Exhibit 10.23
CERTAIN PORTIONS OF THIS EXHIBIT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT. THE OMITTED MATERIALS ARE INDICATED BY "[ **** ]" AND
HAVE BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.
AMENDMENT NO. 5
TO
License Agreement
AMENDMENT NO. 5 TO LICENSE AGREEMENT (this "AMENDMENT NO. 5") is made
this 3rd day of March, 2003, by and between YALE UNIVERSITY, a corporation
organized and existing under and by virtue of a charter granted by the general
assembly of the Colony and State of Connecticut and located in New Haven,
Connecticut ("YALE"), and VION PHARMACEUTICALS, INC. (f/k/a OncoRx Inc.), a
corporation organized and existing under the laws of the State of Delaware and
with principal offices located in New Haven, Connecticut ("LICENSEE").
W I T N E S S E T H:
WHEREAS, YALE and LICENSEE are parties to a license agreement dated
August 31, 1994 (the "ORIGINAL LICENSE AGREEMENT"), under which YALE exclusively
licensed to LICENSEE a series of YALE owned Inventions relating to potential
anti-tumor and antiviral compounds;
WHEREAS, YALE and LICENSEE amended the Original License Agreement
pursuant to an Agreement dated November 15, 1995 to make an additional patent
and patent application subject to the Original License Agreement and provide the
terms of compensation to YALE therefor;
WHEREAS, YALE and LICENSEE again amended the ORIGINAL LICENSE
AGREEMENT, as amended, pursuant to Amendment No. 1 to License Agreement, dated
as of June 12, 1997, to reduce the earned royalties payable on SUBLICENSE INCOME
and Amendment No. 2 to License Agreement, dated as of June 12, 1997, to reduce
the earned royalties payable on SUBLICENSE INCOME, and to make certain other
changes to the Original License Agreement;
WHEREAS, YALE and LICENSEE again amended the ORIGINAL LICENSE
AGREEMENT, as amended, pursuant to Amendment No. 3 to License Agreement, dated
as of September 25, 1998 ("AMENDMENT NO. 3"), to modify and clarify the patents
and technology covered by the ORIGINAL LICENSE AGREEMENT and to add certain
additional terms with respect to the antiviral compound (beta)-L-FD4C;
WHEREAS, YALE and LICENSEE again amended the ORIGINAL LICENSE
AGREEMENT, as amended, pursuant to Amendment No. 4 to License Agreement, dated
as of January 31, 2000 ("AMENDMENT NO. 4"), to provide for an exclusive
sublicense to Achillion Pharmaceuticals, Inc. of LICENSEE's rights in Inventions
relating to (beta)-L-FD4C; and
WHEREAS, YALE and LICENSEE desire to further amend the ORIGINAL LICENSE
AGREEMENT, as amended.
NOW, THEREFORE, in consideration of the premises and of the mutual
covenants herein contained and for other good and valuable consideration, the
receipt and sufficiency of which is hereby acknowledged, YALE and LICENSEE
hereby agree as follows:
1. Exhibit B of the ORIGINAL LICENSE AGREEMENT, as subsequently amended
(as so amended, the "LICENSE AGREEMENT"), shall be deleted and replaced in its
entirety with the Attachment I hereto.
2. Exhibit C of the LICENSE AGREEMENT shall be deleted and replaced in
its entirety with the Attachment II hereto.
3. Exhibit D of the LICENSE AGREEMENT shall be deleted.
4. Exhibit E of the LICENSE AGREEMENT (see AMENDMENT NO. 3) shall be
deleted and replaced in its entirety with the Attachment III hereto.
5. The defined term "RESEARCH" used in the LICENSE AGREEMENT shall be
replaced in all places it appears by the undefined term "research".
6. LICENSEE shall have a worldwide non-exclusive license to the
INVENTIONS set forth in Exhibit E.
7. The definition of "INVENTIONS" in Section 1.1 of the LICENSE
AGREEMENT shall be deleted and replaced with the following new Section 1.1:
1.1 "INVENTIONS" shall mean each of the patent and patent
applications described in Exhibit B, Exhibit C and Exhibit E
attached hereto.
8. The definition of "LICENSED PRODUCTS" in Section 1.3 of the LICENSE
AGREEMENT shall be deleted and replaced with the following new Section 1.3:
1.3 "LICENSED PRODUCTS" shall mean all products for research,
therapeutic or diagnostic uses that may derive from or which result
from the manufacture and production or use of a claim of the
LICENSED PATENTS, wherever used or sold.
