Exhibit 10.5
A G R E E M E N T
THIS AGREEMENT (hereinafter "Agreement"), made effective as of the 10th
day of February, 1993, by and between ENDOGEN, INC., a corporation organized and
existing under the laws of Massachusetts, and having its principal office at 000
X Xxxxxx, Xxxxxx, Xxxxxxxxxxxxx 00000 (hereinafter called "LICENSEE"), and
SCHERING CORPORATION, a corporation organized and existing under the laws of the
State of New Jersey and having its principal office at 0000 Xxxxxxxxx Xxxx Xxxx,
Xxxxxxxxxx, XX 07033(hereinafter called "SCHERING").
W I T N E S S E T H:
WHEREAS, SCHERING has developed and owns certain Patent Rights and/or
Know-How (as the foregoing are hereinafter defined) relating, inter alia, to
certain monoclonal antibodies; and
WHEREAS, LICENSEE desires to receive, and SCHERING is willing to grant,
a non-exclusive license under the Patent Rights and to use Know-How to make, use
and sell Licensed Products in the Field of the Agreement in the Licensed
Territory (as the foregoing terms are hereinafter defined);
NOW, THEREFORE, in consideration of the premises and the mutual
covenants and conditions hereinafter set forth, the parties agree as follows:
1.0 DEFINITIONS
1.1 As used herein the following terms shall have the following
meanings and the singular shall include the plural and vice versa:
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1.1.1 the term "Cell Lines" means the cell lines described in
Exhibit I attached hereto and made a part hereof as such Exhibit may be amended
from time-to-time hereafter by mutual written agreement of the parties.
1.1.2 the term "Monoclonal Antibodies" means the monoclonal
antibodies and their derivatives produced by the Cell Lines described in Exhibit
I as such Exhibit may be amended from time-to-time hereafter by mutual written
agreement of the parties.
1.1.3 the term "Licensed Products" means products containing
Monoclonal Antibodies defined above and promoted and labelled for use as
laboratory reagents.
1.1.4 the term "Field of the Agreement" means the use of the
Licensed Products only for scientific research purposes and excludes any use
whatsoever with respect to human beings including, without limitation, the use,
prevention, diagnosis, treatment or cure of injury or disease.
1.1.5 the term "Licensed Territory" means worldwide.
1.1.6 the term "Affiliate" means any company controlling,
controlled by, or under common control with SCHERING or LICENSEE, as the case
may be. For this purpose the term "control" means ownership, directly or
indirectly, of at least fifty percent (50%) of the equity capital or a right to
at least fifty percent (50%) of the profits.
1.1.7 the term "Know-How" means all of the Cell Lines and
methods employed to produce and isolate monoclonal antibody product from these
cell lines including in vitro and in vivo cell culture.
1.1.8 the term "Net Sales" means the amounts billed or
invoiced to independent, third-party customers by LICENSEE and its Affiliates
for Licensed Products less (a) quantity and/or cash discounts and rebates
actually allowed and taken; (b) freight, postage, duties,
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insurance and taxes directly related to the sale; and (c) amounts repaid or
credited by reason of rejections or returns of goods or because of retroactive
price reductions. Licensed Products shall be considered sold as of the date of
the earliest to occur of shipment, delivery, billing or payment. The value of
any Licensed Products used by LICENSEE or its Affiliates, calculated as if sold
to a third party under an arm's-length transaction, shall be deemed to be
included in Net Sales.
1.1.9 the term "Patent Rights" means the United States issued
patents and United States patent applications filed by or on behalf of, or
assigned to SCHERING, as set forth in Exhibit II attached hereto and made a part
hereof, and all additions, divisions, extensions, reissues, substitutions,
registrations, revalidations, importations, renewals, confirmations,
continuations, continuations-in-part and the like of any of the foregoing as
well as any foreign counterparts of any of the foregoing. Exhibit II may be
amended from time-to-time hereafter to add additional patents by mutual written
agreement of the parties.
1.1.10 the term "Earned Royalty" means an amount equal to five
percent (5%) of the Net Sales of Licensed Products by LICENSEE and its
Affiliates in the Licensed Territory where the manufacture, use or sale of such
Licensed Products would, but for the licenses granted herein, infringe at least
one claim in a pending patent application or issued patent included in the
Patent Rights and/or utilize any Know-How. While the parties recognize that
Patent Rights and Know-How may have different royalty value, they have agreed to
blend the royalty rates as set forth herein for their convenience.
