AGREEMENT





THIS
AGREEMENT, effective November 2, 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 or business at


Fort
Garry Campus, Rm 631 Drake Centre, 181 Freedman Crescent,


Winnipeg,
Manitoba, R3E OW3, 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 OV9,Canada





(hereinafter
referred to as "CCMB")
















2  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, Bristol-Myers
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 OPPE, 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.








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.HCI, 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.





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, particularly 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.





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 CCMS 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.





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 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 CCMS 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 twenty percent (20%) 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 four (4) percent of NET SALES.





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 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 CGMB 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;









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 sale 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 sore
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.





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, defence, 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 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, maintenance, 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 defence.





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: (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





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 anyone 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 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.





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 all 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 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.





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
      PresidentYork
      Medical Inc.5045
      Orbitor Drive, Building 11, Suite 400Mississauga,
      Ontario L4W 4Y4Facsimile:
      (905) 629-495918.2  If
      to UM:
            The
      University of ManitobaRm.
      202 Administration BuildingWinnipeg,
      Manitoba R3T 2N2ATTN:
      Vice-President (Administration)Facsimile:
      (204) 261-1318With
      copy to:
            The
      University of Manitoba631
      Drake Centre, 181, Freedman CrescentWinnipeg,
      Manitoba R3T 5V4Facsimile:
      (204) 261-347518.3  If
      to CCMB:
            CancerCare
      Manitoba675
      McDermot Ave.,Winnipeg,
      Manitoba R3E 0V9ATTN:
      President and CEOFacsimile:
      (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.





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.











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.








Mississauga
      __ 2000
            
            Winnipeg
      __ 2000YORK
      MEDICAL INC.
            
            University
      of Manitoba________________________________
            
            _____________________________By:     
      Mr. David G.P. Allan
            
            By:     
      Mr. M. McAdamTitle:   Chairman
      and Chief Executive Officer
            
            Title:   Vice-President,
      AdministrationAt:      Mississauga,
      Ontario
            
            At:      
      Winnipeg, ManitobaTHE
      MANITOBA CANCER TREATMENT AND RESEARCH FOUNDATION, carrying on its
      undertaking as CANCERCARE MANITOBA________________________________
            
            ______________________________By:      Dr.
      Niclas Stiernholm
            
            By:
      Dr. B. SchacterTitle:   Director,
      Science & Technology
            
            Title:
      President & CEOAt:     
      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 sale 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
__ 2000








________________________________


By:           Dr.
Lorne J. Brandes


Title:        Professor


At:           Winnipeg,
Manitoba











Exhibit
1





Patent
Technology 80.02.113


Improved
Treatment Method for Cancer





File
            Country
            Status
            Ser./Pat.#
            Attorney
              Reference80.02.113.20
            Canada
            Issued
      08/10/99
            2,098,593
            1887-8080.02.113.21
            Australia
            Issued
      04/02/96
            664,978
            1887-8280.02.113.5
            Japan
            Issued
      10/09/97
            2,706,371
            1887-8380.02.113.22
            Korea
            Abandoned
            93-701846
            1887-8480.02.113.17
            Austria
            Issued
      09/07/94
            0563127
            1887-8180.02.113.27
            Switzerland
            Issued
      09/07/94
            0563127
            1887-8180.02.113.10
            Germany
            Issued
      12/07/94
            P69103908.9-08
            1887-8180.02.113.13
            Denmark
            Issued
      09/07/94
            0563127
            1887-8180.02.113.11
            Spain
            Issued
      09/07/94
            0563127
            1887-8180.02.113.16
            UK
            Issued
      09/07/94
            0563127
            1887-8180.02.113.25
            Luxembourg
            Issued
      09/07/94
            0563127
            1887-8180.02.113.18
            Netherlands
            Issued
      09/07/94
            0563127
            1887-8180.02.113.26
            Sweden
            Issued
      09/07/94
            0563127
            1887-8180.02.113.19
            Belgium
            Issued
      09/07/94
            0563127
            1887-8180.02.113.15
            France
            Issued
      09/07/94
            0563127
            1887-8180.02.113.12
            Greece
            Issued
      12/07/94
            3014012
            1887-8180.02.113.24
            Italy
            Issued
      09/07/94
            0563127
            1887-8180.02.113.28
            Monaco
            Issued
      09/07/94
            0563127
            1887-8180.02.113.4
            US
            Abandoned
            627,836
            1887-3980.02.113.4
            US
            Abandoned
            711,975
            1887-6980.02.113.4
            US
            Issued
      08/25/98
            5,798,339
            1887-7980.02.113.7
            US
            Issued
      04/08/97
            5,618,846
            1887-13480.02.113.6
            US
            Issued
      05/05/98
            5,747,543
            1887-13380.02.113.8
            US
            Issued
      01/12/99
            5,859,065
            1887-18480.02.113.2
            PCT
            Entered
      National Phase
            CA91/00449
            1887-6880.02.113.3
            Europe
            Issued
      in Indiv. Countries
              09/07/94
            0563127
            1887-8180.02.113.9
            US
            Abandoned
            09/200,783
            1887-19080.02.113.14
            Brazil
            Not
      Pursued











