DEVELOPMENT AND SUPPLY AGREEMENT between LONZA SALES AG and MICROMET AG
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
between
LONZA
SALES AG
and
MICROMET
AG
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
Table
of Contents
1.
|
Definitions
and Interpretation
|
3
|
2.
|
Provision
of the Works and Services
|
9
|
3.
|
Micromet's
Obligations
|
12
|
4.
|
Governance
|
13
|
5.
|
Inspections;
Person in Plant
|
14
|
6.
|
Delivery,
Transportation of Product and Testing
|
15
|
7.
|
Price
and Terms of Payment
|
17
|
8.
|
Intellectual
Property
|
17
|
9.
|
Warranties
and Indemnification
|
19
|
10.
|
Confidentiality
|
22
|
11.
|
Option
for [***]
|
24
|
12.
|
Termination
of the Agreement, Termination of Certain Works and Services or
Slots
|
24
|
13.
|
[***]
|
27
|
14.
|
Technology
Transfer and License
|
27
|
15.
|
Force
Majeure
|
27
|
16.
|
Governing
Law, Jurisdiction and Enforceability
|
28
|
17.
|
Notices
|
29
|
18.
|
Illegality
|
30
|
19.
|
Quality
Agreement
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30
|
20.
|
Miscellaneous
|
30
|
List
of Schedules:
|
31
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
2
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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THIS
DEVELOPMENT AND SUPPLY AGREEMENT is made the 23rd day of
November 2009 (the "Effective
Date")
BETWEEN
1.
|
LONZA
SALES AG, of Xxxxxxxxxxxxxxxxxxxxxx 00, XX-0000 Xxxxx, Xxxxxxxxxxx (herein
after referred to as "Lonza")
and
|
2.
|
MICROMET
AG, of Xxxxxxxxxxxxxxxxx 0, X-00000 Xxxxxx, Xxxxxxx (herein after referred
to as "Micromet").
|
WHEREAS
A.
|
Micromet
is the proprietor of the single-chain bispecific anti-CD19 antibody (CD19
BiTE®)
known as Blinatumomab or MT103 and controls a manufacturing process and a
cell line for manufacture of MT103;
and
|
B.
|
Lonza
has the expertise in the evaluation and production of monoclonal
antibodies for therapeutic use using different processes and cell lines in
accordance with international regulatory requirements;
and
|
C.
|
Micromet
and Lonza have previously entered into a Services Agreement dated
September 28, 2009 regarding the performance of a [***] to [***] for the
manufacturing of Micromet’s MT103 by Lonza;
and
|
D.
|
Micromet
wishes to contract Lonza for services relating to the development of the
Process (as defined herein) including all documentation, in each case,
suitable to obtain regulatory approval for commercialization of MT103 as a
therapeutic product and the manufacture of MT103 as described in this
Agreement, and
|
E.
|
Lonza
is prepared to perform such services for Micromet on the terms and
conditions set out herein.
|
NOW IT IS
AGREED AS FOLLOWS:
1.
|
Definitions
and Interpretation
|
The
following terms shall have the following meanings unless the context requires
otherwise:
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
3
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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"Affiliate"
|
means
any company, partnership or other entity which directly or indirectly
Controls, is Controlled by or is under common Control with the relevant
Party to this Agreement. "Control" or "Controlled" means the
ownership of more than fifty per cent (50%) of the issued share capital or
the legal power to direct or cause the direction of the general management
and policies of the Party in question;
|
|
"Agreement"
|
means
this Development and Supply Agreement and the Schedules hereto, as amended
or varied from time to time by written agreement of the
Parties;
|
|
"Batch"
|
means
the total Product (Drug Substance) obtained from one fermentation and
associated purification using the Process. Batches which are to
be produced in accordance with cGMP are also referred to as "cGMP
Batches";
|
|
"Batch
Release"
|
means
a release of any Batch by a Qualified Person for distribution or further
processing confirming that the Batch is in accordance with the relevant
requirements for human use (as defined in Directive 2001/83/EC for
medicinal products for human use);
|
|
"Cell
Line"
|
means
the cell line controlled by Micromet and selected by Micromet for the
production of the Product, particulars of which are set out in Schedule
1;
|
|
"CEO"
|
means
chief executive officer;
|
|
"cGMP"
|
means
current good manufacturing practices and general biologics products
standards as promulgated under the European Commission Directives
91/356/EEC, as amended by Directive 2003/94/EC, and 91/412/EEC
respectively; the International Committee for Harmonisation (ICH) Q7A
Guideline on Good Manufacturing Practice for Active Pharmaceutical
Ingredients; the U.S. Federal Food, Drug and Cosmetic Act found in Title
21 of the U.S. Code of Federal Regulations (CFR), including but not
limited to Parts 210, 211 and Parts 11, 310 et seq., 600 to
610, the European Commission Guidelines of Good Manufacturing Practices
for Medicinal Products as promulgated under European Directive 2003/94/EC
(Eudralex – Volume 4) and the respective Japanese directives and
guidelines by the Japanese authorities, as applicable. Lonza meets EU GMP
requirements as defined in Eudralex - Volume 4 Good Manufacturing
Guidelines by the European Commission for medicinal products for human and
veterinary use (EU-GMP Guidelines);
|
|
"cGMP
Product"
|
means
Product which is required under Schedule 2 to
be manufactured in accordance with
cGMP;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
4
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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"COO"
|
means
chief operating officer;
|
|
"Deliver",
"Delivered"
or "Delivery"
|
has the meaning given to it in Clause 6; | |
"Deliverables"
|
means
the reports, documentation, information, material and Product which Lonza
is to make available to Micromet during the Project. The Deliverables and
the timelines to provide the Deliverables are set forth in the Project
Plan in Schedules
8 A and 8 B hereto;
|
|
"Engineering
Batch"
|
means
the first Batch at scale after the pilot Batch in which Lonza will use
commercially reasonable efforts but does not warrant to meet
cGMP;
|
|
"External
Laboratories"
|
means
any Third Party instructed by Lonza, with Micromet’s consent, to conduct
activities required to complete the Works and Services, including but not
limited to, Third Parties that synthesise DNA or perform tests on the Cell
Line, Product or materials derived therefrom;[***]
|
|
"Intellectual
Property"/"IP"
|
means
all intellectual property rights, including (without limitation) patents,
patent applications, divisions, continuations, continuation-in-part
applications, divisionals, substitutions, confirmations, supplementary
protection certificates, reissues, utility models, trademarks, database
rights and copyrights and all inventions, know-how, trade secrets,
techniques and confidential information and other proprietary knowledge
and information which may subsist anywhere in the world, in each case for
their full term, and together with any renewals or
extensions;
|
|
"Lonza"
|
means
Lonza Sales AG and its Affiliates Lonza Biologics plc of Slough, England,
Lonza Biologics Inc of Portsmouth, NH, USA, and Lonza Biologics Xxxxxxx
X.X. of Pontevedra-Galicia, Spain, and their successors in title and
lawful assigns;
|
|
"Lonza
Confidential Information"
|
means
and includes Lonza Technology, any trade secrets or other confidential
information relating to Lonza's technology, business affairs or finances
of Lonza, or of any suppliers, agents, distributors, licensees or other
customers of Lonza and the commercial terms of this
Agreement;
|
|
"Lonza
Know How"
|
means
all technical and other information relating directly or indirectly to the
Lonza Process and/or the performance of the Works and Services, known to
Lonza from time to time, other than Micromet Confidential Information,
Micromet Know How and information in the public domain. Without limiting
the foregoing, the Lonza Know How is identified in Schedule
4
hereto;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
5
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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"Lonza
Patent Rights"
|
means
all patents, patent applications, divisions, continuations,
continuation-in-part applications, divisionals, extensions, substitutions,
renewals, confirmations, supplementary protection certificates and
reissues, throughout the world relating to the Lonza Process and/or the
performance of the Works and Services which from time to time Lonza is the
owner of or is entitled to use, and that is used in the performance of the
Works and Services. Without limiting the foregoing, the Lonza Patent
Rights as of the Effective Date are listed in Schedule
5 hereto;
|
|
"Lonza
Process"
|
means
the proprietary process of Lonza, including any modifications and
improvements, which is used for the manufacture of the Product
hereunder;
|
|
"Lonza
Technology"
|
means
the Lonza Know How and the Lonza Patent Rights;
|
|
"[***]"
|
means
[***];
|
|
"[***]"
|
means
the [***] Agreement between [***] and [***] dated [***] and attached
hereto at Schedule 9;
|
|
"Micromet"
|
means
Micromet AG and its existing Affiliates which are engaged in the research
and development of BiTE®
antibodies, and their successors in title and lawful
assigns;
|
|
"Micromet
Confidential Information"
|
means
and includes Micromet Materials, Micromet Technology and the Results, any
trade secrets or other confidential information relating to Micromet's
technology, development strategies, business affairs or finances of
Micromet, or of any licensors, suppliers, agents, distributors or other
contractors of Micromet, and the commercial terms of this
Agreement;
|
|
"Micromet
Know How"
|
means
all technical and other information relating directly or indirectly to the
Micromet Process, the Cell Line and the Micromet Materials, known to
Micromet from time to time, other than Lonza Confidential Information,
Lonza Know How and information in the public domain. Without limiting the
foregoing, the Micromet Know How is identified in Schedule
6 hereto;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
6
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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"Micromet
Materials"
|
means
the materials and documentation supplied by Micromet to Lonza (including
but not limited to [***]). Without limiting the foregoing, the Micromet
Materials to be transferred are listed in Schedule
1 hereto;
|
|
"Micromet
Patent Rights"
|
means
all patents, patent applications, divisions, continuations,
continuation-in-part applications, divisionals, extensions, substitutions,
renewals, confirmations, supplementary protection certificates and
reissues, throughout the world relating to the Micromet Process, the Cell
Line and the Micromet Materials which from time to time Micromet is the
owner of or is entitled to use, and that is used in the performance of the
Works and Services. Without limiting the foregoing, the Micromet Patent
Rights as of the Effective Date are listed in Schedule
7 hereto;
|
|
"Micromet
Process"
|
means
the process (including but not limited to the [***]) for the production of
Product which is owned or Controlled by Micromet and made available to
Lonza hereunder [***], further improvement and/or production of the
Product;
|
|
"Micromet
Technology"
|
means
the Micromet Know How and the Micromet Patent Rights;
|
|
"[***]"
|
means
[***], including [***];
|
|
"MT103"
|
means
Micromet's single-chain bispecific anti-CD19 antibody (CD19 BiTE®)
also known as Blinatumomab;
|
|
"Party"/"Parties"
|
shall
mean Lonza or Micromet, or Lonza and Micromet, as the context
admits;
|
|
"Price"
|
means
the price specified in Schedule
3 for the Works and Services;
|
|
"Process"
|
means
the process used by Lonza for the production of Product from the Cell Line
in accordance with this Agreement, which may [***] of the [***], and is
modified and/or improved hereunder;
|
|
"Product"
|
means
MT103 manufactured under this Agreement (including any sample thereof),
particulars of which are set out in Schedule
1 and includes all derivatives thereof;
|
|
"Project"
|
means
the program described in the Project
Plan;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
7
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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"Project
Manager"
|
means
a Party's representative who is responsible for the coordination and
supervision of the Project in accordance with Clause 4.1
below;
|
|
"Project
Plan"
|
means
the plan describing all activities to be performed under this Agreement,
including any update and amendment of the Project Plan the Parties may
agree from time to time, and attached hereto as Schedules
8 A and 8 B;
|
|
"Project
Team"
|
means
the working group described in Clause 4.2;
|
|
"Qualified
Person"/"QP"
|
means
a person confirming that the Batch is in accordance with the relevant
requirements (as defined in Directive 2001/83/EC for medicinal products
for human use);
|
|
"Results"
|
means
the Product, any inventions, discoveries, know how, data, Deliverables,
documentation, reports, materials, writings, processes, methods and other
information, recorded in any form, that are discovered, conceived, reduced
to practice, developed or otherwise generated by Lonza, which are related
to the Works and Services and conceived through the performance of the
Works and Services, and any Intellectual Property pertaining to any of the
foregoing (including the [***]), provided,
however, that "Results" shall exclude [***];
|
|
"Service
Agreement"
|
means
the agreement between the Parties dated September 28, 2009 regarding [***]
for the production of Product [***];
|
|
"Specifications"
|
means
the specifications for Drug Substance. The Specifications and the
specifications for Drug Product regarding the testing of Drug Product by
Lonza are set out in Schedule
2;
|
|
"Steering
Committee"
|
means
the committee described in Clause 4.3;
|
|
"Terms
of Payment"
|
means
the terms of payment specified in Schedule
3;
|
|
"Third
Party"
|
means
any party other than Lonza and Micromet;
|
|
"Works
and Services"
|
means
all or any part of the works and services which are the subject of this
Agreement, particulars of which are set out in Schedules
8 A and 8
B.
|
References
to the singular number include the plural and vice versa, references to Clauses
and Schedules are references to clauses and schedules to this
Agreement.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
8
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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2.
|
Provision
of the Works and Services
|
2.1
|
Lonza
shall diligently carry out the Works and Services as provided in Schedule 8 A –
and in Schedule
8 B, once it is finalized - and shall use all reasonable efforts to
achieve the estimated timescales set out in that Schedule. The
Parties agree that the Works and Services set forth in Schedule 8 B are
rough estimates only, and the Parties shall updated and refine such
Schedule 8 B after the transfer of the Micromet Materials and
establishment of the Process at Lonza. Lonza shall perform the
Works and Services under this Agreement according to the current industry
standards and subject to terms and conditions as set out
herein. Lonza shall at all times use reasonable and adequate
safety and protection measures to ensure, as far as is reasonably
possible, that the Results are not endangered by an interruption of
Lonza's research and development
activities.
|
2.2
|
Lonza
shall do all that is reasonably possible to meet the objectives under the
Project Plan, including diligence obligations and commercially reasonable
flexibility regarding alternative work packages and capacity reservations
under this Agreement.
|
2.3
|
Micromet
shall make available to Lonza a data package comprising the Micromet Know
How which is reasonably required to perform the Works and Services and the
Parties shall collaborate to assist Lonza in evaluating such Micromet Know
How. Without undue delay upon completion of the Services
Agreement and delivery of such Micromet Know How, however, no later than
within [***] thereafter, Lonza shall inform Micromet whether the [***],
the [***] and the [***] meet the particulars set out in Schedule 1 and
are suited for the performance of the Works and [***]. If the
[***], the [***] and/or the [***] do not meet the particulars set out in
Schedule
1, Lonza and Micromet shall enter into good faith discussions in
order to identify a [***], a [***] or other [***] for the Works and
Services and to agree on the terms and conditions and adjustments to the
Project Plan to minimize any delay. If the Parties are unable
to agree on an [***] or [***] and the [***] after completion of the later
of (i) completion of services under the Services Agreement or (ii)
transfer of the Micromet Materials and Micromet Technology,
[***].
|
2.4
|
Lonza
shall manufacture cGMP Product to meet the Specifications [***] manufactured or
in respect of the [***]. If the [***] or a combination of the
[***] and the [***] is used, then in addition to the above, Lonza shall be
under no obligation to meet [***] [***]. In the event the [***]
does not meet the Specifications, the Parties shall promptly meet through
the Steering Committee to discuss and agree on how to ensure that the
Specifications can be met, which agreement may include a modification of
the Project Plan.
|
2.5
|
Owing
to the unpredictable nature of the biological processes involved in the
Works and Services, the timescales set down for the performance of the
Works and Services (including without limitation the dates for production
and Delivery of Product) and the quantities of Product for Delivery set
out in Schedules
8 A and 8 B are estimated only. In the event any Party
realizes that the Project Plan needs to be changed, e.g., for a delay of
Works and Services owing to technical or scientific difficulties, such
Party shall immediately inform the Project Team hereof and the Parties,
through the Steering Committee (if needed), shall use commercially
reasonable efforts to come to an adequate solution and agree on an
adequate amendment of the Project Plan. In particular, Lonza
will use commercially reasonable efforts to [***] as early as possible, in
the event any of the [***], provided always that
[***] are taken into account.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
9
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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2.6
|
Lonza
will use its reasonable efforts to perform any additional work which may
become necessary to manufacture Product for [***]. If such
additional work leads to additional costs, Lonza will provide a quotation
for such additional work. In case the Parties agree on the
additional work and the costs for such additional work, Lonza shall
perform additional work to sustain the progress of the Project on terms
and conditions to be agreed by the Parties and defined in an amendment to
the Project Plan. If further quantities of Product are required
[***] which are not part of this Agreement, the Parties will discuss in
good faith how Lonza can satisfy Micromet's needs for such additional
quantities.
|
2.7
|
Without
prejudice to Lonza’s obligations under Clauses 2.1 and 2.2 and the
termination rights under Clause 12, Micromet [***] of the Works and
Services or to [***] on grounds of late performance, late Delivery or
failure to produce the estimated quantities of Product for
Delivery. Lonza shall not be liable for any loss, damage, costs
or expenses of any nature, whether direct or consequential, occasioned
by:
|
(a)
|
[***];
or
|
(b)
|
[***].
|
However,
and to the extent, that (i) [***], [***] [***].
2.8
|
Lonza
shall comply with all applicable laws and regulations regarding the cGMP
production, including but not limited to the EU-GMP Guidelines (Eudralex –
Vol. 4), FDA regulations, Japanese regulations and the International
Committee for Harmonisation regulatory requirements from time to time
applicable to the Works and Services as set out in Schedules 8 A and 8
B.
|
2.9
|
Lonza
shall not use the Cell Line, the Process (not including the Lonza
Process), the Micromet Materials or the Micromet Technology (or any part
thereof) for any purpose other than the performance of the Works and
Services under this Agreement.
|
2.10
|
Lonza
shall:
|
|
(a)
|
at
all times use all reasonable endeavours to keep the Cell Line and/or the
Micromet Materials secure and safe from loss and damage in such manner as
Lonza stores its own material of similar nature during the term of this
Agreement, and obtain and maintain an appropriate insurance against the
risks of loss and damage;
|
|
(b)
|
during
the performance of the Works and Services, inform Micromet as soon as
reasonably possible upon request about all ongoing
activities;
|
|
(c)
|
not
part with possession of the Cell Line and/or the Micromet Materials or the
Product, save for the purpose of activities at the External Laboratories
or as otherwise authorised in writing by
Micromet;
|
|
(d)
|
store
Micromet Materials in accordance with applicable laws, industry standards
and the specifications set forth in Schedule 1,
furthermore, store the Cell Line and the cell banks ([***]) at at least
two (2) different and controlled sites under cGMP
conditions;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
10
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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|
(e)
|
audit
all External Laboratories in accordance with GxP guidelines and confirm
the performance of such audit to Micromet in writing;
and
|
|
(f)
|
procure
that all External Laboratories are subject to obligations of confidence
substantially in the form of those obligations of confidence imposed on
Lonza under this Agreement.
|
2.11
|
Lonza
will not (i) directly or indirectly, take any steps to ascertain [***]
provided by Micromet and or a [***], and (ii) use Micromet's [***] for any
purpose other than manufacturing the Product. In the event
Lonza ascertains or receives the recipe of any of Micromet's [***] through
no fault of its own, Lonza shall promptly inform Micromet of such event
and destroy such information.
|
2.12
|
Lonza
and Micromet will exchange details of [***]. Lonza will obtain
Micromet's consent regarding [***], which Micromet shall not unreasonably
withhold. Lonza shall use reasonable commercial endeavours to
ensure continuity of supply, [***].
|
2.13
|
Lonza
agrees to maintain proper records (the "Records") in respect of
its performance of the Works and Services, including any Results made as
part of the Works and Services. Upon written request by
Micromet, Lonza shall provide copies of the Records or any part(s)
thereof, redacted with regards to [***] and [***] to
Micromet. As part of keeping the Records, Lonza shall ensure
that all of its personnel and all of its agents abide by the regulations
of the International Committee for Harmonisation as per Clause
2.8.
|
2.14
|
Lonza
shall:
|
|
(a)
|
make
available to Micromet the Deliverables set forth in the Project
Plan;
|
(b)
|
make
available to Micromet (i) upon completion of any milestone as outlined in
the Project Plan and or (ii) [***] and upon reasonable request of
Micromet, (i.e., if Micromet requires such documentation for regulatory
purposes or for own development purposes andprovided that such
documentation – in Lonza's reasonable opinion – is accurate); copies of
all relevant documentation and information resulting from the Works and
Services and relating to the Product in order to enable Micromet to
evaluate the status and to meet any statutory or regulatory
requirements. The documentation and information shall be
provided in the CTD format. The documentation and information
shall include but not be limited to
[***];
|
|
(c)
|
support
IND updates and CTAs as well as the submission of dossiers for NDA/MAA
approval;
|
|
(d)
|
make
available to Micromet, upon completion of each stage as outlined in the
Project Plan and upon request of Micromet, material ([***]) resulting from
the Works and Services in order to enable Micromet to test the
supernatant, antibody, cells, Product, and the
like;
|
|
(e)
|
assist
Micromet in respect to regulatory requirements concerning the CMC-part,
including but not limited to the
[***];
|
|
(f)
|
reasonably
support Micromet regarding regulatory matters. Such support
shall include an obligation to make Micromet aware of any specific
regulatory requirements relating to Lonza’s activities, to accompany
Micromet to meetings with the regulatory authorities upon [***] prior
written notice by Micromet (or use reasonable commercial endeavours to
support Micromet where shorter notice is provided by a regulatory
authority), to prepare such meetings jointly with Micromet, and to
actively participate in scientific advice meetings;
and
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
11
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|
(g)
|
promptly
inform Micromet about any [***].
|
|
The
Deliverables and the provision of the Deliverables are defined in more
detail in the Project Plan.
|
2.15
|
Lonza
shall from time to time offer to Micromet [***] [***] (as identified in
Schedule 4). Such new version shall be made available at the
price set forth in the Technology Transfer and License Agreement in Schedule 14
hereto, if applicable, with the only further compensation being for
additional Works and Services which may be required to implement such
improvement or new version for the manufacture of the
Product.
|
2.16
|
Any
subcontracting of Works and Services to be performed hereunder by Lonza to
Third Parties requires the prior written consent of
Micromet.
|
3.
