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EXHIBIT 10.1
***Text Omitted and Filed Separately
Confidential Treatment Requested
Under 17 C.F.R. Sections 200.80(b)(4),
200.83 and 240.24b-2
RESEARCH AND OPTION AGREEMENT
between
BOEHRINGER XXXXXXXXX XXXXXXXXXXXXX XxxX
00000 Xxxxxxxxx
XXXXXXX
(hereinafter referred to as "BII")
and
GENETRONICS, INC.
00000 Xxxxxxxx Xxxxxx Xxxx
Xxx Xxxxx
Xxxxxxxxxx 00000-0000
XXX
(hereinafter referred to as "GENETRONICS")
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TABLE OF CONTENTS
1. DEFINITIONS...............................................................4
2. CONDUCT OF RESEARCH.......................................................8
3. CONSIDERATION............................................................10
4. RESEARCH OPTION..........................................................11
5. DEVELOPMENT AND LICENSE OPTION...........................................13
6. OPTION FEE...............................................................14
7. WARRANTIES AND LIABILITIES...............................................14
8. CONFIDENTIALITY..........................................................16
9. INVENTIONS...............................................................18
10. PATENTS..................................................................18
11. PUBLICATIONS.............................................................20
12. TERM AND TERMINATION.....................................................21
13. CONCLUDING PROVISIONS....................................................22
APPENDIX 1 RESEARCH PLAN......................................................25
APPENDIX 2 LICENSE TERMS......................................................31
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WITNESSETH:
WHEREAS, BII has expressed an interest in the application of in vivo
electroporation for the delivery of DNA in solution, or in particles, into human
skin or other tissue; and
WHEREAS, BII has extensive expertise in the field of gene transfer and tumor
vaccines and has developed a variety of approaches to tumor vaccination; and
WHEREAS, Genetronics has broad technology and expertise in the field of in vivo
electroporation for intradermal and transdermal delivery of genes and drugs and
has, over a period of years, expended considerable effort and resources in the
development of technology in the area of electroporation and related
technologies for drug and gene delivery, and has accumulated extensive
experience in such areas; and
WHEREAS, BII and Genetronics have entered into discussions and have agreed upon
the content of a research project which will include the use of technologies and
methodologies proprietary to either Genetronics or BII; and
WHEREAS, Genetronics is willing to perform the Research Program in collaboration
with BII; and
WHEREAS, BII is willing to provide the funding for the Research Program; and
WHEREAS, BII wishes to obtain an option right with respect to a license to
develop and commercialize electrically assisted DNA vaccine delivery and
Genetronics is willing to grant such option;
NOW, THEREFORE, and in consideration of the foregoing premises and other good
and valuable consideration, the receipt of which is hereby acknowledged, the
parties agree as follows:
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1. DEFINITIONS
1.1 "Affiliates" shall mean any company or business entity which controls,
is controlled by, or is under common control with either Genetronics or
BII. For this purpose "control" shall mean direct or indirect beneficial
ownership of at least fifty per cent (50%) of the voting share capital
in such company or other business entity.
1.2 "BII Invention" shall mean any patentable and/or non-patentable
invention made solely by one or more BII employees, without inventive
contribution of Genetronics employees, pursuant to the Research Program
or in relation to the development, manufacture, marketing or sale of a
Product-Kit.
1.3 "BII Technology" shall mean (i) all Patent Rights and Know How owned by
or licensed to BII as of the Effective Date that are directly related to
tumor antigens, DNA encoding tumor antigens, tumor vaccines, vaccine
formulations, gene transfer technology and/or tumor vaccination, (ii)
all BII Inventions and BII Research Program Know How that are not within
Genetronics Core Technology, and (iii) all Genetronics Inventions,
Genetronics Research Program Know How, Joint Inventions, and Joint
Research Program Know How that are not within Genetronics Core
Technology and are directly related to tumor antigens, DNA encoding
tumor antigens, tumor vaccines, vaccine formulations, gene transfer
technology, and/or tumor vaccination.
1.4 "BII Patent Rights" shall mean any and all Patent Rights in BII
Technology owned by or licensed to BII.
1.5 "BII Product" shall mean one or more nucleic acids encoding [...***...]
and all other material for inclusion in a Product-Kit with the exception
of any components purchased from Genetronics or a Genetronics Affiliate.
1.6 "Biological Material" shall mean all composition of matter provided to
Genetronics by or on behalf of BII for performance of the Research
Program.
1.7 "Confidential Information of BII" shall mean confidential information
disclosed by BII or an Affiliate of BII to Genetronics or an Affiliate
of Genetronics, including but not limited to BII Technology.
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1.8 "Confidential Information of Genetronics" shall mean confidential
information disclosed by Genetronics or its Affiliates to BII or its
Affiliates, including but not limited to Genetronics CoreTechnology and
Genetronics New Technology.
1.9 "Confidential Information" shall mean Confidential Information of
Genetronics and/or Confidential Information of BII.
1.10 "Effective Date" shall mean the date of execution by the last party to
sign this Agreement.
1.11 "Electrically Assisted Delivery" shall mean the delivery of matter
across biological barriers such as cell membranes or layer(s) of the
skin, facilitated by the effect of electrical fields or currents on such
biological barriers and/or on the matter to be delivered.
1.12 "Equipment" shall mean the equipment defined in Appendix 1.
1.13 "Extended Research Program" shall have the meaning set forth in Clause
4.1.
1.14 "Extended Research Program Plan" shall have the meaning set forth in
Clause 4.4.
1.15 "Field" shall mean the field of cancer DNA vaccines, specifically
defined to be [...***...] nucleic acids that code for tumor antigens,
which may be combined with [...***...] or formulation thereof that
elicits a [...***...] immune response against [...***...] or [...***...]
cancer cells or cancerous tissue when administered to [...***...] or
[...***...], respectively. For the sake of clarity, the Field does not
include HIV DNA vaccines.
