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CONFIDENTIAL TREATMENT EXHIBIT 10.12
30th September 1996
Leukosite, Inc.
000 Xxxxx Xxxxxx
Xxxxxxxxx
XX 00000
XXX
Ladies and Gentlemen:
PROFORMA UNDERTAKINGS AND WARRANTIES
We refer you to the Material Release Agreement dated 30th September 1996 between
The Wellcome Foundation Limited and Leukosite, Inc., the heads of a sub-licence
agreement between British Technology Group Limited ("BTG") and Leukosite, Inc.
dated 30th September 1996 ("Sub-Licence").
In this letter the following capitalized terms shall have the following meanings
attributed to them: -
"Company" means The Wellcome Foundation Limited its parent company,
subsidiaries and affiliates from time to time.
"Cell Culture Medium" means the powdered CIV15 cell culture medium more
particularly described and claimed in the patent rights represented by
patent number PA 1 194.
"Cell Line" is cell line obtained from the Chinese Hamster Ovary (CHO)
Clone C I C2 derived from original master cell bank C I M 3D44 10.8.90
and the Master Cell Bank CHO CIH 10.11.93)
"Campath 1H" means the anti CD52 humanized monoclonal antibody that is
produced from the Cell Line and derivatives of the antibody so produced
including conjugates of the antibody with other substances.
"Critical Information" means that information and material listed in
the Material Release Agreement of even date hereof between The Wellcome
Foundation Ltd. and Leukosite, Inc.
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"Drug Substance" means partly purified or purified Campath I H which
originates from the Company.
"Drug Product" means purified Campath IH in vials labelled "not for
human use", which originates from the Company.
"Know How" is as detailed and set forth in the Sublicence Agreement
with BTG.
"Materials" means those materials detailed and set forth in Annex I to
this Letter.
You have agreed in consideration of entering into the Sub-Licence and in
consideration of us entering into the Material Release Agreement to provide our
company with the following undertakings and warranties (which undertakings and
warranties shall be binding from time to time on all your successors and
assigns) and to procure that your subsidiaries, affiliates, sub-contractors,
consultants and agents and duly notified to us (the "Leukosite Group") from time
to time, shall all individually undertake and warrant as follows:
(i) During the term of the Sub-Licence Agreement and the final Sub-Licence
Agreement, not to do any act or thing or through any omission use,
refer to or associate its/themselves with our company name, to bring
our Company name into disrepute or to do anything which would defame
our Company, or its name;
(ii) To immediately notify our Company if either it or they apply for or
have access from time to time through their sub-contractors and agents
to patent rights on any process or formulation invention arising from
its or their use(s) of the Know-How (as defined in the Sub-Licence) and
having application to products other than Campath IH and/or where our
Company may be blocked from using such process or formulation invention
in its development and manufacture of its other products other than
Campath 1H. Our Company shall have the right to take a non-exclusive
licence under such patent rights or analogous intellectual property
rights (exclusive of Campath IH) on reasonable terms to be agreed
including royalty payments which shall in no event exceed *;
(iii) to indemnify and hold and continue to indemnify and hold harmless our
Company, its Affiliates, directors and employees from time to
* Confidential treatment requested: material has been omitted and filed
separately with the Commission.
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time against any and all liability whatsoever and wheresoever in
respect of all acts and omissions in respect of the development,
production, use and/or sale of any products by LEUKOSITE or the
LEUKOSITE Group utilizing Campath 1H and/or any of the Know-How and/or
Drug Product and/or Drug Substance and/or Cell Culture Medium. The
indemnified party shall promptly notify the indemnifying party, who
shall have overall control and conduct of the defense, settlement or
compromise of all claims, Provided That the indemnifying party
regularly advises the indemnified party of the progress of such
defense, settlement or compromise and allows the indemnified party to
reasonably comment on such proceedings;
(iv) to obtain and maintain thereafter suitable insurance cover as set forth
in the sublicence agreement with BTG with sound and reputable
independent insurers at commercially reasonable levels of coverage in
relation to the various obligations and activities being undertaken.
