EXHIBIT 10.4
LICENSING
AGREEMENT
FOR
EO-9 AND ANALOGS
This Agreement is made by and between the undersigned:
NeoTherapeutics, Inc.
157, Technology Drive
Irvine, CA 92618
USA
and
NDDO Research Foundation
Amstelveenseweg 641
1081 JD Amsterdam
The Netherlands
Page 1 of 8
This Agreement to License is made the 29th of June 2001 between
UNDERSIGNED
The "Stichting" NDDO Research Foundation, formerly "The Stichting New Drug
Development Office", having its principal office at Amstelveenseweg 641, 1081 JD
Amsterdam, The Netherlands, hereinafter referred to as NDDO, a foundation for
the development of new anti-cancer agents, organized and existing under the laws
of The Netherlands, acting in its own capacity, and legally represented by its
chairman, Mr. R.J. Vles
AND
The Faculty of Science of the University of Amsterdam, formerly the the Faculty
of Chemistry, having its residence at Kruislaan 404, 1098 SM Amsterdam, The
Netherlands, legally represented in this matter by Prof. W. Hoogland, Dean of
the Faculty of Science, who was granted power of representation by the
University's Executive Board, hereinafter referred to as the UNIVERSITY
AND
New Chemical Entities Limited, hereinafter referred to as NCE, formerly ITI,
having its office at Starboard, Longpark, East Portlemouth, Salcombe TQ8 8PA,
England, represented by the Directors Prof. R.K. Rondel and Mr. M. Ilsley
AND
Dr. E.A. Oostveen, one of the inventors of the compounds covered by the patents
hereinafter defined having his residence at Van Broeckhuysenstraat 25, 6721 TC
Bennekom, The Netherlands, hereinafter referred to as the INVENTOR
AND
NeoTherapeutics Inc., having its place of business at 157 Technology Drive,
Irvine, CA 92618, USA, along with its subsidiary NeoOncoRx, Inc., and
hereinafter referred to as the COMPANY,
CONSIDERING
1. That research undertaken in the Department of Organic Chemistry of the
UNIVERSITY during the period 1982-1989 under the responsibility of Prof.
Dr. W.N. Speckamp has resulted in synthesizing a series of compounds
known as Indoloquinones which hereinafter the compounds and products
derived from the compounds are referred to as the COMPOUNDS
2. That the antitumor activity of the COMPOUNDS has been evaluated by cancer
research institutes in Europe and the USA under the auspices of NDDO, and
much of this research was paid for by NDDO
Page 2 of 8
3. That the COMPOUNDS are covered by the following PATENTS filed in the name
of the UNIVERSITY, mentioning Prof. Dr. W.N. Speckamp and Dr. E.A.
Oostveen as inventors and owned by NDDO, UNIVERSITY, NCE, and INVENTOR:
COUNTRY/TERRITORY PATENT NUMBER
----------------- -------------
Australia 615877
Denmark 171079
Europe 0302874
Japan 2120020
U.S.A. 5079257
4. That the development and exploitation of the COMPOUNDS and PATENTS are
subject to agreements between NDDO, UNIVERSITY, NCE and INVENTOR dated
April 9, 1998 / April 21, 1998 / April 29, 1998 / June 10, 1998, which
agreement makes up Exhibit A of this Agreement. This Agreement replaced
the Agreement attached to the letter of "Ekelmans Den Hollander" to the
Technology Transfer Point of the University of Amsterdam, dated June 21,
1990, made by and between the UNIVERSITY, NDDO, and NCE, which replaced
the agreement between the UNIVERSITY and ITI laid down in the letter of
authority dated 29 July 1984/8 August 1984/20 August 1984.
5. As set out in the co-operation agreement between NDDO, UNIVERSITY, NCE
and INVENTOR dated April 9, 1998 / April 21, 1998 / April 29, 1998 / June
10, 1998, NDDO and NCE are exclusively authorized to act on behalf of the
UNIVERSITY and the INVENTOR in matters detailed below. In such matters
NDDO will be representing all parties and NDDO will be the entity to be
notified by COMPANY.