1.16 "Genetronics Core Technology" shall mean (i) all Patent Rights and Know
How owned by or licensed to Genetronics as of the Effective Date that
are directly related to the Electrically Assisted Delivery of any
substance into or through organismal cells or tissues, and (ii) all
Genetronics Inventions, BII Inventions, Joint Inventions, and Research
Program Know How that are directly related to the Electrically Assisted
Delivery of any substance into or through organismal cells or tissues.
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1.17 "Genetronics Invention" shall mean any patentable and/or non-patentable
invention made solely by one or more Genetronics employees, without
inventive contribution of BII employees, pursuant to the Research
Program or in relation to the development, manufacture, marketing or
sale of a Product-Kit.
1.18 "Genetronics Patent Rights" shall mean any and all Patent Rights owned
by or licensed to Genetronics in Genetronics Core Technology and
Genetronics New Technology.
1.19 "Genetronics NewTechnology" shall mean all Genetronics Inventions and
Genetronics Research Program Know How that are not within Genetronics
Core Technology or BII Technology.
1.20 "Joint Invention" shall mean any patentable and/or non-patentable
invention made jointly by one or more BII employees together with one or
more Genetronics employees pursuant to the Research Program or in
relation to the development, manufacture, marketing or sale of
Product-Kit .
1.21 "Joint Patent Rights" shall mean Genetronics' and BII's joint Patent
Rights in Joint Technology
1.22 "Joint Technology" shall mean all Joint Inventions and all Joint
Research Program Know How that is not within BII Technology or
Genetronics Core Technology.
1.23 "Know How" shall mean information which is not known to the public
including information comprising or relating to inventions, including
patent applications in preparation, concepts, discoveries, data,
designs, formulae, ideas, experience; information comprising or relating
to material, methods, models, assays, research plans, procedures,
designs for experiments and tests and results of experimentation and
testing including results of research or development together with
processes including manufacturing processes, specifications, techniques,
chemical, pharmacological, toxicological, clinical, analytical and
quality control data, trial data, case report forms, data analyses,
reports or summaries and correspondence no matter whether contained in
written documents, tapes, discs, diskettes, CDROM and any other media on
which Know How can be permanently stored. The fact that an item is known
to the public shall not be taken to exclude the possibility that a
compilation including the item, and/or a development related to the
items, is (or
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remains) not known to the public.
1.24 "License Terms" shall mean the licensing terms referred to in Clause 5
below and attached hereto as Appendix 2.
1.25 "Non-Exclusive License to Genetronics Core Technology" shall mean a
non-exclusive, royalty-bearing license to Genetronics Core Technology in
the Territory necessary to develop, make, use, sell, offer to sell, and
import Product-Kits for use in the Field and as referred to in Appendix
2 hereto attached.
1.26 "Net Sales" shall mean [...***...].
1.27 "Patent Rights " shall mean rights in all Know-How, patent applications
and patents, design patents, improvement patents and models and
certificates of addition and all foreign counterparts of them, including
any provisional applications, divisional applications and patents,
refilings, renewals, continuations, continuations-in-part, patents of
addition, extensions, reissues, substitutions, confirmations,
registrations, revalidation and additions of or to any of them, as well
as any supplementary protection certificates, and equivalent protection
rights in respect of any of them.
1.28 "Product-Kit" shall mean the finished product containing a BII Product
combined with components purchased from Genetronics or Genetronics
Affiliates for the Electrically Assisted Delivery of a BII Product. Each
Specified Product-Kit is a subset of Product-Kit and shall be considered
a Product-Kit for all purposes and definitions of this Agreement, except
as expressly stated otherwise.
1.29 "Research Program Know How" shall mean Know How that is created,
generated or developed by or on behalf of BII ("BII Research Program
Know How"), by or on behalf of Genetronics ("Genetronics Research
Program Know How"), or jointly ("Joint Research Program Know How")
pursuant to the Research Program or in relation to development,
manufacture, marketing or sale of the Product-Kit.
1.30 "Research Program" shall mean the research project entitled: "Delivery
of certain cancer DNA vaccines by in vivo electroporation or related
technologies" as set forth in detail in the Research Plan, which will be
conducted by Genetronics and BII in collaboration in the Field pursuant
to Clauses 2 and 7 of this Agreement. The Extended Research Program is a
subset of Research Program and shall be
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considered a Research Program for all purposes and definitions of this
Agreement, except as expressly stated otherwise.
1.31 "Research Plan" shall mean the project as described in the protocol and
the respective timelines attached hereto as Appendix 1, as amended from
time to time in writing with the mutual written consent of both parties.
1.32 "Territory" shall mean the world.
2. CONDUCT OF RESEARCH
2.1 The Research Program is a program for collaborative research under which
Genetronics shall, among other things, develop electrodes for the in
vivo electroporation of DNA encoding one or more tumor antigens to
elicit an antitumor immune response. Genetronics and BII will carry out
the research activities allocated to them in accordance with the
Research Plan set forth in Appendix 1 of this Agreement. The Research
Program shall begin on the Effective Date and shall terminate 18 months
thereafter, except as it may be extended pursuant to Clause 4 of this
Agreement.
2.2 Genetronics shall be responsible to perform all activities necessary to
conduct its part of the Research Program as described in the Research
Plan in Appendix 1 and within the timelines set forth therein at its own
cost and expense.
2.3 BII will use its experience and the BII Technology to discover, develop,
and/or acquire potential BII Products for use in the Research Program at
its own cost and expense.
2.4 The parties shall meet at least every six (6) months to discuss the
progress of the Research Program. The meetings shall be held at
locations that are agreed upon by the parties, and all expenses
associated with attending the meetings shall be borne by BII.
