***Text Omitted and Filed
Separately
Confidential Treatment Requested
Under 17 C.F.R. §§ 200.80(b)(4) and
240.24b-2(b)(1)
IL-13 Development and Manufacturing
Agreement
|
|
|
|
|
|
|
|
|
|
|
|
|
CLAUSE
|
|
PAGE
|
|
|
|
|
1.
|
|
DEFINITIONS
& PURPOSE
|
|
|
1
|
|
|
|
|
2.
|
|
OBLIGATIONS OF BIOTECNOL
|
|
|
6
|
|
|
|
|
3.
|
|
OBLIGATIONS OF
IDM
|
|
|
7
|
|
|
|
|
4.
|
|
PAYMENT
|
|
|
8
|
|
|
|
|
5.
|
|
PROGRAMME
MANAGEMENT
|
|
|
11
|
|
|
|
|
6.
|
|
SUB-CONTRACTING
AND OUTSOURCING
|
|
|
12
|
|
|
|
|
7.
|
|
INTELLECTUAL
PROPERTY RIGHTS
|
|
|
14
|
|
|
|
|
8.
|
|
CONFIDENTIALITY
|
|
|
16
|
|
|
|
|
9.
|
|
WARRANTIES AND
DISCLAIMER
|
|
|
17
|
|
|
|
|
10.
|
|
DURATION AND
TERMINATION
|
|
|
18
|
|
|
|
|
11.
|
|
EFFECT OF
TERMINATION
|
|
|
19
|
|
|
|
|
12.
|
|
FORCE
MAJEURE
|
|
|
20
|
|
|
|
|
13.
|
|
COSTS
|
|
|
20
|
|
|
|
|
14.
|
|
VARIATIONS
|
|
|
20
|
|
|
|
|
15.
|
|
WAIVER
|
|
|
21
|
|
|
|
|
16.
|
|
INVALIDITY
|
|
|
21
|
|
|
|
|
17.
|
|
NOTICES
|
|
|
21
|
|
|
|
|
18.
|
|
NO
PARTNERSHIP
|
|
|
22
|
|
|
|
|
19.
|
|
ASSIGNMENT
|
|
|
22
|
|
|
|
|
20.
|
|
GOVERNING LAW
AND JURISDICTION
|
|
|
23
|
|
|
|
|
21.
|
|
ENTIRE
AGREEMENT
|
|
|
23
|
|
|
|
|
|
|
|
|
|
|
|
|
SCHEDULE 1
Programme
|
|
|
25
|
|
|
SCHEDULE
2
|
|
|
25
|
|
THIS AGREEMENT
is dated November 4, 2003
|
(1)
|
|
BIOTECNOL SA having its principal place of
business at Taguspark, Edificio Inovacao IV, 809 Porto Salvo,
2780-920 Oeiras, Portugal (“Biotecnol”);
and
|
|
|
|
|
|
(2)
|
|
IDM IMMUNO-DESIGNED MOLECULES
S.A. registered at Paris RCS under 632
382 263 and having its main offices at 172 rue de Charonne 75011
Paris FRANCE (“IDM”).
|
|
(A)
|
|
Biotecnol is a biotechnology company
which owns or is licensee of systems for recombinant protein
expression in the bacterium Escherichia coli (“E.
coli ”) and has expertise and know-how in
the design and optimisation of recombinant protein production
processes, expression of recombinant proteins, fermentation media
optimisation, fermentation design, protein purification, protein
characterisation, design and the scale-up of integrated processes
for the production of recombinant proteins, and in the general use
of E. coli as a host for the expression of
proteins.
|
|
|
|
|
|
(B)
|
|
IDM
is a biopharmaceutical company developing a new family of
immunotherapy products called Cell Drugs made of dendritic cells
loaded with antigens to fight cancer , infectious diseases and
auto-immune diseases.
|
|
|
|
|
|
(C)
|
|
IDM
and Biotecnol signed a Prototype Production Contract
(“Initial Contract”) on March 8, 2001. The
objective of the collaboration was to enable IDM to obtain a
preliminary process for the purposes of production of the molecule
Interleukine 13 (“IL-13”) using E. coil as a
host. Based on the final report sent by Biotecnol, a success fee of
[...***...] as been paid on August 2002. Intellectual Property
Rights resulting from the performance of the Initial Contract shall
be considered as Biotecnol’s Background Technology. The
Initial Contract shall be replaced by the Agreement.
|
|
|
|
|
|
(D)
|
|
Biotecnol and IDM have been pursuing
the IL-13 development since April 1 st , 2003, based on a letter of intent
executed by the Parties (“Letter of Intent” or
“LOI”).
|
|
|
|
|
|
|
|
THE PARTIES AGREE AS
FOLLOWS:
|
|
|
|
|
|
1.
|
|
DEFINITIONS & PURPOSE
|
|
|
|
|
|
|
|
In
this Agreement, unless the context otherwise requires, the
following words and expressions have the following
meaning:
|
|
|
|
|
|
|
|
“Affiliate”
means any company,
partnership or other entity which directly or indirectly controls,
is controlled by or is under the common control of either party, as
applicable; “control” means possession, directly
or indirectly, of more than 50% of the voting stock or other
ownership interest of another person or the power to direct or
cause the direction of the management and policies of such
person.
“Agreement” means this agreement, the Programme
and other schedules.