|
Micromet's
Obligations
|
3.1
|
Following
the Effective Date (if not already forwarded to Lonza during the Services
Agreement) and upon conclusion of [***] attached hereto as Schedule 9,
Micromet shall supply to Lonza the Micromet Know How, together with full
details of any hazards relating to the Cell Line, the Micromet Process
and/or the Micromet Materials, their storage and use, in each case, to the
extent required by Lonza to perform the Works and Services. For
the avoidance of doubt, the [***] is embodied in the [***] and is not
disclosed as a separate set of documents. On review and
approval by Lonza’s safety committee of this Micromet Technology, the Cell
Line, the Micromet Process and/or the Micromet Materials shall be provided
to Lonza at Lonza’s request. Property in the Cell Line, the
Micromet Process and/or the Micromet Materials and/or the Micromet
Technology supplied to Lonza shall remain vested in
Micromet.
|
3.2
|
Unless
the Parties agree otherwise during the term of this Agreement, Micromet or
Micromet's Third Party supplier will supply to Lonza the [***] necessary
for the manufacture of Product. Lonza shall not, directly or
indirectly, take any steps to [***] provided by
Micromet. Similarly, should the Lonza Process be used in
the manufacture of the Product, Micromet shall not, directly or
indirectly, take any steps to [***] provided by
Lonza.
|
3.3
|
Micromet
shall pay the Price set out in Schedule 3 for
provision of the Works and Services together with any additional costs and
expenses that fall due under this Agreement in accordance with the Terms
of Payment.
|
3.4
|
Micromet
hereby grants Lonza the non-exclusive right to use the Cell Line, the
Micromet Process, the Micromet Materials, and the Micromet Technology
during the term of this Agreement and solely for the purpose of this
Agreement. Micromet acknowledges that Lonza does not require a
separate licence to Micromet Confidential Information as all necessary
licences are contained in the first sentence of this clause
3.4.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
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3.5
|
From
time to time, as soon as reasonably possible and with at least [***]
advance notice, Lonza may submit to Micromet a written request to provide
or have provided consulting services to Lonza with respect to the Micromet
Process, which request will include the specifics of the consulting
services being requested, and Micromet will use reasonable efforts to
provide or have provided such consulting
services.
|
4.
|
Governance
|
4.1
|
Designation of Project
Manager: Lonza and Micromet shall each identify a
Project Manager who will be responsible for the coordination and
supervision of the Project including communication of all instructions and
information concerning the Project to the other Party. A
written protocol of such communication shall be provided by the Project
Managers. Each Project Manager will be available on an agreed
weekly basis for consultation at prearranged times during the course of
the Project. In the absence of the Project Manager, a
substitute shall be appointed. Additional modes or methods of
communication and decision making may be implemented with the written
consent of each Party.
|
4.2
|
Project
Team: The Parties shall form a Project Team to which
Micromet will delegate professionally and technically qualified
representatives (e.g., qualified in upstream process, downstream process,
analytics, quality assurance and regulatory matters). Each
Project Team member shall have knowledge and ongoing familiarity with the
Project and will possess the authority to make decisions on matters raised
in the Project Team. Each Party shall have the right to
substitute different representatives as its members of the Project Team as
needed from time to time. Each Party shall also be entitled to
invite other employees as ad hoc guests to address specific technical or
commercial issues related to the Project. Consultants of a
Party or other Third Parties may be invited, provided that they are
bound by a confidentiality obligation which is substantially similar to
the Parties' obligations under Clause 10
below.
|
The
Project Team shall meet within [***] after written request for such meeting by
either Party, or sooner, if required, and meetings shall take place on a [***],
and at least one face-to-face meeting shall take place [***].
|
The
Project Team shall oversee the Project. Prior to each meeting
of the Project Team the Parties will distribute to each other written
copies of all materials, data and information arising out of the conduct
of their activities hereunder. Unless otherwise agreed, Lonza
shall present any suggestions regarding the Project Plan and/or
specifications of the Project to the Project Team for discussion and
approval by Micromet.
|
|
Each
Party shall bear its own travel and accommodation costs. The
meetings of the Project Team may also be held by telephone or video
conference if mutually agreed by the Project Team members. It
is the right of each Party to call for a Project Team meeting upon written
request at any time. In that case the meeting will be held at a
time and location to be agreed between the Project Team
members.
|
|
The
inviting Party shall prepare minutes of the meeting which shall be
circulated promptly following the
meeting.
|
4.3
|
Steering
Committee: The Parties shall form a Steering Committee
to which each Party will delegate two (2) executive employees, who are
familiar with the Project. The Steering Committee shall have
general oversight and review of the activities of the Project Team and
shall be responsible for resolving any issues referred to the Steering
Committee by the Parties.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
13
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Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
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|
The
Steering Committee shall meet in person or via teleconferences within
[***] after a written request by either Party to the other Party, or
sooner, if required, and calendar quarterly, if possible towards the end
of a stage of the Project. The request shall describe the
matter in dispute and the solution which the requesting Party proposes to
be decided.
|
|
The
Steering Committee will take action by unanimous consent of its members,
with each representative having a single vote, or by a written resolution
signed by all of the representatives. If the Steering Committee
is unable to reach unanimous consent on a particular matter, then the
matter will be referred to a personal face-to-face meeting between Lonza's
[***] and the [***] of Micromet, who in each case may not be a member of
the Steering Committee and both of whom shall act in good faith and
discuss the issue to seek a resolution amicably acceptable to both Parties
and if resolved the resolution shall be binding and final. The
meeting shall take place within [***] of the relevant
referral. In case such persons cannot agree within further
[***] after such face-to-face meeting, then the following shall
apply:
|
|
(i)
|
If
the dispute is predominantly concerned with scientific or technical issues
then [***]: [***]. The Parties will make available
the same set of documents to [***] and both experts shall provide [***] in
English language within [***] after the [***] has been
[***]. If [***] experts come to dissenting opinions and are
unable to solve the dispute among themselves, [***] shall be appointed
[***], if the Parties cannot agree, [***]. Such [***] shall
have access to the written opinions of [***] as well as to all documents
which were made available to [***]. The [***] shall then [***]
of [***], and such opinion [***] shall be considered final and binding on
the Parties except if there has been a manifest error on the face of the
decision whereupon the Parties may revert to their respective remedies
under Clause 16 below. The reasonable costs of [***] shall be
paid or refunded, as the case may be, by the non-prevailing
Party.
|
|
(ii)
|
If
the dispute is predominantly concerned with an issue other than scientific
or technical then it shall be resolved in accordance with Clause 16
below.
|
5.
|
Inspections;
Person in Plant
|
5.1
|
As
more fully set out in the Quality Agreement in Schedule 10
hereto, Lonza grants to Micromet and/or its consultant the right to
inspect and audit Lonza's Affiliate’s facility located in Slough,
Berkshire, United Kingdom ("Facility") as well as
the documentation generated in connection with the manufacture and testing
of Product including all relevant standard operating procedures.
Lonza grants the right to perform [***] cGMP compliance audit per year,
[***] at a time mutually agreed between Micromet and Lonza. Micromet
can perform [***] cGMP batch documentation audit per cGMP batch which
would be scheduled as appropriate in the project plan. Moreover,
Micromet is entitled to perform additional audits in the event of
complaints, major or critical deviations or other enquiries by regulatory
authorities without any fee, and if necessary, on short-term notice.
Micromet will discuss the results of any inspection with
Lonza. Any inspection by Micromet does not relieve Lonza of its
obligations to comply with all applicable laws and does not constitute a
waiver of any right otherwise available to Micromet. As more fully
set out in Clause 5.3, [***] is also entitled to attend all production
campaigns of the Product at the
Facility.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
14
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Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
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5.2
|
As
more fully set out in the Quality Agreement in Schedule 10
hereto, an employee and/or consultant and /or successor of Micromet or
Micromet’s sublicensee(s) of the Product will have the right to be present
[***]. Furthermore, Lonza will inform Micromet of the results of any
inspection by a regulatory authority (subject to any restraints placed on
Lonza by such regulatory authority, Lonza Confidential Information which
Micromet does not require for purposes of this Agreement or customer
confidentiality) that does or could reasonably be expected to affect the
manufacture of Products.
|
5.3
|
Lonza
agrees to have an employee or consultant of Micromet be present at the
Facility in order to observe the Works and Services performed by Lonza or
its Affiliate ("Person-in-Plant" or
"PiP") in
accordance with this Clause 5.3. Upon request of Micromet,
Lonza shall grant the PiP access to the Facility where the Works and
Services are performed. Such visits, shall last [***], will
take place [***] during regular business hours and [***] prior notice to
Lonza, provided,
however, that PiP will be entitled to perform additional visits
that could [***] manufacturing process subject to Lonza’s consent not to
be unreasonably withheld or delayed, and further provided that PiP will be
entitled to perform visits upon immediate notice in the event of
complaints or failures which may endanger the
Project.
|
5.4
|
Notwithstanding
Clauses 5.1, 5.2 and 5.3, Micromet acknowledges and accepts that the
Facility is a multi-customer facility, and that the PiP’s movement about
and access to the Facility may be restricted and shall be subject to
supervision by Lonza.
|
6.
|
Delivery,
Transportation of Product and
Testing
|
6.1
|
Subject
to Clause 2.4, Product shall be Delivered in accordance with the
Specifications. Delivery shall be made [***] (as defined by
Incoterms 2000) which means (a) [***] and (b) [***]. Subject to
Clause 6.2, Lonza shall deliver to Micromet the Certificate of Analysis,
the Certificate of Compliance, issued by and in responsibility of a
Qualified Person (Batch Release) and such other documentation as is
reasonably required to meet all applicable statutory and regulatory
requirements not later than the date of
Delivery. Transportation of Product, whether or not under any
arrangements made by Lonza on behalf of Micromet,
[***].
|
6.2
|
At
Micromet's request, Lonza will Deliver Product [***]. Such
request shall be accompanied by Micromet's written acknowledgement that
the Product has been Delivered without the transmittal to Micromet of the
Certificate of Analysis and the Batch release documents (QP release), that
accordingly the Product cannot be administered to humans until transmittal
of the Certificate of Analysis, Certificate of Compliance (possibly in one
document) and the Batch release documents (QP release) and that Micromet
nevertheless accepts full risk of loss, title and ownership of the
Product. The Delivery of Product in quarantine shall be subject
to such testing requirements as Lonza may reasonably require, and the
[***] period referred to in Clause 6.9 shall run from Delivery in
quarantine of the Product to
Micromet.
|
6.3
|
Unless
otherwise agreed, Lonza shall package and label Product for Delivery in
accordance with its standard operating procedures. It shall be
the responsibility of Micromet to inform Lonza in writing in advance of
any special packaging and labeling requirements for
Product. All additional costs and expenses of whatever nature
incurred by Lonza in complying with such special requirements shall be
charged to Micromet in addition to the
Price.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
15
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Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
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|
6.4
|
If
requested in writing by Micromet, Lonza will (acting as agent for
Micromet) arrange for storage in accordance with the storage conditions in
Schedule
1 and for insurance of Product whilst held by Lonza after Delivery
(awaiting transportation) for up to [***] after QP release of the Batch,
and in exceptional cases for a maximum of [***], on terms equivalent to
those under which Lonza stores and insures product prior to
Delivery. All additional costs and expenses of whatever nature
incurred by Lonza in arranging such storage and insurance shall be charged
to Micromet in addition to the
Price.
|
6.5
|
If
requested in writing by Micromet, Lonza will (acting as agent of Micromet
for such purpose) [***] together with [***] for Product in transit at its
invoiced value. All [***] of whatever nature
[***].
|
6.6
|
Where
[***], Micromet shall diligently examine the Product as soon as
practicable after receipt. Notice of all claims (time being of
the essence) arising out of:
|
|
(a)
|
visible
damage (i.e., visible without inspection and testing) to or total or
partial loss of Product in transit shall be given in writing to Lonza and
the carrier within [***] of receipt by Micromet;
or
|
|
(b)
|
non-Delivery
shall be given in writing to Lonza within [***] after the date of Lonza’s
dispatch notice.
|
6.7
|
Any
Product Delivered hereunder shall, at the time of Delivery conform
[***] Lonza and Micromet shall use all commercially reasonable
efforts to resolve a non-conformity issue and resume re-delivery of
Products at the earliest time possible. Any dispute regarding
the conformity of Products which cannot be settled within [***] after
receipt of a detailed written notice of rejection shall be submitted for
resolution to the Steering
Committee.
|
6.8
|
Micromet
shall make damaged Product and associated packaging materials available
for inspection and shall comply with the requirements of any insurance
policy covering the Product notified by Lonza to
Micromet. Lonza shall offer Micromet all reasonable assistance
(at the cost and expense of Micromet) in pursuing any claims arising out
of the transportation of Product.
|
6.9
|
Promptly
following receipt of Product or any sample thereof, Micromet may carry out
any of the agreed tests outlined or referred to in Schedule
11. Subject to Clause 2.4, if such tests show that the
Product fails to meet Specifications, Micromet shall give Lonza written
notice thereof within [***] from the date of Delivery and shall return
samples of such Product to Lonza’s premises for further testing and
Micromet shall store the remainder of Product in quarantine. In
the absence of such written notice and subject to any hidden defect which
did not appear in the tests carried out by Micromet in accordance with
Schedule
11, Product shall be deemed to have been accepted by Micromet as
meeting the Specifications. Subject to Clause 2.4, if Product
returned to Lonza fails to meet the Specifications and if such failure is
not due (in whole or in part) to acts or omissions of Micromet or any
Third Party after Delivery, [***].
|
6.10
|
Subject
to Clause 2.4, if there is any dispute concerning whether Product returned
to Lonza fails to meet the Specifications or whether such failure is due
(in whole or in part) to acts or omissions of Micromet or any Third Party
after Delivery, such dispute shall be referred for decision to [***] in
accordance with Clause 4.3 (i)
above.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
16
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
6.11
|
The
provisions of Clauses 6.9 and 6.10 shall be the sole remedy available to
Micromet in respect of Product that fails to meet the
Specifications.
|
7.
|
Price
and Terms of Payment
|
7.1
|
Unless
otherwise indicated in writing by Lonza, all prices and charges are
exclusive of Value Added Tax or of any other applicable taxes, levies,
imposts, duties and fees of whatever nature imposed by or under the
authority of any government or public authority, which shall be paid by
Micromet (other than taxes on Lonza’s income). Payments shall
be made in accordance with the Terms of Payment in Schedule 3
hereto. Lonza will provide to Micromet in regular intervals
upon amendments to the Project Plan updated payment plans. All
invoices are strictly net and payment must be made within [***] of date of
invoice. Payment shall be made without deduction, deferment,
set-off, lien or counterclaim of any
nature.
|
7.2
|
In
default of payment on due date:
|
|
(a)
|
interest
shall accrue on any amount overdue at the rate of [***] above the base
lending rate from time to time of National Westminster Bank plc, interest
to accrue on a day to day basis both before and after judgment;
and
|
|
(b)
|
Lonza
shall, at its sole discretion, and without prejudice to any other of its
accrued rights, be entitled to suspend the provision of the Works and
Services or to treat this Agreement as repudiated on not less than [***]
prior notice in writing to Micromet given at any time
thereafter.
|
8.
|
Intellectual
Property
|
8.1
|
Neither
Party will, as a result of this Agreement, acquire any right, title, or
interest in any Intellectual Property that the other Party owns or
Controls as of the Effective Date, or that the other Party obtains
ownership or Control of separate and apart from the performance of the
Works and Services under this
Agreement.
|
8.2
|
[***].
|
8.3
|
[***]
shall own all right, title and interest in [***], which as used in this
Agreement means Intellectual Property that [***], contractors or agents
develops, conceives, invents, reduces to practice or makes in the course
of performance of the Works and Services and that (i) arises from or
relates to [***] or [***]; and (ii) is severable from the [***] and [***];
and (iii) does not reveal or disclose the [***], or Works and Services
performed under this Agreement. [***] shall provide [***] with
a general description of any [***] in the event that any is developed, in
order to enable [***] to make an assessment as to whether [***] would like
to use the [***] under the [***].
|
8.4
|
Except
for and not including the [***], [***] shall own all right, title, and
interest in [***].
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
17
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Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
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|
8.5
|
In
relation only to the [***] and [***] (and no other product), [***] hereby
grants [***], and [***] hereby accepts [***] under and to all [***], to
the extent such [***] are necessary or useful to research, develop, have
developed, conduct clinical trials for, formulate, manufacture, have
manufactured, test, seek regulatory approval for, market, have marketed,
commercialize, have commercialized, make, have made, use, sell, have sold
import, have imported and distribute and have distributed [***] or
[***]. For the avoidance of doubt, the nature of [***] is as
follows:
|
|
·
|
[***]
ownership of [***] as set out [***] is not
affected;
|
|
·
|
[***]
use of the [***] is limited to use on the [***] and [***];
and
|
|
·
|
[***]
can grant further licences of the [***] to any third party, but may not do
so in relation to the [***] and the
[***].
|
[***] is
entitled to [***] (i) Third Parties registered and operating, with respect of
the manufacturing of Product, [***] and (ii) [***] [***] assessed and approved
by [***] on a case-by-case basis, such approval by [***] not be unreasonably
withheld or delayed. [***] shall execute all documents, give all
declarations regarding the licenses granted under this Clause 8.5 and reasonably
cooperate with [***] to the extent such documents, declarations and/or
cooperation are required for the recordal or registration of the licenses
granted hereunder at the various patent offices for the benefit of [***] and at
[***] cost.
8.6
|
The
Parties shall reasonably assist each other in defending themselves against
a Third Party claim which would impair the exploitation of [***] Patent
Rights, [***] and/or [***] for the production of the
Product. Each Party shall furnish the other with timely written
notice of any and all infringements and other unauthorized uses by any
other person, firm, corporation or other entity of any of [***] Patent
Rights, [***] or [***]. Furthermore, the Parties shall promptly
inform each other in the event either Party receives notice from any Third
Party or becomes otherwise aware that the [***] Patent Rights, the [***]
or the [***] may infringe Third Party Intellectual
Property.
|
8.7
|
In
relation only to the [***] and [***] (and no other product), to the extent
that Lonza Technology (a) is incorporated within the [***] or [***], or
(b) has been used in the manufacture of the [***] or [***], Lonza hereby
grants Micromet, and Micromet hereby accepts a [***] license under and to
Lonza Technology, to research, develop, have developed, conduct clinical
trials for, formulate, manufacture, have manufactured, test, seek
regulatory approval for, market, have marketed, commercialize, have
commercialized, make, have made, use, sell, have sold import, have
imported and distribute and have distributed [***] or
[***]. For the avoidance of doubt, the nature of the above
licence is as follows:
|
|
(i)
|
Lonza’s
ownership of Lonza Technology is not affected, and except as set out in
item (iv) below, [***];
|
|
(ii)
|
There
is no [***] to Micromet;
|
|
(iii)
|
Micromet’s
use of the Lonza Technology is limited to use on the Product and Modified
Product; and
|
|
(iv)
|
Lonza
shall not [***] [***].
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
18
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
9.
|
Warranties
and Indemnification
|
9.1
|
Lonza
warranty: Lonza warrants
that:
|
|
(a)
|
the
Works and Services shall be performed in accordance with Clause
2;
|
|
(b)
|
unencumbered
title (save for any Intellectual Property which may exist) to Product and
Results will be conveyed to Micromet upon
Delivery;
|
|
(c)
|
on
the Effective Date the Lonza Technology is owned by Lonza or Lonza is
otherwise entitled to use it for the purposes of providing Works and
Services under this Agreement and during the term of this Agreement Lonza
shall not do or cause anything to be done which would adversely affect
their ownership or entitlement to use the same for those
purposes;
|
|
(d)
|
Lonza
has the necessary corporate authorisations to enter into this
Agreement;
|
|
(e)
|
[***];
|
|
(f)
|
[***];
|
|
(g)
|
on
the Effective Date to the best of Lonza’s knowledge and belief, the use by
Lonza of the Lonza Process (excluding any modifications or steps made or
developed by Micromet, the Micromet Materials and Micromet Technology) and
Lonza Technology for the performance of the Works and Services as provided
herein will not infringe any rights (including without limitation any
intellectual or industrial property rights) vested in any Third Party
(provided, however,
that Micromet shall waive any breach of this warranty which arises
if a court of competent jurisdiction determines that the use by Lonza of
the Lonza Process, the Lonza Technology for the Works and Services
infringes the Intellectual Property of a Third Party, provided that and for so long as
Lonza actually indemnifies Micromet pursuant to Clause 9.4
below);
|
|
(h)
|
subject
to Clause 2.4, the Product will meet the
Specifications;
|
|
(i)
|
Lonza
shall not use the Micromet Confidential Information, Micromet Materials,
the Micromet Technology, the Process and the [***] for any purposes other
than the Works and Services to be performed for Micromet hereunder;
and
|
|
(j)
|
Lonza
will notify Micromet in writing immediately if it receives or is notified
of a claim from a Third Party that the use by Lonza of the Process and/or
the Lonza Technology or [***] for Works and Services infringes any
Intellectual Property vested in such Third
Party.
|
9.2
|
Micromet
warranty: Micromet warrants
that:
|
|
(a)
|
on
the Effective Date to the best of Micromet's knowledge and belief,
Micromet has the right to supply the Cell Line, the Micromet Process, the
other Micromet Materials and the Micromet Technology to Lonza and the
necessary rights to licence or permit Lonza to use the same for the
purpose of the Works and Services;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
19
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
|
(b)
|
Micromet
has the necessary corporate authorisations to enter into this
Agreement;
|
|
(c)
|
any
of the Cell Line, the Micromet Process, other Micromet Materials, and
Micromet Technology not owned by Micromet are licensed to Micromet under a
licence which will permit their use by Lonza to perform the Works and
Services;
|
|
(d)
|
Micromet
has the right to disclose the Micromet Confidential Information and to
allow the use of the Micromet Confidential Information by Lonza for the
purposes of and in accordance with the terms of this Agreement, and the
disclosure of the Micromet Confidential Information from Micromet to Lonza
and the use of such Micromet Confidential Information by Lonza in
accordance with the terms of this Agreement does not constitute
[***];
|
|
(e)
|
Micromet
has agreed to indemnify [***] regarding the transfer of Micromet
Technology and Micromet Materials and such indemnification obligations
correspond to (or go beyond) the obligations in Section 3.6 of the
[***];
|
|
(f)
|
on
the Effective Date and to the best of Micromet's knowledge and belief, the
timescales as set out in the Project Plan are realistic and Micromet will
be able to provide the Micromet Technology and the Micromet Materials to
perform the Works and Services in a timely
manner;
|
|
(g)
|
on
the Effective Date and to the best of Micromet's knowledge and belief, no
additional work is required to achieve the
Deliverables;
|
|
(h)
|
on
the Effective Date and to the best of Micromet's knowledge and belief, the
use by Lonza of the Cell Line, the Micromet Process, other Micromet
Materials and the Micromet Technology for the Works and Services
(including without limitation the manufacture of the Product and excluding
any modifications or steps made or developed by Lonza and the Lonza
Technology) will not infringe any Intellectual Property of any Third Party
(provided, however,
that Lonza shall waive any breach of this warranty which arises if
a court of competent jurisdiction determines that the use by Lonza of the
Cell Line, other Micromet Materials or the Micromet Technology for the
Works and Services infringes the Intellectual Property of a Third Party,
provided that and
for so long as Micromet actually indemnifies Lonza pursuant to Clause 9.5
below);
|
|
(i)
|
the
Micromet Process had been used to manufacture Product in accordance with
cGMP and the Specifications; and
|
|
(j)
|
Micromet
will promptly notify Lonza in writing if it receives or is notified of a
claim from a Third Party that the Cell Line, the Micromet Process, other
Micromet Materials, the Micromet Confidential Information, Micromet
Technology or that the use by Lonza thereof for the provision of the Works
and Services infringes any Intellectual Property of such Third
Party.