Each party shall provide the other party with all Know How in its
possession as of the Effective Date and during the term of the Research
Program, which it has the right to disclose, to the extent necessary for
the successful conduct of the Research Program.
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2.5 Genetronics shall furnish BII with interim reports of observations and
results of the different phases of the Research Program every 3rd month
(quarterly) after commencement of the Research Program.
2.5 Genetronics hereby nominates [...***...] as the project manager at
Genetronics, and BII hereby nominates [...***...] as the project manager
at BII, who shall be jointly responsible for coordinating all work to be
conducted under the Research Program.
Genetronics shall use its best reasonable efforts to ensure that there
are no changes in the person of the project manager. If a change,
nevertheless, occurs, Genetronics will promptly submit the name and
qualification of any planned replacement for the project manager,
whereupon BII shall, at its sole discretion, approve or reject any such
replacement within a reasonable time.
The parties shall each nominate a deputy for each of these individuals,
who shall be entitled to represent such individuals in the event of
absence of the same.
2.6 Genetronics shall further provide BII with a complete and detailed draft
final report of observations and results of the Research Program to date
no later than 30 (thirty) days before completion of the Research Program
for BII's review and approval. Upon written request of BII provided no
later than 10 (ten) days after receipt of the draft final report,
Genetronics shall make any reasonable modifications in such draft final
report after receipt of BII's written request, such that a final report
shall be complete and provided to BII no later than 18 months after
beginning the Research Program. If BII does not timely request that
modifications be made to the draft final report, as set forth herein,
then the draft final report provided by Genetronics shall become the
final report.
2.7 Genetronics agrees to provide Equipment to BII promptly after initiation
of the Research Program. BII agrees it shall use the Equipment only
within the Field and only pursuant to the Research Program, and shall
abide by the following terms and conditions:
a. BII shall not analyze, have analyzed, structurally modify, or
have modified the Equipment in any way.
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b. Genetronics shall retain all right, title, and interest in the
Equipment provided to BII under this Agreement.
c. Under no circumstances is the Equipment to be used on humans.
d. BII shall not transfer the Equipment to a third party
non-Affiliate without the prior written permission of
Genetronics. BII shall have the right to transfer the Equipment
to an Affiliate pursuant to the Research Program, provided
however, BII shall inform Genetronics regularly on such
transfers.
The provisions of this Clause 2.7 shall apply accordingly for use
of the Biological Material to be supplied by BII to Genetronics.
2.8 Genetronics hereby grants BII a limited license to use Genetronics Core
Technology and Genetronics New Technology to the extent necessary for
BII to perform the Research Program as set forth in the Research Plan
for the term of this Agreement. BII hereby grants Genetronics a limited
license to use BII Technology to the extent necessary for Genetronics to
perform the Research Program as set forth in the Research Plan for the
term of this Agreement. Each party shall have the right to sublicense
such right to its Affiliate(s) solely for fulfilment of its obligations
under this Agreement. No other license is granted by one party to the
other pursuant to this Agreement.
2.9 Genetronics hereby assigns to BII its rights in any Genetronics
Invention, Research Program Know How, and Joint Invention that is not
within Genetronics Core Technology and that relates to tumor antigens,
DNA encoding tumor antigens, tumor vaccines, vaccine formulations, gene
transfer technology, and/or tumor vaccination. BII hereby assigns to
Genetronics its rights in any BII Invention, Research Program Know How,
and Joint Invention that is directly related to the Electrically
Assisted Delivery of any substance into or through organismal cells or
tissues.
3. CONSIDERATION
3.1 In consideration of the work to be conducted by Genetronics under the
Research Program, BII shall place at the disposal of Genetronics the
total sum of [...***...] which shall be payable according to the
provisions of this Clause 3. Said
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total sum shall be exclusive of value added tax which shall be added
thereon by BII, if applicable.
3.2 The sum referred to in Clause 3.1 above shall become duly payable in
accordance with the following schedule:
(i) [...***...] upon execution of this Agreement;
(ii) [...***...]
(iii) [...***...]
(iv) [...***...]
(v) [...***...]
(vi) [...***...] upon receipt of the final report of the Research
Program.
3.3 BII undertakes to make all payments due hereunder within 30 (thirty)
days of receipt of an invoice by Genetronics, detailing value added tax
separately as needed, to a bank account designated by Genetronics.
3.4 The sum referred to in Clause 3.1 above is inclusive of all costs and
expenses of Genetronics (internal and pass-through costs) incurred in
connection with the Research Program, except as explicitly provided
otherwise in this Agreement. Genetronics shall assign [...***...] to the
Research Program, [...***...] shall be a Ph.D. level scientist and
[...***...] shall be at the level of at least a research technician, and
[...***...] shall be qualified to perform the Research Program as set
forth in Appendix 1.
4. RESEARCH OPTION
4.1 BII has the right to request one 18 (eighteen) month extension of the
Research Program if BII, in its sole discretion, decides that further
basic research should be conducted. Such right shall be exercisable by
notice in writing to Genetronics within 3 (three) months after BII
receives the final report of the Research Program. If BII exercises its
option during such period, this Agreement shall be automatically
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extended for one 18 (eighteen) month period, beginning on the date of
such written notice, under the same terms and conditions set forth
herein, but for the right to any additional extensions ("Extended
Research Program"). For the Extended Research Program, a consideration
of [...***...] of the total amount set forth in Clause 3.1 is foreseen.
In the event the Extended Research Program requires increased or
decreased staffing and costs compared to the original Research Program,
the parties shall jointly agree upon amounts greater or lower than
[...***...] to fund the Program as the case may be. The consideration
shall be paid in [...***...] equal installments. The first such payment
shall be due by the beginning of the Extended Research Program, the next
[...***...] installments at the beginning of the then following
[...***...] calendar quarters and the last installment upon receipt of
the final report of the Extended Research Program.
