EXHIBIT 10.4
CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO THE
OMITTED PORTION.
AGREEMENT
FOR
MANUFACTURING AND SUPPLY OF BNP7787
Made as of February 10, 2004 (the "Effective Date")
by and between
BIONUMERIK PHARMACEUTICALS, INC.,
(hereinafter referred to as "BioNumerik"),
a corporation duly organized and validly existing under the laws of the State
of Texas with its principal offices at Suite 1250, 0000 Xxxxxxxxx Xxxxx,
Xxx Xxxxxxx, XX 00000, XXX
and
RHODIA PHARMA SOLUTIONS INC.
,
a corporation duly organized and validly existing under the laws
of Delaware, with its principal offices at 000 Xxxxxxxx Xxxxxx Xxxx, Xxxxxxxx,
XX 00000-0000, XXX (Rhodia Pharma Solutions Inc., together
with its subsidiary Rhodia Pharma Ltd., are hereinafter
collectively referred to as "RPS")
1 DEFINITIONS
Unless otherwise specifically set forth herein, the following terms
shall have the meanings set forth below:
1.1 Compound
Shall mean the compound 2,2'-Dithio-Bis-Ethane sulfonate, disodium
salt, also known as BNP7787 or Tavocept (TM).
1.2 Confidential Information
Shall mean all information, whether technical or non-technical, trade
secrets, discoveries, data, drawings, techniques, documents, models,
samples and know-how, whether or not patented or patentable, owned or
possessed by a Party on the date of this Agreement or later developed
by them.
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WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.
1.3 Party
Shall mean BioNumerik or RPS, and when used in the plural form both
BioNumerik and RPS.
1.4 Product(s) or Finished Dosage Form
Shall mean any pharmaceutical composition or formulation containing the
Compound as the pharmacologically active ingredient.
1.5 Specifications
Shall mean the specifications for the Compound attached on Annex 2
hereto.
2 AGREEMENT SCOPE AND MANUFACTURE AND SUPPLY OF COMPOUND
2.1
(a) Phase 1 - Technology Transfer and Familiarization.
Upon the signing of this Agreement by the Parties, RPS will undertake
receipt of the technology transfer from BioNumerik and laboratory
familiarization with the BNP7787 process as necessary to prepare the
Compound in accordance with the Specifications, all as described in the
Project Description (the "Project Description") attached hereto as Annex 1.
The price for this Phase 1 material will be as described in the Project
Description attached hereto as Annex 1 to be paid as described in Section
2.3 hereof.
(b) Phase 2 - Site Qualification.
Upon successful completion of Phase 1 and following receipt of written
authorization from BioNumerik to proceed with Phase 2, RPS will complete
Phase 2: Site Qualification, during which RPS will prepare under current
U.S. Food and Drug Administration ("FDA") Good Manufacturing Practices
(cGMP) a number of [**] target batch size qualification batches in order
to assure meeting the critical success criteria (the "Success Criteria")
included in Annex 10 hereto. Should the first qualification batch be
prepared under conditions deemed successful based on the Success Criteria,
then the second batch may be eliminated and BioNumerik shall only be
required to pay for such first batch. Should more than two batches be
required in order to meet the Success Criteria, all batches prepared in
excess of the first two batches will be done so at the expense of RPS
without additional cost to BioNumerik. The price for these Phase 2 batches
will be as described in the Project Description attached hereto as Annex 1
to be paid as described in Section 2.3 hereof.
(c) Phase 3 - Validation Batches.
Upon successful completion of Phase 2, RPS will complete Phase 3:
Validation Batches, during which RPS will prepare under cGMP three (3)
[**].
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batches as described in the Project Description. The price for these Phase
3 batches will be as described in the Project Description attached hereto
as Annex 1 to be paid as described in Section 2.3 hereof.
(d) Phase 4 - Commercial Batches.
Upon successful completion of Phase 3, RPS will prepare under cGMP
commercial batches of the Compound with quantities and delivery schedule to
be agreed between BioNumerik and RPS. The price for the commercial batches
will be as described in the Project Description attached hereto as Annex 1.
It is expected that if BioNumerik gives RPS [**] prior notice of a need for
a commercial batch, RPS will do its best to fulfill the order within such
time frame. However, RPS cannot guarantee delivery of Compound [**] prior
notice, but in any event RPS will deliver Compound within a maximum of six
months after notification by BioNumerik, except in the event of an
occurrence of a Force Majeure event described in Section 9.4.
2.2 (a) All Compound shall be manufactured and delivered in accordance with
the Compound Specifications indicated in Annex 2. These Specifications
will be obtained from BioNumerik, or will be developed in conjunction
and with the approval of BioNumerik. Any changes in the Specifications
will be agreed between BioNumerik and RPS prior to scale-up or
commencing the production. In addition, manufacturing of all Compound
by RPS (other than Compound manufactured as part of the Phase 1 Work)
will be conducted in compliance with relevant current U.S. Food and
Drug Administration ("FDA") Good Manufacturing Practices ("cGMP") and
International Conference on Harmonisation ("ICH") guidelines.
(b) Unless otherwise already specified in the Annexes hereto, the batch
records; specifications for raw materials, intermediates and final
products; and analytical test methods for all materials will be
delivered to RPS by BioNumerik subsequent to the signing of this
Agreement or BNPI will develop in conjunction with RPS any additional
requirements. All batch records and production documentation specific
to the Compound must be approved in writing by BioNumerik prior to use.