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2.0 LICENSE GRANT AND FEE
2.1 SCHERING hereby grants to LICENSEE, including its Affiliates, and
LICENSEE hereby accepts from SCHERING, a non-exclusive, non-transferable,
royalty bearing license, with no right to sublicense third parties, under the
Patent Rights and to use the Know-How to make, use and sell Licensed Products
solely for use in the Field of the Agreement in the Licensed Territory. During
the term of this Agreement, LICENSEE agrees and covenants not to sell to any
purchaser Licensed Products containing more than ten (10) miligrams in the
aggregate of any Monoclonal Antibodies during any consecutive six (6) month
period for use by such purchaser. LICENSEE also agrees and covenants not to
knowingly sell Licensed Products to a purchaser who does not itself intend to
use the Licensed Products solely in its own research. SCHERING may, at its
option, and in the exercise of its sole discretion, provide support to LICENSEE
through an affiliated company as set forth in items 5 through 8 of Exhibit III
attached hereto and made a part hereof.
2.2 In partial consideration of the rights and licenses granted herein,
LICENSEE shall pay to SCHERING upon execution of this Agreement, a license fee
of five thousand dollars ($5,000) for each Cell Line to be provided by SCHERING
hereunder, and SCHERING shall promptly thereafter supply customary and
reasonable quantities of such Cell Line(s) to LICENSEE as further described in
Section 7.
2.3 LICENSEE agrees to maintain the Know-How described in (b) of
Section 1.1.7 in confidence and not to disclose any of it to any third parties
during and after the term of this Agreement, except as agreed otherwise by a
duly authorized SCHERING representative in writing.
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3.0 PRODUCT DEVELOPMENT; PATENTS
3.1 LICENSEE shall, at its own cost and expense, diligently perform,
consistent with sound scientific principles, all research and development
activities necessary or appropriate to make, use and sell Licensed Products in
the Licensed Territory, complying with any applicable regulatory and other
applicable legal requirements in each country of the Licensed Territory.
3.2 SCHERING will or will cause its Affiliate(s) to, in its sole
discretion, at its or their own cost and expense, prosecute, maintain and defend
the Patent Rights.
4.0 ROYALTIES
4.1 Within sixty (60) days following the close of each calendar quarter
during the term of this Agreement, LICENSEE shall furnish and deliver to
SCHERING a full and true accounting of its and its Affiliates' Net Sales of
Licensed Products hereunder during such calendar quarter and shall
simultaneously pay to SCHERING a sum equal to the aggregate of the Earned
Royalty due thereon.
4.2 All royalties payable hereunder shall be paid in United States
dollars. If amounts are invoiced in other than U.S. dollars, Net Sales based on
such amounts shall be converted to U.S. dollars in accordance with U.S.
Generally Accepted Accounting Principles at the closing rates of exchange for
buying U.S. dollars, as correctly published in the Wall Street Journal on the
last business day of the calendar quarter for which royalties are being
calculated.
4.3 No Earned Royalty shall be payable in respect of sales among
LICENSEE and its Affiliates, it being understood that royalties are to be paid
on resale of Licensed Products to independent third parties in bona fide,
arms-length transactions; provided, however, in addition to the Earned Royalty
due on Net Sales to third parties, LICENSEE shall pay Earned Royalty on all
Licensed Products used by LICENSEE or its Affiliates in their own research.
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4.4 If LICENSEE shall hereafter be required, in respect of its sales of
any Licensed Product in a country, to pay royalties to any third party whose
patent is infringed by such sales in such country solely because of the use of a
Cell Line, LICENSEE may credit such third party royalties against any Earned
Royalty due SCHERING hereunder in the country, but in no event shall Earned
Royalty due SCHERING for any calendar quarter be thereby reduced to less than
seventy five percent (75%) of the Earned Royalty which otherwise would have been
due to SCHERING for such calendar quarter for Net Sales in such country.