“Background Rights” means the Biotecnol
Background Patents, the Biotecnol
|
|
|
|
|
|
|
|
|
|
*
|
|
Confidential Treatment
Requested
under 17 C.F.R. §§ 200.80 (b)(4) and
240.24b-2(b)(1)
|
|
|
|
Background Technology, the IDM
Background Patents, the IDM Background Technology and the IDM
Materials.
|
|
|
|
|
|
|
|
“Biotecnol Background
Patents” means:
|
|
|
|
|
|
(a)
|
|
all
patent applications and patents, and any and all patents issuing
therefrom, including utility models, design patents and
inventor’s certificates, owned, controlled or licensed by
Biotecnol as of the Effective Date or developed, acquired, licensed
or otherwise obtained by Biotecnol, other than from IDM, during the
term of this agreement, together with any and all substitutions,
extensions (including supplemental protection certificates),
provisionals, divisionals, continuations, continuations-in-part,
re-examinations, re-issues, renewals, revalidations, additions,
substitutions, confirmations and registrations, as well as all
foreign counterparts or equivalents thereof anywhere in the world,
including without limitation all such patents and patent
applications.
|
|
|
|
|
|
(b)
|
|
all
patent applications owned, controlled or licensed by Biotecnol that
may be filed anywhere in the world, which either are based on or
claim priority from any of the foregoing patent applications or
patents, and any and all patents which may issue from any such
patent applications;
|
excluding all
patents and patent applications exclusively relating to inventions
within the Foreground Rights.
“Biotecnol Background
Technology” means
Biotecnol’s proprietary information, know-how, knowledge,
experience, inventions, improvements, processes, technology, ideas,
instructions, data and other technical or commercial information
and materials, including without limitation the Expression Vectors,
the Host Strains and the Expression Systems, and Biotecnol’s
proprietary molecular chaperones, fusion partners, fermentation
media and know-how and protein purification techniques, whether
owned, controlled or licensed by Biotecnol, but excluding any
Foreground Rights; the parties agree that inventions and results
from the performance of the Initial Contract shall be considered as
Biotecnol Background Technology.
“Business Day”
means any day on which banks
generally are open in the City of Lisbon and Paris for the
transaction of normal banking business.
“Confidential
Information” means
all oral or written information, data, Intellectual Property
Rights, processes, procedures, methods, know-how, knowledge,
experience and other valuable information relating to either
party’s business, whether of a financial, technical,
scientific, R&D-related, marketing, sales or legal nature, or
pertaining to its representatives, officers, employees, agents,
consultants or advisers, disclosed or provided by such party to the
other party pursuant to or in connection with the Agreement. The
Biotecnol Background Technology and all confidential information,
know-how, processes, procedures and methods employed by Biotecnol
in the Programme shall constitute Confidential Information of
Biotecnol; the IDM Background Technology, the IDM Materials and all
confidential information, know-how, processes, procedures and
methods employed by IDM in the Programme shall constitute
Confidential Information of IDM; the Foreground Rights
and all
confidential information, know-how, processes, procedures and
methods employed by both Parties in the Programme shall constitute
Confidential Information of the Parties; the Parties agree to
consider any information coming from the Sanofi-Synthelabo SA. or
Sanofi-Synthelabo S.A.’s Affiliates as Confidential
Information.
“Date” means the targeted date for release of Finished
Product, i.e. referred to as T10P3 in SCHEDULE 1.
“Delivery” means the written acknowledgement in Joint
Management Committee minutes, in connection to the Programme,
stating that any agreed milestone as described on the Programme has
been achieved.
“Drug
Master File or DMF” means a drug master file or equivalent required
for any regulatory approval from Regulatory Authority.
“Effective Date”
means April 1
st , 2003.
“End
of the Programme” means the end of the 36 (thirty six)
months’ stability studies on Finished Product.
“Expression System”
means a Host Strain containing an
Expression Vector directing the production of a protein, selected
by Biotecnol pursuant to and for the purposes of this Agreement,
and utilised by Biotecnol in the Programme.
“Expression Vectors”
means any vectors or gene expression
regulatory elements, whether in combination or not, owned,
controlled or licensed by Biotecnol, in each case for use in one or
more Host Strains.
“Field” means the use of IL-13 to differentiate
monocytes into dendritic cells to develop therapeutic
vaccines.
“Finished Product”
means the Product formulated in
vials usable for phase III clinical trial.
“Foreground Rights”
means all patents, patent
applications, know-how, inventions and improvements, whether
patentable or protectable through trade secret, resulting or
emerging from or generated in the course of the Programme, if
any.
“Host
Strain” means any
strain of E. coli owned by or the use of which is licensed
to Biotecnol.
" IDM
” shall mean Immuno-Designed Molecules S.A. and its
affiliated companies.
“IDM
Background Patents” means :
(a) all patent applications and patents, and any and all
patents issuing therefrom, including utility models, design patents
and inventor’s certificates, owned, controlled or licensed by
IDM as of the Effective Date or developed, acquired, licensed or
otherwise obtained by IDM, other than from Biotecnol, during the
term of this Agreement, together with any and all substitutions,
extensions (including supplemental protection certificates),
provisionals, divisionals, continuations, continuations-in-part,
re-examinations, re-issues, renewals, revalidations, additions,
substitutions, confirmations and registrations, as well as all
foreign
counterparts or
equivalents thereof anywhere in the world, including without
limitation all such patents and patent applications.
(b) all
patent applications owned, controlled or licensed by IDM that may
be filed anywhere in the world, which either are based on or claim
priority from any of the foregoing patent applications or patents,
and any and all patents which may issue from any such patent
applications.
" IDM
Background Technology” means IDM’s proprietary
information, know-how, knowledge, experience, inventions,
improvements, processes, technology, ideas, instructions, data and
other technical or commercial information, in the possession of IDM
or developed, acquired, licensed or otherwise obtained by IDM other
than from Biotecnol, excluding any Foreground Rights.
“IDM
Materials” means 5
vials of [...***...] and any and all other materials IDM
transferred to Biotecnol for the purpose of the
Agreement.