Any changes in the production flow steps, analytical methods,
production records, test methods, Specifications, or equipment used by
RPS will require prior written approval by BioNumerik. RPS will provide
a Certificate of Analysis and executed batch record with each shipment
that describes product specifications and results.
(c) All starting material and other raw materials necessary for the
work hereunder will be supplied by RPS without additional charge to
BioNumerik. RPS will have back-up starting material and raw materials
available should BioNumerik decide to proceed with an additional batch
of Compound in the event a batch fails. If a batch fails to meet
Specifications due to factors under the control of RPS or is rejected
by BioNumerik or
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RPS due to critical failure to be manufactured in accordance with cGMP,
and BioNumerik requests RPS to manufacture an additional batch of
Compound or reprocess the batch that is out of specification ("OOS"),
then RPS will conduct such manufacturing or reprocess at no additional
charge to BioNumerik and will schedule the manufacture of such
additional batch of Compound as soon as practical (and in any event
within 30 days of BioNumerik's request, unless the manufacture within
such time period is prevented by catastrophic equipment failure or
other Force Majeure event described in Section 9.4). The specifications
of the starting materials for manufacture of the Compound are as set
forth on Annex 3 to this Agreement.
(d) Procedures for release of the Compound have been agreed to by
BioNumerik and RPS and are attached on Annex 5 hereto. The procedures
to be followed upon the occurrence of an Out of Specification (OOS) or
Out of Trend (OOT) event are contained in the standard operating
procedures (SOPs) for the RPS [**]. Current copies of such SOPs have
been previously provided by RPS to BioNumerik and RPS will promptly
provide BioNumerik with any changes to such SOPs. These procedures
contain specific timelines for investigation of OOS and OOT events.
Timelines to be followed for a batch failure due to circumstances other
than OOS and OOT events are also contained in the SOPs for the RPS
Annan, Scotland facility. RPS will retain samples of each API batch of
Compound and samples of all solid raw materials and intermediates used
in the manufacturing for a period of at least 5 years following
completion of the manufacturing, provided that commodity solid raw
materials will be maintained for a period of at least one month
following completion of the manufacturing.
(e) RPS shall be responsible for conducting an audit program for
vendors (including testing facilities) utilized by RPS in connection
with manufacturing of the Compound as required to comply with cGMP and
ICH Guidelines (including ICH guideline Q7A). RPS will provide
BioNumerik with a copy of RPS' audit procedures and analytical approval
process, and any updates or amendments to such procedures and process.
BioNumerik has the right, during any audits of RPS conducted by
BioNumerik, to review the records for all raw material and starting
material vendor audits conducted by RPS with respect to raw materials
and starting materials (as defined by ICH guidelines) for the Compound.
In addition, BioNumerik shall also have the right to review the
qualification records (as required by cGMP) of the vendors for the
starting materials for the Compound, provided the starting materials
are produced under cGMP. RPS shall promptly inform BioNumerik in the
event of a concern with the quality or manufacturing compliance with
respect to a raw material used in the manufacture of the Compound and
RPS will coordinate with BioNumerik to assure a prompt resolution of
any such concern. The results of all audits that have occurred that
relate to the materials to be used in the manufacture of the Compound
have previously been provided to BioNumerik, and RPS will promptly
provide to BioNumerik the results of
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all such audits conducted in the future. BioNumerik and RPS agree that
the materials listed on Annex 9 are the critical raw materials in
connection with the manufacture of the Compound.
2.3 BioNumerik will pay RPS the payment amounts described in the Project
Description in the following manner:
(i) [**]
(ii) [**]
(iii) [**]
(iv) [**]
(v) Notwithstanding any other provision of the Agreement or the Project
Description, BioNumerik shall have no obligation to pay for (and
RPS shall promptly refund to BioNumerik amounts paid to RPS for)
any Phase 2 Compound amount, any Phase 3 Compound amount, or any
Phase 4 Compound amount unless such Compound amount (i) is
manufactured by RPS in compliance with current U.S. FDA Good
Manufacturing Practices (cGMP), ICH guidelines, the manufacturing
procedures specified herein, and in accordance with the other
manufacturing procedures and information provided by BioNumerik to
RPS, and (ii) is manufactured by RPS in accordance with the
Specifications.
2.4 Except as otherwise specified above, payment for all Compound purchased
from RPS by BioNumerik in accordance with this Agreement shall be made
within 30 days after goods satisfying the required Specifications are
shipped, by wire transfer in accordance with Annex 6.
2.5 RPS shall maintain all of the appropriate specifications and standard
operating procedures related to the manufacturing of the Compound.
These will be treated as controlled documents and will be maintained
utilizing a suitable document control procedure to ensure proper
issuance and change, respectively. During the term of this Agreement
and for a period of at least five years thereafter, RPS shall maintain
records of inspection and testing, lab notebooks and procedures made in
connection with the manufacturing work conducted under this Agreement.