4.2 BII shall reimburse Genetronics for staff allocated to future questions
resulting out of the Research Program in an amount of [...***...] per
month for the period between the end of the original Research Program
and (i) notification of BII's decision to enter the Extended Research
Program or (ii) notification that BII has decided not to enter the
Extended Research Program or (iii) expiry of the option period pursuant
to Clause 4.1 without any notice, whichever of (i) - (iii) occurs first.
Each payment shall be made by BII on a monthly basis until the first to
occur of (i) - (iii).
4.3 The parties may mutually decide to extend the Research Program for a
period shorter than 18 (eighteen) months, and under terms and conditions
they may agree upon, but neither party has an obligation to do so.
4.4 Within a reasonable period of time following notification of BII's
exercise of its option to enter the Extended Research Program, the
parties shall prepare and mutually agree upon a detailed "Extended
Research Program Plan". Such Extended Research Program Plan shall
describe in detail the work to be carried out by Genetronics and BII
during the Extended Research Program.
4.5 In the event the Agreement is not extended pursuant to Clause 4.1 or
4.3, it shall be deemed terminated as of the end of 3 (three) months
after receipt of the final report by BII. Other than rights and
obligations under the option set forth in Clause 5 below, and
obligations that extend after termination, as set forth in Clause 12.1,
the parties shall have no further obligations to each other.
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5. DEVELOPMENT AND LICENSE OPTION
5.1 During the performance of the Research Program or, if extended, the
Extended Research Program or a program extension under Clause 4.3, and
for a three month period after such has been conducted, BII may, in its
sole discretion, decide to enter into a development and license
agreement with Genetronics, the major terms of which are set forth in
the License Terms attached hereto as Appendix 2. Such option right shall
be exercisable by notifying Genetronics at the latest 3 (three) months
after receipt of the final report of the Research Program, receipt of
the final report of the Extended Research Program, or completion of the
Clause 4.3 research extension, as the case may be. In the event BII
exercises the option granted under this Clause 5.1 during the term of
the Research Program, the Extended Research Program, or a program
extension under Clause 4.3, BII shall either (i) terminate the Agreement
pursuant to the terms of Clause 12.3, or (ii) continue to make all
payments to Genetronics as agreed to, and on the schedule, pursuant to
Clauses 3.2, 4.1 or 4.3, as the case may be, as consideration for
development activities to be assigned to Genetronics under the license
and development agreement. The choice between (i) and (ii) shall be made
solely by BII.
5.2 Genetronics and BII shall negotiate all terms of a development and
license agreement that are not already agreed upon in the License Terms
during the initial Research Program, such that a finally negotiated and
drafted development and license agreement shall be in a form for
execution at completion of the Research Program. Upon exercise of the
option pursuant to Clause 5.1, and in the event the development and
license agreement is not yet in finally negotiated and drafted form, the
parties shall enter into good faith, timely, negotiations on all
remaining terms of such development and license agreement not already
agreed upon in the License Terms, including but not limited to
provisions concerning diligent development, warranties, liabilities,
termination, and effect of termination appropriate for such kind of
agreement.
5.3 If the parties fail to agree upon the remaining terms, and (i) such
failure is a result of reasonable differences in opinion between the
parties with respect to a substantive term of the agreement, and (ii)
such failure is not a result of Genetronics desiring to enter into a
license and development agreement with a third party instead of BII, and
(iii) a final development and license agreement has not been concluded
within four (4) months after the option pursuant to Clause 5.1 has been
exercised, then BII's option
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right shall be deemed to have expired. Neither Party shall have any
further right to negotiate with the other party. In the event of such
failed negotiations, and upon request of BII at the end of the four (4)
month negotiation period, Genetronics shall warrant and represent to BII
in writing that its failure to agree with BII as to all terms of the
development and license agreement is a result of a sincere difference of
opinion and is not a result of Genetronics desiring to enter into a
license and development agreement with a third party instead of BII.
6. OPTION FEE
6.1 If BII enters into an extension under Clause 4.1 or 4.3, or exercises
its option to enter into a development and license agreement granted
under Clause 5.1, a one time option fee of [...***...] will be paid to
Genetronics by BII within 30 (thirty) days notifying Genetronics of the
first to occur of an extension or exercise of the development and
license right, and receipt of a respective invoice.
7. WARRANTIES AND LIABILITIES
7.1 Genetronics represents and warrants that:
(i) it will use its best endeavours to carry out the Research Program
as set forth in the Research Plan and within the times agreed
upon in Appendix 1, with all reasonable care and skill in
accordance with all applicable laws, professional standards and
in accordance with all provisions of this Agreement, with both
parties acknowledging that it may not be possible to complete all
research outlined in Appendix 1 within the eighteen month term
due to reasons beyond the parties' control;
(ii) it shall devote the efforts of suitably qualified and trained
employees capable of carrying out the Research Program to a
professional standard and shall provide all necessary facilities
therefor;
(iii) all reports, documentation and information to be provided to BII
hereunder shall be compiled in accordance with best scientific
practice and delivered in a form agreed upon in advance with BII;
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(iv) the Genetronics Core Technology and Genetronics New Technology is
owned by Genetronics or an Affiliate and it will use its best
reasonable endeavours to see that such will continue to be the
case during the term of this Agreement;
(v) the Genetronics Core Technology and Genetronics New Technology is
free of any mortgage, charge or other encumbrance and it will use
its best reasonable endeavours to see that such will continue to
be the case during the term of this Agreement.
7.2 Each party represents and warrants that:
(i) it has legal power, authority and right to enter into this
Agreement and to properly perform its respective obligations in this
Agreement; and
(ii) it is not as of the Effective Date a party to any agreement,
arrangement or understanding with any third party which in any way
prevents it from fulfilling any of its obligations under the terms of
this Agreement.