“Intellectual Property
Rights” means any
and all trade marks, rights in designs, get-up, trade, business or
domain names, copyrights, future copyrights, patents, rights in
databases (whether registered or not and any applications to
register or rights to apply for registration of any of the
foregoing), rights in inventions, know how, trade secrets and other
confidential information and all other intellectual property rights
of a similar or corresponding nature which may now or in the future
subsist in any part of the world.
“Manufacturing Period”
means the [...***...] period
starting upon release of the first successful Finished Product
batch.
“Process” shall mean the cGMP manufacturing, control,
testing and release processes of the Finished Product.
“Product[s]” means recombinant cGMP Interleukine-13
(“IL-13”).
“Programme” means the work to be performed by the Biotecnol
pursuant to this Agreement, as more specifically set out in
SCHEDULE 1. It is made of the Part 1 and Part 2, the
later one being subject to future financial charges which are not
included in actual consideration.
“Programme Materials”
means all cells, molecular
construction, working cell bank, master cell bank, assays, batches
or production lots of Product, generated in the course of the
Programme, containing or specifically dedicated to IL-13
development and manufacturing together with all documentation and
descriptions of and data pertaining thereto, other than Biotecnol
Background Technology and IDM Materials and IDM Background
Technology.
“Regulatory Authority”
shall mean, with respect to any
country, any regulatory agency, ministry, department or other
governmental body having authority in such country substantially
equivalent to the authority of the EMEA or the FDA in the European
Union and the United States of America respectively, to regulate
the development, manufacture, marketing, promotion or sale of
pharmaceutical products.
|
|
|
|
|
|
|
|
|
*
|
|
Confidential Treatment
Requested
under 17 C.F.R. §§ 200.80 (b)(4) and
240.24b-2(b)(1)
|
“Value
Added Tax” means
Value Added Tax or any other tax of a similar nature that may be
substituted for or levied in addition to it, in each case at the
rate current from time to time.
|
1.2
|
|
In
this agreement unless otherwise specified, reference to:
|
|
|
(a)
|
|
a
party means a party to this Agreement and includes its permitted
assignees and/or the respective successors in title to
substantially the whole of its undertaking;
|
|
|
|
|
|
|
|
(b)
|
|
a
person includes any person, individual, company, firm, corporation,
government, state or agency of a state or any undertaking (whether
or not having separate legal personality and irrespective of the
jurisdiction in or under the law of which it was incorporated or
exists);
|
|
|
|
|
|
|
|
(c)
|
|
a
statute or statutory instrument or any of their provisions is to be
construed as a reference to that statute or statutory instrument or
such provision as the same may have been or may from time to time
hereafter be amended or re-enacted;
|
|
|
|
|
|
|
|
(d)
|
|
words denoting the singular shall
include the plural and vice versa and words denoting any gender
shall include all genders.
|
|
1.3
|
|
The
index to and headings in this agreement are for information only
and are to be ignored in construing the same.
|
|
|
|
|
|
1.4
|
|
Purpose :
|
|
|
|
|
|
A
|
|
The
Agreement intends to expand upon the Initial Contract. Under the
Agreement, Biotecnol is assigned to complete the development
according to the Programme of a Process of IL13 to be transferred
to a designated GMP manufacturing sub-contractor for subsequent
cGMP manufacturing. The Process shall be developed as stated into
the Programme, and according to the current good manufacturing
practices (“cGMP”) and the current good
laboratory practices (“cGLP”) accepted by a
“Regulatory Authority” (as defined below) and in
particular the following applicable regulatory guidance documents
:
1.4.1 FDA “Points to Consider in the Production and Testing
of New Drugs and Biologicals Produced by Recombinant DNA
Technology” (1985)
1.4.2 FDA “Supplement to the Points to Consider in the
Production and Testing of New Drugs and Biologic & Produced by
Recombinant DNA Technology: Nucleic Acid Characterization and
Genetic Stability” (1992)
1.4.3 EMEA “Production and Quality Control of Medicinal
Products Derived by Recombinant DNA Technology”
(1995)
|
|
|
|
|
|
B
|
|
IDM
undertakes to let Biotecnol be in charge of the on-going management
of the outsourcing of manufacturing and release of Finished Product
for renewable five years period starting from the release of the
first Finished Product batch.
|
2.
OBLIGATIONS OF BIOTECNOL
|
|
|
Biotecnol shall undertake the work
specified in the Programme and shall use its reasonable endeavours
to ensure that such work is undertaken in accordance with the time
frames set out in SCHEDULE 1 and with all appropriate necessary
license. Outcome of the Programme shall be considered in terms of
(i) a Finished Product batch, (ii) a robust and
validation dependant, reproducible Process and all the
documentation related as required by the Regulatory Authority for
registration and approvals of IDM Cell Drugsand iii) a master
validation plan
|
|
|
|
|
|
2.1
|
|
Upon IDM request, Biotecnol shall
undertake to perform additional work described in Part 2 of
the Programme including comparability studies, formulation and
filling of Product into Finished Product, stability studies,
implementation of the validation plan beyond the first Finished
Product batch and CMC section writing.
|
|
|
|
|
|
2.2
|
|
At
IDM’s request, Biotecnol shall be in charge of the timely
preparation of a dossier containing the chemistry, manufacturing
and control information (“CMC section”) for the
IL-13 in accordance with 1.4.1, 1.4.2 and 1.4.3 for submission to
the Regulatory Authority. The Parties agree that the CMC section
shall include existing stability studies results. Biotecnol shall
also be in charge of updating the CMC section to reflect changes or
updates to the Process. Biotecnol shall also be in charge of
providing a timely response to any question on the CMC section from
Regulatory Authorities. IDM shall have an access and right to
review the CMC section as well as any responses to questions from
Regulatory Authorities related to the CMC section.