In addition, RPS is in a position to either (i) prepare a Drug Master
File (DMF) for BNP7787 for the United States, the European Union, and
Japan, or (ii) provide BioNumerik with the necessary information so
that the same information that would be included in the DMF can be
included in the NDA or equivalent filing in the United States, the
European Union, and Japan. RPS will prepare a DMF for BNP7787 upon
request by BioNumerik and after reaching agreement with BioNumerik on
the amount to be paid to RPS for preparing the DMF [**]. If, instead of
requesting RPS to actually prepare a DMF, BioNumerik requests RPS to
simply provide the information to BioNumerik for inclusion in the NDA
or equivalent filing in the United States, the European Union, and
Japan as described in clause (ii) of the fourth sentence of this
paragraph, then RPS will provide such information without additional
charge to BioNumerik.
2.6 RPS shall keep BioNumerik regularly informed of the status and progress
of all stages of Phases 1, 2, 3, and 4, including manufacturing,
through regular telephone or e-mail updates and through written
summaries. During all periods that RPS is conducting any manufacturing
for BioNumerik, RPS shall perform an annual product review, including a
review of production history, deviations (if any), out of specification
events, investigation programs adopted and the outcome of any
investigations, any reprocessing conducted, ongoing stability results
if generated at an RPS site, and site availability for the upcoming
year. RPS shall communicate the results of its review to BioNumerik in
writing.
2.7 RPS shall be responsible for complying with all transport regulations
applicable to the provision of the Compound to BioNumerik in accordance
with this Agreement.
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THE OMITTED PORTIONS.
2.8 The Compound will be produced in the [**].
2.9 RPS shall promptly provide BioNumerik with written proof of any
destruction of intermediates or API either upon reaching the expiry
date or in the event RPS is requested by BioNumerik to destroy any such
materials.
2.10 In the event of any disqualification of an RPS site relating to the
manufacturing by any regulatory agency, RPS shall be responsible for
the cost of any raw materials, intermediates or API produced up to such
time.
3 INSPECTIONS AND CONTROLS
3.1 Subject to confidentiality obligations contained in Section 7, RPS
agrees, without additional charge to BioNumerik, to allow inspections
of its manufacturing facilities in which the Compound is being
manufactured, analyzed or tested, by representatives of BioNumerik or
its agents (including inspections by regulatory authorities) during
normal working hours upon prior written notice to RPS, which notice
will occur at least three days in advance of the inspection, unless not
possible with respect to an inspection by a regulatory agency. RPS
shall grant access to such premises and to the documentation necessary
for or appropriate to the manufacturing and quality control of the
Compound. During such visits, RPS shall make sure that at least one
technical person from each of Quality Assurance, Quality Control,
project teams, and, if reasonably possible, business
development/coordination is present to answer questions or discuss
matters of concern with the BioNumerik personnel conducting such audit
or inspection.
3.2 RPS shall ensure all relevant and/or critical manufacturing, test and
inspection equipment is maintained under a documented calibration and
maintenance program. This includes providing equipment calibration
certifications as required.
3.3 RPS will maintain environmental controls, including particulate and
bioburden monitoring, pest controls and housekeeping procedures in
accordance with FDA cGMP and ICH guidelines. The use of supplies of
process water, air and particulate handling, etc., for cGMP manufacture
of the Compound, shall be consistent with relevant FDA cGMP
specifications and ICH guidelines.
3.4 RPS shall maintain a quality control department, which is a distinct
department separate from manufacturing. RPS quality control/quality
assurance will perform incoming, in-process and finished product
inspections, review records, perform line clearance inspections,
maintain batch history records, provide batch history records for
review and accuracy and completeness and provide product release
services. RPS
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will promptly inform BioNumerik of any changes in management control
related to the work conducted hereunder.
3.5 The conditions to be maintained for the storage of API, raw materials,
and intermediates are set forth on Annex 7.
3.6 RPS will promptly notify BioNumerik of any FDA or other material
regulatory inspection of RPS related to the Compound, and will promptly
provide BioNumerik with a copy of documentation relating to such
inspection. BioNumerik shall have the right to communicate at any time
with the FDA or any regulatory agency or body regarding such matters,
provided any communication with the FDA regarding potential inspection
of RPS' plants should be done in coordination with RPS. BioNumerik will
provide appropriate support for any such inspection, including data and
information relating to critical parameters and justification for the
process for manufacturing the Compound.
3.7 At all times during the term of this Agreement, each of the parties
shall carry and keep in force a general liability insurance policy, in
support of their liability obligations to one another hereunder.[**]
Certificate of Insurance evidencing RPS's coverage and a Certificate of
Insurance evidencing BioNumerik's coverage are attached hereto as Annex
8 hereto. .
4 PRODUCT WARRANTIES
4.1 RPS warrants and represents that the Compound manufactured by RPS and
delivered to BioNumerik, its affiliates or sub-licensee(s) hereunder
shall conform to the Specifications (except as otherwise provided in
Section 2.2 hereof) when delivered and, when expressly required by the
Project Description, be manufactured in accordance with all applicable
laws and regulations relating to the manufacture of the Compound,
including but not limited to, current U. S. FDA Good Manufacturing
Practices (cGMP) and ICH guidelines. RPS will maintain at least 25 to
50 grams of the Compound from each batch produced as a retained sample.
Such retained sample will be maintained at RPS' facility and RPS will
store such retained sample under suitable storage conditions adequate
for the purpose of development as specified by BioNumerik. RPS further
represents and warrants that RPS is not aware that the manufacturing
process for the Compound or the Product or the use of such process
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infringes or will infringe the claims under any patent or other
intellectual property right of RPS or any third party; RPS will
immediately inform BioNumerik if it should become aware of any such
infringement or potential infringement.