ARE AGREED AS FOLLOWS
6. All information whatsoever known now and after the signing of this
Agreement concerning the COMPOUNDS and their related compounds which are
the subject of PATENTS detailed in the foregoing paragraph 3 shall be
freely exchanged between and used by the UNIVERSITY and the NDDO and the
COMPANY and not released to third parties unless prior agreement has been
given in writing by NDDO to the COMPANY
7. The NDDO and NCE grants the COMPANY the right to a sole and exclusive
License to sell compounds derived from the COMPOUNDS to all markets in
the World, hereinafter called the MARKET
8. The COMPANY shall pay to NDDO the sum of one hundred thousand U.S.
Dollars and transfer ownership of thirty thousand shares of the COMPANY
for an exclusive World-wide License to market the COMPOUNDS and payment
of such sum and transfer of ownership in the shares to be made on signing
this agreement; the COMPANY further undertakes to pay for all subsequent
costs of progressing the PATENTS and developing the COMPOUNDS for sale in
the MARKET
9. The shares in the COMPANY are quoted as NASDAQ:NEOT and may not be sold
until one year has elapsed from the date of signing this contract but if
at one year from the date of signing this contract their value is less
than $100,000 the COMPANY will pay the NDDO such
Page 3 of 8
sum in cash, COMPANY stock, or other negotiable security as will bring
their value up to $100,000
Page 4 of 8
10. Upon filing a New Drug Application in the U.S.A., Australia or Japan or
equivalent application showing proof of efficacy and safety in a major
European market (Germany, United kingdom, France, Italy, Spain) the
COMPANY will pay US $200,000 to NDDO
11. Within one month of the date of approval for marketing the COMPOUND by
the relevant regulatory authorities in the U.S.A., Japan, Australia or
the first European country were the product obtains approval, the COMPANY
will pay NDDO $600,000
12. The COMPANY shall every three months pay to NDDO a Royalty of 5 percent
of the value on net sales, (being the total revenues generated by
NeoTherapeutics or its subsidiaries by the sale of the compounds derived
from the COMPOUNDS, minus taxes, tariffs and shipping) of the COMPOUND in
the MARKET during the proceeding three months and send a copy of the
computation to NDDO and to NCE; annually the COMPANY shall send a
computation of the previous twelve months Sales and Royalties certified
correct by its external Public Accountants. This Article survives the end
of the Agreement as laid down in Article 23.2.
13. NDDO will provide the COMPANY on the date of this contract with a copy of
all data on the COMPOUNDS and will make all clinical supplies and
penultimate drug substances of the COMPOUNDS available to COMPANY. For
the purposes set out below in Articles 14-17, NDDO, UNIVERSITY, NCE and
INVENTOR are allowed to dispose such supplies and substances as well. The
parties are under the obligation to reach an agreement with respect
thereto, before said supplies and substances are made available to
COMPANY.
14. The NDDO and NCE and the COMPANY and their respective Agents shall work
together throughout the development of the COMPOUNDS and thereafter to
facilitate approval by the relevant regulatory authorities in the MARKET
and shall where appropriate negotiate fees to be paid to the UNIVERSITY
or the NDDO or other parties when they undertake inter alia the following
14.1 experimental and clinical trials work to be undertaken during the
continuing development of the compounds
14.2 application and negotiations for clinical trials certificates
14.3 preparation of international registration dossiers
14.4 negotiation of drug registrations
14.5 such other work as shall be agreed between the Parties
15. The COMPANY shall use commercially reasonable efforts in conjunction with
the UNIVERSITY and NDDO to expeditiously undertake development work on
the COMPOUNDS aiming to launch marketable product or products in as many
Countries in the MARKET as soon as is reasonably possible, ensuring that
the names of the INVENTORS are mentioned in all publications and patent
applications based on their work.
16. The COMPANY shall have first right of refusal to license any new
derivatives of the COMPOUNDS including, but not limited to pharmaceutical
compositions, COMPOUND analogues and methods of using same independently
developed by the UNIVERSITY or the NDDO. Moreover, COMPANY shall have the
right to file for patents on any derivatives of the COMPOUNDS including,
but not limited to pharmaceutical preparations, COMPOUND analogous and
methods of using same, that are developed independently by the COMPANY.