|
|
For
the avoidance of doubt, Section 3.3 of the [***] does in no way limit the
warranties given under this Clause
9.2.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
20
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
9.3
|
Disclaimer: THE
WARRANTIES EXPRESSLY SET FORTH IN THIS AGREEMENT ARE IN LIEU OF ALL OTHER
WARRANTIES, AND, EXCEPT FOR THE WARRANTIES EXPRESSLY SET FORTH IN THIS
AGREEMENT, ALL OTHER WARRANTIES, BOTH EXPRESS AND IMPLIED, ARE EXPRESSLY
DISCLAIMED, INCLUDING WITHOUT LIMITATION ANY WARRANTY OF MERCHANTABILITY
OR FITNESS FOR A PARTICULAR
PURPOSE.
|
9.4
|
Indemnification by
Lonza: Subject to Clause 9.6 below, Lonza shall defend,
indemnify and hold harmless each of Micromet, its Affiliates, and their
directors, officers, and employees and the successors and assigns of any
of the foregoing (each a "Micromet Indemnitee")
from and against any Third Party claims, actions, liabilities, costs and
expenses (including court costs and legal fees on a full indemnity basis)
that Micromet may suffer arising directly out
of
|
|
(a)
|
any
breach of the warranties given by Lonza in Clause 9.1 above;
or
|
|
(b)
|
any
claims alleging that Lonza’s use of the Lonza Process (i.e., claims which
do not allege that the Micromet Process is infringing), the Lonza
Technology and/or [***] (i.e., claims which do not allege that the use of
[***] and/or the [***] is infringing) infringes any rights (including
without limitation any Intellectual Property) vested in a Third Party
(whether or not Lonza knows or ought to have known the same), provided that there
shall be excluded from this indemnity all Micromet revenue;
or
|
|
(c)
|
any
negligent or willful act or omission of Lonza in relation to the
Product.
|
9.5
|
Indemnification by
Micromet: Subject to Clause
9.6 below, Micromet shall defend, indemnify and hold harmless each of
Lonza, its Affiliates, and their directors, officers, and employees and
the successors and assigns of any of the foregoing (each a "Lonza Indemnitee") from
and against any Third Party claims, actions, liabilities, costs and
expenses (including court costs and legal fees on a full indemnity basis),
that Lonza may suffer arising directly out
of
|
|
(a)
|
any
breach of the warranties given by Micromet in Clause 9.2 above;
or
|
|
(b)
|
any
claims alleging Lonza’s use of the Cell Line, the Micromet Process, the
Micromet Materials or the Micromet Technology infringes any rights
(including, without limitation, any Intellectual Property) vested in any
Third Party (whether or not Micromet knows or ought to have known about
the same) provided
that there shall be excluded from this indemnity all Lonza actual
or potential revenues other than those which are an integral part of any
Price or fees which Micromet is obliged to pay to Lonza under this
Agreement; or
|
|
(c)
|
any
negligent or wilful act or omission of Micromet in relation to the
Product; or
|
|
(d)
|
any
claims raised by [***] against Lonza under Section 3.6 (b) and/or (c) of
the [***], and any claims resulting from an early termination of the [***]
by [***], provided that Micromet is not required to indemnify Lonza of
such claims under Clause 9.4 above.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
21
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
9.6
|
Indemnification
Procedure: If a Lonza Indemnitee or Micromet Indemnitee (the
"Indemnitee")
intends to claim indemnification under this Clause 9, it shall promptly
notify the other Party (the "Indemnitor") in writing
of such alleged liability. The Indemnitor shall have the right
to control the defence thereof with counsel of its choice as long as such
counsel is reasonably acceptable to Indemnitee; provided, however, that
any Indemnitee shall have the right to retain its own counsel at its own
expense, for any reason, including if representation of any Indemnitee by
the counsel retained by the Indemnitor would be inappropriate due to
actual or potential differing interests between such Indemnitee and any
other Party reasonably represented by such counsel in such
proceeding. The Indemnitee, its employees and agents, shall
reasonably cooperate with the Indemnitor and its legal representatives in
the investigation of any liability covered by this Clause
9. The obligations of this Clause 9.6 shall not apply to
amounts paid in settlement of any claim, demand, action or other
proceeding if such settlement is effected without the consent of the
Indemnitor, which consent shall not be withheld or delayed
unreasonably. The failure to deliver written notice to the
Indemnitor within a reasonable time after the commencement of any such
action, if prejudicial to its ability to defend such action, shall relieve
the Indemnitor of any obligation to the Indemnitee under this Clause
9. It is understood that only Lonza or Micromet may claim
indemnity under this Clause 9 (on its own behalf or on behalf of its
Indemnitees), and other Indemnitees may not directly claim indemnity
hereunder.
|
9.7
|
Disclaimer of Consequential
Damages: Subject to the second sentence of this Clause
9.7, in no event shall either Party be liable to the other Party for
incidental, indirect, special, punitive or consequential damages arising
from or related to breach of this Agreement. The foregoing
disclaimer of damages shall not apply in the case of (a) breach of Clause
10 (Confidentiality), (b) personal injury or death, or (c) grossly
negligent or intentionally wrongful acts or
omissions.
|
9.8
|
Limitation of
Liability: Subject to clause 9.7 and to the second
sentence of this clause 9.8, in no event shall Lonza’s liability to
Micromet for direct damages arising from or related to breach of this
Agreement exceed the total maximum aggregate sum payable under this
Agreement by Micromet. The foregoing limitation of liability
shall not apply in the case of (a) breach of clause 10 (Confidentiality),
(b) personal injury or death, or (c) negligent or intentionally wrongful
acts or omissions.
|
9.9
|
Insurance: Lonza
and Micromet shall obtain and maintain during the term of this Agreement
and for [***] thereafter general liability insurance with a reputable and
solvent insurance provider in the amount of [***] per event or linked
events. Such general liability insurance shall insure against
all mandatory liability including liability for personal injury, physical
injury and property damage. The Parties shall provide each
other with written proof of the existence of such insurance upon
request.
|
9.10
|
[***]: In order to
execute this Agreement, Micromet has required Lonza to enter into the
[***]. Micromet acknowledges and agrees that Lonza has no
liability to Micromet under this Agreement or otherwise, should any action
or step be taken by [***] and/or Lonza in compliance with the
[***].
|
10.
|
Confidentiality
|
10.1
|
Micromet
acknowledges that Lonza Confidential Information, and Lonza acknowledges
that Micromet Confidential Information (jointly the "Confidential
Information") with which they are supplied by the other pursuant to
the Agreement are supplied, subject to Clause 10.5, in circumstances
imparting an obligation of confidence and each agrees to keep such
Confidential Information secret and confidential and to respect the
other's proprietary rights therein and not at any time for any reason
whatsoever to disclose or permit such Confidential Information to be
disclosed to any Third Party save as expressly provided
herein.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
22
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
10.2
|
Micromet
and Lonza shall each procure that all their respective employees,
consultants, contractors and persons for whom it is responsible having
access to Lonza Confidential Information or Micromet Confidential
Information shall be subject to the same obligations of confidence as the
principals pursuant to Clauses 10.1 and 10.3 and shall be bound by secrecy
agreements in support of such
obligations.
|
10.3
|
Lonza
and Micromet each undertake not to disclose or permit to be disclosed to
any Third Party other than to those of its officers, employees, agents,
consultants, licensees and financial investors that have a need to know
the Confidential Information of the disclosing Party for purposes of this
Agreement, provided
that such disclosure will be made under a confidentiality
non-disclosure agreement comprising of terms at least as stringent as the
confidentiality provisions under this Clause
10. [***].
|
10.4
|
Notwithstanding
Clause 10.3, Lonza and Micromet each undertake not to otherwise make use
of or permit to be made use of the Confidential Information of the other
Party or except to the extent that the same is required to be disclosed
pursuant to subpoena, court order, judicial process or otherwise by law,
provided that the
receiving Party provides prompt notice to the disclosing Party of such
requirement in order to give the disclosing Party an opportunity to timely
seek a protective order or other appropriate judicial
relief. In the event the disclosing Party is unable to obtain a
protective order or other appropriate judicial relief, the receiving Party
shall disclose only that portion of the disclosing Party’s Confidential
Information which is legally required to be disclosed, and ensure that all
such Confidential Information of the disclosing Party shall be redacted to
the fullest extent permitted by law prior to such disclosure and that the
disclosing Party shall be given an opportunity to review the Confidential
Information prior to its
disclosure.
|
10.5
|
The
obligations of confidence referred to in this Clause 10 shall not extend
to any information for which the receiving Party can prove by written
evidence that:
|
|
(a)
|
it
was or became generally available to the public otherwise than by reason
of a breach by the receiving Party of the provisions of this Clause
10;
|
|
(b)
|
it
was known to the receiving Party and is at its free disposal prior to its
receipt from the disclosing Party;
|
|
(c)
|
it
was subsequently disclosed to the receiving Party without being made
subject to an obligation of confidence by a Third
Party;
|
|
(d)
|
Lonza
or Micromet are required to disclose under any statutory, regulatory or
similar legislative requirement, subject to the imposition of obligations
of secrecy wherever possible in that relation;
or
|
|
(e)
|
it
was developed by any servant or agent of the receiving Party without
access to or use or knowledge of the information by the disclosing
Party.
|
10.6
|
The
Parties acknowledges that:
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
23
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
|
(a)
|
without
prejudice to any other rights and remedies that the Parties may have, the
Parties agree that the Lonza Confidential Information and Micromet
Confidential Information is valuable and that damages may not be an
adequate remedy for any breach of the provisions of this Clause
10. The Parties agree that the relevant Party will be entitled
without proof of special damage to seek the remedies of an injunction and
other equitable relief for any actual or threatened breach by the other
Party;
|
|
(b)
|
save
as provided herein Lonza shall not at any time have any right, title,
licence or interest in or to the Micromet Technology or any other
Intellectual Property vested in Micromet or to which Micromet is entitled;
and
|
|
(c)
|
save
as provided herein Micromet shall not at any time have any right, title,
licence or interest in or to Lonza Confidential Information, the Lonza
Technology or any other Intellectual Property relating to the Process
which are vested in Lonza or to which Lonza is otherwise
entitled.
|
10.7
|
All
Confidential Information is and shall remain the sole and exclusive
property of the disclosing Party. The receiving Party agrees
that upon termination of this Agreement and subject to Micromet's right to
retain certain Confidential Information under the Technology Transfer and
License Agreement, within [***] thereafter, the receiving Party
shall: (a) cease any use of the Confidential Information,
including any [***], and all copies of the foregoing or any portion
thereof, in whatever form or medium stored, and (b) transfer all
Confidential Information of the disclosing Party, including all documents,
samples, summaries, extracts, records or other materials that contain any
Confidential Information, in whatever form or medium stored, to the
disclosing Party or its designee, and such designee shall be subject to
legally binding nondisclosure and use restrictions that are at least as
restrictive as the terms of this Agreement, and (c) upon completion of
such transfer, certify in writing that such transfer is
complete.
|
11.
|
Option
for [***]
|
11.1
|
Lonza
hereby grants to Micromet an option to conclude a [***] for the
[***]. The terms and conditions of such [***] shall be
negotiated in good faith and based on the conditions provided in Schedule
13. On a regular basis during the term of this
Agreement, Lonza will inform Micromet about the lead times for [***] and
the Parties will agree on any reasonable updates to Schedule 13, such
first update to be agreed after establishment of the Process at
Lonza.
|
11.2
|
Due
to the need of [***], Micromet will [***]. In the event that
such [***] is not concluded before regulatory approval for the Product is
granted, Micromet's option under this Clause 11 will
expire.
|
12.
|
Termination
of the Agreement, Termination of Certain Works and Services or
Slots
|
12.1
|
This
Agreement shall commence on the Effective Date and shall expire upon
completion of the Works and Services, unless earlier terminated in
accordance with this Clause 12.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
24
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
12.2
|
If
it becomes apparent to either Lonza or Micromet at any stage in the
provision of the Works and Services that it will not be possible to
complete the Works and Services for scientific or technical reasons, such
issue shall be discussed in the Steering Committee and a [***] period
shall be allowed for good faith discussion and attempts to resolve such
problems or to agree on a mutual termination of this Agreement. If such
problems are not resolved within such period, Micromet shall be entitled
to terminate the Agreement forthwith by notice in writing and with
immediate effect. Furthermore, Micromet may in its sole
discretion terminate this Agreement in whole or terminate certain Works
and Services or production slots of the Project Plan at any time for any
reason by giving not less than [***] notice in writing to
Lonza. In the event of any such termination outlined above,
Micromet shall pay to Lonza a termination sum calculated by reference to
all the Works and Services performed by Lonza prior to such termination
(including a pro rata proportion of the Price for any stage of the Works
and Services which is in process at the date of termination) and all
expenses reasonably incurred by Lonza in giving effect to such
termination, including the costs of terminating any commitments entered
into under the Agreement, provided, however, that
Lonza will make all reasonable efforts to use any materials and services
intended for Micromet for other purposes. The termination sum
shall not exceed the unpaid Price for the stage in process and any prior
stages and no re-imbursement to Lonza is owed by Micromet in the event
notice to terminate Works and Services pursuant to this Clause 12.2 is
issued to Lonza more than [***] before Lonza's then estimated start date
for any stage.
|
12.3
|
In
the event of termination pursuant to Clause 12.2 and subject to Clauses
12.5, 12.6 and 12.7 Micromet shall pay Lonza a termination sum regarding
terminated production slots calculated in accordance with the principles
of Clause 12.2 above plus:
|
|
(a)
|
in
the event notice to terminate Works and Services pursuant to this Clause
12.3 is issued to Lonza [***] or less before Lonza’s then estimated start
date for any stage of those Works and Services which include activities in
Lonza’s cGMP fermentation and/or purification facilities (i.e., the cGMP
Batches), or is issued to Lonza at any time during any such stage,
Micromet shall pay Lonza a sum equal to [***] [***], which payment to
Lonza shall become due on the date of termination of such Works and
Services; or
|
|
(b)
|
in
the event notice to terminate Works and Services pursuant to this Clause
12.3 is issued to Lonza more than [***] but not more than [***] before
Lonza’s then estimated start date for any stage of those Works and
Services which include activities in Lonza’s cGMP fermentation and/or
purification facilities (i.e. the cGMP Batches), Micromet shall pay Lonza
a sum equal to [***] [***]; which payment to Lonza shall become due on the
date of termination of such Works and Services;
or
|
|
(c)
|
in
the event notice to terminate Works and Services pursuant to this Clause
12.3 is issued to Lonza more than [***] but not more than [***] months
before Lonza’s then estimated start date for any stage of those Works and
Services which include activities in Lonza’s cGMP fermentation and/or
purification facilities (i.e. the cGMP Batches), Micromet shall pay Lonza
a sum equal to [***] [***]; which payment to Lonza shall become due on the
date of termination of such Works and
Services.
|
|
The
price of the [***] shall not include the [***]. Any [***]
ordered at the time of termination which cannot be used by Lonza for other
purposes will be paid by Micromet and Micromet may request transfer of
such [***] to Micromet.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
25
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
|
No
re-imbursement to Lonza is owed by Micromet in the event notice to
terminate Works and Services pursuant to this Clause 12.3 is issued to
Lonza more than [***] months before Lonza's then estimated start date for
any Batch. Furthermore and for the avoidance of doubt, no
re-imbursement to Lonza is owed by Micromet
[***]
|
12.4
|
Lonza
shall use commercially reasonable efforts to otherwise
[***]. The obligation to make payment under Clause12.3 shall be
reduced (retrospectively, and hence Lonza shall make an appropriate refund
to Micromet) to the extent that Lonza mitigates its loss in this regard
(and Lonza shall promptly notify Micromet of any such
mitigation). This provision shall not entitle Micromet to be
refunded an amount greater than that paid by Micromet to Lonza pursuant to
this Clause 12 and Lonza shall be entitled to deduct from the amount due
to be refunded to Micromet its reasonable personnel and associated costs
in attempting to mitigate its loss.
|
12.5
|
For
the avoidance of doubt activities relating to cGMP fermentation shall be
deemed to commence with the date of removal of the vial of cells from
frozen storage for the performance of the
fermentation.
|
12.6
|
The
Parties may each terminate the Agreement forthwith by notice in writing to
the other Party if the other commits a material breach of the Agreement
(which shall include a breach of the warranties set out in Clause 9 above)
which in the case of a breach capable of remedy is not remedied within
[***] in the event of a breach of payment obligations, and within [***] in
the event of any other breach, of the receipt by the other of notice
identifying the breach and requiring its
remedy.
|
12.7
|
Micromet
may terminate this Agreement forthwith by notice in writing to Lonza upon
the occurrence of any of the following
events:
|
|
(a)
|
[***];
|
|
(b)
|
[***];
|
|
(c)
|
[***].
|
12.8
|
Upon
the termination of this Agreement for whatever
reason:
|
|
(a)
|
Lonza
shall promptly return to Micromet all Micromet Know How and shall dispose
of or return to Micromet the Micromet Materials, the Micromet Cell Line
and the Micromet Process and any materials therefrom, as directed by
Micromet;
|
|
(b)
|
Micromet
shall promptly return to Lonza all Lonza Confidential Information it has
received from Lonza;
|
|
(c)
|
Lonza
shall summarize all Works and Services performed up to the termination of
the Agreement and provide such summary documents to
Micromet;
|
|
(d)
|
subject
to Clause 14 below, Micromet shall not thereafter use or exploit the Lonza
Technology in any way whatsoever;
and
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
26
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
|
(e)
|
Lonza
and Micromet shall do all such acts and things and shall sign and execute
all such deeds and documents as the other may reasonably require to
evidence compliance with this Clause
12.8.
|
12.9
|
Termination
of this Agreement for whatever reason shall not affect the accrued rights
of either Lonza or Micromet arising under or out of this Agreement and all
provisions which are expressed to survive the Agreement shall remain in
full force and effect.
|
13.
|
[***]
|
Lonza
agrees that [***] of the [***] for the [***] or [***], it shall not, directly or
indirectly:
|
(a)
|
engage
in, continue in or carry on [***] as the [***] or [***], including [***]
which is so engaged;
|
|
(b)
|
consult
with, advise or assist in any way, whether or not for consideration, any
corporation or other business organization [***] as the [***] or
[***];
|
|
(c)
|
engage
in any practice the purpose of which is to evade the provisions of this
[***];
|
|
provided, however, that
the foregoing prohibition does not extend to [***] of the [***] of the
[***].
|
14.
|
Technology
Transfer and License
|
|
At
any time during the course of this Agreement [***], Micromet has the
option to conclude the Technology Transfer and License Agreement between
Micromet and Lonza attached hereto as Schedule 14, in
order to allow Micromet (or a [***] designated by Micromet) to replicate
the Process (as it exists at the date of such request) in the manufacture
of the Product in order to either establish a second source for supply or
to transfer manufacturing to a Third Party, provided, however, that
[***]). Following exercise of the option and provided [***] of
Lonza have been used for the manufacture of Product, Lonza shall supply to
Micromet such information and assist Micromet regarding access to [***],
as is agreed therein.
|
15.
|
Force
Majeure
|
15.1
|
If
Lonza is prevented or delayed in the performance of any of its obligations
under the Agreement by Force Majeure and shall give written notice thereof
to Micromet specifying the matters constituting Force Majeure together
with such evidence as Lonza reasonably can give and specifying the period
for which it is estimated that such prevention or delay will continue,
Lonza shall be excused from the performance or the punctual performance of
such obligations as the case may be from the date of such notice for so
long as such cause of prevention or delay shall
continue.
|
15.2
|
The
expression "Force
Majeure" shall be deemed to include any cause affecting the
performance by Lonza of the Agreement arising from or attributable to
acts, events, acts of God, omissions or accidents beyond the reasonable
control of Lonza.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
27
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
16.
|
Governing
Law, Jurisdiction and
Enforceability
|
16.1
|
The
construction, validity and performance of the Agreement shall be governed
by the laws of Switzerland.
|
16.2
|
No
failure or delay on the part of either Lonza or Micromet to exercise or
enforce any rights conferred on it by the Agreement shall be construed or
operate as a waiver thereof nor shall any single or partial exercise of
any right, power or privilege or further exercise thereof operate so as to
bar the exercise or enforcement thereof at any time or times
thereafter.
|
16.3
|
Any
disputes relating to issues arising from this Agreement shall, in the
absence of resolution within [***] of the dispute arising, be referred to
the [***] of Micromet and Lonza, who shall discuss the matter and attempt
to resolve it by mutual consent. The [***] of Micromet and
Lonza shall meet once face-to-face within [***] to discuss and resolve the
dispute. If the dispute cannot be resolved within [***], either
Party may, by written notice to the other Party, invoke the mediation
procedure set out in Clause 16.4
below.
|
16.4
|
If
a dispute arises between the Parties that the Parties cannot resolve
pursuant to Clause 16.3 above, the Parties agree to try to solve such
dispute amicably by mediation. The Parties shall conduct a
mediation procedure according to the ICC ADR Rules of the International
Chamber of Commerce (ICC) in effect on the date of the commencement of the
mediation proceedings. The location of the mediation
proceedings will be Basel. The number of mediators will be one
(1). The language of the mediation proceeding will be
English. If the dispute has not been settled pursuant to the
said rules within [***] following the filing of a request for mediation or
within such other period as the Parties may agree in writing, either Party
may submit the dispute to final and binding
arbitration.
|
16.5
|
Any
dispute relating to the validity, performance, construction or
interpretation of this Agreement, which cannot be resolved amicably
between the Parties, shall be submitted to arbitration in accordance with
the ICC Arbitration Rules of the International Chamber of
Commerce. The decision of the arbitrators shall be final and
binding upon the Parties (absent manifest error on the part of the
arbitrator(s)) and enforceable in any court of competent
jurisdiction. The location of arbitration will be
Basel. The arbitration will be heard and determined by one (1)
arbitrator, who will be jointly selected by Lonza and
Micromet. If, within [***] following the date upon which a
claim is received by the respondent, the Parties cannot agree on a single
arbitrator, the arbitration will be heard and determined by three (3)
arbitrators, with one arbitrator being appointed by each Party and the
third arbitrator being selected by the two Party-appointed
arbitrators. If either Party fails to select an arbitrator, or
if the Party-appointed arbitrators cannot agree on a third arbitrator
within [***] of the respondent receiving the claim, such arbitrator will
be appointed by the International Court of Arbitration according to the
ICC Rules. The arbitration award that is consistent with the
provisions of this Agreement that is so given will be binding upon the
Parties, accompanied by a reasoned opinion in writing (in English), and
the judgment on the award may be entered in any court having competent
jurisdiction thereof. Each Party will bear its own costs and
expenses (including its attorney’s fees) associated with any arbitration
initiated under this section, and each Party will bear an equal share of
the arbitrators’ and administrative fees associated with any arbitration
initiated under this section. The language of the arbitration
proceeding will be English. Notwithstanding the provisions of
this Clause 16.5, each Party shall have the right to seek preliminary or
permanent injunctive or other equitable relief in any court of competent
jurisdiction as such Party deems necessary to preserve its rights and to
protect its interests.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
28
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
16.6
|
Nothing
in this Clause 16 shall prevent a Party from exercising any right under
this Agreement, including the right of termination under Clause 12
above.
|
17.
|
Notices
|
17.1
|
Any
notice or other communication to be given under this Agreement shall be
delivered personally or sent by facsimile transmission, or if facsimile
transmission is not available, by first class pre-paid post addressed as
follows:
|
(a)
|
If to Lonza to:
|
Lonza Sales AG
|
Xxxxxxxxxxxxxxxxxxxxxx 00
|
||
XX-0000 Xxxxx
|
||
Xxxxxxxxxxx
|
||
Facsimile: x00 00 000 0000
|
||
Attention: The Head of Legal Services
|
||
with a copy to:
|
Lonza Biologics plc
|
|
000 Xxxx Xxxx
|
||
Xxxxxx
|
||
Xxxxxxxxx XX0 0XX
|
||
Xxxxxxx
|
||
Facsimile: x00 0000 000000
|
||
Attention: The Head of Legal Services
|
||
(b)
|
If to Micromet to:
|
Micromet AG
|
Xxxxxxxxxxxxxxxxx 0
|
||
X-00000 Xxxxxx
|
||
Xxxxxxx
|
||
Facsimile: x00-00-000 277 205
|
||
Attention: Head of Business Development
|
||
|
with a copy to:
|
|
0000 Xxxxxxxxx Xxxxxxxxx
|
||
Xxxxx 000
|
||
Xxxxxxxx, XX 00000
|
||
Xxxxxx Xxxxxx of America
|
||
Attention: General Counsel
|
||
Facsimile: x0 000 000-0000
|
or to
such other destination as either Party hereto may hereafter notify to the other
in accordance with the provisions of this Clause 17.
