK in respect of the sale, use
or other disposition of LICENSED PRODUCT prior to the receipt of all
regulatory approvals required to commence full commercial sales of
LICENSED PRODUCT in a given country, such as sales under a "treatment
IND", "named patient sales", "compassionate use sales", and the sale,
use or other disposition of LICENSED PRODUCT in the course of clinical
trials.
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2.16 PATENTS means:
1) The patents and applications summarized in Exhibit 1 (which may be
updated from time to time during the term of this agreement) and
the patents that mature from those applications.
2) The patents and applications directed to IMPROVEMENTS
3) All divisions, continuations in whole and in part, reissues,
re-examinations, substitutes, extensions and foreign and
international counterparts of 1) and 2) and patents that mature
therefrom.
4) Patents and patent applications relating to DPPE that are or
become owned or controlled by UM and/or CCMB and which are
included in the definition of ASSETS
5) Patents and patent applications related to DPPE licensed to UM
and/or CCMB that UM and/or CCMB YORK are permitted to sub-license
and which are included in the definition of ASSETS.
2.17 SPONSORED RESEARCH means research and clinical development funded by
YORK hereunder and performed in the Inventor's laboratory, or elsewhere
on the Inventor's behalf.
2.18 SUB-LICENSEE means a person or entity who is not an Affiliate and to
whom YORK has sub-licensed all or part of the rights granted to YORK by
UM and CCMB by this Agreement.
2.19 SUBLICENSING REVENUE shall, unless otherwise agreed upon in writing,
mean all payments, whether in cash or otherwise , whether in the form
of up front payments, milestone payments, royalties or otherwise
received by YORK from SUB-LICENSEEs and assignees of, in respect of
LICENSED PRODUCT and in consideration for, the rights granted to YORK
under this Agreement, less DEVELOPMENT COSTS.
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2.20 VALID CLAIM means a granted claim within PATENTS so long as such claim
shall not have been disclaimed or abandoned by the patentee or shall not
have been disallowed by a Patent Office, expired under the patent laws
of a country, or held invalid in a final decision rendered by a court,
government or tribunal of competent jurisdiction from which no appeal
has been, or can be, taken.
2.21 YORK PATENTS means:
1) The patents and applications summarized in Exhibit 4 (which
Exhibit may be updated from time to time during the term of this
Agreement) and relating to DPPE and the patents that mature from
those applications.
2) The patents and applications directed to IMPROVEMENTS.
3) All divisions, continuations in whole and in part, reissues,
re-examinations, substitutes, extensions and foreign and
international counterparts of (1) and (2) and patents that mature
therefrom.
4) Patents and patent applications that are or become owned or
controlled by YORK, for clarity this excludes PATENTS as defined
in 2.16
5) Patents and patent applications licensed to YORK and that YORK is
permitted to sub-license.
3 LICENSE GRANT
3.1 UM and CCMB hereby grant to YORK and its AFFILIATES in the LICENSED
FIELD and LICENSED TERRITORY, an, exclusive license to exploit ASSETS,
particularly including but not limited to PATENTS, to develop and to
make, including contract production by a toll manufacturer, use, sell,
and otherwise dispose of LICENSED PRODUCT. YORK and its AFFILIATES
shall use, exploit and commercialize the ASSETS only within the
LICENSED FIELD as LICENSED PRODUCT and undertakes not to use, exploit
or commercialize the ASSETS in any way contrary to the terms and
conditions of this Agreement.
3.2 The license granted pursuant to Article 3.1 hereof shall be exclusive.
Notwithstanding the foregoing UM and CCMB shall have the right to use
ASSETS and the YORK PATENTS for academic research purposes. In
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addition, the Inventor, and/or his laboratory, shall have the right to
use ASSETS and YORK PATENTS for academic research purposes and for
teaching at universities and hospitals, as defined under SPONSORED
RESEARCH. The Inventor shall also have the right to continue to treat
patients who are currently being treated with DPPE.
3.3 YORK shall have the right to grant sublicenses on fair and reasonable
terms and conditions consistent with the terms and conditions set out
in this Agreement. In the event of a breach of a term of the sublicense
by a SUBLICENSEE (the "SUBLICENSEE'S breach"), York shall forthwith
proceed to enforce the terms of the sublicense and shall further bear
all costs related thereto, thereby eliminating, as against the
University or CCMB, the effect of any such SUBLICENSEE's breach. YORK
agrees to keep UM and CCMB informed of any material sublicensing
discussions and further to provide UM and CCMB each with a true copy of
any and all sublicensing agreements entered into by YORK and a
SUB-LICENSEE.