EXCEPT FOR THE FOREGOING, RPS MAKES NO WARRANTY OR REPRESENTATION OF
ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, THE
WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE AND
ANY REPRESENTATION OR ANY WARRANTY THAT USE OF THE PROCESS FOR
MANUFACTURE OF THE PRODUCT OR USE OR SALE OF PRODUCT, WHETHER OR NOT
SUCH PRODUCT IS MADE BY THE PROCESS FOR MANUFACTURE OF THE PRODUCT,
WILL NOT INFRINGE THE CLAIMS UNDER ANY PATENT OR OTHER INTELLECTUAL
PROPERTY RIGHT OF RPS OR ANY THIRD PARTY.
Limitations. RPS'S SOLE LIABILITY AND BIONUMERIK'S EXCLUSIVE REMEDY IN
THE CASE OF PRODUCT DELIVERED HEREUNDER TO BIONUMERIK THAT DOES NOT
MEET PRODUCT SPECIFICATIONS SHALL BE, AT RPS'S OPTION, TO USE
COMMERCIALLY REASONABLE EFFORTS TO REPLACE THE DEFECTIVE PRODUCT WITH
PRODUCT THAT CONFORMS WITH THE PRODUCT SPECIFICATIONS OR TO REFUND THE
FEES AND CHARGES PAID TO RPS FOR THE SERVICES RELATED TO SUCH
NON-CONFORMING PRODUCT. EXCEPT IN THE CASE OF GROSS NEGLIGENCE OR
INTENTIONAL MISCONDUCT ON THE PART OF RPS, RPS'S LIABILITY FOR ANY
CLAIM OF BIONUMERIK RELATED TO THIS AGREEMENT SHALL NOT EXCEED THE
AGGREGATE FEES AND CHARGES PAID TO AND RECEIVED BY RPS FOR THE SERVICES
PERFORMED TO WHICH ANY SUCH CLAIM RELATES. IN NO EVENT SHALL EITHER RPS
OR BIONUMERIK BE LIABLE TO THE OTHER FOR INDIRECT, SPECIAL,
CONSEQUENTIAL (INCLUDING WITHOUT LIMITATION LOST PROFITS), PUNITIVE,
INCIDENTAL OR SIMILAR DAMAGES IN ANY WAY ASSOCIATED WITH THIS
AGREEMENT, REGARDLESS OF THE FORM OR BASIS OF ANY CLAIM OR ACTION. ALL
CLAIMS CONCERNING PRODUCT DELIVERED TO BIONUMERIK HEREUNDER MUST BE
MADE IN WRITING RECEIVED BY RPS WITHIN NINETY (90) DAYS AFTER THE DATE
OF DELIVERY, FAILING WHICH CLAIM NOTICE SUCH PRODUCT SHALL BE DEEMED
ACCEPTED BY BIONUMERIK "AS IS" AND ALL CLAIMS BY BIONUMERIK IN RELATION
TO SUCH DELIVERED PRODUCT SHALL BE DEEMED WAIVED. NOTWITHSTANDING THE
FOREGOING, NOTHING CONTAINED IN THIS ARTICLE 4 IS INTENDED TO LIMIT THE
INDEMNIFICATION OBLIGATIONS OF THE PARTIES CONTAINED IN ARTICLE 9.
5 DEBARMENT CERTIFICATION
5.1 RPS warrants that it will not knowingly use in connection with the
services rendered under this Agreement in any capacity the services of
any person
debarred under the U.S. Food, Drug & Cosmetic Act or any other similar
law or regulation governing drug manufacturing.
6 INDEPENDENT CONTRACTOR STATUS
6.1 Each of the Parties in performing this Agreement shall be and be deemed
to be acting as an independent contractor and not as the agent or
employee of the other. Neither RPS nor BioNumerik shall have any
authority whatsoever to act as agent or representative of the other
party nor any authority or power to contract or create any obligation
or liability on behalf of the other party or otherwise bind any other
party in any way for any purpose.
7 CONFIDENTIALITY
7.1 Each Party shall hold all Confidential Information received from the
other Party in strictest confidence and shall use the same level of
care to prevent any unauthorized use or disclosure of such Confidential
Information as it exercises in protecting its own information of
similar nature. A Party shall not disclose any Confidential Information
received from the other Party to any third party without the prior
written consent of the other Party.
7.2 The Confidential Information shall be supplied to the Parties in
written form and shall be identified as being confidential and
disclosed under the provisions of this Agreement. Any information that
is disclosed in oral form shall be confirmed in writing within sixty
(60) days after disclosure and be deemed included within the scope of
this Agreement.
7.3 Each Party shall have the right to disclose the Confidential
Information of the other Party to the minimum number of those officers
and employees of such receiving Party who need to know it for the
purposes of this Agreement. Such disclosure is allowed only on
condition that the persons to whom the Confidential Information will be
disclosed shall be, by law, contract or other binding undertaking,
under confidentiality obligations corresponding to those set out in
this Agreement.
7.4 The disclosing Party retains all rights to its Confidential
Information.