9. A new Section 2.1.1 shall be added to the LICENSE AGREEMENT and it
shall read as follows:
2
2.1.1 YALE hereby grants to LICENSEE, subject to all of the terms
and conditions of this Agreement, a non-transferable, non-exclusive
worldwide license for the term defined by ARTICLE III to make, have
made, use, sell and practice the INVENTIONS as described in Exhibit
E.
10. A new Section 4.5 shall be added to the LICENSE AGREEMENT and it
shall read as follows:
4.5 LICENSEE shall pay to YALE (A) a one time payment of [ **** ]
upon [ **** ] or [ **** ] and (B) a one time payment of [ **** ]
upon [ **** ] or [ **** ] for its first product related to any of
the following U.S. PATENTS: 4,648,747; 4,892,887; 5,101,072;
5,214,068; 5,256,820; 5,637,619; and 6,040,338, as well as any
continuations, divisionals, continuations-in-part, reissue,
reexaminations or extensions thereof or substitutes therefor of any
of these U.S. PATENTS and any international equivalents of the
foregoing. For purposes of clarity, the aggregate amount of
potential payment by LICENSEE shall be [ **** ] under this
provision. This payment is apart from any other consideration which
may be due under this agreement.
11. Section 7.1 of the LICENSE AGREEMENT shall be deleted in its
entirety and shall be replaced with the following:
7.1 Each of Exhibits B, C and E describes patent protection in the
United States and, if applicable, any foreign country for INVENTIONS
listed thereon.
12. Exhibit 1 of the LICENSE AGREEMENT (see AMENDMENT NO. 4) shall be
deleted and replace in its entirety with the Attachment IV hereto.
13. LICENSEE agrees not to enforce, assert or bring, and to secure a
like agreement from all of its licensees, sublicensees and transferees not to
enforce, assert or bring, any claim, right or action, whether at law or in
equity, based on U.S. Patent Nos. 5,637,619 or 6,040,338 (and any continuations,
divisionals, continuations-in-part, reissues, reexaminations or extensions
thereof or substitutes therefor, and the international equivalents of the
foregoing) (the "'619" and "'338" patents, respectively) against YALE's
licensees or sublicensees, to block any such person from exercising rights with
respect to patents or other technology licensed from YALE, provided that such
person's exercise of such rights does not result in an end-product that is a
compound, or a pro-drug that is metabolized to produce a compound, covered by
a claim of the `619 or `338 patent.
14. Where an individual licensed product or its use is covered by more
than one patent or patent application as set forth in the accompanying exhibits,
LICENSEE shall be responsible for paying royalties under one patent or patent
application only. In the event that there are different royalty rates for the
applicable patents, LICENSEE shall pay the higher rate.
15. Section (11.1(iv)) of the LICENSE AGREEMENT shall be amended by
replacing ninety (90) days with sixty (60) days in line 3.
3
16. Except as expressly amended hereby, the LICENSE AGREEMENT remains
unchanged and in full force and effect.
17. LICENSEE hereby agrees to transfer all Promycin assets listed on
Exhibit F to YALE.
18. Any reference to the LICENSE AGREEMENT contained in any notice,
request, certificate, or other document executed concurrently with or after the
execution and delivery of this AMENDMENT NO. 5 shall be deemed to include this
AMENDMENT NO. 5 unless the context shall otherwise require.
* * *
4
IN WITNESS WHEREOF, the parties hereto have caused this Amendment No. 5
to be executed and delivered in duplicate originals by their duly authorized
representatives.
YALE UNIVERSITY VION PHARMACEUTICALS, INC.