7.3 BII hereby indemnifies and holds harmless Genetronics from and against
all third party claims, including without limitation, any claims with
respect to death or injury to a person or damage to property, and all
damages, losses, costs and expenses, including reasonable attorney's
fees, which Genetronics may incur arising out of or resulting from (i)
the conduct of the Research Plan solely performed by BII, its
Affiliates or sublicensees, and/or (ii) the negligence, recklessness or
willful misconduct of BII, its Affiliates or sublicensees or each of
their officers, employees or agents.
7.4 Genetronics hereby indemnifies and holds harmless BII and its
Affiliates from and against all third party claims, including without
limitation, any claims with respect to death or injury a person or
damage to property, and all damages, losses, costs and expenses,
including reasonable attorney's fees, which BII or its Affiliates may
incur arising out of or resulting from (i) conduct of the Research Plan
solely performed by Genetronics and/or (ii) the negligence,
recklessness or willful misconduct of Genetronics or its officers,
employees or agents.
7.5 The party seeking indemnification under Clause 7.3 or 7.4 (the
"Indemnified Party") shall (i) give the other party (the "Indemnifying
Party") notice of the relevant claim,
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(ii) cooperate with the Indemnifying Party, at the Indemnifying Party's
expense, in the defence of such claim and (iii) give the Indemnifying
Party the right to control the defence and settlement of such claim,
except that the Indemnifying Party shall not enter into any settlement
that affects the Indemnified Party's rights or interest without the
Indemnified Party's prior written approval. The Indemnified Party shall
have no authority to settle any claim on behalf of the Indemnifying
Party. A party's obligation to indemnify the other pursuant to Clause
7.3 or 7.4 shall be waived with respect to a certain claim in the event
a party seeking to be indemnified does not provide notice of the
relevant claim in sufficient time for the other party to respond or
defend against the claim.
8. CONFIDENTIALITY
8.1 In relation to Confidential Information disclosed by one party to the
other and subject to Clauses 8.2 and 8.3 below, each party agrees:
(i) not to publish or provide or make available any of the other
party's Confidential Information in any form to any third party;
and
(ii) not to use or reproduce any of the other party's Confidential
Information except for use reasonably necessary for its
performance of this Agreement.
8.2 Each party may provide or make available the Confidential Information
disclosed by the other:
(i) to those of its employees who have a need to know consistent with
the receiving party's authorized use of that Confidential
Information; and
(ii) in the case of BII, to official organizations responsible for
granting marketing authorizations; and
(iii) in the case of Genetronics, to [...***...]., (i) only as far as
Genetronics Core Technology is concerned; no information on BII
Technology and no confidential information on BII's or BII's
Affiliates' trade secrets, business affairs or finances are to be
disclosed to [...***...] and (ii) only to the extent necessary
for Genetronics to fulfill its obligation to provide [...***...]
with
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[...***...] with respect to any development and license agreement
pertaining to [...***...].
(iv) to Affiliates of the parties in order to reasonably perform this
Agreement, in which event recipients of the Confidential
Information shall be bound by written obligations of
confidentiality no less onerous than those contained in this
Clause 8; and
(v) to comply with the disclosure obligations of the patent laws of
any jurisdiction in connection with any patent application
relating to BII Technology, Genetronics Core Technology,
Genetronics New Technology, or Joint Technology or any component
thereof.
8.3 The obligations of confidentiality and non-use in Clause 8.1 above shall
not apply to any part of the Confidential Information which:
(i) is in or comes into the public domain in any way without breach
of this Agreement by the receiving party; or
(ii) the receiving party can show was in its possession or known to it
by being in its use or being recorded in its files or computers
or other recording media prior to receipt from the disclosing
party and was not previously acquired by the receiving party from
the disclosing party; or
(iii) the receiving party obtains or has available from a source other
than the disclosing party without breach by the receiving party
or such source of any obligation of confidentiality or non-use
towards the disclosing party; or
(iv) is disclosed by the receiving party (a) with the prior written
approval of the disclosing party or (b) without such approval,
after a period that is the longer of 20 (twenty) years from the
date of this Agreement, 10 (ten) years from the date of
termination of this Agreement, or if executed, 10 (ten) years
from the date of termination of a subsequent business agreement
between the parties that is relevant to this Agreement .
8.4 Notwithstanding the foregoing, the receiving party shall be entitled to
make any disclosure required by any law or by any governmental authority
of the other party's
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Confidential Information provided that it gives the other party not less
than 5 (five) working days notice of such disclosure.
8.5 Each party reserves all rights in its Confidential Information and no
rights or obligations other than those expressly recited herein are
granted or to be implied from this Agreement. In particular, other than
as expressly provided in this Agreement, no license is granted by this
Agreement directly or indirectly under any patent, invention, discovery,
copyright or other intellectual property right now or in the future
held, made, obtained or licensable by either party. Nothing in this
Agreement or its operation shall preclude or in any way impair or
restrict either party from continuing to engage in its business
otherwise than in breach of the terms of this Agreement.
8.6 The parties agree not to disclose the terms of this Agreement to third
parties, other than Affiliates, and neither shall make any announcement
in relation to or otherwise publicize its contents without the prior
written approval of the other, except as necessary under government
rules, regulations and laws. BII agrees that Genetronics shall have the
right to disclose this Agreement in a press release approved by BII in
advance, which approval shall not be unreasonably withheld.
9. INVENTIONS
9.1 By virtue of the Agreement, Genetronics shall not acquire any right to
BII Technology or future BII gene transfer systems, other than as set
forth in Clause 2.8.
9.2 By virtue of the Agreement, BII shall not acquire any right to
Genetronics Core Technology or Genetronics New Technology other than as
set forth in Clause 2.8.