|
|
|
|
|
|
2.3
|
|
Biotecnol shall perform its
obligations in accordance with all applicable laws and generally
accepted good scientific practice, provided that Biotecnol shall
not be required hereby to seek or acquire any certification from
any Regulatory Authority that its facilities or procedures comply
with the good manufacturing practices or other standards
thereof.
|
|
|
|
|
|
2.4
|
|
Biotecnol shall co-operate
reasonably with IDM in undertaking the Programme in accordance with
this Agreement and shall act at all times in such a way as to
further the objectives of the Programme, provided that Biotecnol
shall be under no obligation to comply with any recommendations or
instructions of IDM, unless otherwise required so to do by the
Programme, the Joint Management Committee or the
Agreement.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
Biotecnol shall
ensure that the results of its work pursuant to the Programme are
recorded into laboratory notebooks. Such notebooks shall be
recorded according to scientific and intellectual property uses,
such as but not limited to signature of each page by the
investigator undertaking such work, validation by competent
authority and keeping in a safe and secure place.
|
|
|
|
|
|
|
|
|
|
(b)
|
|
Such notebooks
and the contents thereof shall be the property of Biotecnol,
subject to IDM’s requirements regarding the filing,
prosecution and maintenance of Foreground Rights, although IDM
shall, at its cost, be entitled on reasonable notice, whether
during or following the term of this Agreement, to inspect the same
and to take copies thereof.
|
|
|
|
|
|
|
|
|
|
(c)
|
|
Biotecnol shall
keep such notebooks and identify the same as containing the results
of its work pursuant to the Programme.
|
|
2.6
|
|
Biotecnol shall, whether during or
following the term of this Agreement, ensure that IDM has
reasonable access during working hours to all individuals involved
in undertaking the Programme for the purposes thereof, provided
that such obligation shall cease in respect of each such individual
upon the termination of their employment by Biotecnol.
|
|
|
|
|
|
2.7
|
|
Biotecnol shall , according to the
milestones defined on the Programme, and at the latest on a
quarterly basis, provide IDM with written reports of its progress
in undertaking the Programme.
|
|
|
|
|
|
2.8
|
|
Biotecnol will ensure that the
Process shall be acceptable in terms of compliancy to the
guidelines of the Regulatory Authorities and third party’s
Intellectual Property Rights.
|
|
|
|
|
|
|
|
During the Programme and the
Manufacturing Period, Biotecnol shall ensure appropriate cGLP or
cGMP compliance either by internal resources or though appropriate
consultancy whenever the work is required to be carried out
according to cGMP/cGLP.
|
|
|
|
|
|
2.9
|
|
During the Manufacturing Period,
Biotecnol undertakes to oversee the manufacturing outsourcer and
sub-contractors to deliver in a timely manner at an agreed upon
Transfer Price the batches and or quantity of Finished Product
according to IDM orders. Detailed terms and conditions necessary to
organise providing Finished Product to IDM shall be agreed upon in
a manufacturing agreement. The Parties agree to start negotiating
upon initiation of the first Finished Product batch.
|
|
3.1
|
|
IDM
shall perform the work specified in the Programme to be undertaken
by IDM and shall use its reasonable endeavours to ensure that such
work is undertaken in accordance with the time frames set out
therein.
|
|
|
|
|
|
3.2
|
|
IDM
shall perform its obligations pursuant to clause 3.1 in accordance
with all applicable laws and generally accepted good scientific
practices.
|
|
|
|
|
|
3.3
|
|
IDM
shall co-operate reasonably with Biotecnol in undertaking the
Programme in accordance with this Agreement and shall act at all
times in such a way as to further the objectives of the Programme,
provided that IDM shall be under no obligation to comply with any
recommendations or instructions of Biotecnol, unless otherwise
required so to do by the Programme, the Joint Management Committee
or the Agreement.
|
|
|
|
|
|
3.4
|
|
IDM
shall at its expense using reasonable efforts, deliver to
Biotecnol, such of the IDM Materials, the IDM Background Patents
and the IDM Background Technology related to the performance of the
Programme as Biotecnol notifies IDM that it considers to be
necessary for Biotecnol to perform its obligations hereunder or as
is otherwise specified in the Programme.
|
|
|
|
|
|
3.5
|
|
IDM
shall render to Biotecnol without charge such technical assistance
as Biotecnol may request to interpret and explain any written
information within those materials provided to Biotecnol in
accordance with clause 3.4 and as Biotecnol may otherwise
reasonably require to perform its obligations hereunder. Biotecnol
undertakes not to consider IDM as Breaching Party based on section
10.4 definition, because IDM (i) communicates information
related to the IL-13 development which interpretation is not
certain, (ii) does not communicate information related to the
IL-13 development
|
provided by
IDM’s corporate partners.
3.6 IDM shall
pay Biotecnol the fees specified in clause 4 for PART 1 of the
Programme upon Delivery. Upon IDM request of work specified in PART
2 of the Programme, the parties shall agree on
sub-contractors’ choice and financial support to be paid by
IDM.
|
3.7
|
|
Should IDM decide to complete the
validation of the Process as required by the Regulatory Authority,
IDM will pay
|
|
|
|
|
|
|
|
• the
number of Finished Product batches in excess to the one indicated
in the Programme which total shall amount to the number of
consecutive successful batches required by the Regulatory
Authority,
|
|
|
|
|
|
|
|
• the
work necessary for implementation of the validation master plan. In
that case, any additional Finished Product batch necessary to
validate the Process shall in no case be charged to IDM.
|
IDM financial
support to the PART 1 of the Programme, including an overall
Programme success fee, shall amount to [...***...] to be disbursed
on a milestones and Go/NoGo decisions basis. Main steps and
milestones payments are included in SCHEDULE 2 and coded “
T x P y” The financial support for PART 2 of
the Programme should be negotiated in good faith by the
parties.
