AMENDMENT TO LICENSE AGREEMENT
------------------------------
This Amendment is by and between Cistron Biotechnology, Inc.
("LICENSEE") and the Massachusetts Institute of Technology, New England
Medical Center Hospitals, Inc., Trustees of Tufts College, Tufts University
School of Medicine, and Wellesley College (collectively, the "LICENSOR") and
shall amend the License Agreement entered into between LICENSEE and LICENSOR,
dated December 2, 1983, as has been amended from time to time (the "License
Agreement").
WHEREAS, the parties desire to amend the License Agreement to clarify
and extend the term of the License Agreement, as appropriate;
WHEREAS, the parties desire to modify the royalty rates applicable to
LICENSED PRODUCTS as set forth herein to enable LICENSEE to better perform
its business to benefit the public;
NOW THEREFORE, LICENSEE and LICENSOR hereby agree as follows:
1. Terms in all capital letters not defined herein shall have the
meanings ascribed to them in the License Agreement.
2. Sections 3.1 and 3.2 of the License Agreement are amended to
amend and restate Schedule "A" in its entirety as set forth in full on ANNEX
I hereto.
3. Section 3.6 of the License Agreement is hereby amended to change
the term "GROSS SALES" to "NET SALES" and any and all references in the
License Agreement to "GROSS SALES" are hereby changed to "NET SALES."
4. A new Section 3.7 is hereby added to read as follows:
"3.7 AFFILIATE shall mean any corporation or other business
entity that directly or indirectly controls, is controlled by, or
is under common control with LICENSEE. Control means direct or
indirect ownership of more than 50% of the voting stock or other
voting interest of a corporation or other business entity."
5. Section 5.1 of the License Agreement is hereby deleted in its
entirety and replaced with the following:
"5.1 LICENSOR hereby grants to LICENSEE an exclusive royalty-
bearing license under the PATENTS and TECHNOLOGY to develop,
make, have made, use, sell, lease, and import LICENSED PRODUCTS
until the expiration or abandonment of all PATENTS, unless
earlier terminated in accordance with the provisions of this
Agreement. Upon expiration of the exclusive license granted
under the PATENTS, the license under the TECHNOLOGY shall be
converted to a perpetual, fully paid-up, non-exclusive worldwide
license to make, to have
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made for it, use, lease and sell LICENSED PRODUCTS subject to the
terms and conditions of this Agreement."
6. Section 6.1 of the License Agreement is hereby deleted in its
entirety and replaced with the following:
"6.1 (a) LICENSEE shall pay LICENSOR fifty percent (50%) of any
royalty received by LICENSEE from any sublicensee listed on Annex
II from the sales of LICENSED PRODUCTS. Commencing August 23,
2005, however, Section 6.1(b) of this Agreement shall govern any
obligation of LICENSEE to pay royalties to LICENSOR with respect
to an exclusive license (an "Aventis License Agreement") in the
form of Exhibit 2 to the Collaboration and Option Agreement dated
October 30, 1998, between LICENSEE and Aventis Pasteur (the
"Option Agreement"), which Aventis License Agreement(s) may be
entered into between LICENSEE and Aventis Pasteur upon exercise
of options granted to Aventis Pasteur under Section 2.2.3 of the
Option Agreement.
(b) Commencing August 23, 2005, the royalty payable by LICENSEE to
LICENSOR shall be twenty-five percent (25%) of any royalty
received by LICENSEE from Aventis Pasteur on the sales of
Products under an Aventis License Agreement. For purposes of
this Section 6.1(b) only, Products (as defined in Exhibit 2 of
the Option Agreement) shall mean any and all vaccines or other
biopharmaceutical products intended for use in the Field of
Preventative Vaccines or the Field of Therapeutic Vaccines (as
those terms are defined in Exhibit 2 of the Option Agreement),
which fall under a valid claim of the patents and patent
applications licensed to LICENSEE as of the date hereof under
the License Agreement dated August 1, 1999, between LICENSEE
and Duke University (the "Duke License Agreement").
