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AMENDMENT NO. 1 TO RESEARCH LICENSE & OPTN. AGMNT.

Effective Date: June 28, 1996
Parties:

Abgenix, Japan Tobacco

Sectors: Biotechnology / Pharmaceuticals, Food, Beverages and Tobacco
Law Firms: Wilson Sonsini Goodrich & Rosati
Governing Law:  California
EXHIBIT 10.13A



CONFIDENTIAL TREATMENT REQUESTED BY ABGENIX, INC.



AMENDMENT TO MASTER RESEARCH LICENSE AND OPTION AGREEMENT





This Amendment of Master Research License and Option Agreement (the "Amendment"), effective as of November __, 1997, (the "Amendment Effective Date"), is made by and between Xenotech, L.P., a California limited partnership ("XT"), Abgenix, Inc. ("ABX"), a Delaware corporation and wholly-owned subsidiary of Cell Genesys, Inc., a Delaware corporation ("CGI"), and Japan Tobacco Inc., a Japanese corporation ("JT"), and amends that certain Master Research License and Option Agreement among JT, ABX, and XT effective as of June 28, 1996 (the "1996 Master Agreement").





A. XT is a limited partnership formed in June 1991 by JT Immunotech USA, Inc., a wholly-owned indirect subsidiary of JT, and CGI to research, develop, use, modify, make, have made, sell and otherwise dispose of certain products and hold the rights to certain technology relating to human monoclonal antibodies derived from transgenic mice.



B. CGI has assigned all of its rights and any obligations under the 1996 Master Agreement, and various other agreements, to its wholly-owned subsidiary ABX.



C. The parties desire to amend the 1996 Master Agreement to (i) provide for the transfer of transgenic mice to third parties under certain circumstances provided herein, (ii) modify the 1996 Master Agreement, and the form Product Licenses attached thereto, in order to facilitate commercialization of the XenoMouse(TM) transgenic mice and related technology, and (iii) clarify the manner in which rights obtained by XT from third parties are incorporated into the licenses granted under the 1996 Master Agreement.



NOW THEREFORE, it is agreed by and between the parties to amend the 1996 Master Agreement as follows:





1. All capitalized terms not defined in this Amendment shall have the meanings

given to them in the 1996 Master Agreement.



2. Section 1.10 is amended to read in its entirety as follows:



1.10 "Covered Product" shall mean any Antibody Product which incorporates

(i) an Antibody which binds to a particular Antigen or (ii) Genetic

Material encoding such an Antibody wherein said Genetic Material does not

encode multiple Antibodies.











3. Section 1.19 is amended to read in its entirety as follows:



1.19 "Licensed Technology" shall mean the [***] Technology, the [***]

Technology, and the XT-Controlled Rights.





4. Sections 1.34 and 1.35 are deleted from the 1996 Master Agreement.





5. The following new Sections 1.37, 1.38, 1.39, 1.40, 1.41, 1.42, 1.43, 1.44

and 1.45 are added following Section 1.36 of the 1996 Master Agreement:



1.37 "Antibody" shall mean a composition comprising a whole antibody or a

fragment thereof, said antibody or fragment having been derived from the

Licensed Technology and/or generated from Mice or Future Generation Mice or

having been derived from nucleotide sequences encoding, or amino acid

sequences of, an antibody obtained from Mice or Future Generation Mice.



1.38 "Antibody Product" shall mean any product comprising an Antibody or

Genetic Material encoding an Antibody wherein, in respect of each Antibody

Product, said Genetic Material does not encode multiple Antibodies.



1.39 "Antibody-Secreting Cell" shall mean a cell that secretes an Antibody,

except where such cell is part of a mammal.



1.40 "Antigen Invention" shall mean intellectual property rights in and to

patentable inventions (including patent and patent applications) which both

(i) include claims to the following:



(A) [***]



(B) [***]



(C) [***]







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











(D) [***]



and (ii) wherein, but for a license thereto, such claims would be infringed

by the manufacture, use, sale, offer for sale, or import of Antibody

Products to such Antigen.