4 LICENSING CONSIDERATION AND MINIMUM REMUNERATIONS
4.1 In consideration of the rights granted by UM and CCMB to YORK under
this Agreement, YORK shall pay the consideration set out in this
Article 4. The parties agree that any such payment shall be made to UM,
and that UM shall thereafter allocate a portion of such payment to CCMB
in accordance with the MICB Agreement.
4.2 YORK shall pay a royalty of [*] percent ([*]%) of all SUBLICENSING
REVENUE.
4.3 YORK shall further contribute to the University for the Inventor or his
laboratory CDN$ 100,000.00 in funding of SPONSORED RESEARCH in each of
the 2000, 2001 and 2002 calendar years, as noted in Exhibit 3. The
SPONSORED RESEARCH shall be conducted by Dr. Brandes or by other
researchers, faculty, staff and employees of UM or CCMB working under
the direct supervision and control of Dr. Brandes.
4.4 In the event sales are achieved by YORK or its AFFILIATE independently,
and not either by a SUBLICENSEE or by YORK or its AFFILIATE for a
SUBLICENSEE, YORK shall pay a royalty of [*] percent of NET SALES
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4.5 YORK shall retain Therudex Inc. as consultant according to the
agreement in Exhibit 2. 5 COMMERCIALIZATION AND FURTHER RESEARCH
5.1 Upon execution of this Agreement, YORK either acting for itself or
through a SUBLICENSEE shall ensure that reasonable commercial efforts
are used, in relation to the LICENSED PRODUCT, to:
a) file a request for a transfer of the active Canadian IND within 3
months;
b) identify a manufacturer of drug substance within 6 months;
c) identify a manufacturer of drug product within 12 months;
d) file an IND for randomized Phase II trial within 18 months;
e) initiating a randomized Phase II clinical trial in a first country
in the LICENSED TERRITORY within twenty four months;
all from the date of this Agreement, and to
f) investigate the use of DPPE in combination with other
chemotherapeutic agents and other types of malignancies if
warranted; and
g) use all reasonable efforts to ensure that the LICENSED PRODUCT is
efficiently marketed and distributed in the LICENSED TERRITORY
within five (5) years of the date of this Agreement
5.2 UM and CCMB shall disclose and provide to YORK, and YORK shall be
entitled to use, ASSETS to enable YORK to perform its obligations and
enjoy the rights granted under this Agreement. UM and CCMB shall
provide to YORK, at YORK's request and expense, any technical
assistance reasonably necessary to enable YORK or its SUBLICENSEE to
make, use, sell, sublicense or otherwise dispose of LICENSED PRODUCT.
5.3 INFORMATION, MATERIAL and PATENTS that arise during the term of this
Agreement shall be treated as follows: INFORMATION and MATERIAL, and
PATENTS therefor, generated or invented during the term of this
Agreement by persons engaged in the SPONSORED RESEARCH, and ASSETS that
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are related to DPPE and are owned and controlled by UM and/or CCMB,
shall be hereby licensed exclusively to YORK under terms and conditions
stipulated in this Agreement
5.4 INFORMATION and MATERIAL, and any PATENTS thereforrelating to DPPE,
that are generated and/or invented jointly by persons engaged in the
SPONSORED RESEARCH and by YORK or its employees or consultants during
the term of this Agreement shall be owned jointly by UM and CCMB and
YORK and constitute an ASSET. UM and CCMB's interest in this ASSET
shall be hereby licensed exclusively to YORK under the terms and
conditions stipulated in this Agreement.
5.5 INFORMATION and MATERIAL and any PATENTS therefore relating to DPPE
that during the term of this Agreement are generated or invented solely
and independently by YORK shall belong solely to YORK and shall
constitute YORK PATENTS. UM and CCMB shall have the right to use these
YORK PATENTS for research purposes, under the terms and conditions of
this Agreement.
5.6 For the purpose of this Article 5, determination of inventorship shall
be determined in accordance with United States patent law.