(c) With respect to the sale of any LICENSED PRODUCTS not covered
by Section 6.1(a) or (b), LICENSEE shall pay LICENSOR a
royalty payable in any country in respect of LICENSED PRODUCT
sold in that country whilst there are VALID CLAIMS of the
PATENTS in that country and on the following basis:
(i) One and one-half percent (1.5%) of the NET SALES of
LICENSED PRODUCTS by any sublicensee of LICENSED
PRODUCTS; and
(ii) Three percent (3%) of the NET SALES of LICENSED
PRODUCTS by LICENSEE or any AFFILIATE.
(d) VALID CLAIM shall mean either:
(i) a claim of an issued and unexpired patent included
within the PATENTS, which has not been held
permanently revoked, unenforceable or invalid by a
decision of a court or other
3
governmental agency of competent jurisdiction,
unappealable or un-appealed within the time allowed for
appeal, and which has not been admitted to be invalid or
unenforceable through reissue or disclaimer or otherwise;
or
(ii) a claim of a pending patent application included
within the PATENTS which claim was filed and is being
prosecuted in good faith and has not been abandoned
or finally disallowed without the possibility of
appeal or refiling of the application, provided
always that any such patent application or granted
patent resulting from such patent application shall
only be considered as a VALID CLAIM for the purposes
of this Agreement for a maximum period of ten (10)
years from the first commercial sales for any given
LICENSED PRODUCT.
(e) The parties acknowledge that LICENSEE is engaged in
negotiations relating to the merger of LICENSEE with a wholly
owned subsidiary of Celltech Group plc (the "Merger"). Under
the Merger, it is contemplated that the stockholders of
LICENSEE shall be entitled to merger consideration consisting
of base merger consideration payable at the effective time of
the Merger and contingent subsequent merger consideration
payable if and when Aventis Pasteur exercises any option under
Section 2.2.3 of the Option Agreement in an amount equal to
the option payment then received from Aventis Pasteur less any
payment due hereunder and any other non-recoverable expenses,
including any fees then payable to Duke University under the
Duke License Agreement (the balance of an option payment,
after all such deductions other than the payment then due
hereunder, being a "Net Pasteur Option Payment"). Each of the
two option payments under the Option Agreement equals Three
Million Five Hundred Thousand Dollars ($3,500,000.00).
(i) The parties acknowledge and agree that within 60 days
following the initial exercise by Aventis Pasteur of
such option, LICENSEE shall pay to LICENSOR an amount
in cash equal to 1.7% of the Net Pasteur Option
Payment applicable to the option then being exercised.
(ii) The parties acknowledge and agree that within 60 days
following the second and final exercise by Aventis
Pasteur of such option, LICENSEE shall pay to
LICENSOR an amount in cash equal to 1.7% of the Net
Pasteur Option Payment applicable to the option then
being exercised.
7. In connection with the Merger, LICENSOR:
a. Agrees that the License Agreement, as hereby amended, is in
full force and effect in accordance with its terms and has not
been modified either orally or
4
in writing, except pursuant to the terms of any modifications or
amendments described on Annex III hereto;
b. Hereby expressly acknowledges and consents to the Merger
and LICENSOR agrees that the Merger shall not constitute a
default or breach by LICENSEE under the License Agreement;
c. The surviving corporation in the Merger shall enjoy all of
the rights and privileges of the License Agreement, as hereby
amended;
d. Certifies that, to its knowledge, neither LICENSOR nor LICENSEE
is in default or breach under the License Agreement as hereby
amended nor, to the LICENSOR'S knowledge, has any event occurred
which, with the passage of time, the giving of notice, or both,
would constitute a default or breach or an event of default or
breach under the License Agreement as hereby amended; and
e. Warrants that all rights to the PATENTS necessary for the
grant of rights in Section 5 have been obtained from the U.S.
Department of Health and Human Services and/or other funding
entities, and that all duties necessary to secure these rights
from U.S. Department of Health and Human Services and/or other
funding entities have been carried out.