1.41 "Genetic Material" shall mean a nucleotide sequence, including DNA,

RNA, and complementary and reverse complementary nucleotide sequences

thereto, whether coding or noncoding and whether intact or a fragment.



1.42 "GenPharm Cross License" shall mean that certain Cross License

Agreement, effective as of March 26, 1997, entered into by and among the

parties, GenPharm International, Inc. ("GenPharm") and the other parties

named therein, as the same may be amended from time to time.



1.43 "Research License" shall have the meaning set forth in Article 3 of

this Agreement.



1.44 "Transgenic Product" shall mean any product constituting (i) Mice or

Future Generation Mice, (ii) Genetic Material from Mice or Future

Generation Mice, or (iii) an Antibody-Secreting Cell.



1.45 "XT-Controlled Rights" shall mean all rights to intellectual property

or technology that are licensed to XT pursuant to the agreements listed on

Exhibit H or any other license or similar agreement granting XT rights to

intellectual property or technology (each such agreement an "XT

In-License"), to the extent that XT has the right under the terms of the

applicable XT In-License to further license or sublicense such rights

during the term of this Agreement.



6. Section 2.3 is amended to read in its entirety as follows:



2.3 The Mice shall only be used by a Grantee pursuant to the Research

License set forth in Article 3 hereof for research and development purposes

or pursuant to a Product License and shall not be transferred or otherwise

made available to any third party, except as provided in Sections 2.7 of

this Agreement or as provided under an applicable Product License entered

into between the Grantee and XT.



7. The following new Sections 2.7 and 2.8 shall be inserted following Section

2.6 of the 1996 Master Agreement:



2.7 Transfer of Mice: Notwithstanding any provision to the contrary in this

Agreement or any Material Transfer Agreement entered into between the

parties under Sections 2.1, 2.2 or 2.3 (or any other agreement between

parties to this







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











Agreement, as such agreements are amended from time to time), Grantees and XT shall have the right to transfer physical possession of one or more sterilized male Mice or sterilized male Future Generation Mice (in each case, sterilized using a method agreed upon by JT and ABX) or Transgenic Products, but not other Mice or Future Generation Mice, to third parties (including Affiliates) for research and development purposes, with the proviso that such research and development purposes shall not exceed the rights conferred in accordance with Section 3 hereof; and further provided that, as to transfers of Mice and Future Generation Mice (but not of other Transgenic Products), Grantees shall only be permitted to make transfers of such Mice and Future Generation Mice to third parties on the following terms and conditions:



(a) Mice and Future Generation Mice shall not be transferred to any

third party by a Grantee except under a written agreement (the "Third-Party

Transfer Agreement") providing, among other things, that:



(1) all Mice and Future Generation Mice shall be the property of

the respective owners of such Mice and Future Generation Mice prior to

their transfer to the third party, and the transfer of physical

possession to such third party, and/or possession or use by such third

party, of Mice or Future Generation Mice shall not be, nor be

construed as, a sale, lease, offer to sell or lease, or other transfer

of title to any Mice or Future Generation Mice;



(2) all Mice and Future Generation Mice shall remain in the

control of such third party and shall not be transferred to any other

party (other than the transferring Grantee);



(3) the third party shall not attempt to use the Mice or Future

Generation Mice, or any others materials derived in whole or part from

the Mice or Future Generation Mice (including Genetic Materials) to

reproduce the Mice or Future Generation Mice or to generate or produce

other transgenic mice or other transgenic animals;



(4) if the third party is a for-profit pharmaceutical or

for-profit biotechnology company, [***]; provided, however, that this

provision shall not restrict or prohibit any authorized manufacture,

use, or sale or other commercialization of materials derived from the

Mice or Future Generation Mice in accordance with a license or

sublicense from XT or a Grantee (or a Sublicensee of XT or a Grantee)

under this Agreement, a Product License, or otherwise;







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











(5) the third party shall not sell, have sold, lease, offer to

sell or lease, otherwise transfer title to any Mice, Future Generation

Mice, Antibody-Secreting Cells derived from the Mice or Future

Generation Mice, or (except as provided in (6) below) Genetic

Materials derived from the Mice or Future Generation Mice;



(6) the third party shall not sell, have sold, lease, offer to

sell or lease, otherwise transfer title to, or otherwise distribute or

commercialize any Antibody or Antibody Product without obtaining a

license, sublicense, or other authorization from the transferring

Grantee;



(7) the third party shall not use the Mice or Future Generation

Mice to make or use antibodies to [***]; and



(8) XT shall be a third-party beneficiary of the commitments by

third parties set forth in items (1) through (7) above.