IDM agrees to
pay Biotecnol the following amounts:
|
|
|
|
|
|
|
|
|
Payment
related
|
|
Definition
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon execution
of the LOI. Biotecnol hereby acknowledges that it has already
received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon
identification and confirmation of manufacturing
facility
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon successful
processing of functional IL13 at 10mg/liter according to the
specifications defined in the Programme or agreed upon by the Joint
Management Committee. T2P2 Delivery will trigger payments of: T4P2
and T5P2. Biotecnol hereby acknowledges that it has already
received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of cell banking; Biotecnol hereby acknowledges that it has already
received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon successful
master and working cell bank production
|
|
|
|
|
|
|
|
|
|
*
|
|
Confidential Treatment
Requested
under 17 C.F.R. §§ 200.80 (b)(4) and
240.24b-2(b)(1)
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon master and
working cell bank release according to specifications defined in
the PROGRAMME or agreed upon by the Joint Management
Committee
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of process development fermentation. Biotecnol hereby acknowledges
that it has already received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
to pursue
Process Development Fermentation, Biotecnol hereby acknowledges
that it has already received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon
fermentation protocol finalization
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon report on
reproducible laboratory fermentation process in three batches at
five (5) litres scale
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of process development Down Stream Processing (“ DSP
”). Biotecnol hereby acknowledges that it has already
received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
to pursue
Process Development of DSP, Biotecnol hereby acknowledges that it
has already received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon final
downstream processing protocol finalization
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon report on
reproducible downstream process in three batches at lab’s
scale
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of analytical methods development. Biotecnol hereby acknowledges
that it has already received such payment
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon linked to
SOP’s for process analysis and Product release
testing
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon a transfer
of methods to sub-contractor for validation
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon report of
completion of assays validation
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of process transfer
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon three
successful lab scale runs demonstrating reproducible
process at sub-contractor
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
Upon successful
pre-GMP pilot run, GMP process at large scaleof pilot plant
allowing for cGMP manufacturing meeting the specifications defined
during development work.
|
|
|
|
|
|
|
|
|
|
*
|
|
Confidential Treatment
Requested
under 17 C.F.R. §§ 200.80 (b)(4) and
240.24b-2(b)(1)
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon successful
audit of cGMP documentation prior to initiation of cGMP
manufacturing
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon initiation
of first Product batch
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
upon release of
first Product batch
|
|
|
|
|
|
|
|
|
|
[...***...]
|
|
The Programme
success fee allowing to use the Finished Product in Clinical
trials, upon successful release of Finished Product
|
|
4.1
|
|
Shall Biotecnol fail to deliver to
IDM the first Finished Product batch on the Date, due to the non
performance, fault or negligence from Biotecnol, , Biotecnol shall
be liable of late penalty payment. In the case of an Event of Force
Majeure, then Biotecnol shall not be liable for late penalty
payment.
|
|
|
|
|
|
|
|
Such penalty payment shall amount to
[...***...] per month of delay with a maximum not exceeding
[...***...] of total amount intended for the performance of the
Programme (i.e. total amount : [...***...]). Penalty payment shall
be credited against future invoices.
|
|
|
|
|
|
|
|
Biotecnol shall not be subject to
late penalty payment terms so long as the delay is the consequence
of IDM late decision or action .
|
Biotecnol shall
not be subject to such penalty if it is shown that the late
delivery by Biotecnol did not affect IDMs ability to pursue their
clinical trials program .
|
|
|
|
|
|
|
|
|
*
|
|
Confidential Treatment
Requested
under 17 C.F.R. §§ 200.80 (b)(4) and
240.24b-2(b)(1)
|
|
4.3
|
|
IDM
shall make all payments due pursuant to this clause 4 within twenty
(20) days of receipt of invoice. An invoice shall be paid by
IDM only if the invoice is following a Delivery .
|
|
|
|
|
|
4.4
|
|
Any
payments due in accordance with this clause 4 but not paid on the
due dates shall incur interest at a rate of four (4%) percent above
the lending rate from time to time of 3 M EURIBOR, such interest to
be compounded monthly.
|
|
|
|
|
|
4.5
|
|
The
sums specified in this clause 4 as payable by IDM shall be
exclusive of any due Value Added Tax.
|
|
|
|
|
|
4.6
|
|
The
price of IL-13 (“Transfer Price”) charged to IDM
shall be the Cost of Goods of the IL-13 calculated annually on the
basis of Biotecnol’s manufacturing expenses plus reasonable
allocations of sales and administrative overhead and a management
fee not to exceed twenty percent of the Costs of Good.
|
|
|
|
|
|
|
|
The
“Cost of Goods” shall also include any payments
or share of payment made by Biotecnol to its direct and indirect
licensors through multiple tiers of licenses that become due as a
result of the performance of this Agreement by Biotecnol or IDM.
The Cost of Goods shall not include any transportation insurance
policy and related cost, which shall remain IDM’s. Taxes if
applicable and goods transportation cost are not included in the
Cost of Goods but subject to reimbursement by IDM.
|
|
|
|
|
|
|
|
Upon reasonable advance written
notice, IDM shall have the right to audit the accounting documents
related to the Transfer Price during the Manufacturing Period at
Biotecnol. Detailed definition of Cost of Goods shall be agreed
upon in the manufacturing agreement referred to in section
2.10.