5.7 UM, CCMB and YORK shall receive and maintain all disclosures of
know-how, inventions and other intellectual property information under
this Agreement, and any other information about the business or affairs
of the other relating to the ASSETS, the YORK PATENTS or the Agreement,
in confidence and shall not at any time disclose any such received
information to persons other than their AFFILIATES, officers, employees
and advisers. The disclosure of such information by YORK to a
SUBLICENSEE or prospective SUBLICENSEE or to a person or entity
contracted by YORK to research and/or develop LICENCED PRODUCT or to a
person or entity for bona fide business purposes, including bona fide
financing of YORK, who has agreed to keep such information
confidential, is permitted by this Agreement. Each party shall take all
reasonable steps to ensure that their respective AFFILIATES, officers,
employees and advisers maintain the obligations of confidence imposed
on UM and CCMB and YORK. The obligations of confidentially shall not
apply to any information which:
a) was already known to the receiving party at the time of its
disclosure by the disclosing party;
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b) has been published or is otherwise within the public knowledge or
is generally known to the public without any breach of this
Agreement;
c) became known or available to the receiving party from a source
having the right to make such disclosure to the receiving party
without breach of a secrecy agreement and without restriction on
such disclosure to the receiving party;
d) is disclosed to the public as a result of compliance with any
applicable law or regulation;
e) is disclosed as the result of any applications for, or publication
of, a patent related to ASSETS;
f) is required to be disclosed to the Manitoba Lieutenant Governor
Council; or
g) is developed by the receiving party without reference to the
disclosed information as evidenced by written records.
5.8 Before any permitted publishing of any INFORMATION, the parties shall
disclose the INFORMATION to each other and give each other at least 30
days prior written notice of the proposed publication, and during those
30 days, the parties shall remove from the proposed publication all
information which any party considers to be confidential. If any party
requires more time to protect INFORMATION contained in the proposed
publication the other party shall withhold the publication for a
further 60 days. Notwithstanding the above, each party may in its sole
discretion withhold permission to publish INFORMATION. The parties are
however always entitled to disclose information which they are required
by law, regulation, act or order of any governmental authority to
disclose, but only to the extent so required.
5.9 The parties have agreed on a research and development plan for
SPONSORED RESEARCH that is directed by the parties on an annual basis
and is set out in Exhibit 3 as may be amended from time to time.
6 SUBLICENSING AND ASSIGNMENT
6.1 As per Section 3.3 YORK shall have the right to grant sublicenses to
arms length third parties who are not Affiliates Such sublicenses may,
at YORK's sole election, be either exclusive or non-exclusive. At all
times YORK shall enforce and defend the rights of UM and CCMB in any
such sublicenses as set forth in this Agreement.
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6.2 Unless otherwise agreed in writing, YORK may, after having fulfilled
its obligations according to Clauses 5.1 a) and b) above, wholly or
partly assign or pledge its rights or obligations under this Agreement
subject to the terms and conditions set out in Section 12.1 below.
6.3 YORK shall provide UM and CCMB with a true copy of all agreements
regarding sub-licensing, assignment or disposal of the rights granted
to YORK under this Agreement.
7 PAYMENTS
7.1 Not later than the last day of July and January of each year, YORK
shall furnish to UM and CCMB a written statement of milestones achieved
by YORK and of all NET SALES and SUBLICENSING REVENUE received, if any,
due for the semi-annual periods ended the last days of the June and
December, respectively, and shall pay all amounts due. Such amounts are
due within the earlier of (a) thirty (30) days of the dates the
statements or (b) the last day of August (when dealing with a statement
for the semi-annual period ending on the last day of the immediately
preceding June) or the last day of February (when dealing with a
statement for the semi-annual period ending on the last day of the
immediately preceding December). If no NET SALES or SUBLICENSING
REVENUE is received by YORK during any semi-annual periods, a written
statement to that effect shall be furnished.
7.2 If this Agreement is terminated for any reason before all of the
payments herein provided for have been made, YORK shall submit a final
report as soon as all revenue reporting is available and pay any
remaining unpaid balance which has accrued.
7.3 Payment provided for in this Agreement, when overdue, shall bear
interest at a rate per annum equal to five percent (5 %) in excess of
the prime rate at the Canadian Imperial Bank of Commerce (CIBC)
8 PATENT RIGHTS AND PATENT INFRINGEMENT
8.1 The filing, prosecution, defense, maintenance and enforcement of
PATENTS shall be managed by YORK, which shall diligently pursue
prosecution of the PATENTS. It shall be the responsibility of YORK to
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advise UM and CCMB of the status of the PATENTS, and to involve UM and
CCMB in all portfolio management decisions. YORK shall be responsible
for all fees and expenses that are incurred in connection with the
preparation, filing, prosecution, maintenance and defence and
enforcement of PATENTS necessary for the exploitation of ASSETS
according to this Agreement. YORK shall have the right, in its sole
discretion, to elect not to file, prosecute, maintain, defend and
enforce the PATENTS in one or more countries. With respect to any such
non-elected PATENTS, YORK shall have no rights thereunder in the
country so elected, it shall so advise UM and CCMB on a timely basis so
UM and CCMB can pursue such PATENTS, and UM and CCMB thereafter shall
have the exclusive right to file, prosecute, maintain, defend and
enforce the PATENTS in that country at its expense, provided that the
filing, prosecuting, maintainence, defence or enforcement of the
PATENTS in that country does not compromise the validity, defence or
enforceability of the PATENTS in any other elected country..