However, the COMPANY agrees to grant to the UNIVERSITY and NDDO a royalty
free, paid
Page 5 of 8
up in full, non-exclusive research only license on any COMPOUND related
technology it independently develops and patents. Furthermore, the
COMPANY shall have first right of refusal to license any new derivatives
of the COMPOUNDS including, but not limited to pharmaceutical
compositions, COMPOUND analogues and methods of using same jointly
developed by the COMPANY and the UNIVERSITY and/or the NDDO. The COMPANY
also expressly reserves the right of first refusal to prosecute patents
for any new derivatives of the COMPOUNDS including, but not limited to
pharmaceutical compositions, COMPOUND analogues and methods of using same
independently developed by the UNIVERSITY or the NDDO should they chose
not to, and to prosecute patents on any joint inventions.
17. The UNIVERSITY and the INVENTORS and the NDDO are entitled to publish the
results arising from their work on the COMPOUNDS; A draft copy will be
sent to the COMPANY to identify possible patentable subject matters or
proprietary information. COMPANY may amend the copy or postpone
publication, by means of a written notification to NDDO, UNIVERSITY
and/or INVENTOR, (with a maximum of one year after the date notification)
until all confidential information is deleted from the manuscript and /
or until a patent application, as specified in Article 16, covering the
subject matter disclosed in the submission is filed.
18. This Agreement is entered into in good faith and nothing in the foregoing
implies or is intended to imply that UNIVERSITY or INVENTOR or NDDO or
NCE warrant that COMPOUNDS have or will have ultimate therapeutic utility
in humans or animals. If on the other hand the marketable product derived
from the COMPOUNDS to be sold by COMPANY may cause any damage to humans
or animals, COMPANY shall indemnify UNIVERSITY, INVENTOR, NDDO and NCE
against any liability arising therefrom.
19. The COMPANY and the UNIVERSITY and the INVENTOR and NDDO and NCE shall
each at all times use reasonable efforts to give credit for the work
undertaken by the other Party and uphold the good reputation of the other
Party
20. The COMPANY is responsible for the maintenance of the rights into the
PATENTS by paying the fees due in respect thereof. For that purpose, NDDO
will forward the fee notes concerned to the COMPANY. Copies of such fee
notes shall be returned to NDDO by COMPANY, mentioning SETTLED ON [DATE].
Consequently, the risk of lapse of rights into the PATENTS shall be born
by COMPANY subject to COMPANY having received adequate and timely
pre-notification. UNIVERSITY/NDDO/NCE/INVENTOR shall grant authority to
COMPANY to pursue infringement of the PATENTS, on the basis of which
authority to COMPANY shall vigorously pursue infringements of the
PATENTS. UNIVERSITY/NDDO/NCE/INVENTOR shall grant COMPANY the authority
to file new patent applications with respect to the marketable products
derived from the COMPOUNDS. UNIVERSITY/NDDO/NCE/INVENTOR shall provide
COMPANY with all necessary co-operation with respect to such patent
applications, submitted to the restrictions set out in Article 16.
21. The COMPANY shall, at its own expense, defend and if found guilty, accept
liability for claims by third parties for infringements of patents owned
by third parties and/or, for Product liability
22. COMPANY has the right to sublicense the COMPOUNDS in all MARKETS. The
COMPANY retains the responsibility to ensure that sub-licensee fulfils
the obligations of this Agreement. Except as provided for herein, COMPANY
shall not assign any of its rights or obligations under the terms of this
Agreement, nor shall it grant any sub-licenses with respect to the
Page 6 of 8
COMPOUNDS without prior written approval of UNIVERSITY/NDDO/NCE/INVENTOR,
such written approval will not be unreasonable withheld. NDDO agrees to
respond to such requests within 30 days. However, should such assignment
of rights or obligations of this Agreement, and/or sub-license thereof,
be coincident to the sale of the COMPANY, or should said assignment of
rights or obligations of this Agreement, and/or sub-license thereof be to
a wholly owned subsidiary of the COMPANY, written approval of
UNIVERSITY/NDDO/NCE/INVENTOR shall not be required.