4.5 SCHERING shall have the right, by an independent public accountant
reasonably acceptable to LICENSEE and employed by SCHERING and at SCHERING's own
expense, to examine, during normal business hours and not more than once each
calendar year, the pertinent books and records of LICENSEE, including without
limitation customer sales records of LICENSEE and its Affiliates, for the
purpose of determining the correctness of royalty payments made hereunder and
the compliance by LICENSEE with the quantity sales limitations for Licensed
Products described in Section 2.1, it being understood that such examination
with respect to any calendar quarter hereunder shall take place not later than
three (3) years following the expiration of said period.
4.6 LICENSEE may deduct from Earned Royalties payable to SCHERING
hereunder taxes required to be withheld by any government which are recoverable
by SCHERING in the United States under any tax convention treaty, or regulation.
LICENSEE shall promptly furnish SCHERING with true copies of all official tax
receipts covering such taxes.
5.0 INDEMNITY
5.1 LICENSEE shall indemnify and hold SCHERING harmless from and
against any and all claims, suits, liability, damage, loss, costs or expenses
(including reasonable attorney's
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fees) which result from or arise out of the testing, manufacture, storage,
distribution, use or sale of Licensed Products by LICENSEE or its Affiliates or
any of their respective customers or clients, except for any claims, liability,
damage, loss, cost or expense caused solely by SCHERING's gross negligence or
willful misconduct in connection with its supply of Cell Lines to LICENSEE. Upon
learning of the filing of any such claim or suit, SCHERING shall immediately
notify LICENSEE thereof.
6.0 TERM AND TERMINATION
6.1 Either party hereto may, at its option, cancel the licenses herein
granted to LICENSEE and terminate this Agreement by giving the other party prior
notice in writing to that effect of not less than sixty (60) days in the event
such other party shall materially breach this Agreement and shall fail to cure
such breach during the period of said notice; provided, however, that any such
cancellation and termination shall not release such other party from any
obligations hereunder incurred prior thereto. Without limitation, failure to
comply with the quantity sales restrictions in Section 2.1 shall be deemed a
material breach.
6.2 (a) If LICENSEE shall become insolvent or shall make an assignment
for the benefit of its creditors, or proceedings in voluntary or involuntary
bankruptcy shall be instituted on behalf of or against LICENSEE, or a receiver
or trustee of LICENSEE's property shall be appointed, the licenses herein
granted to LICENSEE shall, without other action or notice, forthwith terminate.
(b) In the event that SCHERING shall reasonably believe, whether as
a result of toxicity, clinical or other studies, or otherwise, that a
substantial question has arisen as to the safety of a Licensed Product, it may,
by written notice to LICENSEE:
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(i) suspend the licenses herein granted for an indefinite
period with respect to such Licensed Product(s). During any such
period of suspension, LICENSEE shall suspend any and all
activities, including testing and sales, related to the Licensed
Product(s), except as otherwise specifically agreed to in writing
with SCHERING; or
(ii) terminate the licenses herein granted to LICENSEE with
respect to the Licensed Product(s), effective immediately, with no
compensation therefore to LICENSEE.
6.3 LICENSEE may surrender the licenses herein granted to it and
terminate this Agreement by giving to SCHERING prior written notice to that
effect of not less than ninety (90) days. In the event of any such termination,
LICENSEE shall promptly deliver to SCHERING all Cell Lines and their progeny
then in its possession, and all inventory containing Monoclonal Antibodies not
yet formatted into Licensed Product.
6.4 Upon any cancellation or termination of this Agreement for any
reason, all Earned Royalty on Net Sales to the effective date of said
cancellation or termination shall accrue and become due and payable on the
sixtieth (60) day thereafter.
6.5 In the event of the cancellation or termination of this Agreement
prior to the expiration thereof, other than as a result of a substantial safety
question having arisen with respect to Licensed Product(s), LICENSEE shall be
permitted to sell its then inventory of Licensed Products for a period of six
(6) months, on condition that LICENSEE pay to SCHERING Earned Royalty thereon
and comply with the other Agreement terms.
6.6 Unless sooner cancelled or terminated under the provisions hereof,
this Agreement shall continue in effect in each country in the Licensed
Territory for the longer period of (a) ten (10) years from the effective date or
(b) The last to expire of the Patent Rights in such country. At the expiration
of such term LICENSEE shall have a paid up license hereunder with respect to
such country.