8.2 Each party shall be entitled to receive for comment copies of all
patent applications relating to PATENTS and correspondence, including
status reports relating to the prosecution, maintenance, issue,
re-issue, re-examination or division of these patent applications.
8.3 If YORK or UM and CCMB is sued by a third party for patent infringement
arising from the SPONSORED RESEARCH or because of the exercise of the
license granted herein, YORK shall settle or defend the suit at its own
expense, but UM and CCMB shall cooperate to the fullest, at YORK's
expense, in the conduct of any such settlement or defense.
8.4 In the event that any infringement of any of the PATENTS comes to the
attention of either party hereto, such party shall promptly notify the
other party thereof. YORK or its SUBLICENSEE shall have the right but
not the obligation to undertake an infringement suit at YORK's expense
and in the name of UM and CCMB or YORK or both, as required by law. In
such event, UM and CCMB shall cooperate fully with YORK or its
SUBLICENSEE, at no expense to UM and CCMB. YORK shall not settle any
such suit without obtaining the prior written approval of UM and CCMB,
which shall not be unreasonably withheld. Any recovery obtained by YORK
as the result of such proceeding, by settlement or otherwise, shall be
applied for the following purposes and in the following order:
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(1) against legal and other expenses of the suit, (2) against
liabilities of YORK or UM or CCMB resulting from the suit, and (3) to
UM and CCMB in accordance with Article 4.2, wherein such money shall be
considered SUBLICENSING REVENUE.
9 REPRESENTATIONS AND WARRANTIES
9.1 UM and CCMB represent and warrant, to their knowledge:
a) that the Inventor is the sole inventor of the inventions described
and claimed in the patents listed in Exhibit 1 and that the Inventor
has assigned such invention to UM and CCMB.
b) i) that they have not, either alone or together, entered into any
agreement regarding the LICENSED PRODUCT, whether in writing or
verbally, with any other person that is inconsistent with the terms of
this Agreement; and
ii) that the B-M agreement described in preamble paragraph 1.4 has
been terminated.
c) that UM and CCMB have the capacity and authority to enter into this
Agreement, subject to CCMB obtaining approval of the licensing of the
PATENTS to York from the Manitoba Lieutenant Governor in Council.
9.2 YORK represents and warrants that it has the capacity and authority to
enter into this Agreement.
9.3 Except as set out in Section 9.1, UM and CCMB make no warranties,
express or implied, as to any matter whatsoever including, without
limitation:
a) the condition of the ASSETS;
b) the ownership, merchantability, or fitness for a particular
purpose of the ASSETS; or
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c) the scope of the PATENTS or that such PATENTS may be exploited by
YORK or a SUBLICENSEE without infringing other patents
9.4 None of the Inventor, UM or CCMB shall have any liability whatsoever to
YORK or any other person for or on account of any injury, loss, or
damage, or any kind of nature, sustained by, or any damage assessed or
asserted against, or any other liability incurred by or imposed upon
YORK or any other person, arising out of or in connection with or
resulting from (1) activities under Section 5.1, (2) the manufacture,
use, or sale of any LICENSED PRODUCT; or (3) any advertising or other
promotional activities with respect to any of the foregoing, and YORK
shall hold UM , CCMB, and the Inventor harmless and indemnify them if
any one of them is held liable. YORK's obligation to indemnify shall
not apply if UM and CCMB has caused injury, loss or damage by gross
negligence or breach of any of the representations or warranties
contained in Section 9.1 above.
9.5 YORK, at its own expense and at all times during the term of this
Agreement, will carry and maintain in full force and effect
comprehensive general liability insurance, including product liability
provisions, in a form and with a carrier acceptable in the
pharmaceutical industry. The limits of such policy shall be sufficient
at all times for YORK's then current activities under this Agreement,
and customary for YORK's business within the industry. UM, CCMB and
Inventor shall be named as an additional insured on such insurance and
the carrier shall be required to agree, where enforceable, not to
cancel same without providing 60 days prior written notice of
cancellation to such additional insured entities. Certificate of
Insurance as evidence of compliance with this Section 9.5 shall be
provided annually to each UM, CCMB and Inventor.