8. Section 14.2 of the License Agreement is hereby amended to read:
"14.2 Any payments of royalties, notices, or other
communications required by this Agreement shall be given by
prepaid, first class, certified mail, return receipt request, or
by private delivery in which a return receipt is requested,
addressed in the case of LICENSOR to:
Director
Technology Licensing Office
Massachusetts Institute of Technology
NE25-230
Five Cambridge Center
Xxxxxxxxx, Xxxxxxxxxxxxx 00000
Fax: 000-000-0000
Telephone: 000-000-0000
and in the case of LICENSEE to:
Cistron Biotechnology, Inc.
P. X. Xxx 0000
Xxxx Xxxxx, Xxx Xxxxxx 00000
or such other address as may be given from time to time under the
terms of this notice provision.
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MIT agrees to keep NEMC, XXXXX and TUSM suitably informed of such
notifications and to distribute royalty payments among the
LICENSOR parties as has been agreed between them."
9. All other terms and conditions of the License Agreement shall
remain in full force and effect. In the event of a conflict between the
terms and conditions contained in this Amendment and the License Agreement,
the terms and conditions of this Amendment shall prevail.
10. This Amendment may be executed in one or more counterparts, all
of which when fully-executed and delivered by all parties hereto and taken
together shall constitute a single agreement, binding against each of the
parties. To the maximum extent permitted by law or by any applicable
governmental authority, this Amendment may be signed and transmitted by
facsimile with the same validity as if it were an ink-signed document. Each
signatory below represents and warrants by his or her signature that he or
she is duly authorized (on behalf of the respective entity for which such
signatory has acted) to execute and deliver this instrument and any other
document related to this transaction, thereby fully binding each such
respective entity.
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IN WITNESS WHEREOF, the parties have caused this Agreement to be
executed by their duly authorized representatives, to be effective as of the
latest date beneath the signatures below.
MASSACHUSETTS INSTITUTE OF NEW ENGLAND MEDICAL CENTER
TECHNOLOGY HOSPITALS, INC.
By: /S/XXXX XXXXXX By: /S/XXXXX XxXXXXX
-------------- ----------------
Name: Xxxx Xxxxxx Name: Xxxxx XxXxxxx
Title: Director, Technology Title: Director,
Licensing Office Technology Transfer
Date: March 21, 2000 Date: March 21, 2000
TRUSTEES OF TUFTS COLLEGE,
TUFTS UNIVERSITY
SCHOOL OF MEDICINE WELLESLEY COLLEGE
By: /S/XXXXXXXX X. XXXXXX By: /S/XXXXXXX X. XXXX
--------------------- -------------------
Name: Xxxxxxxx X. Xxxxxx Name: Xxxxxxx X. Xxxx
Title: Associate Provast Title: Vice President Finace
and Administration
Date: March 21, 2000 Date: March 21, 2000
CISTRON BIOTECHNOLOGY, INC.
By:/S/XXXXXXX X. XXXXXXX
---------------------
Name: Xxxxxxx X. Xxxxxxx
Title: C.E.O.