7.5 The confidentiality obligations of this Agreement shall not apply to:
a) Confidential Information which at the time of the disclosure
is in the public domain; or
b) Confidential Information which, after disclosure, becomes part
of the public domain otherwise than by breach of this
Agreement; or
c) Confidential Information which can be established by
reasonable and competent proof to have already been in the
receiving Party's possession prior to disclosure and was not
acquired, directly or indirectly, from the disclosing Party;
or
d) Confidential Information which a receiving Party shall receive
from a third party who has the legal right to disclose it and
who would by disclosure not breach, directly or indirectly,
any confidentiality obligation to either Party; or
e) Confidential Information which is released for disclosure by
prior written consent of the disclosing Party; or
f) Confidential Information which has been independently
developed by a Party hereto without the use or benefit of
Confidential Information received from the other Party; or
g) Confidential Information which is required to be disclosed by
law or by order of court of competent jurisdiction, provided
that due advance notice is given to the other Party of such a
requirement and also such disclosure is then made only to the
minimum extent so required.
h) In addition to the foregoing, the existing Confidentiality
Agreement (the "Confidentiality Agreement), dated as of June
25, 2003, among BioNumerik, Xxxxxx Oncology GmbH, and RPS
shall remain and continue in full force and effect after the
date hereof in accordance with its terms.
All obligations under Section 7 of this Agreement shall terminate 5
years after the termination of this Agreement.
7.6 The burden of proving that any of the above exceptions is applicable to
a Party to relieve it of its liability or obligations hereunder shall
be upon the Party claiming such exception(s).
8 INTELLECTUAL PROPERTY RIGHTS
8.1 a) As used herein "Intellectual Work Product" means all inventions,
modifications, discoveries, improvements (including, without
limitation, process improvements and improvements in analytical
methods), processes, techniques, documentation, scientific and
technical data, drawings and other information (other than the RPS
Technology) that is generated as a result of any of the manufacturing
services and other projects performed for BioNumerik by RPS. "RPS
Technology" means all present and future documentation, scientific and
technical data, processes, test procedures and other information and
techniques that are owned, developed or licensed by RPS relating to the
development, formulation or manufacture of chemical and pharmaceutical
substances and that are not developed hereunder or in connection with
the manufacturing or other projects performed for BioNumerik by RPS.
BioNumerik shall not own any of the RPS Technology. RPS will, however,
use know-how and experience of RPS to facilitate the efficient
manufacture of the Compound.
b) The parties hereto understand and agree that no rights are being
conveyed to RPS (or any of their affiliates) to use any BioNumerik
Technology (as hereafter defined) for any purpose other than the sole
purpose of preparing the Compound for the benefit of BioNumerik in
accordance with the terms of this Agreement. As used herein,
"BioNumerik Technology" means all present and future documentation,
scientific and technical data, processes, test procedures, information,
techniques, technology, patents, patent rights, inventions and other
intellectual property rights that are owned, developed, or licensed by
BioNumerik.
8.2 a) RPS acknowledges that BioNumerik shall be the sole and exclusive
owner of all Intellectual Work Product (except the RPS Technology, as
described above in Section 8.1). In consideration of the covenants
contained herein, and for other good and valuable consideration set
forth herewith, RPS hereby assigns and transfers to BioNumerik and its
successors and assigns all right, title and interest that RPS has or
may later acquire in and to the Intellectual Work Product under
copyright, patent, trade secret and trademark law. Such assignment
includes the assignment of the entire right, title and interest in and
to all applications for letters patent and any and all letters patents
in the United States of America and all foreign countries which may be
granted on and in connection with the Intellectual Work Product. Upon
request by RPS, BioNumerik will meet with RPS to discuss the
possibility of providing RPS with a non-exclusive, royalty free,
non-sublicensable license to practice the Intellectual Work Product
described in 8.1(a) above for the purpose of manufacturing compounds
other than the Compound that are not similar to or related to the
Compound [**]. BioNumerik will have no obligation to grant such a
license and any determination to grant such a license will be made in
the sole discretion of BioNumerik and will be based upon such
considerations as BioNumerik deems appropriate.
b) RPS agrees to cooperate with BioNumerik so that BioNumerik may enjoy
to the fullest extent the entire right, title and interest in and to
the Intellectual Work Product. In connection therewith, RPS agrees to
execute, if necessary, additional papers and documents and to take all
actions requested by BioNumerik in order to (a) further evidence
ownership of the Intellectual Work Product by BioNumerik and its
successors and assigns and (b) allow BioNumerik to procure, maintain
and enforce all letters patent and intellectual property rights to the
Intellectual Work Product. BioNumerik agrees to reimburse RPS all
reasonable costs in relation to the production of additional papers and
documents.
c) In addition, for the purpose of the work conducted by RPS for the
BNP7787 manufacturing project as described in the Project Description,
RPS will not incorporate any of its proprietary technologies toward a
synthesis or manufacturing process.
d) RPS is hereby granted a worldwide, nonexclusive, royalty-free
license to practice the Intellectual Work Product solely for the
purpose of preparing Compound on behalf of BioNumerik in accordance
with this Agreement and the Project Description.
e) BioNumerik warrants and represents that the Products manufactured
and delivered by RPS under this Agreement will be used solely by
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THE OMITTED PORTIONS.