17.2
|
All
such notices or other communications shall be deemed to have been served
as follows:
|
|
(a)
|
if
delivered personally, at the time of such
delivery;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
29
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
|
(b)
|
if
sent by facsimile, upon receipt of the transmission confirmation slip
showing completion of the
transmission;
|
|
(c)
|
if
sent by first class pre-paid post, ten (10) business days (Saturdays,
Sundays and Bank or other public holidays excluded) after being placed in
the post.
|
18.
|
Illegality
|
18.1
|
If
any provision or term of this Agreement or any part thereof shall become
or be declared illegal, invalid or unenforceable for any reason whatsoever
including but without limitation by reason of the provisions of any
legislation or other provisions having the force of law or by reason of
any decision of any Court or other body or authority having jurisdiction
over the Parties hereto or this Agreement including the EC Commission or
the European Court of Justice:
|
|
(a)
|
such
provision shall, so far as it is illegal, invalid or unenforceable, be
given no effect by the Parties and shall be deemed not to be included in
this Agreement;
|
|
(b)
|
the
other provisions of this Agreement shall be binding on the Parties as if
such provision was not included therein;
and
|
|
(c)
|
the
Parties agree to negotiate in good faith to amend such provision to the
extent possible for incorporation herein in such reasonable manner as most
closely achieves the intention of the Parties without rending such
provision invalid or unenforceable.
|
19.
|
Quality
Agreement
|
|
Simultaneously
with the execution of this Agreement, the Parties will enter into a
separate quality agreement as annexed hereto as Schedule 10
("Quality
Agreement"). The Quality Agreement and its Exhibits
supplement this Agreement. To the extent that inconsistencies
exist between the contents of the Quality Agreement and this Agreement,
the stipulations of this Agreement shall
prevail.
|
20.
|
Miscellaneous
|
20.1
|
Lonza
shall be entitled to instruct one or more of its Affiliates to perform any
of Lonza’s obligations contained in this Agreement, but Lonza shall remain
fully responsible in respect of those obligations. Subject
thereto, neither Party shall be entitled to assign, transfer, charge or in
any way make over the benefit and/or the burden of this Agreement without
the prior written consent of the other which consent shall not be
unreasonably withheld or delayed, save that either Party shall be entitled
without the prior written consent of the other Party to assign, transfer,
charge, sub-contract, deal with or in any other manner make over the
benefit and/or burden of this Agreement to a successor of that Party’s
business by reason of merger, sale or license of all or substantially all
of its assets related to this Agreement or any other form of
acquisition.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
30
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
20.2
|
The
obligations of the Parties under Clauses 8 (Intellectual Property), 9
(Warranties and Indemnification), 10 (Confidentiality), and 12.8 and 12.9
(consequences of termination) and 14 (Technology Transfer and License)
shall survive the termination of this Agreement for any
reason.
|
20.3
|
The
press releases that Micromet and Lonza will issue upon execution of this
Agreement are attached hereto as Schedule
15. The text of any further press release or other
further communication to be published by or in the media concerning the
subject matter of the Agreement shall require the prior written approval
of Lonza and Micromet.
|
20.4
|
The
Agreement embodies the entire understanding of Lonza and Micromet and
there are no promises, terms, conditions or obligations, oral or written,
expressed on implied, other than those contained in the
Agreement. The terms of the Agreement shall supersede all
previous agreements (if any) which may exist or have existed between Lonza
and Micromet relating to the Works and
Services.
|
20.5
|
The
Parties to this Agreement do not intend that any term hereof should be
enforceable by any person who is not a Party to this
Agreement.
|
20.6
|
No
variation of or addition to this Agreement or any part thereof shall be
effective unless in writing and signed on behalf of both
Parties. Notwithstanding the above the Parties hereby confirm
that amendments to the Specifications shall be effective if reduced to
writing and signed by the quality and/or regulatory representative of both
Parties, which quality and/or regulatory representative shall be nominated
from time to time by each Party.
|
List
of Schedules:
Schedule 1:
|
Micromet
Materials including Cell Line Particulars
|
Schedule 2:
|
Product
Specifications
|
Schedule 3:
|
Prices
and Terms of Payment
|
Schedule 4:
|
Identification
of Lonza Know How
|
Schedule 5:
|
List
of Lonza Patent Rights
|
Schedule 6:
|
Identification
of Micromet Know-How
|
Schedule 7:
|
List
of Micromet Patent Rights
|
Schedule 8 A:
|
Project
Plan up to Stage 30
|
Schedule 8 B:
|
Project
Plan for pre-LA (as of Stage 31)
|
Schedule 9:
|
[***]
Agreement
|
Schedule 10:
|
Quality
Agreement
|
Schedule 11:
|
Testing
of Product
|
Schedule 12:
|
Territories
|
Schedule 13:
|
Terms
and Conditions for [***]
|
Schedule 14:
|
Technology
and License Agreement
|
Schedule 15:
|
Micromet
Press Release and Lonza Press
Release
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
31
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
AS
WITNESS the hands of the duly authorised representatives of the Parties hereto
the day and year first above written.
Micromet
AG
|
Lonza
Sales AG
|
|
Signature:
|
/s/ Xxxx Xxxxxxxx
|
Signature:
|
/s/ Una
Hultry
|
Printed
Name:
|
Xxxx Xxxxxxxx
|
Printed
Name:
|
Una
Hultry
|
Title:
|
SVP Business Development
|
Title:
|
Authorized Signatory
|
|
Signature:
|
/s/ Xxxxxxx Xxxxxxxx
|
Signature:
|
/s/ Xxxxx
Xxxxxxx
|
Printed Name:
|
Xxxxxxx Xxxxxxxx
|
Printed
Name:
|
Xxxxx
Xxxxxxx
|
Title:
|
SVP, Chief Scientific
Officer
|
Title:
|
Authorized
Signatory
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
1
Micromet Materials including
Cell Line Particulars
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
2
Product
Specifications
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
3
Price and Terms of
Payment
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
4
Identification of Lonza
Know-How
(to
be licensed to Micromet under Schedule 14)
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
5
List of Lonza Patent
Rights
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
6
Identification of Micromet
Know How
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
7
List of Micromet Patent
Rights
Application
Number
|
Application
Filing Date
|
Country
|
Title of Application
|
Status
|
Patent Number
|
|||||||||||||||
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE 8
A
Project
Plan
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text Omitted and Filed
Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE 8
B
Project Plan for pre-LA (as
of Stage 31)
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
9
[***] AGREEMENT
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
10
Dated
November 23, 2009
LONZA
SALES AG
AND
MICROMET
AG
QUALITY
AGREEMENT
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
Schedule
10
|
THIS
QUALITY AGREEMENT is made
BETWEEN
1.
|
LONZA SALES AG, of
Xxxxxxxxxxxxxxxxxxxxxx 00, XX-0000, Xxxxx, Xxxxxxxxxxx (hereinafter
referred to as "Lonza")
and
|
2.
|
MICROMET AG, of
Xxxxxxxxxxxxxx 0, X-00000, Xxxxxx, Xxxxxxx (hereinafter referred to as
"Micromet")
|
WHEREAS:
A
|
Lonza
and Micromet have entered into a Development and Supply Agreement pursuant
to which Lonza agreed to provide Micromet with development, manufacturing
and supply services ("Works and Services") for
Micromet's Intermediate Biological (Investigational) Medicinal Product
(IB(I)MP) MT103 (also known as Blinatumomab) for use as proprietary
investigational medicinal product (the "Product").
|
B.
|
The
Parties now wish to further define the pharmaceutical roles and
responsibilities of each Party for the Manufacture, testing and Release of
Product with respect to relevant current Good Manufacturing Practices
("cGMP") and
Applicable Laws. Nothing in this Quality Agreement shall limit a Party’s
obligation to comply with cGMP and Applicable Laws (as defined below) on
the occasion that Lonza Manufactures Product for Micromet for further
manufacturing use in the preparation of human drug products for clinical
trial supply.
|
C
|
This
Quality Agreement takes the form of a detailed checklist of the activities
associated with the production, analysis, release, and distribution of
Product. Responsibility for each activity is assigned to either Lonza
and/or Micromet in the appropriate box in the delegation responsibility
checklist that follows. To facilitate routine communications between the
Parties, a list of key contacts is provided in Annex 1. For each
responsibility listed, the respective Party is required to put into effect
all applicable procedures and to take all necessary actions to execute
that responsibility in accordance with cGMP and Applicable
Laws.
|
D.
|
The
Parties wish that Lonza, having particular expertise in the activities
contained in this Quality Agreement (as defined below), may perform the
activities and obligations set forth in this Quality
Agreement.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
Schedule
10
|
Table
of Contents
1
|
.
|
Preface
/ Overall Responsibilities
|
4
|
|
2
|
.
|
Definitions
and Interpretation
|
5
|
|
3
|
.
|
Facilities
/ Materials Controls
|
8
|
|
3.1
|
Organization
and Key Personnel
|
8
|
||
3.2
|
Buildings,
Facilities, Utilities and Equipment
|
9
|
||
3.3
|
Raw
Materials Controls
|
10
|
||
4
|
.
|
Process
Controls
|
11
|
|
4.1
|
Cell
Banks
|
11
|
||
4.2
|
Product
Specification
|
11
|
||
4.3
|
Production,
Process Handling and Process Control
|
11
|
||
4.4
|
Product
Storage, Labeling, Packaging and Shipment
|
13
|
||
5
|
.
|
Quality
Control Laboratories
|
13
|
|
5.1
|
QC
Laboratory Controls
|
13
|
||
6
|
.
|
Quality
Assurance / Quality Management Systems
|
15
|
|
6.1
|
Complaints,
Recalls and Adverse Events
|
15
|
||
6.2
|
Batch
Review and Product Disposition
|
16
|
||
6.3
|
Records
Retention
|
16
|
||
6.4
|
Deviations
/ Investigation Reports
|
16
|
||
6.5
|
Change
Control Procedures
|
17
|
||
7
|
.
|
Regulatory
Authorizations and Inspections
|
18
|
|
7.1
|
Regulatory
Agency Inspections
|
18
|
||
7.2
|
Regulatory
Authorizations / Submissions
|
18
|
||
8
|
.
|
Micromet
Oversight
|
19
|
|
8.1
|
Audit
Allowance
|
19
|
||
8.2
|
Periodic
Review of Quality Agreement
|
20
|
||
9
|
.
|
Term
|
21
|
|
10
|
.
|
Miscellaneous
|
22
|
|
Annex
1 - Key Contacts
|
23
|
|||
Annex
2 - Multi Site Responsibilities Matrix
|
24
|
|||
Annex
3 - Additional Considerations for IB(I)MP Intended for Commercial
Use
|
25
|
|||
Annex
4 - Information to be provided to Micromet
|
26
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
Schedule
10
|
NOW IT IS
AGREED as follows:
1. Preface
/ Overall Responsibilities
1.1
|
This
Quality Agreement outlines the responsibilities of Micromet and Lonza with
respect to the quality assurance of Product Manufactured by Lonza for
Micromet under the terms of the Development and Supply Agreement and in
accordance with cGMP and Applicable
Laws.
|
1.2
|
Micromet
acknowledges that certain activities and obligations under the Quality
Agreement may be performed by Lonza’s Affiliates having expertise in the
relevant areas, provided that (i) Lonza shall remain responsible to
Micromet for the acts and omissions of their Affiliates; and (ii) Micromet
is at any time informed which of Lonza's Affiliates is in charge of that
certain activities and obligations.
|
1.3
|
The
following delegation responsibility checklist describes generic quality
activities that are to be performed by both Parties for Product used by
Micromet for further manufacturing use in the preparation of human drug
products for clinical trial supply / in market supply. The
specific Works and Services to be provided by Lonza are set out in the
Development and Supply Agreement (and any amendments to the Development
and Supply Agreement) on Price and other terms accepted by both
Parties.
|
1.4
|
Lonza
is responsible for ensuring that the quality requirements for Product are
as specified in the approved Product Specification and that Product is
Manufactured in accordance with cGMP and all Applicable
Laws.
|
1.5
|
Lonza
is responsible for final review, approval and QP certification of the
Product for further processing.
|
1.6
|
LONZA
is responsible for analytical testing of the Product and the further
processed Drug Product.
|
1.7
|
Micromet
or its designee is responsible for shipping and the final review, approval
and Release of the final Drug Product for use in clinical trial
supply.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
2.
Definitions and Interpretation
For
purposes of this Quality Agreement, the following terms shall have the following
meanings unless the context requires otherwise. Capitalized terms used herein
and not defined herein shall have the meaning as defined in the Development and
Supply Agreement.
|
Applicable
Laws
|
means
all applicable provisions of all statutes, laws, rules, regulations,
administrative codes, permits and licenses from regulatory authorities or
agencies applicable to the Manufacture of the
Product;
|
|
Batch
|
means
the total Product (Drug Substance) obtained from the fermentation and
associated purification using the Process and carried out in accordance
with cGMP and Applicable Laws;
|
|
Batch
Records
|
means
the completed documentation associated with the manufactured Product on
each Batch for official and cGMP compliant documentation
purposes;
|
|
Certification
|
means
a certification of any Batch by a Qualified Person for further processing
confirming that the Batch is manufactured in accordance with the relevant
requirements for human use (as defined in Directive 2001/83/EC for
medicinal products for human use), commonly known as “QP batch
release”;
|
|
CofA
|
means
Certificate of Analysis;
|
|
CofC
|
means
Certificate of Compliance;
|
|
cGMP
|
means
current Good Manufacturing Practice and general biologics products
standards as promulgated under the European Commission Directives
91/356/EEC, as amended by Directive 2003/94/EC, and 91/412EEC
respectively; the International Committee for Harmonisation (ICH) Q7
Guideline on Good Manufacturing Practice for Active Pharmaceutical
Ingredients; the U.S. Federal Food, Drug and Cosmetic Act found in Title
21 of the U.S. Code of Federal Regulations (CFR), including but not
limited to Parts 210, 211 and Parts 11, 310 et seq., 600 to 610, the
European Commission Guidelines of Good Manufacturing Practices for
Medicinal Products as promulgated under European Directive 2003/94/EC
(Eudralex – Volume IV) and the respective Japanese directives and
guidelines by the Japanese authorities, as applicable. Lonza meets EU GMP
requirements as defined in Eudralex - Volume IV Good Manufacturing
Guidelines by the European Commission for medicinal products for human and
veterinary use (EU-GMP Guidelines);
|
|
Development
and
Supply
Agreement
|
means the
Development and Supply Agreement to which this
Quality Agreement is attached as Schedule
10;
|
|
Drug
Product
|
Product
or a combination of Product with other substances being in its final
container suitable for administration to human beings (bulk unlabeled and
final product labeled).
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
Drug Product
Specification
|
means
the specification for Drug Product, set forth under Sections B and C of
Schedule 2 of the Development and Supply Agreement, and any amendments to
any of the foregoing specifications regarding the Drug Product as agreed
upon by the Parties from time to
time;
|
|
Facility/
Facilities
|
means
the facilities of Lonza where the Product is Manufactured in compliance
with cGMP and Applicable Laws. Facilities of sub-contractors of Lonza
shall only be deemed Facilities under this Quality Agreement upon prior
written approval of Micromet;
|
|
FDA
|
means
U.S. Food and Drug Administration;
|
|
FEFO
|
means
First Expired First Out;
|
|
FIFO
|
means
First In First Out;
|
|
ICH
|
means
International Conference on
Harmonization;
|
|
IB(I)MP
|
means
Intermediate Biological (Investigational) Medicinal Product also known as
Drug Substance;
|
Manufacture /
Manufacturing
|
means
and includes all operations of the Process used by Lonza for the
production of the Product in accordance with the Product Specification and
cGMP, i.e., receipt of materials, production, packaging, repackaging,
labeling, relabeling, quality control, quality assurance, Release, storage
and distribution of the Product;
|
|
Product
|
means
IB(I)MP of MT103 Manufactured under the Development and Supply Agreement
in accordance with the Product Specifications, cGMP and Applicable
Laws;
|
|
Product
Specification
|
means
the receiving, in-process and finished Product specification for Drug
Substance, set forth in Section A of Schedule 2 of the Development and
Supply Agreement applicable to the Product, as amended in accordance with
the Development and Supply Agreement and this Quality Agreement, and any
amendments to any of the foregoing specifications regarding the Product as
agreed upon by the Parties from time to
time;
|
|
Qualified Person/
QP
|
means
a person qualified pursuant to Applicable Laws confirming that the Batch
is in accordance with the relevant requirements (as defined in Directive
2001/83/EC for medicinal products for human
use);
|
|
Quality
Agreement
|
means
this Quality Agreement which is attached to the Development and Supply
Agreement as Schedule 10;
|
|
Raw
Materials
|
means
all raw materials, supplies, components and packaging necessary to
Manufacture the Product in accordance with the Product Specification, but
not including the Product
|
|
Reprocessing
|
means
the process by which a lot or portion of a lot is purified through repeat
of established and approved Manufacturing steps to produce Product that
meets appropriate standards, specifications and any other relevant control
limit criteria;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
Schedule
10
|
|
SOP(s)
|
means
the standard operating procedures in effect at Lonza which are applicable
to the Manufacture of the Product and which comply with cGMP and
applicable Laws;
|
|
TSE/BSE
|
means
Transmissible Spongiform Encephalopathy / Bovine Spongiform
Encephalopathy.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
3. Facilities
/ Materials Controls
3.1 Organization
and Key Personnel
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Will maintain a quality unit that is independent of the production
unit and has the responsibility and authority to approve or reject
components, Raw Materials/ [***], bulk packaging materials, Product, SOPs,
master Batch Records, deviation/investigations, and executed production
Batch Records.
|
N/A
|
|
·
Will provide and document initial and on-going cGMP and process
specific technical training of employees involved in GMP
operations.
|
N/A
|
|
·
Will ensure that the use of consultants is supported by documented
verification that the consultant(s) has(have) the sufficient education,
training, experience, or any combination thereof, to advise on the subject
for which they are retained.
|
N/A
|
|
·
Ensure and allocate adequate number of personnel have appropriate
training, skills, knowledge and experience to perform and supervise the
Manufacture and testing of the Product and the Drug Product in accordance
to cGMP and Applicable Laws.
|
N/A
|
|
·
Will ensure that responsibilities and procedures applicable to the
quality unit are documented in writing and consistently
followed.
|
N/A
|
|
·
Will conduct internal audits of all relevant activities to ensure
compliance with cGMP and applicable SOPs. Audit findings and corrective
actions will be documented, brought to the attention of Lonza’s Facility
management, and resolved in a timely and effective manner.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
3.2 Buildings,
Facilities, Utilities and Equipment
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Ensure Facilities, premises, environment, utilities, equipment and
computerised systems are properly designed, validated and maintained in
accordance with cGMP and Applicable Laws.
|
N/A
|
|
·
Will be responsible for ensuring that any Facility owned and
operated by a sub-contractor who performs GMP relevant work operates in
compliance with cGMP and Applicable Laws. Will inform Micromet in advance
of its intent to sub-contract. Will sub-contract only upon written
approval from Micromet for sub-contracting.
|
·
Approval of Facilities.
|
|
·
Provide a list, upon request, to Micromet of any sub-contractors
used to perform GMP operations, or GMP support operations.
|
·
Review list.
|
|
·
Maintain controlled access to Facilities.
|
N/A
|
|
·
Via change control will notify Micromet as soon as reasonably
practicable of any known changes in ownership of sub-contractors used by
Lonza (See Change
Control Section under Section 6.5 for further
details).
|
N/A
|
|
·
Ensures appropriate separation and controls are in place for
operation of multi-product Facilities. An example of a multi site
responsibilities matrix is attached hereto as Annex 2.
|
N/A
|
|
·
Review data provided by Micromet.
|
·
Upon request, will provide Lonza with Product data/samples required
to conduct cleaning studies.
|
|
·
Label and store any Product dedicated equipment to adequately
prevent unintended use for other products.
|
N/A
|
|
·
Maintain an environmental water and clean steam monitoring program
to ensure compliance with environmental monitoring regulations and
SOPs.
|
N/A
|
|
·
Will qualify, maintain and calibrate equipment and utility services
associated with Manufacturing the Product in accordance with cGMP,
Applicable Laws, and SOPs.
|
N/A
|
|
·
Will ensure, via validation or verification, that cleaning
processes carried out on Product contact surfaces between batches of
different products and Raw Materials/[***] are adequate to prevent
contamination.
|
N/A
|
|
·
Will maintain complete and accurate cleaning and use logs of
equipment used for the Manufacture of Product
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
3.3 Raw
Materials Controls
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Source, test and release Raw Materials and/or primary packaging of
appropriate quality for processing of Product.
|
N/A
|
|
·
Ensure that all animal derived Raw Materials used for Product are
appropriately tested in line with cGMP and Applicable
Laws.
|
·
As applicable, provide information to Lonza on any known animal
derived Raw Materials requested for use in the
Manufacturing.
|
|
·
Assess and approve Suppliers of Raw Materials and components in
accordance with the relevant Lonza SOPs.
|
N/A
|
|
·
Retain representative samples of critical Raw Materials, as
appropriate and in accordance with the relevant SOP(s) and cGMP for
retention samples;
·
Store, under appropriate conditions, a quantity sufficient to
perform at least two (2) full analyses, according to the relevant
SOP.
|
N/A
|
|
·
Establish and maintain specifications for GMP materials as per
SOPs.
|
·
As applicable, specify any special requirements for specifications
of GMP materials used in the process.
|
|
·
Utilize either FEFO or FIFO strategy for consumption of GMP
materials.
|
N/A
|
|
·
Use Product bulk packaging and labelling information specified by
Micromet;
·
If not specified by Micromet, utilize Lonza generic bulk packaging
and labelling configurations as per SOP(s).
|
·
Approve Product bulk packaging and information on the
label
|
|
·
Will be responsible for maintenance of specifications of the Raw
Materials / [***].
|
N/A
|
|
N/A
|
·
Will approve all sources of Raw Materials/ [***] and other
materials used in the process.
|
|
·
Will be responsible for procurement, storage, sampling, testing,
release, assigning expiration or re-test dating, and maintaining records
for each delivery of Raw Materials/[***].
|
N/A
|
|
·
Will maintain a program to audit (if required) and qualify
suppliers of critical Raw Materials/ [***] used in the
Manufacturing of Product to ensure full compliance with
cGMP and Applicable Laws and to verify the status of Raw Materials/[***]
of animal origin with respect to Transmissible Spongiform Encephalopathy
(TSE) issues.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
4.