Patent
Technology 80.02.171


Cancer
Treatment





File
            Country
            Status
            Ser./Pat.#
            Attorney
              Reference80.02.171.4
            PCT
            Entered
      Natl.
              Phase
            CA94/00087
            1887-9580.02.171.5
            Japan
              Japan
            Issued
      12/09/98 Pending
            2,834,328
              167/98
            1887-147
              1887-18580.02.171.6
            US
            Under
      review at Patent Office
            08/505,269
            1887-14880.02.171.7
            Canada
            Under
      review at Patent Office
            2,156,162
            1887-15180.02.171.8
            Australia
            Under
      review at Patent Office
            14804/97
            1887-17980.02.171.9
            Europe
            Under
      review at Patent Office
            94906813.4
            1887-15080.02.171.10
            Brazil
            Potential
      Application
            
            1887-9580.02.171.11
            Korea
            Abandoned
            95-703444
            1887-14680.02.171.12
            US
            Under
      review at Patent Office
            08/773,987
            1887-17480.02.171.13
            Australia
            Issued
      02/17/94
            693,780
            1887-149








Patent
Technology 80.02.194


Method
of Treatment of Hormone-Unresponsive Metastatic Prostate Cancer





File
            Country
            Status
            Ser./Pat.#
            Attorney
              Reference80.02.194.1
            US
            Issued
      07/11/95
            5,432,168
            1887-9380.02.194.2
            PCT
            Entered
      Natl. Phase
            CA94/00676
            1887-11980.02.194.4
            Canada
            Under
      review at Patent Office
            2,179,377
            1887-16180.02.194.5
            Korea
            Abandoned
            96-703457
            1887-16280.02.194.6
            Europe
            Under
      review at Patent Office
            95902723.6
            1887-16580.02.194.7
            Japan
            Published
            517694/95
            1887-16380.02.194.8
            Australia
            Issued
      04/01/99
            699,798
            1887-16680.02.194.9
            US
            Issued
      01/26/99
            5,863,912
            1887-164














Exhibit
2.





CONSULTANCY
AGREEMENT





Effective,
_________, 2000 ("Effective Date") York Medical Inc. having an address at 5045
Orbiter Drive, Building 11, Suite 400, Mississauga, Ontario, L4W 4Y4 ("YORK
MEDICAL") and Therudex Inc. of 223 Cordova Street, Winnipeg, Manitoba, R3N 1A3
("CONSULTANT") agree to the following terms and conditions under which
CONSULTANT has agreed for a term of three years to provide YORK MEDICAL with
Consulting Services from the Effective Date of the Agreement ("Term"). Therudex
will employ a duly qualified consultant/principal investigator, who shall be
approved by YORK MEDICAL in advance. YORK MEDICAL hereby approves Dr. Lome
J. Brandes as such consultant.