BioNumerik or its designated assignees, licensees, representatives or
alliance partners for legally permissible purposes. BioNumerik further
represents and warrants that it has the right to disclose its
Confidential Information to RPS, including without limitation all
technology made available by BioNumerik to RPS for the manufacture of
the Compound subject to and in accordance with the provisions of this
Agreement, and that BioNumerik has the right to license such technology
to RPS for such purpose and RPS may use it accordingly, all free and
clear of any intellectual property or other rights of third parties,
all subject to and in accordance with the provisions of this Agreement.
8.3 Except as specifically described in this Agreement, no right, title,
interest, or license in or to any trademark, patent, copyright or
service xxxx or symbol or any other intellectual property right of a
party is granted to the other party under this Agreement.
9 INDEMNIFICATION PROVISIONS; FORCE MAJEURE; ARBITRATION
9.1 BioNumerik will indemnify and hold harmless RPS, its affiliates, any
present or future parent or subsidiary of them, and their respective
officers, directors, employees, counsel, agents and affiliates (the
"Indemnified RPS Parties") against any and all losses, liabilities,
damages, costs and expenses including, but not limited to, reasonable
attorney fees and any and all reasonable expenses incurred in defending
against any litigation, commenced or threatened, or any claim, and any
and all amounts reasonably paid in settlement of any claim or
litigation, commenced or threatened ("Losses"), arising out of (i)
product liability and patent and trademark infringement suits regarding
any active pharmaceutical ingredient or raw materials relating to the
projects hereunder, including but not limited to, any bulk drug, or the
Compound, (ii) any failure by BioNumerik to comply with any applicable
governmental regulation (including, without limitation, any applicable
environmental laws), (iii) the breach of any representation, warranty,
or covenant of BioNumerik contained in this Agreement, (iv) the use by
RPS of any raw or component material(s) supplied by BioNumerik to RPS
or by a third party on BioNumerik's behalf, or (v) the promotion,
marketing, distribution and sale, whether directly or through
distributors, of BNP7787; PROVIDED, HOWEVER, THAT IN NO EVENT SHALL
BIONUMERIK INDEMNIFY OR HOLD HARMLESS ANY OF THE INDEMNIFIED RPS
PARTIES IN THE EVENT RPS OR ANY INDEMNIFIED RPS PARTY, IS IN ANY WAY
RESPONSBILE BY NEGLIGENCE OR WILLFUL ACT FOR SUCH LOSSES, LIABILITIES,
DAMAGES, COSTS AND EXPENSES.
9.2 RPS will indemnify and hold harmless BioNumerik, its affiliates, any
present or future parent or subsidiary of any of them, and their
respective officers, directors, employees, counsel, agents and
affiliates (the "Indemnified BioNumerik Parties") against any and all
Losses arising out of (i) any breach of any representation, warranty,
covenant or agreement of RPS contained in this Agreement, (ii) any
failure by RPS to comply with any applicable governmental regulation
(including, without limitation, any applicable environmental laws), or
(iii) any product recalls or withdrawals,
personal injury, product liability or property damage relating to or
arising from any Compound supplied by RPS under this Agreement, BUT
ONLY TO THE EXTENT SUCH RECALLS OR WITHDRAWALS, PERSONAL INJURY,
PRODUCT LIABILITY OR PROPERTY DAMAGE REFERRED TO WITHIN (iii) OF THIS
PARAGRAPH IS ATTRIBUTABLE TO RPS'S BREACH OF THIS AGREEMENT, OR RPS'S
FAILURE TO MANUFACTURE ANY PRODUCT IN CONFORMANCE WITH THE
SPECIFICATIONS AND REQUIREMENTS SET FORTH IN THIS AGREEMENT; provided
further that RPS will not indemnify or hold harmless Indemnified
BioNumerik Parties for any losses arising out of BioNumerik's
negligence.
9.3 Conditions of Indemnification: With respect to any indemnification
obligations of either Party to the other Party under this Agreement,
the following conditions must be met for such indemnification
obligations to become applicable:
a) The indemnified Party shall notify the indemnifying Party promptly
in writing of any claim which may give rise to an obligation on the
part of the indemnifying Party hereunder;
b) The indemnifying party shall be allowed to timely undertake the sole
control of the defense of any such action and claim, including all
negotiations for the settlement, or compromise of such claim or action
at its sole expense;
c) The indemnified Party shall at its sole expense render reasonable
assistance, information, cooperation and authority to permit the
indemnifying Party to defend such action.
9.4 Force Majeure. Neither party shall be liable to the other for damages
of any sort arising from any delay or default in such party's
performance hereunder caused by events or conditions beyond such
party's reasonable control and which such party is unable through the
exercise of due diligence to prevent, including, but not limited to,
acts of nature, government or regulatory action, war, civil commotion,
destruction of synthesis or production facilities or materials by
earthquake, fire, flood or storm, or public utilities ("Force
Majeure"). Each party agrees promptly to notify the other party of any
event of Force Majeure and to employ all reasonable efforts toward
prompt resumption of its performance when possible. If Force Majeure
prevents performance by one party of its obligations hereunder in whole
or in part for more than thirty (30) days, the other party shall have
the right to terminate any remaining Phase or Phases of the Project or
the remainder of this Agreement upon written notice to the
non-performing party. In no event shall Force Majeure affecting RPS
obligate RPS to procure supplies of Product for BIONUMERIK from
alternate suppliers, or to allocate its available manufacturing
resources and product supplies in other than a fair and reasonable
manner giving equal consideration to the internal manufacturing needs
of RPS and its affiliates and to the needs of BioNumerik and RPS'
regular customers whether or not they are then under contract.