By: /s/ ▇▇▇ ▇▇▇▇▇▇▇▇▇▇ By: /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
---------------------------------- ---------------------
Name: ▇▇▇ ▇▇▇▇▇▇▇▇▇▇ Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇▇
-------------------------------- -------------------
Title: Managing Director/Office Cooperative Research Title: CFO
---------------------------------------------- ------------------
ATTACHMENT I
TO
AMENDMENT NO. 5
TO
LICENSE AGREEMENT
EXHIBIT B
PATENT LISTING
U.S. Patent No. 5,101,072, Issued 3/3/1992
Sulfonylhydrazines and Their Use as Antineoplastic Agents and as
Antitrypanosomal agents
All international patents and patent applications, if any, related to 5,101,072
U.S. Patent No. 5,214,068, Issued 5/25/1993
Sulfonylhydrazines and Their Use as Antineoplastic Agents and as
Antitrypanosomal Agents
All international patents and patent applications , if any, related to 5,214,068
U.S. Patent No. 5,256,820, Issued 10/26/1993
1-Alkyl-2-Acyl-1, 2-Disulfonylhydrazines
All international patents and patent applications , if any, related to 5,256,820
U.S. Patent No. 5,281,715, Issued January 25, 1994
2-formylpyridine thiosemicarbazone compounds
All international patents and patent applications , if any, related to 5,281,715
U.S. Patent No. 5,721,259, Issued February 24, 1998,
Method of Using 2-formylpyridine thiosemicarbazone compounds
All international patents and patent applications, if any, related to 5,721,259
U.S. Patent No. 5,637,619, Issued 6/10/1997
Antitumor 2-Aminocarbonyl-1, 2-bis (methylsulfonyl)-1-(substituted) Hydrazines
International Publication Number WO 97/02029
Antitumor 2-Aminocarbonyl-1, 2-bis (methylsulfonyl)-1-(substituted) Hydrazines
All other international patents and patent applications, if any, related to
5,637,619
Yale's interest in the following Patents and patent applications:
U.S. Patent No. 6,040,338 issued March 21, 2000
N,N-Bis(Sulfonyl)Hydrazines Useful as Antineoplastic Agents
All international patents and patent applications, if any, related to 6,040,338
U.S. Patent Application Serial No. [****]
[****]
All international patents and patent applications, if any, related to [****]
2
ATTACHMENT II
TO
AMENDMENT NO. 5
TO
LICENSE AGREEMENT
EXHIBIT C
PATENT LISTING
U.S. Patent Application Serial Number [****]
[****]
U.S. Patent Application Serial Number [****]
[****]
U.S. Patent Application Serial Number [****]
[****]
U.S. Patent Application Serial Number [****]
[****]
All international patents and patent applications, if any, related to [****]
3
ATTACHMENT III
TO
AMENDMENT NO. 5
TO
LICENSE AGREEMENT
EXHIBIT E
PATENT LISTING
U.S. Patent Number 4,684,747, Issued 8/4/1997
N,N'-Bis (Sulfonyl) Hydrazines Having Antineoplastic Activity
All international patents and patent applications , if any, related to 4,684,747
U.S. Patent Number 4,892,887, Issued 1/9/1990
N,N'-Bis (Sulfonyl) Hydrazines Having Antineoplastic Activity
All international patents and patent applications , if any, related to 4,892,887
4
ATTACHMENT III
TO
AMENDMENT NO. 5
TO
LICENSE AGREEMENT
EXHIBIT F
PROMYCIN ASSETS
Subject to Vion's agreements with Boehringer Ingelheim International, the
following Promycin assets are available for transfer:
Clinical bioanalytical data for Promycin generated by Vion to which Vion
has rights
Preclinical formulation, manufacturing information, or know-how related to
proprietary formulations or manufacturing processes to which Vion has
rights
IND or equivalent regulatory approvals to which Vion has rights
Orphan drug status applied for and received
Bulk pharmaceutical manufacturing process
Stability data for bulk
Analytical methods for bulk
Characterization data package for bulk substance
Finished product manufacturing process
Stability data for finished drug product
Analytical methods for finished drug product
Characterization data package for finished drug product
Animal pharmacokinetic data
In vitro and in vivo metabolism data
Animal toxicological data
IND for U.S. regulatory submission
5
Clinical trial application (CTX) with Medicines Control Agency (MCA) in
United Kingdom
Data on Phase I/II trial
Clinical investigator's brochure
Phase III global clinical protocol using Porfiromycin as an adjuvant for
radiation
List of 40 centers involved with Phase 3 trial in the U.S. and Europe
Copy of Orphan Drug Designation by the FDA for Promycin for treatment of
head and neck cancer
Copy of Orphan Drug Designation by the FDA for Promycin for treatment of
cervical cancer
6
ATTACHMENT IV
TO
AMENDMENT NO. 5
TO
LICENSE AGREEMENT
EXHIBIT 1
SUBLICENSED PATENTS
1. U.S. Patent Application Serial Number [****], entitled [****]
2. US Patent Application Serial Number [****] entitled [****]
7