(b) Grantees shall not grant any license, sublicense, or other

authorization of the type described in Section 2.7(a)(6) to third parties

unless such license, sublicense, or other authorization does not conflict

with the applicable terms of this Agreement, any applicable Product

License, and the GenPharm Cross-License.



(c) Nothing in this Section 2.7 shall be construed as granting

Grantees the right to sublicense any third party to sell, have sold, lease,

or offer to sell or lease, any Covered Product, other than pursuant to a

sublicense under a Product License entered into by Grantee under the terms

of this Agreement.



2.8 Transfer of Transgenic Products and Antibody Products: When transferring physical possession of any Transgenic Product or Antibody Product to a third party, the transferring Grantee shall obtain a written agreement from the third party that such transferred materials remain the property of the respective owner of such materials prior to their transfer to the third party, and the transfer of physical possession to such third party, and/or possession or use by such third party, of such materials shall not be, nor be construed as, a sale, lease, offer to sell or lease, or other transfer of title to such transferred materials. If a Grantee has authority to sell or otherwise transfer title to materials pursuant to a Product License, the terms of this Section 2.8 shall not apply to the transfer of such materials by such Grantee.





8. Article 3 ("Grant of Research License") is amended to read in its entirety as follows:



3.1 Grant. XT hereby grants to each Grantee a co-exclusive (with each other and XT), worldwide, royalty-free, fully paid up, perpetual, irrevocable license (or sublicense, as appropriate) under the Licensed Technology to use for research, and to







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.















develop, make, have made, use, import, export or otherwise transfer

physical possession of (but not to sell, lease, offer to sell or lease, or

otherwise transfer title to) Transgenic Products and Antibody Products (the

"Research License"); provided, however, that (i) the right to transfer

physical possession of Mice and Future Generation Mice pursuant to this

Research License shall be limited as set forth in Section 2.7 of this

Agreement, and (ii) as to all XT-Controlled Rights, the foregoing grant

shall be subject in all respects to the applicable XT In-License(s)

pursuant to which such XT-Controlled Rights were granted to XT.



3.2 Sublicenses.



(a) Each Grantee may grant to third parties non-exclusive sublicenses

under the Research License (i) to use Transgenic Products and (ii) to

research, develop, make, have made, use, import and export (but not to

sell, lease, offer to sell or lease, or otherwise transfer title to)

Antibody Products, Antibody-Secreting Cells, and Genetic Materials, solely

for research and development purposes; provided, that the transfer of Mice

and Future Generation Mice by Grantees shall be subject to the restrictions

set forth in Section 2.7 of this Agreement.



(b) [***]; provided, however, that this Subsection 3.2(b) shall not

restrict or prohibit any authorized manufacture, use, or sale or other

commercialization of materials derived from the Mice or Future Generation

Mice in accordance with a license or sublicense from XT or a Grantee (or a

Sublicensee of XT or a Grantee).



(c) Sublicenses under this Section 3.2 shall not include the right to

grant further sublicenses to use the Mice or Future Generation Mice, but

may include the right to grant further sublicenses as to other rights

sublicensed hereunder upon the approval of the Grantee which sublicensed

such rights. Except as set forth in this Section 3.2, Grantees shall have

no other right to grant sublicenses under the Research License unless

otherwise agreed in writing by Xenotech. It is understood that after a

Grantee has entered into a Product License under this Agreement for

Antibody Products related to a particular Antigen, that Grantee may, among

other things, sublicense third parties under such Product License to use

any Mice or Future Generation Mice transferred to that third party by the

Grantee pursuant to Section 2.7 of this Agreement to research, develop,

make, have made, use, import, export, sell, lease, offer to sell or lease,

otherwise transfer title, or otherwise distribute or commercialize Antibody

Products covered by such Product License.