9.5 [**]
10 TERM AND TERMINATION
10.1 This Agreement shall enter into force as of the Effective Date of the
Agreement and unless earlier terminated, shall continue in full force
and effect until one year after completion of the projects described in
the Project Description. Sections 4, 8, 9, and 13 shall survive any
termination of this Agreement. The obligations under Section 7 of this
Agreement shall terminate 5 years after the termination of this
Agreement.
10.2 Either Party shall have the right, without prejudice to any other
rights or remedies available to it, to terminate this Agreement for
cause with immediate effect by written notice to the other Party in any
of the following events:
a) The other Party defaults in the performance of any of its
obligations under this Agreement and such default continues
unremedied for thirty (30) days from notice to the defaulting
Party;
b) The other Party intentionally makes (or is discovered to have
intentionally made) any material false representations,
reports or claims in connection with the business
relationships of the Parties;
[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.
c) Any of the representatives of the Parties engages in (or is
discovered to have engaged in) fraudulent, criminal or
negligent conduct in connection with the business
relationships of the Parties;
d) The other Party files a petition in bankruptcy, is adjudicated
bankrupt, files for reorganization, is placed in liquidation,
makes a general assignment for the benefit of its creditors,
becomes insolvent or is otherwise unable to fulfill its
business obligations.
10.3 BioNumerik may also terminate this Agreement at any time with or
without cause upon [**] written notice to RPS, provided that, upon
termination of this Agreement by BioNumerik without cause, BioNumerik
will pay to RPS the price as agreed in the Project Description up to
the costs incurred at the point of termination of the Agreement.
10.4 RPS may terminate this Agreement upon [**] written notice to
BioNumerik if, as a result of the services performed by RPS prior to
such termination and RPS's findings relevant thereto, RPS has
determined that, after expending diligent efforts towards the
manufacture of the Compound, it simply cannot make the Compound
required for future phases of this Agreement within the Specifications
(as defined in this Agreement), such written notice to include an
explanation of the basis for any such decision by RPS. In the event of
any such termination of this Agreement by RPS, BioNumerik shall only be
responsible for the payment of fees and charges for services performed
by RPS hereunder through the termination date specified in RPS's
termination notice, and then only to the extent that BioNumerik is able
to utilize the Compound resulting from such services.
11 CRITICAL INTERFACES AND NOTICES
11.1 All notices referred to herein shall be sent by prepaid registered
mail, by recognized courier service (such as Federal Express), or by
facsimile and shall be deemed delivered if sent to the addresses of the
respective Parties hereinbelow indicated, or such other address as is
furnished by such notice to the other Party.
Notices and payments to RPS shall be made in accordance with the RPS
contact information contained in the Project Description:
Notices and invoices to BioNumerik shall be made to:
BIONUMERIK PHARMACEUTICALS, INC.
Suite 1250,
0000 Xxxxxxxxx Xxxxx,
Xxx Xxxxxxx, XX 00000, XXX
Attn: Xx. Xxxxx Xxxxxx, Senior Manager
Chemistry & Manufacturing Operations
Fax: x0 000 000 0000
Phone: x0 000 000 0000
e-mail: xxxxx.xxxxxx@xxxx.xxx
[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.
with a copy to:
Xxxxxxxxx X. Xxxxxxxx, M.D.,
Chairman and CEO
BioNumerik Pharmaceuticals, Inc.,
Suite 1250,
0000 Xxxxxxxxx Xxxxx
Xxx Xxxxxxx, XX 00000, XXX
Fax: x0 000 000 0000
Phone: x0 000 000 0000
11.2 STATUS UPDATES.
RPS shall keep BioNumerik regularly informed of the status and progress
of all stages of the Phase 1, 2, 3, and 4 work, including
manufacturing, through regular telephone or e-mail updates and through
written summaries.
11.3 CONTACT PROCEDURES.
The following individuals shall serve as initial points of contact at
RPS and BioNumerik with respect to any questions or occurrences that
may arise with respect to the Agreement and the work conducted
hereunder:
RPS CONTACTS:
TECHNICAL MATTERS: Xxxx Xxxxxxx
PAYMENT OR FINANCIAL MATTERS: Xxxx Xxxx
BUSINESS OR CONTRACT MATTERS: Xxx Xxxxxxx (with copy to Xxxxxx
Xxxxxxxx)
BIONUMERIK CONTACTS:
TECHNICAL MATTERS:
Xx. Xxxxx Xxxxxx
Xxxxx Xxxxxxxxxx
PAYMENT OR FINANCIAL MATTERS:
Xxxxx Xxxxxx - Vice President & Chief Financial Officer
Xxxxxxx Xxxxxxx - Controller
BUSINESS OR CONTRACT MATTERS:
Xx. Xxxx Xxxxxxxx - Chief Executive Officer
Xxxxx Xxxxxxxx - Vice President, Administration & General Counsel
Xxxxx Xxxxxx - Vice President & Chief Financial Officer
11.4 CHANGE MANAGEMENT.
RPS will promptly notify BioNumerik whenever there is a change in
management or key personnel on the project for the work to be conducted
hereunder.
11.5 Complaint Procedures: Procedures to address any complaint related to
the manufacturing of the Compound are contained in the standard
operating procedures (SOPs) for the RPS Annan, Scotland facility.