|
|
|
|
|
|
4.7
|
|
IDM
may decide not to renew after the Manufacturing Period the
outsourcing of manufacturing and release of IL-13 to Biotecnol upon
payment of cancellation fees. First termination notice shall be
communicated no later that than twelve (12) months prior to
the end of the Manufacturing Period. The amount of the cancellation
fees shall be agreed upon in good faith by the Parties and shall
not exceed the management fee of one Finished Product batch. This
amount shall decrease by twenty (20) percent per year
following the end of the Manufacturing Period.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
Following the
Effective Date, the parties shall form a joint management committee
(the “Joint Management Committee”), which shall
be responsible for promoting the co-operation of the parties in
accordance with this Agreement and in particular but without
limitation for assisting each party in:
|
|
|
(i)
|
|
monitoring and evaluating its
progress in undertaking the Programme;
|
|
|
|
|
|
|
|
(ii)
|
|
reporting such progress to the other
party;
|
|
|
|
|
|
|
|
(iii)
|
|
co-ordinating the parties’
co-operation in advancing the Programme; and
|
|
|
|
|
|
|
|
(iv)
|
|
proposing timelines in respect of
advancing the Programme and possibly modifying/updating the
Programme
|
|
|
|
|
|
|
|
(v)
|
|
agreeing on the completion of
milestones and in particular Delivery linked to payments as defined
in clause 4
|
|
|
|
|
|
|
|
(vi)
|
|
agreeing on the choice of
outsourcing company for cGMP, Cell Banking, Quality Control
development, Quality Control testing etc... based on expertise,
risk assessment, timing and pricing.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
The Joint
Management Committee shall comprise three (3) core
representatives of each party, who shall each be an employee,
officer or consultant of the party which they represent.
IDM’s representatives shall be the Director, Business
Expansion, the Director Manufacturing and the Director Quality
System. Biotecnol’s representatives shall be the Chief
Scientific Officer, the Chief Operating Officer and the Development
Manager .
|
|
|
|
|
|
|
|
|
|
|
|
Other persons,
including but not limited to regulatory representative will be
asked to contribute on an adhoc basis.
|
|
|
|
|
|
|
|
|
|
(b)
|
|
All members of
the Joint Management Committee shall have an ongoing familiarity
with the Programme and appropriate knowledge having regard to the
Joint Management Committee’s responsibilities.
|
|
|
|
|
|
|
|
|
|
|
|
Each party may
replace those core members of the Joint Management Committee which
it has appointed at will and at any time upon written notice to the
other party.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
The Joint
Management Committee shall meet as frequently as it chooses but in
any event no less often than once every twenty (20) Business
Days.
|
|
|
|
|
|
|
|
|
|
(b)
|
|
The Joint
Management Committee shall meet either by telephone conference call
or in person, provided that where the Joint Management Committee
meets in person, such meetings shall alternate between the
parties’ respective principal places of business or such
other locations as the Joint Management Committee may
agree.
|
|
|
|
|
|
|
|
|
|
(c)
|
|
All meetings of
the Joint Management Committee shall be conducted in English or
such
|
|
|
|
|
|
|
|
|
|
other language
as the Joint Management Committee may unanimously agree.
|
|
|
|
|
|
|
|
|
|
(d)
|
|
The quorum for
any key decision of the Joint Management Committee to be valid
shall be of at least one (1) core member appointed by each of
the parties
|
|
|
|
|
|
|
|
|
|
(e)
|
|
In the event
that both parties consent, third parties may attend meetings of the
Joint Management Committee as observers, provided that such
representatives are subject to binding obligations of
confidentiality in favour of the parties at least as restrictive as
those in this Agreement.
|
|
|
|
|
|
|
|
|
|
(f)
|
|
Each party
shall bear its own costs in connection with meetings of the Joint
Management Committee.
|
|
|
|
|
|
|
|
|
|
(e)
|
|
Joint
Management Committee minutes shall be draft by each party
alternatively no later than five (5) Business Days after the
meeting. The non-drafting party shall comment within five
(5) Business Days so as to communicate the final Joint
Management Committee minutes within ten (10) Business Days to
interested persons at each party.
|
|
5.5
|
|
Each party shall provide all
reasonable assistance to the Joint Management Committee in
assisting the Joint Management Committee to execute its
responsibilities hereunder.
|
|
|
|
|
|
5.6
|
|
The
Joint Management Committee shall have no authority to require
either party to take or to refrain from taking any particular steps
or other action, provided that this clause 5.6 shall not operate to
exempt either party from fulfilling its obligations pursuant to
this Agreement or the Programme.
|
|
|
|
|
|
5.7
|
|
If
the Joint Management Committee members disagree as to whether any
and/or what steps should be taken during the Programme, either
party may within twenty (20) days of such disagreement refer
the disagreement to the President of IDM and the CEO of Biotecnol.
In the event that within forty (40) days of referral to the
President & CEO of IDM and the CEO of Biotecnol the Parties
have failed to resolve the disagreement, either Party may refer the
disagreement to arbitration in Belgium who shall appoint an expert
to determine the dispute (the “Expert”). The decision
of the Expert, who shall act as expert and not as arbitrator shall
be final and binding on the Parties. The costs of the Expert shall
be shared equally.
|
6. SUB-CONTRACTING
AND OUTSOURCING
6.1 Principles
to be applied by Biotecnol during the Programme and the
Manufacturing Period:
6.1.1 Biotecnol
shall in all circumstances remain liable to IDM with regard to any
part of the Programme or Process it decided to sub-contract to
third parties.
6.1.2 Outsourcing
and sub-contracting agreements shall comply with the terms and
conditions set forth herein.
6.1.3 Biotecnol
undertakes in its name and on behalf of its outsourcers or
sub-contractors to cooperate with IDM if inspections by health
authorities are required with respect to Product, Finished Product
and Process.