3.3 Direct Sublicense to CGI. With regard to rights and sublicenses under

the GenPharm Cross License sublicensed to ABX under Section 3.1 above

("ABX's







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











GenPharm Research Rights"), it is understood and agreed that, in the event

that CGI obtains (i) a sublicense of rights from ABX under a Product

License and (ii) a corresponding sublicense related to the Product Antigen

from XT (a "Direct CGI Sublicense") pursuant to that certain Direct

Sublicense to Cell Genesys entered into by and between CGI and XT effective

as of October __, 1997, the grant of ABX's GenPharm Research Rights under

this Article 3 shall be subject to the Direct CGI Sublicense, and ABX's

GenPharm Research Rights shall be subordinate to the rights granted under

the Direct CGI Sublicense to the extent, and for so long as, required under

the GenPharm Cross License. Upon any termination or expiration of the

Direct CGI Sublicense (and all sublicenses, if any, thereunder), ABX's

GenPharm Research Rights shall no longer be subject to the grant of rights

and sublicenses under the Direct CGI Sublicense.





9. Section 4.2(i)(a) and (b) are amended to read in their entirety as follows:



(a) During the term of this Agreement, the Grantees shall meet [***],

at such times and locations as they may agree. Each Grantee may select

[***] Additional Antigens at [***]. Thereafter, each Grantee may, at such

quarterly meetings, select (i) up to three (3) Additional Antigens per

calendar six-month period during the time from January 1, 1997 to June 30,

1997, and (ii) up to four (4) Additional Antigens per calendar six-month

period thereafter. At the time that a Grantee selects an Antigen [***], it

shall also provide to the other Grantee a summary of the scientific

background to the selection of such Antigen, [***]. Such disclosure shall

be without any warranty regarding, or agreement to license, such rights.

The Grantee selecting an Antigen shall also inform the other Grantee of

[***].



(b) If a Grantee does not select an Additional Antigen at a particular

[***], provided, however, that it may not [***]. Once selected an

Additional Antigen shall [***].



The remainder of Section 4.2 shall not be changed by this Amendment.







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











10. Section 6.1 is amended to read in its entirety as follows:



6.1 Limitations on Product Licenses. Upon execution by XT and a Grantee

(and unless and until terminated), each of the Product Licenses shall be

deemed to be a "[***] License." [***], the license shall no longer be

deemed to be a "[***] License." At no time shall either Grantee have the

right to hold [***]. In the event that a Grantee terminates a Product

License in its entirety, such license shall no longer be deemed to be held

by such Grantee for the purpose of the limitations set forth in this

Section 6.1.



11. Section 7.1 is amended to read in its entirety as follows:



7.1 In order to [***]. The right of a Grantee to license or sublicense

pursuant to this Section 7.1 shall not require the consent of the other

Grantee or of XT, and shall not require any additional obligations to XT

other than acceptance by the Grantee of the terms and conditions of the

applicable Exclusive Worldwide Product License from XT to such Grantee

related to the Antigen. A Grantee selecting an Antigen governed by the

terms of this Section 7.1 shall notify the other Grantee, at the time the

Antigen is selected, that this Section 7.1 applies. It is understood and

agreed that the other Grantee [***].



12. Section 7.2 is amended to read in its entirety as follows:



In the event that [***]







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











[***]. XT will confer with CGI and JTI as to how to [***].



13. Article 8 is amended to read in its entirety as follows:



8. IN-LICENSING OR ACQUISITION; INVENTIONS



8.1 In-Licensing Third Parties Antigen Inventions.



(a) If either Grantee is licensing or otherwise acquiring from a third

party (or negotiating to license or acquire from a third party) patent

rights in an Antigen Invention that were made by a third party without the

use of Mice or Future Generation Mice, such Grantee (the "In-Licensing

Grantee") [***]. Subject to Section 4.2(iv) above, the Grantee that selects

an Antigen pursuant to Section 4.2(i)(a) above shall [***]. If both

Grantees have selected the same Antigen pursuant to Section 4.2(iv) above,

they shall mutually agree, subject to Section 4.2(iv)(d), on control of

in-licensing negotiations.