Process Controls
4.1
Cell Xxxxx
Xxxxx
Responsibility
|
Micromet
Responsibility
|
|
·
Review and approve characterisation data and store working stock of
Cell Banks in accordance with the Development and Supply Agreement
and Applicable Laws.
|
·
Supply Cell Banks and characterisation
data.
|
|
·
Discuss any unexpected result with Micromet and agree action(s) to
be taken.
|
·
If Cell Banks are tested by any other organisation other than
Lonza, any unexpected results must be reported to Lonza within
[***].
|
|
·
Review data.
|
·
Provide shipping validation for shipping container used to ship
Cell Banks.
|
|
·
Will store the [***] (as well as the [***] [***] after generation
through Lonza) [***].
|
N/A
|
|
·
Prepare, characterize and store [***] per SOPs.
|
N/A
|
4.2 Product
Specification
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Jointly review, approve and issue the following
Product Specification(s) as required per Development and Supply
Agreement:
· IB(I)MP
· Drug
Product.
|
·
Jointly review and approve, via the Micromet approval form, the
following Product Specification(s) as required per Development and
Supply Agreement:
· IB(I)MP
· Drug
Product.
·
Complete review, resolution of any questions and approval of
Product Specification within [***] from date of receipt or within another
timeline that has been mutually agreed by Micromet and
Lonza.
|
|
·
In accordance with Lonza Quality Standard GROUP-2500, jointly
review, approve and issue the master certification documents (e.g. CofA,
CofC...etc), as required per Micromet.
|
·
Review and approve, via the Micromet approval form, the required
master certification documents, as applicable;
·
Complete review, resolution of any questions and approval of master
product certification documents within [***] from date of receipt or
within another timeline that has been mutually agreed by Micromet and
Lonza.
|
4.3 Production,
Process Handling and Process Control
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Prepare, approve and maintain process documents relating to
facility, equipment and test methods.
|
N/A
|
|
·
Will develop, optimize and scale up Manufacturing processes in
compliance with the requirements set forth in the guideline ICH Q8,R1
(Pharmaceutical Development) and make use of Quality by
Design.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
·
Will perform quality risk management as Part of development in
compliance with the requirements set forth in chapter II.3 of the
guideline ICH Q9 (Pharmaceutical Development) and therefore
will:
·
assess the critical attributes of Raw Materials;
·
identify critical process parameters and establish manufacturing
controls.
|
N/A
|
|
·
Will compile a development report in a form suitable for
incorporation into regulatory submissions (i.e. IMPD/IND).
|
N/A
|
|
·
Will ensure that Product Manufactured is appropriately tested
according to agreed upon sampling and testing plans, Product Specification
and approved procedures.
|
N/A
|
|
·
Jointly review, approve and issue process
descriptions.
|
·
Complete review of technical content, resolution of any questions
and approval of process description within [***] from date of receipt or
within another timeline that has been mutually agreed by Micromet and
Lonza. Approval to be captured via the Micromet approval
Form;
·
Subsequent updates to technical content will be captured by change
control (see under
Section 6.5 below).
|
|
·
Prepare master Batch Records for each processing step and make
available for Micromet to review during audit or other mutually defined
frequency.
|
·
Review master Batch Records for accuracy of technical content for
each processing step and agree.
|
|
·
Define specifications and perform in-process controls and testing
program.
|
·
Agree in-process testing strategy.
|
|
·
With Micromet, define process validation plans and timing for
Product including analytical validation and stability
studies;
·
Annex 3
contains additional considerations for Product intended for commercial
use.
|
· With Lonza, define process validation
plans and timing for Product including analytical validation and stability
studies;
·
Annex 3
contains additional considerations for Product intended for commercial
use.
|
|
·
Designate unique Batch numbers for Raw Materials, process materials
and Product.
|
N/A
|
|
·
Maintain the Specifications file for Product
·
Notify Micromet of any changes to the Specifications
file;
·
Assurance of consistency of current Specifications file and IMPD/
IND versions and notify Micromet.
|
N/A
|
|
·
Unless due to emergency whereby product integrity is at risk, Lonza
will not Reprocess Product without prior notification and written approval
of Micromet.
|
·
If notification received prior to Reprocessing by Lonza, complete
review, resolution of any questions and approval of Reprocessing requests
within [***];
·
Following emergency Reprocessing by Lonza, complete review,
resolution of any questions and approval of Reprocessing
deviation/investigation within
[***].
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
·
Provide documented reason and justification for Reprocessing
event.
|
N/A
|
|
·
With Micromet, agree the appropriate testing required prior to the
release of processed or Reprocessed Product.
|
·
With Lonza, agree the appropriate testing required prior to the
release of processed or Reprocessed
Product.
|
4.4 Product
Storage, Labeling, Packaging and Shipment
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Will maintain procedures to ensure Product is stored under
appropriate environmental conditions as defined by
Micromet.
|
·
Specify to Lonza all applicable storage requirements for
Product.
|
|
·
Store, label and package (including transport packaging) Product as
defined in the Product Specification.
|
N/A
|
|
·
Notify Micromet of proposed shipment date.
|
·
Agree shipment date.
|
|
·
Ship Product on behalf of Micromet to locations designated by
Micromet.
|
·
Acknowledge receipt of Product in writing within [***] of
receipt.
|
|
·
Provide generic shipping validation data, where available, for
Product if requested by Micromet.
|
·
Provide Product specific shipping validation OR, where applicable,
request in writing to utilize Lonza generic shipping validation for
Product.
|
|
·
If Product is to be shipped under quarantine ensure written
confirmation received from Micromet to authorise shipment of Product under
quarantine prior to shipment.
|
·
Provide Lonza with written confirmation to authorise shipment of
Product under
quarantine.
|
5. Quality
Control Laboratories
5.1
QC Laboratory Controls
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Assess and approve contract testing laboratories for Raw Material,
Cell Banks, Product Release testing and Drug Product
testing.
|
N/A
|
|
·
Notify Micromet of contract testing laboratories used for Product
Release testing and Drug Product testing.
|
·
Agree proposed use of contract testing
laboratories.
|
|
·
Audit contract testing laboratories in accordance with GxP
guidelines and confirm audit to Micromet in writing.
|
N/A
|
|
·
Facilitate audit by Micromet if requested.
|
·
May perform audits of Lonza contract testing laboratories providing
Micromet is authorized to do so by the contract laboratory and accompanied
by a Lonza representative.
|
|
·
Review and approve Micromet strategy and deliverables for
establishing analytical methods for process.
|
·
Define strategy and deliverables for establishing analytical
methods to be used in support of process, including:
o Methods to be developed by
Lonza;
o Methods to be transferred
to Lonza from
external
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
·
Will submit any proposed major changes to analytical methods
related to the testing of Product and Drug Product to Micromet for review
and approval prior to the implementation of such changes. Change request
notification and approval will be documented according to the applicable
SOP.
|
·
Will submit any proposed major changes to analytical methods
related to the Drug Product and Product to Lonza for review and approval
prior to the implementation of such changes. Change request notification
and approval will be documented.
|
|
·
Will not implement proposed major changes until written approval is
received from Micromet.
|
N/A
|
|
·
Will be responsible for performing [***] identification test on
each lot of Raw Materials in accordance with approved analytical methods
and specifications, compendial methods and SOPs.
|
N/A
|
|
·
Will be responsible for performing all in-process testing in
accordance with approved procedures.
|
N/A
|
|
·
Will provide Micromet with a Certificate of Analysis and a
Certificate of Compliance as well as a QP Certification statement
individually or as combined documentation.
|
N/A
|
|
·
Perform Product and Drug Product testing against Product and Drug
Product Specification.
|
N/A
|
|
·
Notify Micromet of confirmed out of Specification results (OOS)
regarding Product Release testing and Drug Product testing.within target
of [***], not to exceed [***], of the OOS being confirmed.
|
·
Complete review, resolution of any questions and approval of
investigation reports within [***] regarding any out of Specification
result (OOS) of Product and Drug Product
·
For target specifications agree impact on quality and safety of
Product and Drug Product.
|
|
·
Will provide Micromet with a written report on the investigation
and resolution of the OOS test result within [***] of confirmation of the
result, unless granted approval by Micromet for a longer
period.
|
N/A
|
|
·
Take bulk Product retention samples from each Batch with sufficient
volume for at least [***] full biochemical Product Specification
analyses for use in the event of an investigation on Product Released for
clinical trial supply.
|
·
Define number of samples required to complete full biochemical
analysis.
|
|
·
Store retains under appropriate conditions for the period defined
in SOPs.
|
N/A
|
|
·
Upon completion of sample retention period notify Micromet of
option to either destroy or ship retention in accordance with
SOPs.
|
·
Within [***] respond in writing to Lonza and approve destruction of
samples or request receipt of
samples.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
·
Jointly agree to analytical method development and/or method
transfer strategy for Product and Drug product testing;
·
Strategy to include deliverables for all applicable methods to be
developed, validated, transferred and qualified, as
applicable.
|
·
Jointly agree to analytical method development and/or method
transfer strategy for Product testing;
·
Strategy to include deliverables for all applicable methods to be
developed, validated, transferred and qualified, as
applicable.
|
|
·
Will be responsible for qualifying and maintaining all laboratory
equipment used for all testing applicable to the Manufacture of
Product.
|
N/A
|
|
·
Perform Product stability testing according to Development and
Supply Agreement;
·
Prepare stability protocols.
|
·
Jointly define stability testing requirements and
responsibilities;
·
Approve stability protocols.
|
|
·
Notify Micromet within target of [***], not to exceed [***], of any
confirmed stability failure of the Product at the intended storage
temperature.
|
·
Acknowledge receipt of Lonza notification, in writing, within
[***].
|
|
·
Prepare, characterise and store Product reference standard per
SOPs.
|
·
Agree to reference characterisation package.
|
|
·
Provide reference standard characterisation report to
Micromet.
|
·
Agree to reference characterisation package.
|
|
·
Store characterised Product reference standard under appropriate
conditions as per SOPs.
|
·
Supply characterised Product reference standard with
Certificate of Analysis.
|
6. Quality
Assurance / Quality Management Systems
6.1 Complaints,
Recalls and Adverse Events
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Upon request, support Micromet in their Product complaint or
adverse event investigations for events possibly related to
Lonza;
·
Jointly agree to investigation plan, actions and time lines for
response, as applicable.
|
·
Receive and investigate Product complaint and adverse events and
request Lonza support, as applicable;
·
Jointly agree to investigation plan, actions and time lines for
response, as applicable;
·
Responsible for all notifications to regulatory agencies, as
applicable, related to product complaints or adverse
events.
|
|
·
Upon request, support Micromet in activities related to Product
recall where recall relates to Lonza.
|
·
Responsible for decision to initiate a Product recall;
·
Responsible for overall management of Product recall
activities.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
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|
6.2 Batch
Review and Product Disposition
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Review Batch Record for compliance to cGMP, SOPs and the Product
Specification.
|
N/A
|
|
·
Will provide Micromet upon its request, one (1) agreed copy of
Product Batch documentation for each production Batch (as detailed in
Annex 4). This
will include Product analysis as defined in the Product Specification, a
summary of Batch related deviations, environmental monitoring summaries,
TSE / BSE statements, Certificate of Compliance, Release certificate.
Proprietary information such as media and feed preparations may be
excluded. Lonza to provide information directly to regulatory
authorities.
|
N/A
|
|
·
Prepare Certificate of Analysis for Product as specified
by Micromet.
|
N/A
|
|
·
Responsible for Certification of Product to Micromet "for use in
further manufacturing" of clinical trial materials by a Qualified
Person.
|
·
Responsible for Certification of Product for use in clinical trials
and/or markets supplied (unless otherwise specified contractually with
Lonza).
|
6.3 Records
Retention
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Retain records associated with Manufacture of Product and testing
of Product and Drug Product, including records associated with the
inspection and Release of Raw Materials and primary packaging components,
for minimum of [***] from date of Manufacture of Product.
|
N/A
|
|
·
Notify Micromet of intent to destroy records with option to send
records (Lonza proprietary information will be omitted) to
Micromet
OR
·
Agree terms with Micromet for future storage.
|
·
Approve destruction or request receipt of
records.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
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|
6.4 Deviations
/ Investigation Reports
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Deviation handling, investigation and clarification of any cell
culture contamination, any deviation potentially bearing a risk of a
defective batch run, potential loss of a batch due to technical defects or
operator errors
·
General deviation handling in accordance with Lonza procedures,
initiate deviations/investigations, evaluate and define follow up actions
and final approval of deviations / investigation reports.
|
N/A
|
|
·
Notify Micromet of all significant deviations within target of
[***], not to exceed [***] of the event;
·
A significant deviation is as defined as per Lonza’s relevant
SOPs;
·
Upon request, provide Micromet with copy of draft report of
significant deviation for review and comments.
|
·
Acknowledge receipt of significant deviation draft report, in
writing, within [***];
·
Provide any questions/comments to draft Lonza report within
[***].
|
|
·
Notify Micromet of failed Batches within target of [***], not to
exceed [***] of failure being identified.
|
·
Acknowledge receipt of failure investigation draft report, in
writing, within [***];
·
Provide any questions/comments to draft Lonza report within
[***].
|
|
·
Within target of [***], not to exceed [***], notify Micromet of any
events noted which may impact Batches previously shipped or
Released;
·
Upon request, provide Micromet with copy of draft report of noted
deviation for review and comments.
|
·
Acknowledge receipt of notification, in writing, within
[***];
·
Provide any questions/comments to draft Lonza report within
[***].
|
6.5 Change
Control Procedures
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
For a Product specific change proposed by Micromet: process change
through change control and notify Micromet of change
approval. If change rejected discuss reasons for rejection with
Micromet.
|
·
Propose Micromet changes and provide rationale in
writing.
|
|
·
Will provide Micromet with all information required to evaluate the
proposed changes and, if necessary, obtain amended clinical trial
applications, as applicable.
|
N/A
|
|
·
Lonza will not implement major changes (i.e., changes which are
relevant for regulatory approval) until written change request approval is
received from Micromet.
|
·
Approval of major change or rejection.
|
|
·
For major changes proposed by Lonza, Lonza will provide Micromet
with all information required to evaluate such proposed changes and, if
necessary, to obtain amended clinical trial applications, as
applicable.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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|
·
Notify Micromet, through change control, of any proposed changes to
Product or process specific attributes prior to
implementation.
|
·
Complete review, resolution of any questions and approval within
[***] of receipt of change controls.
|
|
·
Inform Micromet of changes to key personnel.
|
N/A
|
|
·
Notify Micromet, through change control, of relevant changes to
major equipment, premises and utilities used for Manufacture of
Product.
|
·
Acknowledge receipt of notification, in writing, within
[***].
|
|
·
With Micromet, define strategy for notifying change
to regulatory agency as appropriate.
|
·
With Lonza, define strategy for notifying changes
to regulatory agency as
appropriate.
|
7. Regulatory
Authorizations and Inspections
7.1
Regulatory Agency Inspections
|
||
Lonza
Responsibility
|
Micromet
Responsibility
|
|
·
Provide Micromet with daily verbal debriefs of inspection scope
during inspections.
|
·
Provide required technical, quality and regulatory representatives
on site for pre-approval inspections, as agreed with Lonza;
·
Provide up to [***] ([***] to be agreed by Lonza) to be present
directly in meetings with agency inspectors.
|
|
·
Provide copies of inspection reports and notify Micromet of
proposed responses and corrective action plans regarding the Product,
process or systems relating to Product.
|
·
Agree on proposed inspection responses to observations relevant to
Product.
|
|
·
Inform Micromet of any regulatory agency inspections at
Facilities.
|
·
For regulatory agency inspections regarding Product provide
assistance to Lonza.
|
|
·
Notify Micromet of inspection observations (including deficiency
letters) regarding the Product, process or systems relating to the
Product.
|
·
Agree on proposed inspection responses to observations relevant to
Product.
|
|
·
Will permit an employee and/ or consultant and/or successor of
Micromet or Micromet's sublicensee(s) to be present as silent
observer.
|
N/A
|
|
·
Will appropriately and promptly correct verifiable complaints of
regulatory agencies;
·
Will implement appropriate actions as agreed upon by the
Parties.
|
·
Agree on proposed actions to complaints by regulatory
agencies.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
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|
7.2
|
Regulatory
Authorizations / Submissions
|
Lonza Responsibility
|
Micromet Responsibility
|
|
·
Maintain
all licenses and authorizations as are required by Applicable Laws to
operate a cGMP pharmaceutical bulk manufacturing, packaging, and/or
testing facility.
|
N/A
|
|
·
Will provide copies of all documentation necessary for Micromet to
respond to inquiries by regulatory agencies relating to
Product.
|
·
Will provide copies of all documentation necessary for Lonza to
respond to inquiries by regulatory agencies relating to
Product.
|
|
· Provide
data pack to Micromet covering activities performed by Lonza (Lonza
proprietary information will be omitted) for review and
comment;
· Provide
Micromet with final copy of data pack.
|
·
Review and comment on draft data pack.
|
|
· For
US submissions, provide letter authorising cross referral to [***] if
requested by Micromet.
|
·
Provide Lonza with copy of relevant sections of regulatory
application as submitted to regulatory agency.
|
|
· Review
and comment on relevant sections of Micromet’s regulatory
application.
|
· Prepare
and provide Lonza with copy of relevant sections of regulatory application
for review and comment prior to submission to regulatory
agency.
|
|
N/A
|
·
Provide Lonza with copy of relevant sections of regulatory
application as submitted to regulatory agency.
|
|
· Attend
teleconferences and meetings between Micromet and regulatory agencies
arranged to specifically discuss topics relating to Lonza’s
responsibilities, if requested by Micromet.
|
·
Arrange for Lonza personnel to have option to attend
teleconferences and meetings between Micromet and regulatory agencies
to specifically discuss topics relating to Lonza’s
responsibilities.
|
8.
|
Micromet
Oversight
|
8.1
|
Audit
Allowance
|
Lonza Responsibility
|
Micromet Responsibility
|
|
· [***] standard
cGMP compliance audit permitted per [***] and per [***], not to exceed
[***] and [***];
·
Will permit Micromet's Person-in-Plant (PiP) observe Works and
Services in accordance with the Development and Supply
Agreement;
·
Micromet may request ‘for cause’ audits and investigations to
address Product quality issues after prior notification.
|
· Provide
reasonable notice of intention to audit;
· Hold
an exit meeting to discuss observations;
· Provide
an audit report within [***] of completion of audit.
|
|
· Permit
Micromet representatives or third parties commissioned by Micromet for a
permitted audit to have access to GMP warehousing, manufacturing areas,
laboratories and Manufacturing documents including all standard operating
procedures (Lonza proprietary information will be omitted) for audit
purposes;
·
Micromet representatives to be escorted at all times by Lonza
personnel.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately
with the Securities and Exchange Commission pursuant to Rule 24b-2 of the
Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
· Per
lot, allow a [***] on site review for up to [***] to review completed
process Batch Records, if requested by Micromet.
|
· Per
lot, provide reasonable notice of intention to review executed Batch
Records.
|
|
|
||
· Provide
a written response to all audit findings that require corrective action
within [***] of receipt of the audit report. Response to
include expected timelines.
|
N/A
|
|
|
||
· Will
appropriately and promptly correct any defects found by audits and
inspections and take any necessary action.
|
N/A
|
|
|
||
· The
QP responsible for final Release or [***] is entitled to attend all
production campaigns of Product at the Facility as detailed in the
Development and Supply Agreement.
|
8.2
|
Periodic
Review of Quality Agreement
|
Lonza Responsibility
|
Micromet Responsibility
|
|
· Jointly
review Quality Agreement and revise, as necessary, at least every
[***].
|
· Jointly
review Quality Agreement and revise, as necessary, at least every
[***].
|
|
· Written
approval from both Parties for any amendments to the Quality
Agreement.
|
· Written
approval from both Parties for any amendments to the Quality
Agreement.
|
|
· Will
provide revision control of the Quality Agreement and issue a revised
document as appropriate.
|
N/A
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately
with the Securities and Exchange Commission pursuant to Rule 24b-2 of the
Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
9.
|
Term
|
This
Quality Agreement becomes effective on the Effective Date of the Development and
Supply Agreement and runs for the term of the Development and Supply Agreement.