6.1.4 Upon
reasonable advance written notice, IDM shall have the right to
inspect the facilities and the means used to perform the Programme
or the Process and later on during the Manufacturing Period at
Biotecnol and/or chosen sub-contractors or outsourcers to ensure
that the Programme or the Process is carried out in accordance with
cGMP, cGLP, rules and regulations, whenever the work needs to be
carried out according to the said cGMP, cGLP, rules and
regulations.
|
|
6.1.5
|
|
Biotecnol, its sub-contractors and
out-sourcers shall be held liable for any default in supply, such
as but not limited to contamination issue that may arise during the
Programme and the Manufacturing Period. IDM shall not be bound to
financial compensation in excess of the agreed upon Programme fees
and Transfer Price.
|
|
|
|
|
|
|
|
6.1.6
|
|
Regarding any outsourcing and
sub-contracting agreements, Biotecnol shall negotiate
that
|
|
|
(a)
|
|
in
case of early termination of the Agreement,
|
|
|
|
|
|
|
|
(b)
|
|
in
case of expiration of the Agreement,
|
|
|
|
|
|
|
|
(c)
|
|
in
case of Biotecnol’s bankruptcy, then
|
IDM shall be
entitled, at no costs and at its sole discretion, to substitute
itself to Biotecnol vis-à-vis the outsourcing and
sub-contracting party.
|
6.2
|
|
Principles specific to the Programme
performance :
|
|
|
6.2.1
|
|
Biotecnol is not authorised to
sub-contract or out-source the performance of its obligations
pursuant to clause 2.1 unless otherwise specified in the Programme,
the Agreement or authorised by the Joint Management
Committee.
|
|
|
|
|
|
|
|
6.2.2
|
|
However, IDM will allow Biotecnol to
outsource or sub-contract activities such as Cell Banking, QC
development, QC testing. Choices of sub-contractors or outsourcers
shall be agreed upon in accordance with section 5.1
(vi).
|
|
|
|
|
|
|
|
6.2.3
|
|
During the performance of the
Programme, Biotecnol shall be bound by late delivery penalties as
defined in Clause 4.2 even though the delay is due to
Biotecnol’s sub-contractors.
|
|
6.3
|
|
Principles specific to the
Manufacturing Period :
|
|
|
-
|
|
Biotecnol undertakes that it shall
take all reasonable means to sustain continued manufacturing
capabilities during the Manufacturing Period.
|
|
|
|
|
|
|
|
-
|
|
Biotecnol is not authorized to
substitute any sub-contractor or out-sourcer in charge of part or
all of the Process, which have been agreed upon during the
Programme performance by the Joint Management Committee without
prior adequate notice and authorization by IDM.
|
|
|
|
|
|
|
|
-
|
|
The
Parties evaluate the time for transferring the Process at 18
(eighteen) months. As a consequence the production agreement signed
by the sub-contractor or out-sourcer and Biotecnol shall provide
that:
|
|
|
•
|
|
in
the case where said production agreement is terminated, expired or
assigned, then IDM or any other person IDM may decide, shall
benefit from the production agreement rights and
obligations
|
|
|
|
|
|
|
|
•
|
|
any
without cause termination shall be given eighteen (18) months
in advance to ensure manufacturing continuity.
|
7.
INTELLECTUAL PROPERTY RIGHTS
|
|
|
|
|
|
|
|
|
(a)
|
|
Subject as
expressly provided in clause 7.5, Biotecnol is and shall remain the
sole owner or the licensee, as applicable, of all Intellectual
Property Rights in the Biotecnol Background Patents and Biotecnol
Background Technology.
|
(b) Subject
as expressly provided in clause 7.3, IDM is and shall remain the
sole owner or licensee, as applicable, of all Intellectual Property
Rights in the IDM Materials, the IDM Background Technology and the
IDM Background Patents and the Programme Materials.
|
7.2
|
|
IDM
acknowledges and agrees to the findings and recommendations
contained in the preliminary Biotecnol’s study of the freedom
to operate received On November 28, 2002 which drove some
technical choices of the Process. However during the development of
the Process, Biotecnol will take appropriate measures to verify
that the Process developed for IL-13 production and
commercialisation is not dependant upon third parties intellectual
property rights and will keep IDM informed, through a study update,
of this verification before executing the milestone of transfer to
pilot facility (T7P1). In case of such dependence, Biotecnol will
negotiate the license agreement required, and provide IDM or any
third party IDM shall require, with the opportunity to be assigned
in cases described below. In all cases where a license is to be
negotiated by Biotecnol, IDM shall be informed and will be given a
reasonable opportunity to comment on or discuss the
proposal.
|
With regard to the
above, Biotecnol shall negotiate that in case of early termination,
expiration of the Agreement, in case of Biotecnol’s
bankruptcy then :
|
|
(a)
|
|
IDM
shall be entitled, at no costs and at its sole discretion, to
substitute to Biotecnol itself or its affiliated, merging or
acquiring company vis-à-vis the licensing party.
|
|
|
|
|
|
|
|
(b)
|
|
IDM
shall remain the sole owner of all Foreground Rights.
|
|
7.3
|
|
IDM
hereby grants Biotecnol a non-exclusive royalty-free licence to use
any and all IDM Materials, IDM Background Technology and IDM
Background Patents disclosed or otherwise provided or available to
Biotecnol pursuant to this Agreement or otherwise, for the purpose
of permitting and assisting Biotecnol in performing its obligations
under the scope of the Agreement and exercising it rights pursuant
hereto.
|
|
|
|
|
|
7.4
|
|
Foreground Rights shall be jointly
owned by the Parties.
|
Biotecnol shall
promptly notify IDM, in writing, of any Foreground Rights conceived
and/or reduced to practice during the term of the Agreement. If the
parties deem it appropriate that a patent application be filed in
respect of such Foreground Rights, IDM shall be responsible for and
share with Biotecnol all costs incurred in connection with the
preparation, filing, prosecution and maintenance of European and
foreign patent applications. Biotecnol and IDM agree to negotiate
in a co-ownership agreement the percentage of patent ownership in
good faith and to apply said percentage to the sharing of costs
related. Biotecnol
shall be given
an opportunity to review and provide input into the scope and
content of any such preparation, filing and prosecution. IDM shall
supply Biotecnol with copies of main documents received or filed in
connection with the prosecution of such patents in sufficient time
so as to provide Biotecnol an opportunity to comment thereon, as
the case may be.