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6.7 Upon any termination of this Agreement by SCHERING pursuant to
Section 6.1 or 6.2, LICENSEE and/or its Affiliates shall promptly deliver and
account to SCHERING for all SCHERING Cell Lines and progeny in its possession or
control.
7.0 SUPPLY OF CELL LINES AND DISCLAIMER OF WARRANTIES
7.1 SCHERING agrees to promptly provide to LICENSEE reasonable and
customary quantities of the Cell Lines (two (2) vials each of frozen hybridoma
cell stock containing approximately 5 x 10(6) cells) within thirty (30) days of
the effective date of this Agreement, provided LICENSEE has remitted to SCHERING
the applicable license fee(s) described in Section 2.2. At the request of
LICENSEE, SCHERING will provide LICENSEE reasonable additional quantities of the
Cell Line(s) in the future one (1) time without cost, if LICENSEE reasonably
documents legitimate reasons for its request. The foregoing shall at all times
remain the property of SCHERING. LICENSEE agrees:
(a) to use such Cell Lines solely and exclusively as expressly
permitted in this Agreement; and
(b) to maintain the quality of the Cell Lines, keep them safe
and secure from all loss or damage, and not to transfer them to any
third party, other than an Affiliate, or as allowed under the express
terms of this Agreement, without the express written consent of
SCHERING;
(c) at SCHERING'S option, to destroy such Cell Lines or return
them to SCHERING at the termination or expiration of this Agreement;
and
(d) to allow access to SCHERING'S representatives at all
reasonable times to monitor compliance with this paragraph 7.1.
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7.2 SCHERING makes no express or implied representations or warranties
as to any of the subject matter of this Agreement, including without limitation,
materials supplied by it hereunder or the Know-How and Patent Rights licensed
hereunder and disclaims any liability, to the maximum extent permitted by law,
arising out of LICENSEE'S or its customers' use of Licensed Products.
8.0 MISCELLANEOUS
8.1 Choice of Law. This Agreement shall be construed and the legal
relations between the parties hereto determined in accordance with the laws of
the State of New Jersey, U.S.A., without giving any regard to its conflicts of
law provisions.
8.2 Nonassignability. This Agreement and the license granted herein
shall not be assignable by LICENSEE without consent in writing first having been
obtained from SCHERING.
8.3 Modification. This Agreement constitutes the entire understanding
between the parties hereto with respect to the subject matter hereof, and no
modification or amendment shall be valid or binding upon the parties hereto
unless made in writing and duly executed on behalf of each of the parties
hereto.
8.4 Notice. Any notice or other communication required or permitted to
be given to the other party hereto pursuant to this Agreement shall be
sufficiently given if sent to such party by certified or registered mail, return
receipt postage prepaid, addressed to the care of the Vice-President, Business
Development Schering-Plough Corporation at the address set forth in the preamble
of this Agreement or to such other address as it shall designate by written
notice given to the other party. Time of notice or other communication shall be
deemed to be the date of postmark.
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8.5 Separability. If any provision of this Agreement or portion hereof,
or the application thereof to any person or circumstance or in any country,
shall be held to any extent invalid or unenforceable, the remainder of this
Agreement (or of such provision) and the application thereof to other persons or
circumstances or in other countries shall not be affected thereby.
8.6 Waivers. No waiver of breach or default by any party of any
provision of this Agreement shall be deemed or construed to be a waiver of any
succeeding breach or default of the same or any other provision.
8.7 Performance by Affiliates. SCHERING may satisfy any of its
obligations hereunder through any of its Affiliates; provided, however, that
SCHERING guarantees the performance at all times of its obligations so delegated
pursuant to this Section.
8.8 Authority to Enter Agreement. Each party hereby covenants and
represents to the other party that to the best of its knowledge it has full
right and authority to enter into this Agreement without the consent or approval
of any third party.
8.9 Article Headings. The article headings are placed herein merely as
a matter of convenience and are not to be construed as a part of this Agreement.
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IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
duly executed as of the day and year first above written.
SCHERING CORPORATION
By: /s/ Xxxxxxx X. Xxxxxxx
-----------------------------------------
Xxxxxxx X. Xxxxxxx
Title: Vice President, Bus. Dev.
ENDOGEN, INC.