1.
 Scope of
Work





The
services performed by CONSULTANT for YORK MEDICAL pursuant to this
Agreement shall be deemed to be within the general scope of cancer
therapeutics, specifically, but not limited to,
N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine.HCI (“DPPE")("Field of
the Agreement"). The "DPPE Project" is defined as any commercialization
activities operating under patents summarized in Appendix A. "Consulting
Services" include clinical and technical information, advice and opinions
in the field of oncology, as related to the DPPE Project.





2.  Compensation





It is
further understood and agreed that YORK MEDICAL shall pay CONSULTANT for
Consulting Services rendered hereunder at the rate of CDN $50,000.00, plus GST,
per year, which is to be paid in four equal quarterly installments in advance,
with the first payment (to include a prorated sum for any portion of a
quarter prior to the last quarter of the year 2000) to


be made
on ________, 2000.





In the
event that YORK MEDICAL requests CONSULTANT to provide Consulting Services at
a


location
away from the metropolitan area of CONSULTANT's regular place of business,
YORK


MEDICAL
will reimburse CONSULTANT for reasonable travel and living expenses incurred
by


CONSULTANT.
lt is understood and agreed that YORK MEDICAL will stipulate the places and
locations wherein CONSULTANT will provide the Consulting Services. Payment for
any travel expenses will be made within thirty (30) days of submission by
CONSULTANT of an itemized account to YORK MEDICAL of the travel expenses
incurred and payments due. It is understood that the CONSULTANT will not be
expected to travel more than 10 days/calendar year, excluding actual travel
time.





3.  Manner of
Performance





CONSULTANT
represents that CONSULTANT has the requisite expertise and ability to render the
Consulting Services, and will perform the Consulting Services in an efficient
manner and in accordance with the terms of this Agreement. CONSULTANT will abide
by all laws, rules and regulations that apply to the performance of the
Consulting Services and when on YORK MEDICAL's premises, will comply with YORK
MEDlCAL's policies with respect to conduct of visitors. CONSULTANT is an
independent contractor, and shall not be considered an employee of YORK
MEDICAL.











4.  Confidentiality





All
communications between the parties hereto and all information and other material
supplied to or received by a party hereto from the other party which is either
marked "confidential" or is by its nature intended to be exclusively the
knowledge of the parties hereto alone, and any information concerning the
business transactions or the financial arrangements of YORK MEDICAL coming to
the knowledge of the CONSULTANT shall be kept confidential by each
of


the
parties hereto unless and until it is agreed that it is, or part of it is, in
the public domain, whereupon, to the extent that it is public, this obligation
shall cease. In any case of uncertainty a party shall treat information and
material as confidential until clearance is obtained from the other
party.





The
parties shall take all reasonable steps to minimize the risk of disclosure of
confidential information, by ensuring that only persons whose duties will
require them to possess any such information shall have access thereto, and they
shall be instructed to treat the same as confidential.





The
CONSULTANT shall keep confidential, all information coming to his knowledge in
the course of the performance of his duties hereunder relating to the business
associations and transactions of YORK MEDICAL with other persons or bodies
including other technical or commercial co-operative arrangements.





The
obligations of confidentiality herein shall survive the expiration or
termination of this Agreement.





5.  Relationship
with Others





During
the Term of this Agreement, CONSULTANT agrees not to perform any service within
the Field of the Agreement or which may utilize any of the information obtained
from YORK MEDICAL or any information developed during the course of performing
the Consulting Services for YORK MEDICAL for any competitor or potential
competitor of YORK MEDICAL. It is understood that CONSULTANT is permitted to
continue to serve in an advisory capacity to the pharmaceutical industry as long
as this is done in accordance with Article 4 of this Agreement.