You shall ensure that all your sub-contractors and agents from time to
time, likewise have similar suitable insurance covering activities by
them
(v) not to use the Materials, the Know-How, the Cell Line, Cell Culture
Medium, Drug Substance, Drug Product or the Critical Information (all
as defined in the Sub-Licence) for any purpose whatsoever except for
developing, using, making, having made and sell Campath 1H product and
you shall use best endeavors to ensure at all times that any
affiliates, subsidiaries, sub-contractors and agents from time to time
at all times comply with this provision;
(vi) to keep the Materials, the Know-How, the Cell Line, the Cell Culture
Medium and the Critical Information strictly confidential and secure at
all times and shall store the same separately from other information
and materials;
(vii) except as may be necessary to develop, make, register and sell Campath
1H product and subject to the provisions of sub-clause (x) below. not
to disclose or cause or authorize or permit the Materials, the
Know-How, the Cell Line, the Cell Culture Medium and the Critical
Information to be disclosed to any third party without first obtaining
our Company's prior written consent and to ensure at all times that all
your employees, consultants and experts from time to time prior to
being allowed access to the same are individually bound by similar
terms of confidentiality and non-use herein contained;
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(viii) not to reproduce transform or store any of the Know-How, Critical
Information or details of the Cell Culture Medium on an externally
accessible computer or electronic information retrievable system;
(ix) subject to the terms of the sub-licence agreement with BTG, in the
event the Sub-Licence is terminated, to return or destroy and ensure
your subsidiaries, affiliates. sub-contractors and agents from time to
time return or destroy to our Company's satisfaction the Know-How, the
Materials and the Cell Culture Medium, Drug Substance and Drug Product,
the Cell Line and Company information (all as defined in the
Sub-Licence) within thirty (30) days of our Company's written request
and in accordance with our Company's specific instructions and you will
issue a certificate signed by a director confirming that these
provisions have been complied with and shall ensure your subsidiaries,
affiliates, sub-contractors and/or agents from time to time (as
appropriate) issue a certificate signed by one of their directors
confirming that these provisions have been duly complied with;
(x) to promptly notify our Company, in advance where from time to time,
where you contract out the development/production of Campath 1H to a
subsidiary, affiliate or any third party sub-contractor or agent, prior
to such appointment(s) you shall on each occasion enter into an
agreement which includes similar provisions to those contained herein;
(xi) not to use Drug Product or Drug Substance transferred under the
Material Release Agreement for human therapeutic administration and
shall procure that its subsidiaries, affiliates, sub-contractors and
agents from time to time do not use Drug Substance or Drug Product for
human therapeutic administration.
Please indicate your agreement and acknowledgment of these provisions by signing
and returning to us the duplicate copy of this letter.
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Yours faithfully
For and on behalf of
THE WELLCOME FOUNDATION LIMITED
Signed: [signature appears here]
Name print:________________________
Position: _________________________
Accepted, acknowledged and agreed for and on behalf of
LEUKOSITE, INC.
Signed: [signature appears here]
Name print: _______________________
Position: __________________________
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ANNEX 1 TO PROFORMA WARRANTIES AND UNDERTAKINGS
KNOW-HOW
Contents
A. CRITICAL INFORMATION
Defined in the Material Release Agreement with Leukosite.
B. OTHER INFORMATION:-
(1) Clinical Trial Data
The Case Report Forms from the trials (photocopied at
Leukosite's expense).
The clinical database (transferred as SAS transfer files on
data tape).
(2) Cell and material stocks and reports on manufacturing process
(see attached).
(3) Other reports held in Glaxo Wellcome Documentation Centre.
(4) Other reports, not included in (3) above, supporting IND (list
to be added by end August).