If IDM, for any
reason, declines responsibility for any such patent or patent
application, it shall provide reasonable prior written notice to
Biotecnol of such abandonment or decline of responsibility within
at least thirty (30) Business Days from any office action to
be decided.
In such an
event, Biotecnol shall have the right, at its expense, to prepare,
file, prosecute and maintain such patent rights, without divesting
IDM from its rights described hereof.
The parties
agree that neither parry shall be entitled to license or assign in
any way its part of patent ownership to third parties without the
other party’s agreement, which shall not be unreasonably
withheld. If, pursuant to the Agreement, any party licenses any
Foreground Rights to any third party, it shall reimburse on third
party’s income the other party for all reasonable attorney
fees and costs paid as a result of the prosecution, preparation,
filing and maintenance of such Foreground Rights.
|
7.5
|
|
Biotecnol hereby grants IDM a
payment-free non-cancelable worldwide exclusive license solely for
the “ Field ” (including the right to grant
sub-licences thereunder) of its share in respect of the Foreground
Rights and shall grant a licence on like terms under any patent
which IDM obtains pursuant to clause 7.3 (for the purposes of this
clause 7, a “ Patent ”), in all the countries in
which such patent protection is obtained, for the full duration of
such Patent. Should the Foreground Rights be used or licensed by
Biotecnol to manufacture IL-13 for use outside of the Field,
subject to Sanofi-Synthelabo S.A.’s approval — or from
Sanofi Synthelabo’s Affiliates’ approval, a royalty
compensation or a fixed payment to IDM shall be due to IDM. For the
sake of clarity and avoidance of doubt the choice between receiving
a royalty compensation or a fixed payment will be at IDM’s
sole discretion, and in either way will be negotiated in good faith
between the parties.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
Each party
shall inform the other party of any infringement or suspected
infringement of any Patent forthwith upon such infringement or
suspected infringement coming to its notice and shall provide such
other party with full particulars thereof.
|
|
|
|
|
|
|
|
|
|
(b)
|
|
If either party
becomes aware that any other person alleges that any Patent is
invalid or that the use of any Foreground Rights infringes any
rights of another party or that any such Patent is otherwise
attacked or attackable by a third party, it shall immediately give
the other party full particulars in writing thereof and shall make
no comment or admission to any third party in respect
thereof.
|
|
|
|
|
|
|
|
|
|
(a)
|
|
Both Biotecnol
and IDM shall have the conduct of all judiciary proceedings
relating to any Patents and shall jointly decide what action if any
to take in respect of any infringement or alleged infringement
thereof or any other claim or counterclaim brought or threatened in
respect of the use or registration thereof.
|
(b) Notwithstanding
the foregoing, in the event of any infringement or alleged
infringement of any Patent and in the event that either party
chooses not to pursue the infringer or alleged infringer thereof,
the other party may take all legitimate steps to halt any such
infringement and the abandoning party shall, at the other
party’s expense, provide all reasonable assistance to such
other party, (including without limitation the use of its name in
or being joined as a party to proceedings) in connection with such
steps.
|
7.8
|
|
Nothing in this Agreement shall give
or grant to either party any right in any trademark, patent or
other Intellectual Property Right of the other party expect as
specifically provided herein.
|
|
8.1
|
|
Each party shall, during the full
term of this Agreement and thereafter, keep secret and confidential
the contents of this Agreement and all Confidential Information of
the other party and shall not use or disclose the same to any
person, save to the extent necessary to perform its obligations
pursuant to this Agreement in accordance with its terms or save as
expressly authorised in writing to be disclosed by the other
party.
|
|
|
|
|
|
8.2
|
|
The
obligation of confidentiality contained in clause 8.1 shall not
apply or (as the case may be) shall cease to apply to details of
the contents of this Agreement or to Confidential Information
which:
|
|
|
(a)
|
|
at
the time of its disclosure by the disclosing parry is already in
the public domain or which subsequently enters the public domain
other than by breach of the terms of this agreement by the
receiving party;
|
|
|
|
|
|
|
|
(b)
|
|
is
already known to the receiving parry (as evidenced by written
records) at the time of its disclosure by the disclosing party and
was not otherwise acquired by the receiving party from the
disclosing party under any obligations of confidence;
|
|
|
|
|
|
|
|
(c)
|
|
is
at any time after the date of this Agreement acquired by the
receiving party from a third party having the right to disclose the
same to the receiving party without breach of obligation owed by
that third party to the disclosing party; or
|
|
|
|
|
|
|
|
(d)
|
|
is
required to be disclosed by applicable law or order of a court of
competent jurisdiction or government department or agency or the
rules and requirements of any other regulatory body, provided that
prior to such disclosure the receiving party shall advise the
disclosing party of the proposed form of the disclosure.
|
|
8.3
|
|
Notwithstanding the foregoing, each
parry may disclose Confidential Information of the other party and
details of the contents of this Agreement to its professional
advisors, and for IDM to Sanofi-Synthelabo S.A. or
Sanofi-Synthelabo S.A.’s Affiliates provided that they are
subject to obligations of confidentiality at least as restrictive
as those herein and the parties may disclose:
|
|
|
(a)
|
|
the
existence of this Agreement to its actual or potential financial
backers for the purposes of seeking or obtaining finance therefrom;
and
|
|
|
(b)
|
|
the
scope of the Programme for the procurement of
subcontractors
|
|