This Quality Agreement automatically terminates upon expiry or termination of
the Development and Supply Agreement, unless the Parties agree to extend the
Quality Agreement.
10.
|
Miscellaneous
|
10.1
|
Sections
1 (Definitions and Interpretation), 5 (Inspections; Person in Plant), 10
(Confidentiality), 15 (Force Majeure), 16 (Governing Law, Jurisdiction and
Enforceability), 17 (Illegality) and 20.1 (Affiliates; Assignment) of the
Development and Supply Agreement shall also apply to this Quality
Agreement.
|
10.2
|
In
case of conflicts between this Quality Agreement and the Development and
Supply Agreement, the provisions of the Development and Supply Agreement
shall govern and control.
|
10.3
|
No
variation of or addition to this Quality Agreement or any part thereof
shall be effective unless in writing and signed on behalf of both
Parties. Notwithstanding the above the Parties hereby confirm
that amendments to the Product Specification and the Drug Product
Specifications shall be effective if reduced to writing and signed by the
quality and/or regulatory representative of both Parties, which quality
and/or regulatory representative shall be nominated from time to time by
each Party.
|
AS
WITNESS the hands of the duly authorised representatives of the
Parties.
Micromet
AG
|
Lonza
Sales AG
|
|||
Signature:
|
/s/ Xxxx Xxxxxxxx
|
Signature:
|
/s/ Una Hultry
|
|
Printed
Name: Xxxx Xxxxxxxx
|
Printed
Name: Una Hultry
|
|||
Title: SVP
Business Development
|
Title: Authorized
Signatory
|
|||
Signature:
|
/s/ Xxxxxxx Xxxxxxxx
|
Signature:
|
/s/ Xxxxx Xxxxxxx
|
|
Printed
Name: Xxxxxxx Xxxxxxxx
|
Printed
Name: Xxxxx Xxxxxxx
|
|||
Title: SVP,
Chief Scientific Officer
|
Title: Authorized
Signatory
|
[Signature
Page to the Quality Agreement]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the
Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities
Exchange Act of 1934, as amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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10
|
Micromet
|
Lonza
|
|||
Head
of Quality: Xxxxx Xxxxxxxxx
|
Head
of Quality (LBP): Xxx Xxxxx
|
|||
Signature:
|
/s/ Xxxxx Xxxxxxxxx
|
Signature:
|
/s/ Xxx Xxxxx
|
|
Head
of Manufacturing: Xxxxxx Xxxxx
|
Head
of Operations: Xxxxxx
Xxxxx
|
Signature:
|
/s/ Xxxxxx Xxxxx
|
Signature:
|
/s/ Xxxxxx
Xxxxx
|
Head
of Quality Control: Xxxxxxx Xxxx
|
Head
of Quality Control: Xxx
Xxxxx
|
Signature:
|
/s/ Xxxxxxx Xxxx
|
Signature:
|
/s/ Xxx
Xxxxx
|
[Page
of Quality Signatures]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the
Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities
Exchange Act of 1934, as amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Execution
Copy
|
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|
Annex
1 - Key Contacts
Micromet
|
Lonza
|
|||
Head
of Site: N/A
|
Head
of Site: [***]
|
|||
Tel:
|
[***]
|
|||
Fax:
|
[***]
|
|||
Email:
|
[***]
|
|||
Head
of Quality: [***]
|
Head
of Quality: [***]
|
|||
Tel:
|
[***]
|
Tel:
|
[***]
|
|
Fax:
|
[***]
|
Fax:
|
[***]
|
|
Email:
|
[***]
|
Email:
|
[***]
|
|
Head
of Manufacturing: [***]
|
Head
of Operations: [***]
|
|||
Tel:
|
[***]
|
Tel:
|
[***]
|
|
Fax:
|
[***]
|
Fax:
|
[***]
|
|
Email:
|
[***]
|
Email:
|
[***]
|
|
Head
of Quality Control: [***]
|
Head
of Quality Control: [***]
|
|||
Tel:
|
[***]
|
Tel:
|
[***]
|
|
Fax:
|
[***]
|
Fax:
|
[***]
|
|
Email:
|
[***]
|
Email:
|
[***]
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the
Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities
Exchange Act of 1934, as amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Annex
2 - Multi Site Responsibilities Matrix
Where
multiple Lonza sites are involved in supporting any GMP operations for a
Micromet Product/process it is recommended that a matrix be appended to the
Quality Agreement which details site specific responsibilities, as
applicable. An example of such a matrix is provided
below. In the event of multi site responsibilities being applicable
to a given Quality Agreement then all affected parties should approve the
Quality Agreement in writing. Additionally, the key contacts
identified in Annex 1
should include the appropriate contacts for each affected Lonza
Facility.
The
content provided in this matrix is for example only and may be altered, as
necessary, to highlight multi site specific responsibilities:
Site Specific Responsibility
|
Responsible Lonza Facility
|
Comments
|
||
GMP
Manufacture, process development, cell bank creation and
storage
|
[***]
|
Primary
Manufacturing Facility ([***])
|
||
Serve
as back-up storage facility for Micromet's cell banks
|
[***]
|
Storage
facility for Micromet cell banks
|
||
Pre-Licence
Stability Studies and Bioassays
|
[***]
|
Primary
Facility for stability studies and bioassays for Product produced at the
slough Facility
|
1
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the
Securities and Exchange Commission pursuant to Rule 24b-2 of the Securities
Exchange Act of 1934, as amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Annex
3 - Additional Considerations
for
IB(I)MP Intended for Commercial Use
2
[***]
Lonza Responsibility
|
Micromet Responsibility
|
|
·
For Lonza supplied materials, finalize critical supplier and
critical Raw Material qualifications for the Product
|
·
For Micromet supplied materials, finalize critical supplier and
critical Raw Material qualifications for the
Product.
|
[***]
Lonza Responsibility
|
Micromet Responsibility
|
|
· Jointly
with Micromet, define strategy and responsibilities for process validation
activities including (but not limited to):
o Process
validation master plan, protocols and reports (issued before phase III
material is manufactured);
o Product specific
assay validations;
o Cleaning
validation of the Product
o Hold
times for buffers/medias used in process;
o Intermediate Product
stability;
o Product
yield specifications.
|
· Jointly
with Lonza, define strategy and responsibilities for process validation
activities including (but not limited to):
o Process
validation master plan, protocols and reports;
o Product specific
assay validations;
o Cleaning
validation of the Product
o Hold
times for buffers/medias used
in process;
o Product
stability;
o Product
yield specifications.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Annex
4 – Information to be provided to Micromet
This
Annex describes what Batch record documentation and other information Lonza will
provide to Micromet during the manufacture of MT103 and the route by which this
information is provided. The information may be provided as separate
documents or within existing documentation. Any additional requests for
information will be progressed through the Project Team on a case by case
basis.
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
11
Testing of
Product
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
12
Territories
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
13
Terms and
Conditions for
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
14
TO
THE DEVELOPMENT AND SUPPLY AGREEMENT
DATED
NOVEMBER 23, 2009
LONZA
SALES AG
and
MICROMET
AG
TECHNOLOGY
TRANSFER AND LICENSE AGREEMENT
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
BETWEEN:
(1)
|
LONZA SALES AG, of
Xxxxxxxxxxxxxxxxxxxxxx 00, XX-0000, Xxxxx, Xxxxxxxxxxx (hereinafter
referred to as “the
Licensor”).
|
(2)
|
MICROMET AG, of
Xxxxxxxxxxxxxxxxx 0, X-00000 Xxxxxx, Xxxxxxx (hereinafter referred to as
“the Licensee”).
|
WHEREAS:
(A)
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Pursuant
to the Development Agreement (as defined below), the Licensor has
performed certain development and manufacturing services on behalf of the
Licensee relating to the Product, and accordingly the Licensor possesses
confidential and proprietary information and data concerning the
manufacture of the Product.
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(B)
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The
Licensor and the Licensee have previously entered into the Development
Agreement dated November 23, 2009 relating to, inter alia, the Licensee’s
use of certain Intellectual Property of the Licensor in the research,
development and manufacture of the
Product.
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(C)
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The
Licensor has agreed to transfer the Product specific documentation and
appropriate information and grant the licenses needed for the Licensee and
its Permitted Sublicensees (as defined below) to replicate the Process in
the event Licensee or its successor exercises its option for a technology
transfer and license as set forth in Clause 14 of the Development
Agreement. Upon exercise of the option, the Licensor shall make
available to the Licensee such confidential and proprietary information
and shall grant to the Licensee a non exclusive licence to use the
Licensed Know-How, the Licensed Patents and other Intellectual Property
for the further development and manufacture of the
Product.
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IT
IS HEREBY AGREED AS FOLLOWS:
1.
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INTERPRETATION
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|
1.1
|
The
definitions and rules of interpretation in this Clause apply in this TTL
Agreement.
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1.1.1
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Affiliate means any company,
corporation, limited liability company, partnership or other entity which
directly or indirectly Controls, is Controlled by or is under common
control, directly or indirectly, with the relevant Party to this
Agreement. Control for purposes of this Clause
1.1.1 shall mean the ownership of more than fifty percent (50%) of the
issued share capital of the Party in question or the legal power to direct
or cause the direction of the general management and policies of the Party
in question.
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***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
1.1.2
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Approved
Purpose means,
in relation to the Product only (and no other product), the further
development of the Process and the manufacture of the Product using the
Process and the Intellectual Property, the Licensed Know-How and the
Licensed Patents by the Licensee and/or its Permitted Sublicensees, and
the sale and use of the Product for any
purpose.
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|
1.1.3
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Control or
Controlled means
with respect to any (i) item of Information, including, without
limitation, know-how, or (ii) Intellectual Property, the possession
(whether by ownership or license, other than pursuant to this
TTL Agreement) by a Party of the ability to grant to the other Party
access or a license as provided herein under such item or right without
violating the terms of any agreement or other arrangements with any Third
Party.
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|
1.1.4
|
Development Agreement means that
certain agreement dated November 23, 2009 between the Licensor and the
Licensee relating to the development of the Process and the manufacture of
the Product.
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1.1.5
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Disclose includes discussion (or any
communication) or disclosure, by whatever means, and Disclosed,
Discloses, Disclosing and Disclosure are to be construed
accordingly, and in relation to an obligation to Disclose means the most appropriate form
of Disclosure.
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1.1.6
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Effective Date of this TTL Agreement means the date on which the
Licensee exercises the option for a technology transfer and license in
accordance with Clause 14 of the Development
Agreement.
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1.1.7
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Improvement means
any addition, alteration, change, development, enhancement, improvement or
modification to and non-severable from the Licensed Know-How and/or
Licensed Patents, and includes all Information in respect of the same, to
the extent severable from the Product and the Licensee’s patents and
know-how.
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1.1.8
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Information means any information,
including technical information and know-how, obtained from development,
experimentation, observation and operation by the Disclosing Party or on
its behalf or to which it is or becomes entitled and all analyses,
assessments, data, designs, details, diagrams, drawings, opinions,
specifications and statements in the Control and possession or within the
knowledge of the Disclosing
Party.
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***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
1.1.9
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Intellectual Property means all intellectual property
rights, including (without limitation) patents, patent applications,
divisions, continuations, continuation-in-part applications, divisionals,
substitutions, confirmations, supplementary protection certificates,
reissues, utility models, trademarks, database rights and copyrights and
all inventions, know-how, trade secrets, techniques and confidential
information and other proprietary knowledge and information which may
subsist anywhere in the world, in each case for their full term, and
together with any renewals or
extensions.
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1.1.10
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Licensed
Know-How means
all technical and other Information or data owned or Controlled by the
Licensor and used in the development and/or manufacture of the
Product. Licensed Know-How shall include but not be limited to
scientific, technical, and commercial information relating to the Process,
such as specifications, know-how, technologies, manufacturing processes,
research, inventions and the Licensor’s commercial activities, and further
including any know-how comprised in the New General Application
Intellectual Property, as defined in the Development Agreement as
well as know-how comprised in the Improvements. In the event
the Licensee exercises its option under Clause 14 of the Development
Agreement also for a technology transfer and license of the [***],
Licensed Know-How shall also include the [***]. Without
limiting the foregoing, the Lonza Know How as of the effective date of the
Development Agreement is identified in Schedule
A and
Schedule
C hereto.
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1.1.11
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Licensed
Patents means
patents and patent applications, divisions, continuations,
continuation-in-part applications, divisionals, extensions, substitutions,
renewals, confirmations, supplementary protection certificates and
reissues, throughout the world owned
or Controlled by the Licensor and used in the development and/or
manufacture of the Product. Licensed Patents shall also
include, but not be limited to patents and patent applications that cover
the New General Applications Intellectual Property, as defined in the
Development Agreement, as well as patents and patent applications
comprised in the Improvements. In the event the Licensee
exercises its option under Clause 14 of the Development Agreement also for
a technology transfer and license of the [***], Licensed Patents shall
also include the [***]. Short particulars of the Licensed
Patents as of the effective date of the Development Agreement are set out
in Schedule
B hereto.
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***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
1.1.12
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Lonza means Lonza Sales AG and its
Affiliates Lonza Biologics plc of Slough, England, Lonza Biologics Inc of
Portsmouth, NH, USA, and Lonza Biologics Xxxxxxx X.X. of
Pontevedra-Galicia,
Spain.
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1.1.13
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Micromet means Micromet AG and its
existing Affiliates which are engaged in the research and development of
BiTE® antibodies, and their
successors in title and lawful
assigns.
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1.1.14
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Net Selling Price means all monies received by
or on behalf of the Licensee or its sublicensee hereunder in respect of
the sale of Product in the Territory to a Third Party in a bona fide arm's
length transaction, less the following items to the extent that they are
paid or allowed and included in the invoice price, whether or not invoiced
separately, and determined in accordance with consistently applied and
recognized accounting
standards:
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(a)
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normal
discounts actually granted, including without limitation, quantity, trade,
cash and other discounts, rebates and charge-backs, including government
rebates, governmental price reductions and
charges;
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(b)
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amounts
refunded or credits allowed for Product or other goods returned or not
accepted by customers;
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|
(c)
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packaging,
transportation and prepaid insurance charges on shipments or deliveries to
customers; and
|
|
(d)
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taxes,
tariffs, customs duties, surcharges and other governmental charges
actually incurred and paid by Licensee or its sublicensee hereunder in
connection with the sale, exportation, importation or delivery of Product
or other goods to customers.
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In the
event Product is sold as part of combination product with either one or more
other pharmaceutically active ingredient(s) or with a product or device for
delivery of the Product (a Combination Product), the Net
Selling Price of the Product, for the purposes of determining royalty payments,
shall be determined by multiplying the Net Selling Price of the Combination
Product by the fraction, A/A+B where A is the average sale price of Product when
sold separately and B is the average sale price of the other part of the
Combination Product sold separately. If such average sales price
cannot be determined for both the Product and the other part of the Combination
Product, the Net Selling Price for purposes of determining royalty payments
shall be calculated by multiplying the Net Selling Price of the Combination
Product by the fraction C/C+D where C is the cost of goods of Product and D is
the cost of goods of the other part of the Combination Product, determined in
accordance with the method of accounting normally employed by the Licensee in
computing cost of goods.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
If the
sale of a Product by or on behalf of Licensee or its sublicensee referenced
above is not exclusively for money but partly or in whole for other
consideration, then the average Net Selling Price, on a country by country
basis, of Licensee or its sublicensee if sold exclusively for money shall be
deemed to be the Net Selling Price for such sales of Product. If no such average
Net Selling Price exists in a particular country, the average Net Selling Price
in the EU, and if no such average Net Selling Price exists in the EU, the
average Net Selling Price in the USA shall be considered the Net Selling Price
of such sales of Product.
For the
avoidance of doubt, the supply of Product free of charge as commercial samples,
or for use in clinical studies, or to Third Parties for evaluation purposes,
shall not be included in this provision.
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1.1.15
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Party / Parties means Licensor or
Licensee, or Licensor and Licensee, as the context
permits.
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1.1.16
|
Permitted Sub-licensee means a Third Party
collaboration partner of the Licensee or a Third Party who manufactures
the Product on behalf of the Licensee or the Third Party collaboration
partner of the Licensee subject to a sublicense in accordance with Clause
2.3 below.
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1.1.17
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Process means the process
(including but not limited to the fermentation process and the downstream
process) for the production of Product which is owned or Controlled by
Licensor and was further developed and/or improved and used for the
manufacture of Product by the Licensor under the Development
Agreement.
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1.1.18
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Product means
Licensee's single-chain bispecific anti-CD19 antibody (CD19
BiTE®)
also known as Blinatumomab or MT103, and any [***],
including [***].
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1.1.19
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[***] means Licensor’s chemically defined, [***]
consisting of the [***] used either in combination or individually, as it
is used in the development and/or manufacture of the Product and owned or
Controlled by
Licensor.
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(a)
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[***] means [***], as more fully
set out in Schedule
C;
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(b)
|
[***] means [***], as more fully
set out in Schedule
C;
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(c)
|
[***] means the [***] set out in
Schedule
C;
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(d)
|
[***] means any Information
specifically relating to the [***]. The [***] as of the
effective date of the Development Agreement is identified in more detail
in Schedule
C hereto;
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***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
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(e)
|
[***] means any patents and
applications covering the [***]. The [***] as of the effective
date of the Development Agreement are identified in more detail in Schedule C
hereto;
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(f)
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[***] means the [***], as more
fully set out in Schedule
C.
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[***] forms part of the Licensed Patents and the Licensed Know-How.
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1.1.20
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Territory means
worldwide.
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1.1.21
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Third
Party means
any party other than the Licensor and the
Licensee.
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1.1.22
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TTL Agreement means this Technology
Transfer and License
Agreement.
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1.1.23
|
Valid Claim means an issued claim
of an issued patent that has not (i) expired or been cancelled, (ii) been
declared invalid by a decision of a court or other appropriate body of
competent jurisdiction, from which no appeal is or can be taken, (iii)
been admitted to be invalid or unenforceable through reissue, disclaimer
or otherwise, or (iv) been abandoned or
disclaimed.
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1.2
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Any
reference to a Clause is to a Clause of this TTL Agreement, unless it
expressly refers to the Development
Agreement.
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1.3
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Clause
headings do not affect the interpretation of this TTL
Agreement.
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1.4
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Words
in the singular include the plural and in the plural include the
singular.
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1.5
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A
reference to one gender includes a reference to the other
gender.
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1.6
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A
person includes a corporate or unincorporated
body.
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1.7
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A
reference to a particular law is a reference to it as it is in force for
the time being taking account of any amendment, extension, application or
re-enactment and includes any subordinate legislation for the time being
in force made under it.
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1.8
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Writing
or written includes faxes but not
e-mail.
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2
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GRANT
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2.1
|
All
Intellectual Property in and to the Licensed Know-How and the Licensed
Patents and the [***] are and shall remain the exclusive property of the
Licensor. Neither this TTL Agreement nor any Disclosure of the
Intellectual Property, the Licensed Know-How, the Licensed Patents, and
the [***] shall be deemed by implication or otherwise to vest in the
Licensee any present or future rights in any Intellectual Property, the
Licensed Know-How, the Licensed Patents, and the [***] and no licence is
granted except as explicitly stated in this TTL
Agreement.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
2.2
|
The
Licensor hereby grants to the Licensee, and the Licensee accepts, in
relation only to the Product, a non exclusive licence to use the
Intellectual Property, the Licensed Know-How, the Licensed Patents and/or
the [***] to develop, have developed, to manufacture, have manufactured,
to supply, have supplied, to import, have imported, to use, have used, and
to sell and have sold, the Product in the Territory for the Approved
Purpose only.
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2.3
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The Licensee shall have the right to authorize
and grant sub-licences through multiple tiers under this TTL Agreement to
specific [***] and any other Third Party registered and operating within
the permitted territories (but not to [***], their Affiliates or any other
Third Party registered and operating outside the permitted territories)
listed in Schedule
D (any [***] or Third Party other than those named, or outside
those territories listed, are to be assessed and consented to by Licensor
on a case by case basis, provided
that such consent by the Licensor shall not be unreasonably
withheld or delayed) with respect to the rights and licences granted under
this TTL Agreement, and further provided
that:
|
the
Licensee shall ensure that there are included in the terms of any sub-licence
the like obligations and undertakings on the part of the sub-licensee as are
contained in this TTL Agreement, including in particular, but not limited to,
this Clause 2.3 (obligations on the sublicensee for sub-sublicensing) and Clause
6 (Confidentiality) and shall further ensure that all sub-licensees duly observe
and perform the same;
|
2.3.1
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the
Licensee shall at all times indemnify and keep indemnified the Licensor
against all or any cost, claims, damages or expenses incurred by the
Licensor or for which the Licensor may become liable as a result of the
default or negligence of any sub-licensee, (including sub-sub-licensees,
and as further sub-licensed as the case may be), relating to this TTL
Agreement; and/or
|
|
2.3.2
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each
sub-license, (including sub-sub-licensees, and as further sub-licensed as
the case may be), shall be expressly subject and subordinate to the terms
of this TTL Agreement, and it shall be the Licensee's responsibility to
ensure the strict adherence by any sublicensee hereunder to the terms and
conditions of this TTL Agreement.
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2.4
|
With
regard to the [***] and provided
that the Licensee exercises its option regarding the [***] under
Clause 14 of the Development Agreement, the following provisions shall
apply:
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2.4.1
|
The
Licensor shall offer to Licensee [***]. Such new version shall
be made available at the price set forth in Clause 7.2 below, with the
only additional compensation being for additional Works and Services which
may be required to implement such improvement or new version for the
manufacture of the Product.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
2.4.2
|
The
Licensor shall provide the Licensee with details of a Third Party
supplier, from whom the Licensee and/or the Permitted Sub-licensee will be
able to purchase [***] to enable the Licensee and/or the Permitted
Sub-licensee, to make and use the [***], and the Licensor shall also
provide the Licensee or at Licensee's direction the Permitted Sublicensee
with the [***] to the extent required by the Licensee and/or the Permitted
Sub-licensee to use the [***], and to make and use the [***] for the
Approved Purpose.
|
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2.4.3
|
For
the avoidance of doubt, the formulation of the [***] and/or the [***] will
not be Disclosed to the Licensee, and the Licensee hereby confirms that it
shall not perform any analysis, test, experiment, modification or
reverse-engineering on the [***]. With regard to any regulatory
filings necessary to support the Product, the Licensor shall file such
formulations directly with the appropriate regulatory
authority.
|
|
2.4.4
|
Upon
the request of Licensee, Licensor shall provide to the Licensee or
directly to the appropriate regulatory authority (as the case may be),
such documents and reasonable assistance regarding the [***] as may be
required to be submitted by Licensee in filings with any applicable
regulatory authorities for the
Product.
|
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2.4.5
|
The
Licensor will provide to certain designated safety experts of the Licensee
or at the Licensee's direction its Permitted Sublicensee with [***] in
order to enable the Licensee or the Permitted Sublicensee to evaluate the
safety of the [***].