C. LIST OF CLINICAL AND ACADEMIC INVESTIGATORS (to be added at Intended
Agreement stage)
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ATTACHMENT TO ANNEX I
B(2)
CELL AND MATERIAL STOCKS AND REPORTS ON MANUFACTURING PROCESS
1. Specification C1H.SPEC/1.150 Volume I Cell Banks 1 Sept 1994
2. Specification C1H.SPEC/1.150 Volume II Production 30 Aug 1994
Campath-1H Inventory - Building 138
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
BATCH HARVEST REVIVAL PROCESS TOTAL QUANTITY
NO. DATE BANK STAGE MG/ML* GRAMS (G)
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
CH70 29/06/93 MCB1-WCB2 S-SEPH CONC 40.9 424.91 424.91
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
CH78 25/10/94 MCB2-WCB1 VIRESOLVE 2.0 145.0 145.0
CYCLE 3 1.5
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
CH78 25/10/94 MCB2-WCB1 S-SEPH CONC 41.4 70.38 70.38
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
CH78 25/10/94 MCB2-WCB1 SUPERDEX 23.1 159.39 159.39
------------- --------------- -------------------- ------------------------ -------------- ------------- ----------------
Campath-1H CTM Inventory
------------------------------ ---------------------------- ----------------------------- ------------------------------
TOTAL VIALS
BATCH NO. FILLING DATA REVIVAL BANK (APPROXIMATE)
------------------------------ ---------------------------- ----------------------------- ------------------------------
------------------------------ ---------------------------- ----------------------------- ------------------------------
A3227A Mar 94 MCB1 22,000 *
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* the majority to be retained by Glaxo Wellcome
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Cell Bank
Reports on the stability of cells in culture are as follows:
Growth and monoclonal antibody production by cells from the XX Xxxxxxx BZDR/93/001
second CHO Campath-1H Working Cell Bank.
Growth and monoclonal antibody production by cells from the XX Xxxxxxx BZDR/93/008
third CHO Campath 1-H Working Cell Bank.
Growth and monoclonal antibody production by Campath-1H X. Xxx BZDR/95/007
producing CHO cells from the Xxxxxx Cell Bank, CHO C1H 10.11.93.
Growth and monoclonal antibody production by Campath-1H X. Xxx BZDR/95/008
producing CHO cells from Working Cell Bank, CHO 6/12/93.
The inventory of cell banks is given in the table below:
----------------------------------------------- ---------------- --------------------------------------------------------
LOCATION NUMBER TYPE
----------------------------------------------- ---------------- --------------------------------------------------------
----------------------------------------------- ---------------- --------------------------------------------------------
LIQUID NITROGEN, B119
----------------------------------------------- ---------------- --------------------------------------------------------
D1C5TD 50 CHO C1H 10.11.93 (MCB2)
----------------------------------------------- ---------------- --------------------------------------------------------
D1C5TC 47 CHO C1H 6.12.93 (0xx XXX from MCB2)
----------------------------------------------- ---------------- --------------------------------------------------------
D1C3TB 50 DCC CTM post production cell banks
----------------------------------------------- ---------------- --------------------------------------------------------
LIQUID NITROGEN TPP, B115
----------------------------------------------- ---------------- --------------------------------------------------------
B115 (TPP) location B1 45 CHO C1H 10.11.93 [MCB2]
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B115 (TPP) location B2 43 CHO C1H 6.12.93 (0xx XXX from MCB2)
----------------------------------------------- ---------------- --------------------------------------------------------
Production
Other documents available:
Campath-1H cell line selection for Master Cell Bank production XX Xxxxxxx BZDR/95/006
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The growth of Chines Hamster Ovary cells producing Campath-1H in XX Xxxxxxx BZDR/93/006
medium containing Xxxxxxxxxxxx xx Xxxxxxxxxx (XX 000X)
Growth and monoclonal antibody production by cells derived from XX Xxxxxxx BZDR/94/003
the Master Cell Bank (C1H 3D44 10.8.90) in medium containing
Xxxxxxxxxxxx xxx/xx Xxxxxxxxxx (XX 000X)
Potential impurities arising from the Campath-1H purification J Relton BZPP/95/002
process
Dilution of C-1H Inj. 00.xx/x0 with 5% Dextrose injection in XX Xxxxx DPPP/94/001
previously empty sterilized vials
Summary report sanctioning changes to the Campath-1H Process to XX Xxxxxxxxx BZPP/94/0042
be implemented at the onset of the Autumn 1994 production
campaign