10. PATENTS
10.1 BII shall have full responsibility for, and shall bear all expenses for,
the filing, prosecution, maintenance or other protection of BII Patent
Rights.
10.2 Genetronics shall have full responsibility for, and shall bear all
expenses for, the filing, prosecution, maintenance or other protection
of Genetronics Patent Rights.
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10.3 Joint Technology shall be jointly owned by both partners. The parties
will discuss and agree which party shall have responsibility for the
filing, prosecution and maintenance of the Joint Patent Rights on Joint
Inventions worldwide and on the cost sharing related thereto.
10.4 Each party agrees to assist the other party in every proper way,
including the execution of all proper documents requested by the filing
party. If a party decides not to file, prosecute or maintain a Patent
Right on its own Invention, or on a Joint Invention, in any country, it
shall give the other party reasonable notice to that effect; upon
receipt of such notice, the other party may, at its expense, file,
prosecute or maintain such Patent Right unless the first party has
determined to protect such invention as an intellectual property right
other than a patent.
10.5 Each party shall promptly inform the other party of any BII,
Genetronics, or Joint Invention of which it becomes aware during the
term of this Agreement.
10.6 At least fourteen (14) days prior to filing of any patent application
for an Invention within the scope of this Agreement, the party
responsible for the filing will provide the other party with an English
language summary of the patent application for the non-filing party's
review and comment. The filing party will also provide the non-filing
party with a full copy of each such patent application actually filed in
the language in which it was originally filed.
10.7 If either party becomes aware that a Genetronics Patent Right or a Joint
Patent Right is infringed by a third party in any country, that party
shall promptly notify the other party in writing. Genetronics shall have
the primary right, but not the obligation, to bring and prosecute at its
own expense an action concerning such infringement. If Genetronics does
not commence such an action within [...***...] of learning of such
infringement, BII shall have the right but not the obligation to bring
and prosecute at its own expense an action concerning such infringement.
The parties shall cooperate with each other in connection with any
action brought under this Clause 10.7. Any monetary award granted to the
prosecuting party hereunder shall be applied first to the costs and
expenses of the party prosecuting the action, then to the costs and
expenses of the other party. The party bringing the suit shall be
entitled to any monetary awards in excess.
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10.8 The parties shall assist each other to secure the proper documentation
to assign rights consistent with the grants set forth in Clause 2.9.
10.9 The inventorship of a BII Invention, Genetronics Invention and Joint
Invention will be determined pursuant to relevant appropriate laws of
the jurisdiction in which a patent application directed to the Invention
is to be filed. To the extent it is necessary to determine inventorship
or ownership of intellectual property that is not the subject of a
patent application, Genetronics and BII will make a determination based
on the facts, fairness, and, if applicable, relevant laws.
11. PUBLICATIONS
During the term of this Agreement, Genetronics and BII each acknowledges
the other party's interest in publishing certain of its results to
obtain recognition within the scientific community and to advance the
state of scientific knowledge. Each party also recognizes the mutual
interest in obtaining valid intellectual property protection and
maintaining as confidential any information related to non-patentable
technology which would have commercial value when undisclosed.
Consequently, either party, its employees or consultants wanting to make
a publication (including any oral disclosure) relating to work performed
by such party as part of the Research Program (the "Publishing Party")
shall transmit to the other party (the "Reviewing Party") a copy of the
proposed written publication at least ninety (90) days prior to
submission for publication, or an outline of such oral disclosure at
least sixty (60) days prior to presentation. The Reviewing party shall
have the right (a) to propose modification to the publication for patent
or other reasons and (b) to request a delay in publication in order to
protect patentable information.
If the Reviewing Party requests such a delay, the Publishing Party shall
delay submission or presentation of the publication for a period not
longer than ninety (90) days to enable patent applications protecting
each party's rights in such information to be filed in accordance with
Article 10. If the Reviewing Party reasonably claims that such
information, whether or not patentable, may have significant commercial
value and can be maintained as a trade secret, the Publishing Party
shall publish or disclose only such information which would not
adversely affect such commercial value. Upon the expiration of ninety
(90) days or sixty (60) days from transmission to the Reviewing Party,
as applicable, the Publishing Party shall be free to proceed with
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the written publication or the presentation, respectively, unless the
Reviewing Party has requested the trade secret protection described
above.
12. TERM AND TERMINATION
12.1 This Agreement shall commence on the Effective Date and shall terminate
upon the first to occur of (i) completion of the Research Program with a
duration of 18 (eighteen months and expiration or termination of the
option in Clause 4.1 or 4.3 without exercise, (ii) completion of the
Extended Research Program with a duration of 18 (eighteen) months and
expiration, termination, or exercise of the option in Clause 5.1, if BII
has exercised its option pursuant to Clause 4.1, or (iii) completion of
an extended research program the parties may agree upon pursuant to
Clause 4.3 and expiration, termination, or exercise of the option in
Clause 5.1. The following Clauses shall survive termination of this
Agreement: 2.6 (final report); 5.3 (in event of no agreement on
license); 6.1 (option fee); 7.3, 7.4 and 7.5 (indemnification); 8
(confidentiality); 9 (invention); 10 (patents); 11 (publications); 12.1
(survival); 12.3 (early termination), 12.4 (effects of termination);
12.5 (return of equipment); 13.1 (Affiliates); 13.6 (choice of law);
Appendix 2 (partial license terms).
12.2 This Agreement may be terminated with immediate effect by written notice
by either party, if the other party breaches this Agreement in any
material manner and shall have failed to remedy such default within 30
(thirty) days after written notice thereof by the terminating party.