6.  Ownership
of Developments





CONSULTANT
agrees and does hereby assign to YORK MEDICAL, any and all of CONSULTANT's
interest in any inventions or discoveries created by the CONSULTANT during the
direct performance of Consulting Services within the Field of the Agreement
during the Term, which includes all written material and unpatentable
information, discoveries, and ideas (including but not limited to any computer
software) which are made, conceived or written by CONSULTANT during the Term and
which are based upon any information received from YORK MEDICAL, and/or
developed as a result of the direct performance of the Consulting Services for
YORK MEDICAL during the Term (herein "Developments"). CONSULTANT agrees to hold
all such Developments confidential in accordance with Article 4 of this
Agreement. CONSULTANT shall disclose promptly to YORK MEDICAL Developments and
upon YORK MEDlCAL's request and at YORK MEDICAL's expense, CONSULTANT will
assist YORK MEDICAL, or anyone it designates, in filing and prosecuting patent
or copyright applications covering such Developments in any country in the
world. Each copyrightable work, to the extent permitted by law, will be
considered a work made for hire and the authorship and copyright of the work
shall be in YORK MEDICAL's name. CONSULTANT will execute all papers and do all
things which may be necessary or advisable, in the opinion of YORK MEDICAL, to
prepare, file and prosecute such applications, and to evidence the assignment in
YORK MEDICAL, or its designee, of all right, title and interest in and to such
Developments.









YORK
MEDICAL acknowledges that CONSULTANT is required to assign inventions to his
employer, and this obligation shall supercede this Article.





YORK
MEDICAL agrees to compensate CONSULTANT for any time CONSULTANT actually spends
in response to a specific request for assistance by YORK MEDICAL under this
Article, at a rate of CDN$ 1,000.00 per day.





7.  Term





The Term
of this Agreement is as specified on the first page of this Agreement. The
parties agree that this Agreement may be extended by mutual agreement. In the
event that YORK MEDICAL chooses to terminate the DPPE Project, YORK MEDICAL has
the right to terminate this Agreement upon thirty (30) days written
notice.





8.  Indemnification
and Warranties





YORK
MEDICAL agrees to hold harmless, indemnify and defend CONSULTANT from any and
all claims for damages, expenses, losses or injuries arising out of the use,
manufacture, design, or distribution of products developed in connection with or
arising out of Consulting Services, by YORK MEDICAL, its directors, employees,
contractors, subcontractors, by any party acting on behalf of or under
authorization from YORK MEDICAL, or by third parties. Such indemnity shall
include all costs and expenses, including legal costs and any costs of
settlement.





9.  General





No
assignment by CONSULTANT of this Agreement, or any sums due under it. will be
binding on YORK MEDICAL without YORK MEDICAL's prior written consent. This
Agreement supersedes all prior agreements and understandings between the parties
respecting the subject matter of this Agreement. No change in any provision of
this Agreement shall be binding unless it is in writing and signed by both the
CONSULTANT and a duly authorized representative of YORK MEDICAL. This Agreement
shall be construed according to the laws of the Province of
Ontario.





10.  Severability





If any of
the provisions of this Agreement are void or unenforceable, the remaining
provisions shall nevertheless be effective, the intent being to effectuate this
Agreement to the fullest extent possible.





11.  Entire
Agreement





This
Agreement is the entire agreement with respect to the subject matter of this
Agreement













IN
WITNESS WHEREOF, the parties have executed this Agreement on the date first
written above.







______________________________
            
            ______________________________David
      G.P. Allan
            
            Therudex
      Inc.Chairman
            
            Dr.
      Lorne J. Brandes (President)______________________________
            
            ______________________________Date:
            
            Date:














Appendix
A





Patent
Technology 80.02.113


Improved
Treatment Method for Cancer





File
            Country
            Status
            Ser./Pat.#
            Attorney
              Reference80.02.113.20
            Canada
            Issued
      08/10/99
            2,098,593
            1887-8080.02.113.21
            Australia
            Issued
      04/02/96
            664,978
            1887-8280.02.113.5
            Japan
            Issued
      10/09/97
            2,706,371
            1887-8380.02.113.22
            Korea
            Abandoned
            93-701846
            1887-8480.02.113.17
            Austria
            Issued
      09/07/94
            0563127
            1887-8180.02.113.27
            Switzerland
            Issued
      09/07/94
            0563127
            1887-8180.02.113.10
            Germany
            Issued
      12/07/94
            P69103908.9-08
            1887-8180.02.113.13
            Denmark
            Issued
      09/07/94
            0563127
            1887-8180.02.113.11
            Spain
            Issued
      09/07/94
            0563127
            1887-8180.02.113.16
            UK
            Issued
      09/07/94
            0563127
            1887-8180.02.113.25
            Luxembourg
            Issued
      09/07/94
            0563127
            1887-8180.02.113.18
            Netherlands
            Issued
      09/07/94
            0563127
            1887-8180.02.113.26
            Sweden
            Issued
      09/07/94
            0563127
            1887-8180.02.113.19
            Belgium
            Issued
      09/07/94
            0563127
            1887-8180.02.113.15
            France
            Issued
      09/07/94
            0563127
            1887-8180.02.113.12
            Greece
            Issued
      12/07/94
            3014012
            1887-8180.02.113.24
            Italy
            Issued
      09/07/94
            0563127
            1887-8180.02.113.28
            Monaco
            Issued
      09/07/94
            0563127
            1887-8180.02.113.4
            US
            Abandoned
            627,836
            1887-3980.02.113.4
            US
            Abandoned
            711,975
            1887-6980.02.113.4
            US
            Issued
      08/25/98
            5,798,339
            1887-7980.02.113.7
            US
            Issued
      04/08/97
            5,618,846
            1887-13480.02.113.6
            US
            Issued
      05/05/98
            5,747,543
            1887-13380.02.113.8
            US
            Issued
      01/12/99
            5,859,065
            1887-18480.02.113.2
            PCT
            Entered
      National Phase
            CA91/00449
            1887-6880.02.113.3
            Europe
            Issued
      in Indiv. Countries
              09/07/94
            0563127
            1887-8180.02.113.9
            US
            Abandoned
            09/200,783
            1887-19080.02.113.14
            Brazil
            Not
      Pursued













Patent
Technology 80.02.171


Cancer
Treatment





File
            Country
            Status
            Ser./Pat.#
            Attorney
      Reference80.02.171.4
            PCT
            Entered
      Natl.
              Phase
            CA94/00087
            1887-9580.02.171.5
            Japan
              Japan
            Issued
      12/09/98 Pending
            2,834,328
              167/98
            1887-147
              1887-18580.02.171.6
            US
            Under
      review at Patent Office
            08/505,269
            1887-14880.02.171.7
            Canada
            Under
      review at Patent Office
            2,156,162
            1887-15180.02.171.8
            Australia
            Under
      review at Patent Office
            14804/97
            1887-17980.02.171.9
            Europe
            Under
      review at Patent Office
            94906813.4
            1887-15080.02.171.10
            Brazil
            Potential
      Application
            
            1887-9580.02.171.11
            Korea
            Abandoned
            95-703444
            1887-14680.02.171.12
            US
            Under
      review at Patent Office
            08/773,987
            1887-17480.02.171.13
            Australia
            Issued
      02/17/94
            693,780
            1887-149








Patent
Technology 80.02.194


Method
of Treatment of Hormone-Unresponsive Metastatic Prostate Cancer





File
            Country
            Status
            Ser./Pat.#
            Attorney
      Reference80.02.194.1
            US
            Issued
      07/11/95
            5,432,168
            1887-9380.02.194.2
            PCT
            Entered
      Natl. Phase
            CA94/00676
            1887-11980.02.194.4
            Canada
            Under
      review at Patent Office
            2,179,377
            1887-16180.02.194.5
            Korea
            Abandoned
            96-703457
            1887-16280.02.194.6
            Europe
            Under
      review at Patent Office
            95902723.6
            1887-16580.02.194.7
            Japan
            Published
            517694/95
            1887-16380.02.194.8
            Australia
            Issued
      04/01/99
            699,798
            1887-16680.02.194.9
            US
            Issued
      01/26/99
            5,863,912
            1887-164















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
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.