By: /s/ Xxxx X. Xxxxxxx
----------------------------------------
Title: President & CEO
Exhibit I
AntiHuman Cytokine Hybridoma Cell lines for Licensing as of Jan 1, 1993.
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Cytokine MAb Neutralizing Immuno- Immunogen Isotype(a) References
Designation Ability assay Use Source
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hIL-4 MP4-25D2 blocking detect CHO IgG1 [1, 2, 6, 9, 13, 14, 15, 17, 19]
-----------------------------------------------------------------------------------------------------------------------------------
hIL-5 XXX0-00X00 xxxxxxxx xxxx XXX XxX0x [1, 2, 5, 7, 11, 12, 13, 14, 18, 20]
XXX0-0X00 xxxxxxxx xxxxxx XXX XxX0x
-----------------------------------------------------------------------------------------------------------------------------------
hIL-7 BVD10-40F6 blocking coat E.coli IgG1 [1]
BVD10-11C10 non-blocking detect E.coli IgG2a
-----------------------------------------------------------------------------------------------------------------------------------
hIL-10/vIL-10 JES3-9D7 blocking coat COS IgG1 [1, 3, 8, 16, 21]
JES3-12G8 blocking detect COS XxX0x
xXX-00 specific JES3-6B11 non-blocking detect COS IgG1
-----------------------------------------------------------------------------------------------------------------------------------
hGM-CSF XXX0-00X0 xxxxxxxx xxxx X.xxxx XxX0x [1, 2, 4, 10, 12]
BVD2-21C11 blocking detect E.coli IgG2a
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(a) All antibodies are rat immunoglobulin unless otherwise indicated.
REFERENCES
1. Xxxxxx, X. X., M.G. Roncarolo, H. Yssel, U. Andersson, X. X. Xxxxxx and J.
Silver. Strategies of anti-cytokine monoclonal antibody development: Immunoassay
of IL-10 and IL-5 in clinical samples. Immunol. Rev. 127: 5-24, 1992.
2. Bacchetta, R., X. xx Xxxx Malefjt, H. Yssel, J. Xxxxxx, X. X. de Vries, H.
Spits and M. G. Roncarolo. Hostreactive CD4+ and CD8+ T cell clones isolated
from a human chimera produce XX-0, XX-0, IFN-y and
granulocyte/macrophage-colony-stimulating factor but not IL4. J. Immunol.
144(3): 902908, 1990.
3. Xxxxxx, X. X., X. Xxxxxxxxxx, X. X. Xxxxxx, X. Xx, X. Xxxx, X. Xxxxxxxx, X.
X. Xxxxxxx and X. X. Xxxxxx. Cytokine production induced by M. Tuberculosis
lipoarabinomannan: Relationship to chemical structure. J. Immunol. 149: 541-547,
1992.
4. Xxxxxx, X. X., X. X. Xxxxxx, X. X. Xxxxxx, H. Band, T. H. Rea and X. X.
Xxxxxx. yo T-lymphocytes in human tuberculosis. J. Infect. Dis. 165: 506-512,
1992.
5. Xxxxxxxxxxx, X. X., K. M. Leifemen, X. X. Xxxxxx, X. X. Silver. X. Xxxxx, X.
Xxxxxxxxxx and X. X. Glcich. Elevated serum levels of interleukin-5 in patients
with the syndrome of episodic angioedcma and eosinophilia. Blood. 79(3):
688-692, 1992.
6. DeKruyff. R. H., X. Xxxxxx, X. X. Xxxxxx, M. A. Xxxxxxxxx Jr. and X. X.
Xxxxxx. Induction of human IgE synthesis by CD4+ T cell clones. Requirement for
interloukin 4 and low molecular weight B cell growth factor. J. Exp. Med. 170:
147-71493, 1989.
7. Xxxxxxx, X. X., X. X. Silver and X. X. Xxxxxx. Interleukin-5 is a human
basophilopoietin: induction of histamine content and basophilic differentiation
of HL-60 cells and of peripheral blood basophil-eosinophil progenitors. Blood.
77(7): 14628, 1991.
8. Xxxxxxx, X. X., X. X. Xxxxxx, X. X. Xxxxxx, X. Xxxx, X. X. Xxxxx and 0.
Xxxxxxxx-Xxxx. Presence of IL-10 in the ascites of patients with ovarian and
other intra-abdominal cancers. Cytokine. 4: 385-390, 1992.