12.3 BII shall be entitled to terminate this Agreement forthwith at any time
upon written notice to Genetronics thereof. In such an event, BII shall
be obligated to pay Genetronics the difference between (i) the amount
set forth in Clause 3.1 or agreed upon pursuant to Clause 4.1 or 4.3, as
the case may be and (ii) the amount that will have been paid to
Genetronics as of the date of early termination.
However, if BII has terminated this Agreement in accordance with the
provisions of Clause 12.2 above, BII shall only be obliged to pay to
Genetronics the amounts due on the date of termination pursuant to
Clause 3 or 4, as the case may be.
12.4 Upon termination of this Agreement for any reason, any license or option
right granted from one party to the other, either expressly or
impliedly, pursuant to this Agreement, including but not limited to the
license grants under Clause 2.8, shall revert to the
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granting party, with the exception of any such right granted in a
subsequent license or other agreement between the parties. BII shall
retain all ownership rights in BII Technology, regardless of
inventorship. Genetronics shall retain all ownership rights in
Genetronics Core Technology and Genetronics New Technology, regardless
of inventorship. Absent an express license subsequently granted by one
party to the other, neither party shall have the right to practice
within the other's Technology.
12.5 Upon termination of the Agreement, each party shall promptly return the
Equipment or the Biological Material, as the case may be, or dispose of
any unused portions as the other party may direct in writing.
13. CONCLUDING PROVISIONS
13.1 Neither party shall be entitled to assign or otherwise transfer its
rights and obligations under this Agreement in whole or in part to any
third party without the prior written consent of the other party except
to its Affiliates. BII shall have the right to exercise any of its
rights or perform any of its obligations hereunder through any of its
Affiliates and to the extent it does so it hereby guarantees such
performance. BII shall be responsible for all payments due to
Genetronics under this Agreement and BII shall ensure that any Affiliate
performs all its obligations under the sub-license granted to it by BII.
BII indemnifies Genetronics against all loss, damage, cost or expense
which Genetronics may incur as a result of failure by such Affiliate or
BII to perform obligations under any such sub-license equivalent to any
obligation of BII hereunder. If also Genetronics wishes to exercise its
rights or perform its obligations through an Affiliate the provisions of
this Clause 13.1 shall apply accordingly to Genetronics.
With respect to any reference to BII or Genetronics in the definition of
a party's sole or Joint Invention, Technology, Patent Rights, Product,
Confidential Information, Core Technology, Know How, and Research
Program Know How, it is the parties' intent that "BII" shall mean "BII
or its Affiliates" and "Genetronics" shall mean "Genetronics or its
Affiliates".
13.2 This Agreement sets forth the entire agreement between the parties and
supersedes all previous agreements, written or oral regarding the
subject matter hereof. This Agreement may be amended only by an
instrument in writing duly executed on behalf of the parties.
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13.3 Neither party shall be liable for delay or failure to perform hereunder
due to any contingency beyond its control, including, but not limited to
acts of God, fires, floods, wars, civil wars, sabotage, strikes,
governmental laws, ordinances, rules or regulations or failure of third
party delivery, provided, such party promptly gives to the other party
hereto written notice claiming force majeure and uses its best efforts
to eliminate the effect of such force majeure, insofar as is possible
and with all reasonable dispatch. If the period of delay of failure
should extend for more than 3 (three) months then either party shall
have the right to terminate this Agreement forthwith upon written notice
at any time after expiration of said 3 (three) months period.
13.4 Any waiver shall be made in writing for it to be effective and unless
expressly stated shall not be a continuing waiver not shall it prevent
the waiving party from acting upon that or any subsequent breach or from
enforcing any term or condition of this Agreement.
13.5 The invalidity of any provision of this Agreement shall not affect the
validity of any other provision hereof. The parties undertake to replace
any invalid provision in the Agreement with another provision which
reflects legally the originally intended commercial objectives of the
parties as closely as possible.
13.6 This Agreement shall be governed exclusively by [...***...] law. In the
event of any controversy or claim arising out of or relating to any
provision of this Agreement, the parties shall first try to settle those
conflicts amicably between themselves. All disputes arising in
connection with this Agreement, which cannot be settled amicably, shall
be litigated in the [...***...], provided any lawsuit shall be filed in
the Federal Courts and the parties hereby consent to waive any
Constitutional, Statutory or Common Law of trial by Jury.
13.7 In the performance of this Agreement each party shall be an independent
contractor, and therefore, no party shall be entitled to any benefits
applicable to any employee of the other party. No party is authorized to
act as an agent for the other party for any purpose, and no party shall
enter into any contract, warranty or representation as to any matter on
behalf of the other party.
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IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be executed
in duplicate by their duly authorized representatives.
Ingelheim, Germany San Diego, California
BOEHRINGER INGELHEIM GENETRONICS, INC.
INTERNATIONAL GMBH
ppa.
/s/ Prof. Xx. Xxxxx Xxxxxx Xx. Xxxxxxxxx Xxxxx /s/ Xxxxxx Xxxx 10/27/99
------------------------------------------------ -------------------------
11/02/99
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APPENDIX 1
RESEARCH PLAN
BI AUSTRIA- GENETRONICS DNA VACCINE DELIVERY PROJECT
GOAL:
The goal of this project is to determine parameters of DNA delivery by
electroporation which will yield an optimal immune response against tumor cells.
BACKGROUND/ASSUMPTIONS:
Three important factors of DNA vaccination include the design of the DNA
construct, the choice of the target tissue and the mode of DNA delivery. The
immune response will greatly depend on each one of these factors.
This project outline will focus on the [...***...] as the target tissue and
electrical pulses as the means of DNA delivery. In addition, [...***...] will be
investigated.