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2.4.6
|
The
Licensor shall use reasonable commercial endeavours to ensure continuity
of supply of the [***] and [***], through the establishment of a second
supplier where possible, the establishment of a second source from the
same supplier (e.g. second production site) or the establishment of supply
through an emergency plan/security
stock.
|
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2.4.7
|
The
Licensee acknowledges that, subject only to [***]; certain Licensor
proprietary information (including the formulation for any elements of
[***]) may be a Licensor trade secret and will only be supplied [***] and
not to [***].
|
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2.5
|
No
right or licence is granted by the Licensor to the Licensee by this TTL
Agreement, except as expressly set out in this Clause 4.
|
2.6
|
The
Licensor shall execute all documents, give all declarations regarding the
licenses granted under this Clause 2 and reasonably cooperate with the
Licensee to the extent such documents, declarations and/or cooperation are
required for the recordal or registration of the licenses granted
hereunder at the various patent offices for the benefit of the Licensee
and at the Licensee’s cost.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
3
|
TECHNOLOGY
TRANSFER; PROVISION OF TECHNICAL
ASSISTANCE
|
|
The
Licensor shall transfer and make available to the Licensee, or at the
Licensee's direction to a Permitted Sub-licensee within [***] after the
Effective Date of this TTL Agreement (subject only to Clause 3.2) and from
time to time regarding the [***] a data package that shall include all of
the Information, Licensed Know-How, the Licensed Patents and, upon
exercise of the option regarding the [***] also the [***], in order to
enable the Licensee and/or the Permitted Sub-licensee, to develop,
manufacture, sell and use the Process and the Product. The
Licensee and the Permitted Sub-licensee shall not use any of the know-how
furnished by the Licensor under this Clause 3 for any purpose whatsoever,
except for the Approved Purpose, or as otherwise specifically authorized
in writing by the Licensor. In the event that the Licensee
reasonably believes that the Licensed Know-How, to the extent applicable,
included in the data package furnished by the Licensor under this Clause 3
is incomplete, the Licensee shall provide written notice thereof to the
Licensor, and the Licensor shall undertake reasonable efforts to furnish
the missing materials or amended copies of the missing know how and to
answer all reasonable questions received from the Licensee regarding the
Licensed Know How as soon as reasonably possible after receipt of the
Licensee's written notice.
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|
3.2
|
Upon
completion of the technology transfer under Clause 3.1, at the latest
[***] after the Effective Date of this TTL Agreement, the Parties shall
meet to discuss the status of the technology transfer, any missing
know-how and information and the assistance to be provided by the Licensor
in order to allow the Licensee or its Permitted Sub-licensee to
manufacture the Product using the Process. The Licensee may
invite representatives of its Permitted Sub-licensees to participate in
such meeting.
|
|
3.3
|
After
the Effective Date of this TTL Agreement and until [***] after the meeting
as set forth in Clause 3.2 above took place, the Licensor shall transfer
to the Licensee, or at the Licensee's discretion to its Permitted
Sub-licensee the [***]. Clause 3.1 above shall apply
respectively for the transfer of such
[***].
|
|
3.4
|
During
the term of this TTL Agreement, the Licensor shall reasonably make
available to the Licensee as outlined in the following sentence, the
services of fully qualified and experienced members of its staff to advise
the Licensee on the use of the Information, the Licensed Know-How, the
Licensed Patents and the [***] for the Approved Purpose. Upon
prior written notice of the Licensee of at least [***] FTEs of the
Licensor will be available for technical assistance for the first [***]
after the Effective Date of this TTL Agreement. Thereafter,
Licensor will be available for at least [***] during any [***] period.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
The
technical assistance will be provided on the following conditions:
|
3.4.1
|
the
Licensee reimburses the preapproved reasonable travel, hotel and living
expenses of such persons for the period from departure to
return;
|
|
3.4.2
|
the
Licensee pays to the Licensor a fee for the services of such person in
relation to time spent with the Licensee and in travelling to and from the
Licensee at the Licensor’s then commercial daily
rate. Licensor's commercial daily rate on the effective date of
the Development Agreement is [***] subject to annual UK's PPI
adjustments;
|
|
3.4.3
|
the
Licensor's representative shall act merely in an advisory capacity and
neither the Licensor nor such person shall be liable in any manner for any
loss (including, but not limited to, consequential loss, pecuniary loss
and loss of profits), damage or injury, other than (i) liability for death
or personal injury resulting from the implementation of or reliance on any
actual or alleged advice or assistance of such person or (ii) liability
resulting from the Licensor's or its representatives' negligence or wilful
misconduct;
|
|
3.4.4
|
for
the avoidance of doubt, the Licensor is not required to allow any
Permitted Sub-licensee access to its facilities and/or its trade
secrets.
|
LICENSEE'S
OBLIGATIONS
|
|
The
Licensee shall at all times indemnify, and keep indemnified, the Licensor
against all or any costs, claims, damages, liabilities or expenses
incurred by the Licensor or for which the Licensor may become liable with
respect to any product liability claim relating to the Product
manufactured by the Licensee, its sub-licensee or the Third Party contract
manufacturer of Licensee or its sub-licensee. The Licensee
shall maintain adequate product liability insurance and shall supply to
the Licensor the policy on request.
|
IMPROVEMENTS
|
|
5.1
|
The
Licensee undertakes that subject to any obligations as to confidence, the
Licensee must immediately Disclose to the Licensor any Improvements
created or developed by, for or on behalf of the Licensee upon it becoming
aware that an Improvement has been or may be created or
developed.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
5.2
|
In
consideration of the rights granted under Clause 2 with respect to
Disclosure of the Licensed Know-How, Licensed Patents, and/or the [***]
all Intellectual Property in Improvements shall vest in and be owned by
the Licensor. The Licensee hereby assigns to the Licensor, with
full title guarantee (subject only to the obligation to assign to
Licensor), such rights, title and interest in and to any Intellectual
Property in any Improvements it owns or will own, together with any
related rights and powers arising or accrued, including but not limited to
the rights to xxx for damages (and the right to retain any damages
obtained) for all past infringements. To the extent that any
assignment of future rights is prevented by law, the Licensee shall hold
any such right on trust for the Licensor absolutely until such purported
transfer of rights is perfected. The Licensee further agrees to
execute or procure the execution of such deeds or documents and do or
procure the doing of such acts and things as may be necessary or desirable
to perfect the transfer of title to the Licensor or effect the recording
or registration of the assignment of any such Intellectual Property to the
Licensor (all reasonable costs incurred by the Licensee in providing such
co-operation shall be paid for by the Licensor). Any such
Improvement transferred to the Licensor hereunder shall be considered
Licensed Know-How and/or Licensed Patents for purposes of this TTL
Agreement.
|
CONFIDENTIALITY
|
|
The
Licensed Know-How and/or Licensed Patents may be Disclosed in electronic,
oral, written or other tangible form. Any Information which is
orally or visually Disclosed to the Licensee shall constitute Licensed
Know-How:
|
6.1.1
|
if
it would be apparent to a reasonable person, familiar with the Licensor’s
business and the industry in which it operates, that such Information is
of a confidential or proprietary nature the maintenance of which is
important to the Licensor; or
|
|
6.1.2
|
if
the Licensor, within [***] after such Disclosure, delivers to the Licensee
a written document or documents describing such Information and
referencing the place and date of such oral, visual or written Disclosure
and the names of the persons at the receiving Party to whom such
Disclosure was made.
|
|
6.2
|
The
Licensee hereby represents to the Licensor that it shall not, without the
prior written consent of the
Licensor:
|
|
6.2.1
|
use
the Licensed Know-How and/or Licensed Patents for any purpose other than
the Approved Purpose; or
|
|
6.2.2
|
Disclose
the Licensed Know-How to any Third Party for any purpose, except as
provided for in Clause 6.5; or
|
|
6.2.3
|
publish
the Licensed Know-How or otherwise place the Licensed Know-How in the
public domain; or
|
|
6.2.4
|
duplicate
the Licensed Know-How or produce extracts or documents containing Licensed
Know-How except for limited copies, extracts or documents made as needed
and provided on a need-to-know
basis.
|
6.3
|
Furthermore,
the Licensee undertakes not to engage in or to procure the decompilation,
disassembly, or otherwise reverse engineering of any or all of the
Licensed Know-How and/or Licensed Patents, except and only to the extent
that such activity is expressly permitted by applicable law
notwithstanding this limitation. The terms of this Clause 6.3
shall continue to apply notwithstanding termination of this TTL Agreement
or any other cessation of any business relationship between the
Parties.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
6.4
|
The
Licensee shall limit access to the Licensed Know-How to those of its
employees, consultants and Permitted Sub-licensees who need to receive it
for the Approved Purpose and then only to the extent deemed
necessary. The Licensee shall ensure that such employees,
consultants and Permitted Sub-licensees are made aware of its obligations
to maintain the Licensed Know-How in confidence and shall not Disclose
Licensed Know-How to any Third Party except as permitted by this TTL
Agreement.
|
6.5
|
The
Licensee undertakes not to Disclose or permit to be Disclosed to any Third
Party other than to those of its officers, employees, agents, consultants,
licensees and financial investors that have a need to know the Licensed
Know-How of the Licensor for purposes of this Agreement, provided
that such Disclosure will be made under a confidentiality
non-Disclosure agreement comprising of terms at least as stringent as the
confidentiality provisions under this Clause 6. Furthermore,
the Licensee will be entitled to Disclose the Process and the terms and
conditions of this Agreement to (i) potential licensees or collaboration
partners regarding the Product, and to (ii) potential acquirers of the
Licensee, provided,
however, that such potential sub-licensees, collaboration partners
or acquirers are in [***], that such Disclosure is necessary to evaluate
the respective project , that such potential sub-licensee or collaboration
partner is [***], based on [***], and is organised and operating in the
permitted territories listed in Schedule
D (but may not be disclosed to Affiliates outside these permitted
territories) and that such Disclosure will be made under a
confidentiality non-Disclosure agreement comprising of terms at least as
stringent as the confidentiality provisions under this Clause
6. With respect to any other potential sub-licensees,
collaboration partners and acquirers Disclosure can only be made upon the
Licensor's prior written consent, such consent not to be unreasonably
withheld or delayed. For the avoidance of doubt, Licensee shall
remain fully liable for any disclosure by Licensee’s potential
sub-licensee, collaboration partner or acquirer of their respective
confidentiality obligations.
|
6.6
|
The
foregoing restrictions on Disclosure and use shall not be applicable to
any Licensed Know-How which the Licensee can
demonstrate:
|
|
6.6.1
|
was
rightfully in its possession prior to the date of
Disclosure;
|
|
6.6.2
|
was
in the public domain prior to the date of
Disclosure;
|
|
6.6.3
|
has
subsequently entered into the public domain by publication or other means,
except by means of an unauthorised act or omission by the
Licensee;
|
|
6.6.4
|
was
supplied to the Licensee without restriction on use or Disclosure by a
Third Party who was under no restriction directly or indirectly to the
Licensor or any of its Affiliates regarding the use or Disclosure of said
information;
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
6.6.5
|
that
the Licensee is required by law to Disclose, provided
that the Licensor is given prompt written notice of any such
requirement prior to any Disclosure of Licensed Know-How so that it may
contest such requirement, if necessary;
or
|
|
6.6.6
|
was
independently developed by the Licensee or its Affiliates without access
to the Licensed Know-How and/or Licensed Patents, as evidenced by
documentary records.
|
Provided, however, that the
foregoing exceptions shall not apply to
|
(a)
|
Licensed
Know-How contained within more general Information that may fall within
one or more of the exceptions; or
|
|
(b)
|
any
combination of features or items of Licensed Know-How where one or more of
the relevant individual features or items (but not the combination itself)
may fall within one or more of the
exceptions.
|
6.7
|
The
non-disclosure and non-use provisions under this TTL Agreement shall
continue in force unless and until the Licensed Know-How enters the public
domain, other than through a breach of this TTL Agreement by the
Licensee.
|
6.8
|
In
consideration of the Licensee receiving the Licensed Know-How and/or
Licensed Patents, the Licensee acknowledges that a breach of the
provisions of this TTL Agreement by the Licensee, or any of its employees
could result in serious damage being sustained by the Licensor and as a
result the Licensee hereby agrees:
|
|
6.8.1
|
to
indemnify the Licensor fully for any losses, damages or expenses that may
be occasioned by any such breach;
and
|
|
6.8.2
|
that
since money damages alone may be a wholly inadequate measure of the loss,
the Licensor shall be entitled to specific enforcement of the terms hereof
(by injunction or otherwise) on such terms as any court with jurisdiction
may deem just and proper.
|
7
|
PAYMENTS
|
|
7.1
|
In
the event the Process is based on the Lonza Process, as defined in the
Development Agreement, the Licensee shall pay within [***] after the first
regulatory approval of the Product in the United States, in the European
Union or in Japan a non-refundable and irrevocable disclosure fee in the
amount of
|
|
(a)
|
£[***]
if the [***] of such Lonza Process is
used,
|
|
(b)
|
£[***]
if the [***] of such Lonza Process is
used,
|
|
(c)
|
no
additional payment if the [***] of such Lonza Process are being
used,
|
|
provided,
however, that if [***], the Licensee shall only be required to pay
a pro-rata amount corresponding [***] , and further provided
that each of the payments under this Clause 7.1 shall only be made
once and the total payments shall in no event exceed
[***].
|
|
7.2
|
In
consideration of the rights granted under Clause 2 regarding the [***],
and upon termination of the Development Agreement (i.e., in the event the
Licensor does no longer develop and manufacture the Product on behalf of
the Licensee) the Licensee shall pay to the
Licensor:
|
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
(a)
|
within
[***] of the date of this TTL Agreement the sum of [***];
and
|
(b)
|
a
royalty of [***] on a country-by-country basis of the Net Selling Price of
each Product sold in the Territory by the Licensee (or its sublicensee),
such royalty being payable for as long as the manufacture, use or sale of
the Product (or any other infringing act) is covered under a Valid Claim
within the [***] (with the exception only of Improvements assigned to
Licensor under Clause 5 above);
or
|
|
provided,
however, that regarding [***] the following shall apply: although [***] is
not covered by a Valid Claim, the Parties have agreed to link the duration
of royalty payments to a Valid Claim, and Licensee shall pay as follows: a
royalty of [***] on a country-by-country basis of the Net Selling Price of
each Product sold in the Territory by the Licensee (or its sublicensee),
for as long as royalties under Clause 7.2 would be payable as if the
Product was covered under a Valid Claim of the patent in Schedule B
hereto; and
|
|
and
that regarding [***] the following shall apply: in the event of no Valid
Claim within [***] subsisting on the Effective Date; a royalty of [***] of
the Net Selling Price of each Product sold in the Territory by the
Licensee (or its sublicensee), for a period of [***] post first commercial
sale of the Product.
|
|
7.3
|
To
the extent the Licensee requires a license to any Licensed Patents and/or
Licensed Know-How which is generated by the Licensor during the term of
this TTL Agreement, the Parties shall agree in good faith on any
reasonable consideration for such license, if
any.
|
|
7.4
|
The
Licensee shall keep true and accurate records and books of account
containing all data necessary for the calculation of royalties payable to
the Licensee under Clause 7.2 above. Such records and books of
account shall, upon reasonable notice having been given by the Licensor
(which in no event shall be less than [***] prior notice), be open at all
reasonable times during regular business hours for inspection by
independent, certified and internationally recognized auditors selected by
the Licensor and reasonably acceptable to the Licensee. Such
independent auditors shall agree to maintain the confidentiality of the
information and materials disclosed during the audit. Any such
audit shall be conducted during regular business hours, in a manner that
does not interfere unreasonably with the operations of the Licensee’s
business and, save for cause, not more often than once every calendar
year. Each audit shall begin upon reasonable prior written
notice to the Licensor and shall be completed as soon as reasonably
practicable. The Licensor shall pay the costs of the
independent auditors conducting such audit, unless the results of the
audit reveal an underpayment of [***] or more by the Licensee, in which
case, the Licensee shall pay the reasonable costs of the independent
auditors. If an audit concludes that an overpayment or
underpayment has occurred during the audited period, such payment shall be
remitted by the Party responsible for such payment to the other Party
within [***] after the date such auditor’s written report identifying the
overpayment or underpayment is delivered to the Party responsible for such
payment.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
7.5
|
The
Licensee shall prepare a statement in respect of each calendar quarter
which shall show for the immediately preceding quarter details of the
sales of Product and the royalty due and payable to the Licensor
thereon. Such statement shall be submitted to the Licensor
within [***] after the end of the calendar quarter to which it relates,
together with a remittance for the royalties due to the
Licensor.
|
7.6
|
All
sums due under this TTL
Agreement:
|
7.6.1
|
shall
be made in pounds sterling to the Licensor. Payments due to the
Licensor in currencies other than pounds sterling shall first be
calculated in the relevant local currency before being calculated at the
rate of exchange in effect at the close of business on the day payment is
due or made, whichever is earlier, provided
always that where payment is made after the date provided therefore
herein conversion shall be at the rate in effect at the date of payment if
this is more favourable to the Licensor. The rate of exchange
shall be the mean value of the Pound Spot Rate in London first published
in the Financial Times on the day following the day for determining such
rates;
|
7.6.2
|
are
exclusive of any Value Added Tax or of any other applicable taxes, levies,
imposts, duties and fees of whatever nature imposed by or under the
authority of any government or public authority, and shall be paid by the
Licensee (other than taxes on the Licensor’s income). The
Parties agree to co-operate in all respects reasonably necessary to take
advantage of such double taxation treaties as may be
available.
|
7.7
|
In
the event of any delay in effecting payment due under this TTL Agreement
by the due date, the Licensee shall pay to the Licensor interest
calculated on a daily basis on the overdue payment, from the date after
such payment was due to the date of actual payment, at a rate of
[***].
|
PROTECTION
OF THE LICENSED KNOW-HOW
|
8.1
|
In
the event that any unlicensed activities are carried on by any Third Party
which could constitute unauthorised Disclosure or the misuse of any of the
Licensed Know-How, the Party becoming aware of such a matter shall
immediately notify the other of it, and the Licensee shall join the
Licensor in taking all steps (if any) as, in the total discretion of the
Licensor, shall be desirable for the protection of the Licensor's rights
under the Licensed Know-How. The expenses incurred in taking
such steps, and any profits or damages which may be obtained, shall be (in
the absence of any agreement to the contrary) for the account of the
Licensor.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
8.2
|
Subject
only to Clause 9 below, nothing in this TTL Agreement shall constitute any
representation that the Products or the use of the Licensed Know-How does
not fall within the scope of any Third Party Intellectual
Property.
|
WARRANTIES
AND INDEMNITIES
|
9.1
|
Each
of the Parties warrants that it has full power and authority to carry out
the actions contemplated under this TTL Agreement, and that its entry into
and performance under the terms of this TTL Agreement will not infringe
the rights of any Third Party or cause it to be in breach of any
obligations to a Third Party.
|
9.2
|
The
Licensor warrants to the Licensee
that:
|
|
9.2.1
|
all
Information, data and materials provided by it to the Licensee hereunder
will be, to the best of its knowledge, accurate and complete in all
material respects, and it is entitled to provide the same to the Licensee
without recourse to any Third Party;
and
|
9.2.2
|
to
the best of its knowledge and belief, the Information, the Licensed
Know-How, the Licensed Patents and/or the [***] do not infringe, the
rights of any Third Party, and no Third Party has threatened or, so far as
it is aware, is currently threatening proceedings in respect of such
infringement, and none of its Information, the Licensed Know-How, the
Licensed Patents and/or the [***] is the subject of any actual or, so far
as it is aware, threatened challenge or opposition or revocation
proceedings; and
|
9.2.3
|
to
the best of its knowledge and belief, the [***] if used per the
instructions provided by the Licensor is suitable for the Approved
Purpose. If during the term of this TTL Agreement Licensor
learns that the [***] is not suitable for the Approved Purpose or causes
adverse effects, the Licensor shall promptly inform the Licensee hereof;
and
|
9.2.4
|
to
the best of its knowledge and belief, the suppliers of [***] and [***]
will be able and willing to supply such [***] to the Licensee or its
sublicensee or Third Party contract manufacturer of Licensee or
sublicensee for the manufacture of the Product for clinical and commercial
supply at terms and conditions of supply customary in the
industry.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
9.3
|
Each Party (“Indemnifying Party”) shall defend, indemnify and hold
harmless the other Party (“Indemnified Party”) and its directors, officers, employees
and agents and the successors and assigns of any of the foregoing at all
times from and against any Third Party claims actions, liabilities, costs
and expenses (including court costs and legal fees on a full indemnity
basis) that the Indemnified Party may suffer arising directly out of the
Indemnifying Party’s breach of this TTL Agreement, including breach of
representations and warranties, violation of applicable law, or the
Indemnifying Party's negligent or wilful act or
omission.
|
9.4
|
With
respect to liability claims or proceedings, the following shall apply; (a)
except to the extent provided in (b) below, the Licensee shall indemnify
and hold harmless the Licensor and its directors, officers, employees and
agents and the successors and assigns of any of the foregoing at all times
from any against any Third Party claims, actions, liabilities, costs and
expenses (including court costs and legal fees on a full indemnity basis)
that the Indemnified Party may suffer as a direct result of any tortious
claims or proceedings of death or bodily injury relating to the Product
and this TTL Agreement, and (b) the Licensor shall indemnify and hold
harmless the Licensee and its directors, officers, employees and agents
and the successors and assigns of any of the foregoing at all times from
any against any Third Party claims, actions, liabilities, costs and
expenses (including court costs and legal fees on a full indemnity basis)
that the Indemnified Party may suffer as a direct result of any tortious
claims or proceedings of death or bodily injury relating to the Product to
the extent such claims or proceedings result from defects in the
Information, the Licensed Know-How or the Licensed Patents, or from
Licensor's breach of this TTL
Agreement.