10 TERM AND TERMINATION
10.1 This Agreement shall commence on the Effective Date and, unless
terminated sooner, in accordance with the terms hereof, shall remain in
force as long as any PATENT is valid in any part of the LICENSED
TERRITORY.
10.2 In the event either party shall be in default in the performance of any
of its material obligations hereunder, including but not limited breach
of representation or warranty, and if the default has not been remedied
within ninety (90) days following the date of receipt of a notice in
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writing from the other party specifying such default and its claim of
right to terminate, the other party may terminate this Agreement by
written notice in addition to any other remedies available to it by law
or equity
10.3 Either party shall have the right to terminate this Agreement with
immediate effect if the other party should enter into liquidation,
either voluntary or compulsory, or become insolvent, or enter a
corporate reorganization proceedings or if execution be levied on any
goods and effects of the other party or the other party should enter
into receivership or bankruptcy.
10.4 YORK may voluntarily terminate this Agreement, without cause, at any
time on ninety (90) days written notice providing there is no
SUBLICENSEE. Termination will take effect immediately at the end of the
notice period. If YORK voluntarily terminates within the first three
(3) years of the Agreement then YORK covenants that it will not
develop, sponsor research or market any product in the LICENSED FIELD
for a period of five (5) years post-termination. In this event, UM and
CCMB shall be free to pursue other commercial opportunities related to
the ASSETS as they shall solely determine.
10.5 Upon the termination of this Agreement by UM and CCMB under Sections
10.2 or 10.3, or by YORK under Section 10.4,
a) YORK and its AFFILIATES shall make no further use of the ASSETS.
YORK shall discontinue to use and exploit the ASSETS and shall
promptly return all paper, data, drawings, manuals,
specifications, descriptions and material of any kind supplied to
it by UM and CCMB hereunder. YORK shall, when transmitting such
material, acknowledge in writing that the documentation thus
transmitted is complete and that YORK does not retain any copies
thereof.
b) UM, CCMB and Inventor shall make no further use of the YORK
PATENTS. UM, CCMB and Inventor shall discontinue all use of YORK's
INFORMATION and YORK's MATERIAL and shall promptly return all
paper, data, drawings, manuals, specifications, descriptions and
material of any kind supplied to it by YORK hereunder. UM, CCMB
and Inventor shall, when transmitting such material, acknowledge
in writing that the documentation thus transmitted is complete and
that UM, CCMB and Inventor do not retain any copies thereof.
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10.6 This Article 10 and the following rights and obligations shall survive
any termination of this Agreement to the degree necessary to permit the
fulfillment or discharge by each party of their rights and obligations
noted below;
a) YORK's obligation to supply a final report as specified in Article
7.2 of this Agreement.
b) UM's right to receive or recover and YORK's obligation to pay
amounts accrued at the date of termination under Article 4 of this
Agreement.
c) YORK's obligation to maintain records and make them available
under Section 11.1 of this Agreement.
d) The representations, warranties and indemnities under Article 9 of
this Agreement.
10.7 The obligations of confidentiality as provided in this Agreement will
survive termination of this Agreement for a period of five (5) years
post termination, except where termination occurs due to default by
York under Section 10.2 or the liquidation, insolvency or corporate
reorganization or enter into receivership or bankruptcy as described in
Section 10.3 above in which case UM and CCMB shall have no further
obligations to YORK, including those under Article 5.
10.8 Notice of termination shall be effectively served on YORK only when
written notice of termination is received from both UM and CCMB.
11 RECORDS
11.1 YORK shall keep accurate records relating to all matters relevant to
this Agreement (including payments due hereunder) and shall permit UM
and CCMB or its duly authorized representative to inspect all such
records and to make copies of or extracts from such records during
regular business hours and on reasonable notice throughout the term of
this Agreement and for a period of six (6) years thereafter. YORK shall
fully co-operate at such inspection and shall give any explanations
that may be requested. If any such inspection discloses any
underpayment of royalties, YORK shall promptly pay the amount of any
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shortfall plus interest at the rate determined in accordance with
Section 7.3 hereof from the date such payment was due until the date
that YORK pays the shortfall.
11.2 YORK shall at each time of payment of royalties render a report to UM
and CCMB including copies of the SUB-LICENSEES reports to YORK, giving
an accurate account of total manufacture and sale of LICENSED PRODUCT
and SUBLICENSING REVENUES during the preceding two (2) quarters.