Current copies of such SOPs have been previously provided by RPS to
BioNumerik and RPS will promptly provide BioNumerik with any changes to
such SOPs.
11.6 Responsibility for Regulatory Communications.
(a) BioNumerik will have responsibility for initial regulatory
communication with the FDA and other regulatory agencies regarding the
manufacture of the Compound.
(b) RPS will have responsibility for providing back-up assistance and
support as requested by BioNumerik in connection with communications
with the FDA and other regulatory agencies regarding the manufacture of
the Compound. In addition, RPS will have responsibility for regulatory
communication with the FDA and other regulatory agencies (following
coordination with BioNumerik) with respect to the process of RPS'
manufacture of the Compound up to the point that the manufactured
Compound is delivered to the U.S. main port for further shipment as
designated by BioNumerik.
12 ASSIGNMENT
12.1 This Agreement is deemed personal to BioNumerik and RPS. Neither Party
shall, without prior written consent of the other Party, assign this
Agreement or any of its rights nor delegate any of its duties or
obligations herein. Both Parties agree not to unreasonably withhold
consent if such an assignment is contemplated in connection with the
sale or merger by a Party of all or substantially all of its business
or assets to a third Party, providing the non-assigning Party receives
and accepts such written assurances of continued performance and
commitments from the assignee under this Agreement as it may reasonably
require prior to such an assignment becoming effective. Any assignment
or delegation in derogation of this provision shall be deemed null and
void.
13 MISCELLANEOUS
13.1 WAIVERS: Failure of either Party at any time to require strict
performance by the other Party of any of the provisions of the
Agreement shall in no way affect the right thereafter to enforce the
same, nor shall the waiver of any
term, provision, covenant or condition hereof be taken or held to be a
waiver of any subsequent breach hereof or as nullifying the
effectiveness of such term, provision, covenant or condition.
13.2 COUNTERPARTS: This Agreement may be executed in two or more
counterparts, which all together shall constitute one instrument.
13.3 ENTIRE AGREEMENT: This Agreement and its annexes (including, without
limitation, the Project Description) embody the entire understanding of
the Parties and shall supersede all previous communications,
representations, or understandings, either oral or written, between the
Parties relating to the subject matter hereof.
13.4 AMENDMENTS: No amendments or modifications of this Agreement will be
deemed legally binding unless made in writing and signed by both
Parties hereto.
13.5 SEVERABILITY: In case one or more of the provisions contained in this
Agreement shall, for any reason, be held invalid, illegal, or
unenforceable in any respect, such invalidity, illegality or
unenforceability shall not affect any other provision of this
Agreement, but this Agreement shall be construed by amending or
limiting such invalid, illegal, or unenforceable provision so as to
conform as closely as possible to the intent of the Parties or, if such
is not possible, by deleting such provision from this Agreement.
13.6 ANNEXES: The Annexes form an integral part of this Agreement. Should
any internal discrepancies or variances occur between this Agreement
and its Annexes (including the Project Description), this Agreement
shall take precedence.
13.7 GOVERNING LAW: THIS AGREEMENT IS MADE UNDER AND SHALL BE CONSTRUED IN
ACCORDANCE WITH THE LAWS OF THE STATE OF TEXAS, WITHOUT REGARD TO THE
CONFLICTS OF LAW PRINCIPLES THEREOF. EACH PARTY TO THIS AGREEMENT
HEREBY IRREVOCABLY CONSENTS AND SUBMITS TO THE JURISDICTION OF THE
COURTS OF THE STATE OF TEXAS AND OF THE UNITED STATES OF AMERICA FOR
ALL PURPOSES IN CONNECTION WITH ANY PROCEEDING THAT ARISES OUT OF OR
RELATES TO THIS AGREEMENT.
13.8 HEADINGS: The headings in this Agreement may not be used in the
interpretation of any provisions hereof.
13.9 USE OF NAMES: Except as expressly required pursuant to law, neither
party will without prior written consent of the other:
(a) Use in advertising, publicity, promotional premiums or
otherwise, any trade name, trademark, trade device, service
xxxx, symbol, or any abbreviation, contraction or simulation
thereof owned by the other party, or
(b) Represent, either directly or indirectly, that any product or
service of one party is a product or service of the other.
In Witness Hereof,
the Parties hereto through their authorized representatives have
executed this Agreement as of the date first written above.
RHODIA PHARMA SOLUTIONS INC.,
on behalf of itself and its subsidiary, Rhodia Pharma Ltd.
By: /s/ [ILLEGIBLE]
Title: President
Date: February 23, 2004
BIONUMERIK PHARMACEUTICALS, INC.
By: /s/ XXXXXXXXX X. XXXXXXXX
Title: Chief Executive Officer
Date: effective as of February 10, 2004
ANNEXES
Annex 1: [**]
Annex 2: [**]
Annex 3: [**]
Annex 4: [**]
Annex 5: [**]
Annex 6: RPS Wire Transfer Information
Annex 7: [**]
Annex 8: [**]
Annex 9: [**]
Annex 10: [**]
[**] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.
ANNEX 6: RPS WIRE TRANSFER INFORMATION
HSBC
Newcastle upon Tyne City Branch
Account Number: 00000000 (605-480771-130)
IBAN CODE: XX00 XXXX 0000 0000 0000 00
Swift Code: XXXXXX00