Date: March 21, 2000
Annex I Restated Schedule A identifying list of Patents
Annex II Existing Agreements between LICENSEE and third parties,
under which LICENSEE has an obligation to pay a portion
of the royalties received thereunder to LICENSOR, as
provided herein
Annex III Schedule of Amendments to License Agreement
7
ANNEX I
-------
Schedule "A" to License Agreement - List of Patents
---------------------------------------------------
(i) U.S. Applications Abandoned:
------------------------------------------------------------------------------------------
Serial No. Patent Descriptive Title Inventor(s) Date Filed
Applicant
------------------------------------------------------------------------------------------
07/880,476 New England Il-1B Antibodies and Proteins Auron et al. 5/6/92
Medical Center
07/302,647 New England An Arg-Serpin Human Plasminogen Auron et al. 1/26/89
Medical Center Activator Inhibitor Designated
XXX-0
00/000,000 Xxx Xxxxxxx Xx-0 Biological Inhibitors Xxxxxx et al. 5/19/92
Xxxxxxx Xxxxxx
00/000,000 Xxx Xxxxxxx Xx-0 Muteins: Their Preparation Xxxxxx et al. 7/28/92
Medical Center and Method of Use to Inhibit
Il-1 Activity
(ii) U.S. Applications in Prosecution Before U.S. Patent Office Examiner:
------------------------------------------------------------------------------------------
Serial No. Patent Descriptive Title Inventor(s) Date Filed
Applicant
------------------------------------------------------------------------------------------
09/410,790 New England Recombinant DNA Which Codes Auron et al. 10/1/99
Medical Center for Interleukin-1
Together with all divisionals, continuations, continuations in part,
reissues, extensions and foreign counterpart of the U.S. applications
listed in (i) and (ii) above, including but not limited to:
(iii) U.S. Patents Issued:
-------------------------------------------------------------------------------------------
Patent No. Holder of Title Inventor(s) Date Issued
Patent
-------------------------------------------------------------------------------------------
4,766,069 New England Recombinant DNA Which Codes Auron et al. 8/23/88
Medical Center for Interleukin-1
5,510,462 Xxx Xxxxxxx XX-0 Protein Precursor Auron et al. 4/23/96
Medical Center [as amended]
5,681,933 New England IL-1 Antibodies and Proteins Auron et al. 10/28/97
Medical Center
8
5,985,657 New England Recombinant DNA Which Codes Auron et al. 11/16/99
Medical Center for Interleukin-1
5,998,578 New England Biologically Active Fragments Auron et al. 12/7/99
Medical Center of IL-1 [as amended]
-------------------------------------------------------------------------------------------
Patent No. Holder of Title Inventor(s) Date Issued
Patent
-------------------------------------------------------------------------------------------
4,762,914 New England Human IL-1 cDNA Sequences Auron et al. 8/9/88
Medical Center Encoding Biologically Active
Human IL-1 Proteins
5,001,057 New England Truncated Human IL-1 cDNA Auron et al. 3/19/91
Medical Center Sequences Encoding Biologically
Active Human IL-1 Proteins
5,077,219 New England Truncated Human IL-1 cDNA Auron et al. 12/31/91
Medical Center Sequences Encoding Biologically
Active Human IL-1 Proteins
4,923,807 New England An Arg-Serpin Human Plasminogen Xxxx et al. 5/8/90
Medical Center Activator Inhibitor Designated
PAI-2
5,286,847 Xxx Xxxxxxx XX-0 Biological Xxxxxx et al. 2/15/94
Medical Center Inhibitors (muteins of IL-1)
(iv) Patent Applications in Prosecution Before Foreign Patent Office Examiners:
----------------------------------------------------------------------------------------------
Serial No./ Patent
Publ. No. Applicant Country Descriptive Title Inventor(s) Date Filed/
Date Published
----------------------------------------------------------------------------------------------
Serial No./ Holder of
Publ. No. Patent Country Descriptive Title Inventor(s) Date Filed/
Date Published
----------------------------------------------------------------------------------------------
93104177.6 New England EPO Human IL-1 cDNA Auron et al. 3/15/93
0569687 Medical Sequences Encoding
Center Biologically-Active
Human IL-1 Proteins
556,827 New England Canada An Arg-Serpin Human Xxxx et al. 1/19/88
Medical Plasminogen Activator
Center Inhibitor Designated
PAI-2
2,046,303 New England Canada IL-1 Biological Xxxxxx et al. 2/23/90
Medical Inhibitors (muteins of
Center IL-1)
9
(v) Foreign Patents Issued:
----------------------------------------------------------------------------------------------
Patent No. Holder of Issue or
Patent Country Title Inventor(s) Grant Date
----------------------------------------------------------------------------------------------
Serial No./ Holder of
Publ. No. Patent Country Descriptive Title Inventor(s) Date Filed/