(b) If the In-Licensing Grantee licenses or acquires rights to one or

more Antigen Inventions from a third party and secures such rights for the

other Grantee pursuant to Section 8.1(a) above, and [***].



8.2 Inventions By Grantees.



(a) Inventions Made Before Selection. Subject to Sections 8.2(c), 8.4

[***] and 8.7 of this Agreement, each Grantee shall, promptly following the

selection of an Antigen by either Grantee ("selection" referring to the







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.











set forth in Section 4.2 above), disclose to the other all Antigen

Inventions related to that Antigen made, conceived and reduced to practice

by the disclosing Grantee prior to selection of the Antigen. At such time

as the non-disclosing Grantee has [***], the disclosing Grantee shall,

[***].



(b) Inventions Made After Selection. Subject to Sections 8.2(c), 8.4

[***] and 8.7, each Grantee shall, after an Antigen has been selected,

disclose to the other Grantee within a reasonable time after invention all

Antigen Inventions related to that Antigen that are made, conceived and

reduced to practice by the disclosing Grantee after the selection of the

Antigen; provided, however, that such disclosure shall only be required if

the other Grantee, at the time of invention, has [***].



(c) Limitation. Notwithstanding the foregoing Subsections 8.2(a) and

(b), neither Grantee shall be obligated to disclose, license to the other

Grantee, or negotiate for such licenses, each as set forth in Subsections

8.2(a) and (b), for [***]. The limitations set forth in this Section 8.2(c)

shall not limit the obligations set forth in Section 8.3(a).







[***] Certain information on this page has been omitted and filed separately

with the Commission. Confidential treatment has been requested with

respect to the omitted portions.















8.3 Inventions Where One Grantee Has Worldwide Exclusive Product License.



(a) Mandatory License to Inventions of Grantee: If either Grantee (the

"Exclusive Grantee") enters into an Exclusive Worldwide Product Sublicense

with respect to a particular Antigen, the other Grantee shall grant to the

Exclusive Grantee, for so long as such Exclusive Worldwide Product License

is in effect, a non-exclusive, worldwide, royalty-free license under all

Antigen Inventions specifically related to such Antigen made, conceived and

reduced to practice by the other Grantee after the time that the Exclusive

Grantee entered into the Exclusive Worldwide Product License.



(b) Mandatory License to Inventions of Third Parties: If either

Grantee (the "Exclusive Grantee") has in effect an Exclusive Worldwide

Product Sublicense with respect to a particular Antigen, the other Grantee

(i) shall not transfer to a third party any Transferred Materials for such

Antigen without the prior written consent of the Exclusive Grantee and (ii)

shall, when negotiating the terms of any material transfer agreement in

connection with transferring to a third party Transferred Materials for

such Antigen, obtain the right to license on a non-exclusive, worldwide,

royalty-free basis, to the other Grantee all Antigen Inventions

specifically related to such Antigen which are made by the third party (or

jointly by the third party and the Grantee) through use of the Transferred

Materials for such Antigen, and shall so license such Antigen Inventions to

the Exclusive Grantee for so long as such Exclusive Worldwide Product

License is in effect.



(c) Transferred Materials for an Antigen. As used in Sections 8.3, 8.4

and 8.5 of this Agreement, "Transferred Materials for X", where "X" is an

Antigen, shall include Mice or Future Generation Mice for use with such

Antigen, Antibody Products comprising Antibodies that bind to such Antigen,

and Antibody-Secreting Cells that secrete such Antibodies and Genetic

Materials that encode such Antibodies.



8.4 Third Party Inventions With Mice- [***]. The terms of this Section 8.4

shall apply when (A) an Antigen (i) has not yet been selected by either

Grantee (or has been selected and later abandoned so that it is again

available for selection) or (ii) has been selected by the transferring

Grantee or (iii) has been selected by both Gr ...

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