9. Xxxxxx, X. X., X. X. Xxxxxxxx, X. Xxxxxxxx, X. Xxxxxx, X. Xxxx, X. Xxxxxx, A.
M. Xxxxxx, M. C. Lavigne, J. Banchereau, J. , XxXxxxx, et al. Induction of
interieukin-4-dependent IgE synthesis and interleukin-5-dependent eosinophil
differentiation by supernatants of a human helper T-cell clone. J Clin Immunol.
8(6): 437-46, 1988.
10. Kita, H., T. Ohnishi, X. Xxxxx. X. Xxxxxx, X. X. Xxxxxx and X. X. Xxxxxx.
GM-CSF and interleukin-3 released by human peripheral blood eosinophils and
neutrophils. J.Exp. Med. 174: 745-748, 1991.
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11. Xxxxxx, X. X., X. X. Xxxxxx, X. Xxxxxx,H. F. Xxxxxxx, X. X. Silver, X. X.
Xxxxxxx and X. X. Xxxxxx. Interleukin-5 and the post treatment eosinophilia in
patients with onchocerciasis. J. Clin. Inv. 88: 1418-1421, 1991.
12. Xxxxxx, X. X., X. X. Xxxxxx, X. X. Silver, X. X. Xxxxxxx and X. X. Xxxxxx.
Regulation of parasite-induced eosinophilia: Selectively increased interleukin-5
production in helminth-infected patients. J. Exp. Med. 172: 399-402, 1990.
13. Xxxxxxx, S., X. X. Xxxxxx, X. X. Xxxx, X. X. Xxxxxx and X. Xxxxxx B.
Parallel regulation of IL-4 and IL-5 in human helminth infections. J. Immunol.
3567-3571, 1992.
14. Xxxxxxx, S., X. X. Xxxxxx, X. X. Xxxxxx and X. X. Xxxxxx. Linkage of
Interleukin-4 and Interieukin-5 production in human helminth infections. Trans.
Assoc. Amer. Physicians. CIV: 296-303, 1991.
15. Paliard, X., X. xx Xxxx Malefijt, H. Yssel, X. Xxxxxxxxx, 1. Xxxxxxxx, X.
Xxxxxx, 1. de Vries and H. Spits. Simultaneous production of XX-0, XX-0 and IFNy
by activated human CD4 + and CD8 + T cell clones. J. Immunol. 141: 849. 1988.
16. Saigame, P., X. X. Xxxxxx, X. Xxxxxxxxxx, X. Xxxxxxxxx, X. X. Xxxxxx and B.
R. Bloom. Differing lymphokine profiles of functional subsets of human CD4 and
CD8 Tcell clones. Science. 254: 279y282, 1991.
17. Xxxxxxxxx, X. X., X. X. Xxxxx, X. Xxxxxxxxx, X. X. Xxxxxx, X. X. Xxxxxx, X.
X. Xxxx and X. Xxxxxxxx. Lymphokine profile in bone marrow transplant
recipients. Blood. 78: 3076y3080, 1991.
18. Xxxxxxxx, X. X., X. X. Xxxxxxx, 0. X. Xxxxxx, X. Xxxx, X. X. Xxxxxx, X. X.
Xxxxxxxx, X. Xxxxxxxx, M. Xxx-Xxxxxx and X. X. Xxxxx. Immediate and late
allergic airway response of allergic rhinitis patients to segmental antigen
challenge: Characterization of eosinophil and mast cell mediators. Amer. Rev.
Respir. Dis. 144: 1274-1281, 1991.
19. Umetsu, D., X. Xxxxxx,,rT. DeKruyff, X. Xxxxx, X. Xxxxxx and X. Xxxx.
Functional heterogeneity among human inducer T-cell clones. J. lmmunol. 140:
4211, 1988.
20. van Haelst Xxxxxx, C., X. X. Xxxxxx, X. Xxxx, X. X. Xxxxxxxxx, X. X. Xxxxxx,
X. X. Silver and X. X. Xxxxxx. Administration of interleukin-2 (IL-2) results in
increased plasma concentrations of IL-5 and eosinophilia in patients with
cancer. Blood. 78: 15381544, 1991.