12 ASSIGNABILITY
12.1 Subject to the other party's prior written consent the parties shall
have the right to assign this Agreement together with all rights and
obligations herein to any other person. Such consent shall not be
unreasonably withheld or delayed provided the terms and conditions of
the Agreement of assignment are consistent with the terms and
conditions of this Agreement. Notwithstanding the foregoing YORK shall
always be entitled to assign its rights and obligations to an
AFFILIATE. YORK shall the fulfilment by an AFFILIATE of the terms and
conditions of this Agreement.
13 SEVERABILITY
13.1 The parties agree that if any part, term, or provision of this
Agreement shall be found illegal or in conflict with any valid
controlling law, the validity of the remaining provisions shall not be
affected thereby.
14 USE OF LICENSOR'S NAME
14.1 YORK shall not use the UM or CCMB name or trademark, nor the name of
any employee or agent, in any advertising or promotional material or
publicity release relating to the ASSETS or the LICENSED PRODUCTs
without UM and CCMB prior written consent.
15 WAIVER, INTEGRATION, ALTERATION
15.1 The waiver of a breach hereunder may be effected only by a written
document signed by the waiving party and shall not constitute a waiver
of any other breach.
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Page 18 (35)
15.2 A provision of this Agreement may be altered only by a written document
signed by both the parties.
16 DISPUTE RESOLUTION
16.1 If the parties are unable to resolve any dispute arising under this
Agreement, such matter shall first be referred for resolution to the
Presidents of UM and CCMB and YORK. In the event that no resolution is
reached within 10 business days, or such further period as the
Presidents may mutually agree, resolution of the dispute shall be
determined by arbitration to be held in the English language in
Manitoba , in accordance with Manitoba Law.
17 APPLICABLE LAW
17.1 This Agreement shall be governed and construed in accordance with the
laws of Manitoba.
18 NOTICES UNDER THE AGREEMENT
18.1 All written communications and notices between the parties shall be
delivered or sent by prepaid mail, registered mail or facsimile
transmission to the attention of the party at the addresses provided
below, or any other addresses of which either party shall notify the
other party in writing. Notices sent by prepaid or registered mail
shall be effective on the date delivered and notices sent by facsimile
shall be effective on the date transmitted.
If to YORK: The President
York Medical Inc.
5045 Orbitor Drive, Building 11, Suite 400
Mississauga, Ontario L4W 4Y4
Facsimile: (905) 629-4959
18.2 If to UM: The University of Manitoba
Rm. 202 Administration Building
Winnipeg, Manitoba R3T 2N2
ATTN: Vice-President (Administration)
Facsimile: (204) 261-1318
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Page 19 (35)
With copy to: University Industry Liaison Office
The University of Manitoba
631 Drake Centre, 181, Freedman Crescent
Winnipeg, Manitoba R3T 5V4
Facsimile: (204) 261-3475
18.3 If to CCMB: CancerCare Manitoba
675 McDermot Ave.,
Winnipeg, Manitoba R3E 0V9
ATTN: President and CEO
Facsimile: (204) 787-1184
19 EXTENDED MEANING
19.1 The use of the singular in this Agreement shall include the plural and
vice versa.
20 FORCE MAJEURE
20.1 The parties shall be relieved from liability for a failure to perform
any obligation under this Agreement during such period and to the
extent that the due performance thereof by either of the parties is
prevented by reason of any circumstance beyond the control of the
parties, such as war, warlike hostilities, mobilization or general
military call-up, civil war, fire, flood or other circumstances of
similar nature.
20.2 The party desiring to invoke an event of force majeure shall give
immediate notice to the other party of the commencement and the
cessation of such event of force majeure, failing which the party shall
not be discharged from liability for any non-performance caused by such
event of force majeure.
20.3 Both parties shall make all reasonable efforts to prevent and reduce
the effect of any non-performance of this Agreement caused by an event
of force majeure.
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Page 20 (35)
21 CURRENCY
21.1 All amounts due under this Agreement shall be paid in Canadian currency
and shall be calculated into Canadian currency using the exchange rate
published in the Wall Street Journal on the date that the payment is
due.
22 ENTIRE AGREEMENT
22.1 This Agreement represents the entire understanding between the parties,
and supersedes all other agreements, express or implied, between the
parties concerning subject matter of this Agreement.
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IN WITNESS WHEREOF the parties have caused this Agreement to be executed by
their duly authorized officers on the respective dates and at the respective
places hereinafter set forth.