|
9.5
|
If
an Indemnified Party intends to claim indemnification under this Clause 9,
it shall promptly notify the Indemnifying Party in writing of such alleged
liability. The Indemnifying Party shall have the right to
control the defence thereof with counsel of its choice as long as such
counsel is reasonably acceptable to Indemnified Party; provided,
however, that
the Indemnified Party shall have the right to retain its own
counsel at its own expense, for any reason, including if representation of
the Indemnified Party by the counsel retained by the Indemnifying would be
inappropriate due to actual or potential differing interests between such
Indemnified Party and any the Indemnifying Party. The
Indemnified Party, its employees and agents, shall reasonably cooperate
with the Indemnifying Party and its legal representatives in the
investigation of any liability covered by this Clause 9. The
obligations of this Clause 9 shall not apply to amounts paid in settlement
of any claim, demand, action or other proceeding if such settlement is
effected without the consent of the Indemnifying Party, which consent
shall not be withheld or delayed unreasonably. The failure to
deliver written notice to the Indemnifying Party within a reasonable time
after the commencement of any such action, if prejudicial to its ability
to defend such action, shall relieve the Indemnifying Party of any
obligation to the Indemnified Party under this Clause 9. It is
understood that only the Licensor and the Licensee may claim indemnity
under this Clause 9 (on its own behalf or on behalf of its indemnitees),
and other indemnitees may not directly claim indemnity
hereunder.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
9.6
|
Any
condition or warranty other than those set forth in Clause 9.2 and/or
relating to title which might otherwise be implied or incorporated within
this TTL Agreement by reason of statute or common law or otherwise is
hereby expressly excluded.
|
9.7
|
IN
NO EVENT (OTHER THAN WILFUL MISCONDUCT) SHALL EITHER PARTY BE LIABLE TO
THE OTHER PARTY FOR LOSS OF PROFITS, SPECIAL, INDIRECT, INCIDENTAL,
PUNITIVE OR CONSEQUENTIAL DAMAGES ARISING OUT OF THIS TTL
AGREEMENT.
|
10
|
DURATION
AND TERMINATION
|
10.1
|
This
TTL Agreement shall come into force on the Effective Date of this TTL
Agreement and shall, unless terminated in accordance with Clause 10.2 or
10.3 below, remain in force until the Licensee has no further need to use
the Information, the Licensed Know-How, the Licensed Patents and/or the
[***].
|
10.2
|
The
Licensee shall be entitled to terminate this TTL Agreement at any time by
giving [***] prior written notice.
|
10.3
|
The
Licensor shall have the right to terminate this TTL Agreement immediately
by notice in writing to the
Licensee:
|
|
(i)
|
in
the event that the Licensee fails to perform or observe any of the
obligations on its part to be performed or observed under this TTL
Agreement, provided, that, in a case where the breach is remediable, such
notice from the Licensor shall also require the Licensee to remedy such
breach and if the Licensee so remedies within [***], in the event of a
breach of [***], and within [***], in the event of any other breach, of
such notice being served, such notice to terminate this TTL Agreement
shall be deemed to be void and of no effect;
or
|
|
(ii)
|
in the event an interim order is applied for
or made, or a voluntary arrangement approved, or a petition for a
bankruptcy order is presented or a bankruptcy order is made against the
Licensee, or a receiver or trustee in bankruptcy is appointed of the
Licensee's estate or a voluntary arrangement is proposed or approved or an
administration order is made, or a receiver or administrative receiver is
appointed of any of the Licensee's assets or undertaking, or a winding-up
resolution or petition is passed or presented (otherwise than for the
purposes of reconstruction or amalgamation), or any circumstances arise
which entitle the court, a creditor, the company or its directors to
appoint a receiver, administrative receiver or administrator or to present
a winding-up petition or make a winding-up order or other similar or
equivalent action is taken against or by the Licensee by reason of its
insolvency or in consequence of debt, and
provided that following such proceedings the Licensee is Controlled
by companies, partnerships and/or other entities which are registered and
operating, with respect to the manufacturing of the Product, outside the
permitted territories listed in Schedule
D.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
10.4
|
Upon
termination of this Agreement in accordance with Clause 10.3 (i), the
Licensee shall offer to each sublicensee and/or sub-sublicensee a direct
license agreement on substantially the same the terms and conditions as
this TTL Agreement, provided,
however, that the Licensor is not required to grant such direct
licence if the sublicensee is in breach of its sublicense agreement at the
time such direct licence is to be
granted.
|
10.5
|
In
the event of expiry or termination of this TTL Agreement for any reason,
and subject to any express provisions set out elsewhere in this TTL
Agreement:
|
10.5.1
|
all
rights and licences shall
cease;
|
|
10.5.2
|
the
Licensee shall cease all exploitation of the Licensed Know-How and/or
Licensed Patents and any other know-how provided by the Licensor to the
Licensee, except insofar as the Licensed Know-How, or such other know-how,
ceases or has ceased to be confidential, unless this is or was as a
consequence of the default of the
Licensee;
|
10.5.3
|
the
Licensee shall return promptly to the Licensor all technical material in
its possession relating to the Information, the Licensed Know-How and/or
the Licensed Patents and all copies of such material to the extent that
such material remains
confidential;
|
10.5.4
|
the
Licensee shall have the right to dispose of all stocks of the Product in
its possession and all Product in the course of manufacture at the date of
termination; and
|
10.5.5
|
irretrievably
delete any Licensed Know-How, stored on any magnetic or optical disk or
memory and all matter derived from such sources which is in its possession
or under its control.
|
10.6
|
The
expiry or termination of this Agreement for any reason shall be without
prejudice to the provisions of this Clause 10 and to any rights of either
Party which may have accrued by, at or up to the date of such
termination.
|
ASSIGNMENT
|
Neither
Party shall assign, transfer, charge nor deal in any other manner with this TTL
Agreement or its rights under it or part of it, or purport to do any of the same
under this TTL Agreement without the prior written consent of the other Party
(which consent not to be unreasonably withheld or delayed) save that the Parties
may at any time and at its absolute discretion assign or transfer its rights
under the TTL Agreement (i) to an Affiliate; or (ii) to a Third Party which
acquires all or substantially all of the such Party's assets which are covered
under and necessary for this TTL Agreement.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
12
|
SEVERANCE
|
In the
event that any clause or any part of any clause in this TTL Agreement is
declared invalid or unenforceable by the judgment, decree by consent or
otherwise of a court of competent jurisdiction from whose decision no appeal is
or can be taken, all other clauses or parts of clauses contained in this TTL
Agreement shall remain in full force and effect and shall not be affected by
such finding for the term of this TTL Agreement. The invalid or
unenforceable clause shall be replaced by a valid and enforceable clause which
best meets the commercial intent of the invalid or unenforceable
clause.
NO
WAIVER
|
No
relaxation, forbearance, delay or indulgence by either Party in enforcing any of
the terms and conditions of this TTL Agreement or the granting of time by either
Party to the other shall prejudice, affect or restrict the rights and powers of
that Party, nor shall any waiver by either Party of any breach of this TTL
Agreement operate as a waiver of or in relation to any subsequent or any
continuing breach of it.
VARIATION
|
This TTL
Agreement may only be amended by a document in writing signed by a duly
authorised officer of each Party.
FURTHER
ASSURANCE
|
The
Parties shall execute all further documents as may be necessary or desirable to
give full effect to the terms of this TTL Agreement and to protect the rights of
the Parties under it.
ENTIRE
AGREEMENT; SURVIVAL
|
16.1
|
This
TTL Agreement and the documents referred to in it, constitute the entire
agreement and understanding of the Parties and upon the Effective Date of
this TTL Agreement supersede any previous agreement between the Parties
relating to the subject matter of this TTL Agreement. For the
avoidance of doubt, the [***] dated [***] shall not apply to the
manufacture of the Product.
|
16.2
|
Each
of the Parties acknowledges and agrees that, in entering into this TTL
Agreement and the documents referred to in it, it does not rely on, and
shall have no remedy in respect of, any statement, representation,
warranty or understanding (whether negligently or innocently made) of any
person (whether party to this TTL Agreement or not) other than as
expressly set out in this TTL Agreement as a warranty or
representation. The only remedy available to it for breach of
such warranties or representations shall be for breach of contract under
the terms of this TTL Agreement. Nothing in this clause shall
operate to limit or exclude any liability for
fraud.
|
16.3
|
The
obligations of the Parties under Clauses 4 (The Licensee's Obligations), 5
(Improvements), 6 (Confidentiality), 9 (Warranties and Indemnities) and
10.4 (consequences of termination) shall survive the termination of this
Agreement for any reason.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
17
|
NOTICE
|
17.1
|
Any
notice or other communication to be given under this TTL Agreement shall
be delivered personally or sent by facsimile transmission, or if facsimile
transmission is not available, by first class pre-paid post addressed as
follows:
|
|
(a)
|
If
to Lonza to:
|
Lonza
Sales AG
Xxxxxxxxxxxxxxxxxxxxxx
00
XX-0000
Xxxxx
Xxxxxxxxxxx
Facsimile:
x00 00 000 0000
Attention: The
Head of Legal Services
|
with a copy to: |
Lonza
Biologics plc
000
Xxxx Xxxx
Xxxxxx
Xxxxxxxxx
XX0 0XX
Xxxxxxx
|
||
Facsimile: | x00 0000 000000 | ||
For the attention of: | The Head of Legal Services | ||
(b) | If to Micromet to: |
Micromet
AG
Xxxxxxxxxxxxxxxxx
0
X-00000
Xxxxxx
Xxxxxxx
|
|
Facsimile: | x00-00-000 277 205 | ||
For the attention of: | Head of Business Development | ||
with a copy to: |
0000
Xxxxxxxxx Xxxxxxxxx
Xxxxx
000
Xxxxxxxx,
XX 00000
Xxxxxx
Xxxxxx of America
|
||
Attention: | General Counsel | ||
Facsimile: | x0 000 000-0000 |
|
or
to such other destination as either Party hereto may hereafter notify to
the other in accordance with the provisions of this Clause
17.
|
17.2
|
All
such notices or other communications shall be deemed to have been served
as follows:
|
(a)
|
if
delivered personally, at the time of such
delivery;
|
|
(b)
|
if
sent by facsimile, upon receipt of the transmission confirmation slip
showing completion of the
transmission;
|
|
(c)
|
if
sent by first class pre-paid post, ten (10) business days (Saturdays,
Sundays and Bank or other public holidays excluded) after being placed in
the post.
|
18
|
GOVERNING
LAW, DISPUTE RESOLUTION
|
|
18.1
|
The
construction, validity and performance of the TTL Agreement shall be
governed by the laws of
Switzerland.
|
|
18.2
|
No
failure or delay on the part of either Licensor or Licensee to exercise or
enforce any rights conferred on it by this TTL Agreement shall be
construed or operate as a waiver thereof nor shall any single or partial
exercise of any right, power or privilege or further exercise thereof
operate so as to bar the exercise or enforcement thereof at any time or
times thereafter.
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
|
18.3
|
Any
disputes relating to issues arising from this TTL Agreement shall, in the
absence of resolution within [***] of the dispute arising, be referred to
the CEOs of Licensee and COO of Licensor, who shall discuss the matter and
attempt to resolve it by mutual consent. The CEOs of Licensee
and COO of Licensor shall meet once face-to-face within [***] to discuss
and resolve the dispute. If the dispute cannot be resolved
within [***], either Party may, by written notice to the other Party,
invoke the mediation procedure set out in Clause 18.4
below.
|
|
18.4
|
If
a dispute arises between the Parties that the Parties cannot resolve
pursuant to Clause 18.3 above, the Parties agree to try to solve such
dispute amicably by mediation. The Parties shall conduct a
mediation procedure according to the ICC ADR Rules of the International
Chamber of Commerce (ICC) in effect on the date of the commencement of the
mediation proceedings. The location of the mediation
proceedings will be Basel. The number of mediators will be one
(1). The language of the mediation proceeding will be
English. If the dispute has not been settled pursuant to the
said rules within [***] following the filing of a request for mediation or
within such other period as the Parties may agree in writing, either Party
may submit the dispute to final and binding arbitration.
|
|
Any
dispute relating to the validity, performance, construction or
interpretation of this TTL Agreement, which cannot be resolved amicably
between the Parties, shall be submitted to arbitration in accordance with
the ICC Arbitration Rules of the International Chamber of
Commerce. Save in the face of manifest error, the decision of
the arbitrators shall be final and binding upon the Parties and
enforceable in any court of competent jurisdiction. The
location of arbitration will be Basel. The arbitration will be
heard and determined by one (1) arbitrator, who will be jointly selected
by Licensor and Licensee. If, within [***] following the date
upon which a claim is received by the respondent, the Parties cannot agree
on a single arbitrator, the arbitration will be heard and determined by
three (3) arbitrators, with one arbitrator being appointed by each Party
and the third arbitrator being selected by the two Party-appointed
arbitrators. If either Party fails to select an arbitrator, or
if the Party-appointed arbitrators cannot agree on a third arbitrator
within [***] of the respondent receiving the claim, such arbitrator will
be appointed by the International Court of Arbitration according to the
ICC Rules. The arbitration award that is consistent with the
provisions of this TTL Agreement that is so given will be binding upon the
Parties, accompanied by a reasoned opinion in writing (in English), and
the judgment on the award may be entered in any court having competent
jurisdiction thereof.
|
|
18.6
|
Each
Party will bear its own costs and expenses (including its attorney’s fees)
associated with any arbitration initiated under this Clause, and each
Party will bear an equal share of the arbitrators’ and administrative fees
associated with any arbitration initiated under this
Clause. The language of the arbitration proceeding will be
English. Notwithstanding the foregoing, Parties agree that the
non-prevailing Party shall reimburse the costs of the prevailing
Party.
|
|
18.7
|
Notwithstanding
the provisions of Clause 18.5, each Party shall have the right to seek,
without proof of special damage, a preliminary, permanent injunctive or
other equitable relief in any court of competent jurisdiction as such
Party deems necessary to preserve its rights and to protect its
interests.
|
19
|
RIGHTS
OF THIRD PARTIES
|
Parties intend that no term of this TTL Agreement shall be enforceable by any Third Party, but this does not affect any right or remedy of a Third Party which exists or is available under the laws of Switzerland. |
This TTL
Agreement has been entered into on the date stated at the beginning of
it.
Signed
by
|
|
for
and on behalf of LONZA
SALES AG
|
|
Signed
by
|
|
for
and on behalf of LONZA
SALES AG
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Signed
by
|
|
for
and on behalf of MICROMET
AG
|
|
Signed
by
|
|
for
and on behalf of MICROMET
AG
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
A – LICENSED KNOW-HOW
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE B- LICENSED
PATENTS
[***]
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE C – THE
[***]
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
[***]SCHEDULE
D
Territories
|
·
|
[***]
|
·
|
USA | |
·
|
EU, EFTA and Switzerland | |
·
|
Japan | |
·
|
Australia | |
·
|
New Zealand | |
·
|
Canada |
Approved Contract
Manufacturing Organizations*
Contract
Manufacturing Organization
(and
their Affiliates in the permitted territories
listed
above)
|
Company
Details
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
|
[***]
|
[***]
|
*
Approved CMOs shall include Affiliates of the above listed CMOs which are
registered and operate in the territories set forth above.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
15
Lonza Press
Release
News
Release
Lonza
and Micromet Enter into Agreement for the Manufacture of
Blinatumomab
Basel,
Switzerland, 23 November 2009 – Lonza Group Ltd, a market leading custom
manufacturer of Biopharmaceuticals, announces that it has entered into an
agreement with Micromet, Inc. for the process development and manufacture of
Micromet’s blinatumomab (MT103). Micromet is a biopharmaceutical company
developing novel, proprietary antibodies for the treatment of cancer,
inflammation and autoimmune diseases.
Under the
terms of the agreement, Lonza will manufacture blinatumomab for clinical trials.
In addition, Lonza will develop the commercial scale process and will supply
blinatumomab for the market if so requested by Micromet.
Blinatumomab
(MT103) is a BiTE antibody for the treatment of various hematologic cancers.
Blinatomumab has achieved the primary endpoint in a phase 2 clinical trial for
the treatment of patients with acute lymphoblastic leukemia (ALL), and has shown
significant clinical activity in an ongoing phase 1 clinical trial for the
treatment of patients with non-Hodgkin's lymphoma (NHL).
About
Xxxxx
Xxxxx is
one of the world's leading suppliers to the pharmaceutical, healthcare and life
science industries. Its products and services span its customers’ needs from
research to final product manufacture. Lonza is the global leader in the
production and support of active pharmaceutical ingredients both chemically as
well as biotechnologically. Biopharmaceuticals are one of the key growth drivers
of the pharmaceutical and biotechnology industries. Lonza has strong
capabilities in large and small molecules, peptides, amino acids and niche
bioproducts which play an important role in the development of novel medicines
and healthcare products. Lonza is a leader in cell-based research, endotoxin
detection and cell therapy manufacturing. Lonza is also a leading provider of
value chemical and biotech ingredients to the nutrition, hygiene, preservation,
agro and personal care markets.
Lonza is
headquartered in Basel, Switzerland and is listed on the SIX Swiss Exchange. In
2008, Lonza had sales of CHF 2.937 billion. Further information can be found at
xxx.xxxxx.xxx.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
For
further Information
Lonza
Group Ltd
|
Lonza
Group Ltd
|
Lonza
Group Ltd
|
Head
Corporate Communications
|
Media
Relations
|
Investor
Relations
|
Xxxxxxx
Xxxxxxxx
|
Xxxxxxx
Xxxxxx
|
Xxxx
Xxxxxxx
|
Tel
x00 00 000 0000
|
Tel
x00 00 000 0000
|
Tel
x00 00 000 0000
|
Fax
x00 00 000 0000
|
Fax
x00 00 000 0000
|
Fax
x00 00 000 0000
|
xxxxxxx.xxxxxxxx@xxxxx.xxx
|
xxxxxxx.xxxxxx@xxxxx.xxx
|
xxxx.xxxxxxx@xxxxx.xxx
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
SCHEDULE
15
Micromet Press
Release
PRESS
RELEASE
Micromet
Enters into Agreement with Lonza for the Manufacture of
Blinatumomab
BETHESDA, MD— November 23, 2009 —
Micromet, Inc. (NASDAQ: MITI), a biopharmaceutical company developing
novel, proprietary antibodies for the treatment of cancer, inflammation and
autoimmune diseases today announced that it has entered into an agreement for
the process development and manufacture of blinatumomab (MT103) with Lonza AG, a
market leading custom manufacturer of antibodies and other
biologics.
Under the
terms of the agreement, Lonza will manufacture blinatumomab for clinical trials.
In addition, Lonza will develop the commercial scale process and will supply
blinatumomab for the market if so requested by Micromet.
Blinatumomab
(MT103) is a BiTE antibody for the treatment of various hematologic cancers.
Blinatomumab has achieved the primary endpoint in a phase 2 clinical trial for
the treatment of patients with acute lymphoblastic leukemia (ALL), and has shown
significant clinical activity in an ongoing phase 1 clinical trial for the
treatment of patients with non-Hodgkin's lymphoma (NHL). Micromet controls the
worldwide rights to develop and commercialize blinatumomab after it reacquired
MedImmune’s remaining rights to this product candidate on November 4,
2009.
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
About
BiTE Antibodies
BiTE®
antibodies are designed to direct the body's cytotoxic, or cell-destroying, T
cells against tumor cells, and represent a new therapeutic approach to cancer
therapy. Typically, antibodies cannot engage T cells because T cells lack the
appropriate receptors for binding antibodies. BiTE antibodies have been shown to
bind T cells to tumor cells, ultimately inducing a self-destruction process in
the tumor cells referred to as apoptosis, or programmed cell death. In the
presence of BiTE antibodies, T cells have been demonstrated to serially
eliminate tumor cells, which explains the activity of BiTE antibodies at very
low concentrations. Through the killing process, T cells start to proliferate,
which leads to an increased number of T cells at the site of
attack.
About
Micromet, Inc.
Micromet,
Inc. is a biopharmaceutical company developing novel, proprietary antibodies for
the treatment of cancer, inflammation and autoimmune diseases. Its product
development pipeline includes novel antibodies generated with its proprietary
BiTE® antibody platform, as well as conventional monoclonal antibodies. Two of
Micromet’s BiTE antibodies and three of its conventional antibodies are
currently in clinical trials. Micromet's preclinical product pipeline
includes several novel BiTE antibodies generated with its proprietary BiTE
antibody platform technology. Micromet’s collaboration partners
include sanofi-aventis, Bayer Schering Pharma, Nycomed, Merck Serono, and
MedImmune.
Forward-Looking
Statements
This
release contains certain forward-looking statements that involve risks and
uncertainties that could cause actual results to be materially different from
historical results or from any future results expressed or implied by such
forward-looking statements. These forward-looking statements include statements
regarding the manufacture of blinatumomab for clinical trials and the
development of a commercial manufacturing process for this product candidate.
You are urged to consider statements that include the words "ongoing," "may,"
"will," "believes," "potential," "expects," "plans," "anticipates," "intends,"
or the negative of those words or other similar words to be uncertain and
forward-looking. Factors that may cause actual results to differ materially from
any future results expressed or implied by any forward-looking statements
include the risk that the manufacturing process for blinatumomab cannot be
successfully established at Lonza AG, that blinatumomab does not demonstrate
safety and/or efficacy in future clinical trials, or that we will not obtain
approval to market blinatumomab, and the risks associated with reliance on
outside financing to meet capital requirements. These factors and others are
more fully discussed in Micromet's Quarterly Report on Form 10-Q for the fiscal
quarter ended September 30, 2009, filed with the SEC on November 6, 2009, as
well as other filings by the company with the SEC.
# #
#
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Execution
Copy
***Text
Omitted and Filed Separately
Confidential
Treatment Requested
Under
17 C.F.R. §§ 200.80(b)(4), and 240.24b-2
Contact
Information
US
Media:
|
European
Media:
|
Xxxxxx
xxxXxxxx/Xxxxx Xxxxx
|
Xxxxxx
Xxxx
|
(000)-000-0000
|
x00
(00) 0000 0000
|
xxxxxxxx@xxxxxxxx-xx.xxx
|
xxxxxx@xxxxxxxx.xxx
|
US
Investors:
|
European
Investors:
|
Xxxxx
Xxxxxx
|
Xxxx-Xxxxxx
Xxxx
|
(000)
000-0000
|
x00
(00) 0000 0000
|
xxxxx@xxxxxxxx.xxx
|
xxxx@xxxxxxxx.xxx
|
***
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.