Date Published
----------------------------------------------------------------------------------------------
BE0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Belgium Encoding Biologically-
Center Active Human IL-1 Proteins
FR0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical France Encoding Biologically-
Center Active Human IL-1 Proteins
P3587669.7 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Germany Encoding Biologically-
Center Active Human IL-1 Proteins
------------------------------------------------------------------------------------------
Patent No. Holder of Issue or
Patent Country Title Inventor(s) Grant Date
------------------------------------------------------------------------------------------
GB0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Great Encoding Biologically-
Center Britian Active Human IL-1 Proteins
IT0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Italy Encoding Biologically-
Center Active Human IL-1 Proteins
NL0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Nether- Encoding Biologically-
Center lands Active Human IL-1 Proteins
XX0000000 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Sweden Encoding Biologically-
Center Active Human IL-1 Proteins
10
P0161901 New England EPO Human IL-1 cDNA Sequences Auron et al. 12/1/93
Medical Xxxxxxx- Encoding Biologically-
Center land Active Human IL-1 Proteins
2650026 New England Japan Human IL-1 cDNA Sequences Auron et al. 5/16/97
Medical Encoding Biologically-
Center Active Human IL-1 Proteins
2805008 New England Sweden Human IL-1 cDNA Sequences Auron et al. 7/24/98
Medical Encoding Biologically-
Center Active Human IL-1 Proteins
AT 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Austria (muteins of IL-1)
Center
------------------------------------------------------------------------------------------
Patent No. Holder of Issue or
Patent Country Title Inventor(s) Grant Date
------------------------------------------------------------------------------------------
BE 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Belgium (muteins of IL-1)
Center
DK 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Denmark (muteins of IL-1)
Center
FR0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical France (muteins of IL-1)
Center
69032251.8 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Germany (muteins of IL-1)
Center
11
GB 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Great (muteins of IL-1)
Center Britian
IT 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Italy (muteins of IL-1)
Center
LU 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Xxxxx- (muteins of IL-1)
Xxxxxx xxxxx
XX 0000000 Xxx Xxxxxxx XXX XX-0 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Nether- (muteins of IL-1)
Center lands
ES 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Spain (muteins of IL-1)
Center
------------------------------------------------------------------------------------------
Patent No. Holder of Issue or
Patent Country Title Inventor(s) Grant Date
------------------------------------------------------------------------------------------
SE 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Sweden (muteins of IL-1)
Center
P 0460052 New England EPO IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical Xxxxxxx- (muteins of IL-1)
Center land
2122040 New England Japan IL-1 Biological Inhibtors Xxxxxx et al. 5/15/98
Medical (muteins of IL-1)
12
ANNEX II
--------
Existing Agreements between LICENSEE and third parties,
under which LICENSEE has an obligation to pay a portion of the royalties
received thereunder to LICENSOR, as provided herein
1. Settlement Agreement, dated May 17, 1993, between LICENSEE, Biotech
Australia Pty. Limited and the Institutions, named therein
2. Domestic Patent License Agreement dated February 26, 1997, between
LICENSEE and PeproTech, Inc.
3. International Patent License Agreement dated February 26, 1997, between
LICENSEE and PeproTech, Inc.
4. Exclusive License Agreement(s) in the form of Exhibit 2 to
Collaboration and Option Agreement dated as of October 30, 1998,
between LICENSEE and Pasteur Merieux Serums & Vaccins, S.A., any such
license agreement being entered into upon exercise of an option under
Section 2.2.3 of such Collaboration and Option Agreement.
5. License Agreement, dated February 16, 1999, between LICENSEE and R&D
Systems, Inc.
13
ANNEX III
---------
Schedule of Amendments to License Agreement
-------------------------------------------
Sponsored Research Agreement October 1, 1983
December 2, 1983
Amendment to Sponsored Research Agreement July 9, 1986
and License Agreement
Amendment to Sponsored Research Agreement February 19, 1987
and License Agreement
Amendment to License Agreement May 1992