Mississsauga 10 /10 2000 Winnipeg 2 /11 2000
YORK MEDICAL INC. University of Manitoba
"David GP Allan" "M. McAdam"
- ------------------------------------------- -----------------------------------------
By: Mr. David G.P. Allan By: Mr. M. McAdam
Title: Chairman and Chief Executive Officer Title: Vice-President, Administration
At: Mississauga, Ontario At: Winnipeg, Manitoba
THE MANITOBA CANCER TREATMENT AND RESEARCH
FOUNDATION, carrying on its undertaking as
CANCERCARE MANITOBA
"Niclas Stiernholm" " B. Schacter "
- --------------------------------------- -----------------------------------------
By: Dr. Niclas Stiernholm By: Dr. B. Schacter
Title: Director, Science & Technology Title: President & CEO
At: Mississauga, Ontario At: Winnipeg, Manitoba
I, the undersigned party, acknowledge and fully accept the provisions of this
Agreement.
I also represent and warrant, to my knowledge, that:
a) I am the sole inventor of the inventions described and claimed in the
patents listed in Exhibit 1 and that I have assigned such inventions to UM
and CCMB; and
b) I have not entered into any agreement regarding the LICENSED PRODUCT,
whether in writing or verbally, that is inconsistent with the terms of this
Agreement.
Winnipeg 13 /10 2000
" Lorne J. Brandes"
- -------------------------------
By: Dr. Lorne J. Brandes
Title: Professor
At: Winnipeg, Manitoba
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Page 22 (35)
EXHIBIT 1
PATENT TECHNOLOGY 80.02.113
IMPROVED TREATMENT METHOD FOR CANCER
+------------------+------------------+-------------------+-------------------+----------------+
| FILE | COUNTRY | STATUS | SER./PAT.# | ATTORNEY |
| | | | | REFERENCE |
+==================+==================+===================+===================+================+
| 80.02.113.20 | Canada | Issued 08/10/99 | 2,098,593 | 1887-80 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.21 | Australia | Issued 04/02/96 | 664,978 | 1887-82 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.5 | Japan | Issued 10/09/97 | 2,706,371 | 1887-83 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.22 | Korea | Abandoned | 93-701846 | 1887-84 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.17 | Austria | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.27 | Switzerland | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.10 | Germany | Issued 12/07/94 | P69103908.9-08 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.13 | Denmark | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.11 | Spain | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.16 | UK | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.25 | Luxembourg | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.18 | Netherlands | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.26 | Sweden | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.19 | Belgium | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.15 | France | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.12 | Greece | Issued 12/07/94 | 3014012 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.24 | Italy | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.28 | Monaco | Issued 09/07/94 | 0563127 | 1887-81 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.4 | US | Abandoned | 627,863 | 1887-39 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.4 | US | Abandoned | 711,975 | 1887-69 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.4 | US | Issued 08/25/98 | 5,798,339 | 1887-79 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.7 | US | Issued 04/08/97 | 5,618,846 | 1887-134 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.6 | US | Issued 05/05/98 | 5,747,543 | 1887-133 |
+------------------+------------------+-------------------+-------------------+----------------+
| 80.02.113.8 | US | Issued 01/12/99 | 5,859,065 | 1887-184 |
+------------------+------------------+-------------------+-------------------+----------------+
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Page 23 (35)
PATENT TECHNOLOGY 80.02.113
IMPROVED TREATMENT METHOD FOR CANCER CONTINUED
+-------------------+------------------+-------------------------+----------------+--------------+
| FILE | COUNTRY | STATUS | SER./PAT.# | ATTORNEY |
| | | | | REFERENCE |
+===================+==================+=========================+================+==============+
| 80.02.113.2 | PCT | Entered National Phase | CA91/00449 | 1887-68 |
+-------------------+------------------+-------------------------+----------------+--------------+
| 80.02.113.3 | Europe | Issued in Indiv. | 0563127 | 1887-81 |
| | | Countries 09/07/94 | | |
+-------------------+------------------+-------------------------+----------------+--------------+
| 80.02.113.9 | US | Abandoned | 09/200,783 | 1887-190 |
+-------------------+------------------+-------------------------+----------------+--------------+
| 80.02.113.14 | Brazil | Not Pursued | | |
+-------------------+------------------+-------------------------+----------------+--------------+
PATENT TECHNOLOGY 80.02.171
CANCER TREATMENT
+------------------+-------------------+-------------------------+-------------------+-----------------+
| FILE | COUNTRY | STATUS | SER./PAT.# | ATTORNEY |