23. Term and Termination
23.1 Unless otherwise terminated under provisions of Article 23.2, this
Agreement and the license granted under Article 7 shall continue
until such time as all Patents have Expired, at which time the
exclusive license rights of the COMPANY set forth in Article 7
shall be deemed to be converted into a fully paid, exclusive,
worldwide, irrevocable, sublicensable license of the COMPOUNDS to
make, have made, use, sell, offer to sell, import and have sold
products incorporating or utilizing, practice methods covered
thereby, and otherwise to commercialize and exploit, the
COMPOUNDS.
Furthermore, in consideration for continued technical support and
know how, COMPANY agrees to pay NDDO a royalty of 2.5% on net
sales as defined in section 12 after the expiration of the last
PATENT covered by this license. However, COMPANY's obligations
under this section and section 12 of this LICENSE AGREEMENT will
cease no later than the earliest of: 1) five (5) years after the
last PATENT expires, or 2) the sale of any generic form of the
COMPOUNDS by a third party after the last PATENT expires.
23.2 The COMPANY may terminate this Agreement, at their option and
without prejudice to any of its other legal and equitable rights
and remedies, by giving the UNIVERSITY/NDDO/NCE/INVENTOR notice
in writing at least three (3) months in advance of the effective
date of such termination.
23.3 Should the COMPANY terminate this Agreement without cause, the
provisions of Articles 6, 9, 12, and 17 shall remain in force
until all obligations under the aforementioned Articles have been
fulfilled.
23.4 Upon termination of this Agreement, each party will within thirty
(30) days return to the other all tangible Confidential
Information and Property of the other party (except one copy which
may be retained by legal counsel solely for evidentiary purposes
in the event of a dispute), and each party will deliver to the
other a copy of any documentation in its possession or control
specifically relating to the Joint Inventions.
24. COMPANY, NDDO, NCE, UNIVERSITY and INVENTOR shall be excused from
performance under this Agreement for any period and to the extent that it
is prevented from performing any Services pursuant to this Agreement, in
whole or in part, as a result of any event of force majeure, including an
act of God, war, civil disturbance, court order, labour disputes, or
other cause beyond its reasonable control, and such non-conformance shall
not be a default hereunder or a ground for termination of this Agreement
as otherwise provided herein.
Page 7 of 8
25. This Agreement (including any Attachments hereto) constitutes the entire
Agreement between COMPANY, NDDO, NCE, UNIVERSITY and INVENTOR and
supersedes all prior oral or written agreements or understandings with
respect to this Agreement. This Agreement may not be waived, amended,
modified or cancelled except by a written instrument executed by one of
the Parties against whom such waiver, amendment, modification or
cancellation is sought to be enforced. This agreement shall be governed
by and construed in accordance with the law of The Netherlands. Any
disputes arising out or in connection with this agreement of the
performance there of shall be submitted to the Amsterdam court, which
shall have exclusive jurisdiction.
Waiver by either Party or the failure by either Party to claim a breach of any
provision of this Agreement or exercise any right or remedy provided by this
Agreement or applicable law, shall not be deemed to constitute a waiver with
respect to any subsequent breach of any provision hereof. The terms and
provisions hereof shall bind and inure to the benefits of PARTIES and their
respective successors and permitted assigns.
UNDERSIGNED
NDDO Research Foundation The University of Amsterdam
/s/R. J. Vles /s/Walter Hoogland
By: R.J. Vles, By: Prof. W. Hoogland
Title: Chairman Title: Dean, Faculty of Science
Date: July 3, 2001 Date: July 6, 2001
New Chemical Entities Limited Inventor
/s/Martin Ilsley /s/ E. A. Ostveen
By: Martin Ilsley By: Dr. E.A. Oostveen, Ph.D.
Title: Director Title: Inventor
Date: July 11, 2001 Date: July 5, 2001
Company
/s/Alvin J. Glasky
By: Dr. A.J. Glasky, Ph.D.
Title: Chairman, Chief Executive Officer & Chief Scientific Officer
Date: July 17, 2001
Page 8 of 8