21. Yssel, H., X. xx Xxxx Xxxxxxx, X.X. Roncarolo, X. X. Xxxxxx, X. Xxxxxxxx, H.
Spits and X. X. de Vries. Interleukin 10 is produced by subsets of human CD4+ T
cell clones and peripheral blood T cells. J. Immunol. 149: 2378-2384, 1992.
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EXHIBIT II
U. S. PATENTS
Antibodies to
Human Cytokines Patent Application Filing Date Patent No. Date of Patent
--------------- ------------------ ----------- ---------- --------------
GM-CSF 5,070,013 12/3/91
IL-4 5,041,381 8/20/91
IL-5 07/832,842 2/6/92
IL-10 07/372,667 6/28/89
07/917,806 7/20/92
(CIP of 07/372,667)
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EXHIBIT III
DNAX SUPPORT
1. Per contract 2 vials each of frozen hybridoma cell stock will be
supplied.
a. The vials contain approximately 5 X 10(6) cells.
b. No obvious contamination has become apparent during culturing
in antibiotic-free medium in the DNAX lab.
2. Information will be provided with samples regarding growth conditions
that have been used at the DNAX facility.
3. 1 mg of purified MAb immunoglobulin product will serve as standard for
each of the hybridoma cell lines licensed to the licensee.
4. Cell stock will be replaced without additional charge if any of the
following is established to not be true or to have not occurred, as the
case may be.
a. A hybridoma cell line that grows under culture conditions as
recommended by DNAX staff.
b. A cell line that produces immunoglobulin of the appropriate
(rat) isotype.
c. A cell line whose monoclonal antibody product has the
specificity claimed as verified by the purified antibody
standard.
5. No assurances or guarantees are given that:
a. The cell line will remain mycoplasma free or sterile after it
has been subsequently passaged at the licensee's facility.
b. Any support will be given to the licensee in obtaining a
working assay or in vitro bioassay system in which to
characterize the monoclonal antibody product; this activity is
the licensee's responsibility.
c. Any support will be given to licensee with respect to
interactions with customers, field customer questions, or to
answer customer questions passed on by the licensee.
d. Any support will be given to licensee in putting together
information for licensee product data sheets.
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e. Any cytokine standards for assay development by the licensee
will be provided to licensee.
6. To the extent that problems arise in terms of shipment or receipt of
the cell lines:
a. DNAX will make a reasonable effort to insure that the licensee
receives working material by shipping a second time at no
additional expense. Subsequently, DNAX will ship again at
licensor's discretion.
7. To the extent that additional help, advice, or information regarding
techniques is required by the licensee:
a. DNAX is willing to provide hands-on training at its
facilities, for a limited period (2 days), completely at
licensee's expense.
b. Alternatively, DNAX is willing to provide additional help
under a consulting arrangement, reimbursed at DNAX's (industry
standard) rate which is currently $1500 per diem. This amount
is payable to Schering Corporation (similar to the payment of
licensing fees).
8. It is the responsibility of the licensee to comply with all Federal and
State regulations regarding shipment or materials to DNAX's facility,
in the event that mutually agreed upon analytical work is to be carried
out at this facility.
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Xx. Xxxxxxx X. Xxxxxxx
Vice President
Business Development
Schering Corporation
0000 Xxxxxxxxx Xxxx Xxxx
Xxxxxxxxxx, XX 00000
Dear Xx. Xxxxxxx:
Enclosed herein are the two original license agreements for the hybridoma cell
lines producing monoclonal antibodies against human cytokines executed on our
behalf. Also enclosed is payment in the amount of $10,000 dollars for the Cell
Lines listed below as specified under Articles 2.2 and 7.0.
CYTOKINE MAS DESIGNATION ISOTYPE
-------- --------------- -------
hIL-10 JESS-9D7 IgG(1)
hIL-10 JESS-12G8 IgG(23)
Upon receipt by Schering Corporation of the executed agreement and fees, it is
understood that Schering will promptly arrange to provide the Cell Lines
indicated above.
Company: Endogen, Inc.
-----------------------------------------
By: /s/ Xxxx Xxxx
-----------------------------------------
Title: Business Development Manager
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Date: February 9, 1993
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