| | | | | REFERENCE |
+==================+===================+=========================+===================+=================+
| 80.02.171.4 | PCT | Entered Natl. Phase | CA94/00087 | 1887-95 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.5 | Japan | Issued 12/09/98 | 2,834,328 | 1887-147 |
| | Japan | Pending | 167/98 | 1887-185 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.6 | US | Under review at | 08/505,269 | 1887-148 |
| | | Patent Office | | |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.7 | Canada | Under review at | 2,156,162 | 1887-151 |
| | | Patent Office | | |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.8 | Australia | Under review at | 14804/97 | 1887-179 |
| | | Patent Office | | |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.9 | Europe | Under review at | 94906813.4 | 1887-150 |
| | | Patent Office | | |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.10 | Brazil | Potential Application | | 1887-95 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.11 | Korea | Abandoned | 95-703444 | 1887-146 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| 80.02.171.12 | US | Under review at | 08/773,987 | 1887-174 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
| | | Patent Office | | |
| 80.02.171.13 | Australia | Issued 02/17/94 | 693,780 | 1887-149 |
+------------------+-------------------+-------------------------+-------------------+-----------------+
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PATENT TECHNOLOGY 80.02.194
METHOD OF TREATMENT OF HORMONE-UNRESPONSIVE METASTATIC PROSTATE CANCER
+------------------+----------------+-----------------------+-----------------+----------------+
| FILE | COUNTRY | STATUS | SER./PAT.# | ATTORNEY |
| | | | | REFERENCE |
+==================+================+=======================+=================+================+
| 80.02.194.1 | US | Issued 07/11/95 | 5,432,168 | 1887-93 |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.2 | PCT | Entered Natl. Phase | CA94/00676 | 1887-119 |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.4 | Canada | Under review at | 2,179,377 | 1887-161 |
| | | Patent Office | | |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.5 | Korea | Abandoned | 96-703457 | 1887-162 |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.6 | Europe | Under review at | 95902723.6 | 1887-165 |
| | | Patent Office | | |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.7 | Japan | Published | 517694/95 | 1887-163 |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.8 | Australia | Issued 04/01/99 | 699,798 | 1887-166 |
+------------------+----------------+-----------------------+-----------------+----------------+
| 80.02.194.9 | US | Issued 01/26/99 | 5,863,912 | 1887-164 |
+------------------+----------------+-----------------------+-----------------+----------------+
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EXHIBIT 3
SPONSORED RESEARCH
PAYMENT SCHEDULE: Annually, in advance
RESEARCH PLAN:
Our synthesis of DPPE, an arylalkylamine derivative of tamoxifen, led us to
characterize microsomal and nuclear sites, designated HIC , through which
histamine acts as an intracellular mediator, and DPPE as an inhibitor, of
diverse cell processes, including human platelet aggregation and proliferation,
e.g. lymphocyte mitogenesis. A major proportion, at least, of the microsomal HIC
sites with which Histamine and DPPE interact, are on cytochromes P450, an
important family of microsomal enzymes that are present in all cells, but most
abundant in the liver. These enzymes are involved in the metabolism of
xenobiotics (including many antineoplastic agents) and natural substrates,
including lipid hormones that modulate gene function and cell growth. In
previously published studies, we demonstrated that, like DPPE, various
growth-modulatory substances such as polyamines, hormones (including estrogen,
testosterone and progesterone), anti-hormones (including tamoxifen and
flutamide) antidepressants and antihistamines, all inhibit histamine binding to
P450; we have postulated that, through binding to the heme moiety, intracellular
histamine regulates cell function by modulating the catalytic activity of P450
enzymes, an action that may be perturbed by endogenous and exogenous substances.
Since the family of non-P450 heme enzymes (e.g. cytochrome C, cyclooxygenase,
nitric oxide synthase) also may represent common targets where multiple
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bioamines, hormones and drugs (e.g.DPPE) interact to influence cell function and
growth, studies funded over 3 years through a grant by York Medical, Inc., will
assess whether (a) in addition to histamine, the biogenic amines dopamine,
serotonin and noradrenaline, as well as melatonin, may bind to P450 isozymes
and/or interact at other heme enzymes that modulate cell function and (b)
whether DPPE and other growth-modulatory drugs, hormones and antihormones may
bind to/interact with the various amines and with each other at P450 and other
heme enzymes.
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EXHIBIT 4
YORK PATENTS
(This page is intentionally left blank)
CONFIDENTIAL