By designing appropriate conditions, we expect that DNA delivery into the
[...***...] by electroporation will allow, at least to some extent, us to
control DNA delivery into a certain [...***...]. This will determine the types
of cells which will receive the DNA vaccine. We also expect to be able to
control, within limits, the percentage of cells which will be transfected. These
parameters will indirectly influence the level and time course of antigen
expression, secretion and interstitial or systemic distribution. It is also
conceivable that a second series of electroporation pulses to antigen-producing
cells will substantially influence the immune response by facilitating antigen
dissemination from these cells.
Presently, the two main methods for DNA delivery are (1) direct needle injection
of a DNA solution into skin or muscle and (2) shooting DNA-coated particles into
the skin with a "gene gun." Direct needle injection into the skin or muscle is
effective to some extent in eliciting immune responses in various mammals,
including humans. However, large quantities of DNA are required and it remains
to be seen whether this approach will meet safety and economic requirements for
routine use.
Administering DNA precipitated on the surface of microscopic gold particles via
"gene gun" technology results in direct delivery of DNA into skin cells. The
amount of DNA required in
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this method is relatively small but mass production of the coated particles and
a safe, consistently effective delivery gun are still formidable obstacles to
overcome.
Genetronics has demonstrated that electrical pulses can be used to deliver DNA
in solution into cells of living tissue, including [...***...]. Genetronics'
technology can also deliver particles which could be coated or loaded with DNA
into [...***...]. The proposed research aims at determining the feasibility of
inducing a therapeutically or prophylactically effective immune response by
electroporation-mediated DNA delivery into [...***...].
During this project the following questions will be addressed:
1. What are the optimal electrode designs and pulse conditions for
introducing DNA vaccines into tissue?
2. How does the Genetronics delivery technology compare to other methods in
the resulting immune response? What are the advantages for vaccine
delivery by Genetronics' technology? (e.g., [...***...])
3. What adjuvants and/or co-factors are suitable and appropriate for
modulation of resulting immune responses and can they be delivered
together with DNA?
4. Does the Genetronics delivery of vaccines elicit immune responses in
large animals?
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EXPERIMENTAL OUTLINE
Research phase (18 months)
The proposed program is open to modifications upon mutual written agreement.
Genetronics will provide the following equipment to BII ("Equipment"):
(i) one (1) 830 Electroporation System;
(ii) one (1) auto switcher and one (1) manual switcher;
(iii) various 2 needle arrays and various 6 needle arrays;
(iv) various flat (surface) electrodes (meander, micropatch); and
(v) any composition of matter provided to BII by or on behalf of
Genetronics for performance of the Research Program
1. GENE EXPRESSION PROFILE IN MOUSE [...***...]
Determine DNA delivery parameters to achieve optimal antigen expression in mouse
[...***...]
Test [...***...] DNA and two different BI formulations in mice Administration:
[...***...]
Determine gene expression profile: [...***...]
Electrode design: Meander or other non-invasive electrode
Needle array
Novel needle array
Other
Pulse design: Pulse (wave) form
Polarity
Current
Field strength and field homogeneity
Pulse length
Number and frequency of pulses
Homogeneous or heterogeneous pulses
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If delivery through [...***...] is ineffective, [...***...]
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2. CHARACTERIZE IMMUNE RESPONSES AFTER IN VIVO ELECTROPORATION
Genes/Models:
Genetronics will work on: [...***...]
BI Austria will work on: [...***...]
2.1. Humoral immune responses in mice
Dose response
Effect of booster immunisation
Isotype profile of specific antibodies after electroporation
Longevity of response
2.2. Cellular immune responses
[...***...]
2.3. Efficacy in mouse models
[...***...]
3. STUDIES TO MODIFY THE TYPE OF IMMUNE RESPONSE
[...***...]
4. GENE EXPRESSION PROFILE IN PIG SKIN
Short term parameter study in pigs, similar to 1., using best devices and
protocols
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WORK PACKAGES (OVERVIEW)
0 6 9 18 months
[...***...]
[...***...]
[...***...]
[...***...]
[...***...]
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APPENDIX 2
LICENSE TERMS
1. DEFINITIONS
The definitions set forth in Clause 1 of the Research and Option
Agreement and Clause 13.1 are incorporated herein by reference and shall
control, unless the text in this Appendix clearly indicates to the
contrary.
2. CERTAIN RIGHTS GRANTED TO BII UPON BII'S EXERCISE OF OPTION TO NEGOTIATE
AND ENTER INTO A DEVELOPMENT AND LICENSE AGREEMENT AND THE EXECUTION OF
SUCH AN AGREEMENT
(i) Non-Exclusive License to Genetronics Core Technology.
Genetronics shall grant BII a non-exclusive, royalty-bearing
license in the Territory to Genetronics Core Technology necessary
to develop, make, use, sell, offer to sell, and import
Product-Kits for use in the Field.
(ii) Exclusive License to Genetronics New Technology.
Genetronics shall grant BII an exclusive, royalty-bearing license
in the Territory to Genetronics New Technology necessary to
develop, make, use, sell, offer to sell, and import Product-Kits
for use in the Field.
(iii) In case of early termination of the license agreement because of
Genetronics bankruptcy or material breach of contract by
Genetronics, BII shall have a fully paid up right to manufacture,
or have manufactured, the disposable delivery devices (e.g.,
electrodes) for use in the Field and Genetronics will supply to
BII all Know How and technical assistance necessary to exercise
such manufacturing right.
(iv) All rights granted to BII under a development and license
agreement shall include the right to sublicense such rights to an
Affiliate. BII shall remain responsible to Genetronics for any
acts, sales, and obligations of a
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sublicensee as if they were made by BII.
(v) This Agreement shall expire and the licenses granted by
Genetronics to BII shall become fully paid on a
country-by-country basis upon the last to occur of (i) expiration
of all valid claims on Genetronics Technology in each such
country or (ii) ten (10) years from the first commercial sale of
a Product-Kit in each such country.
3. CONSIDERATION
(i) Milestone payments:
[...***...]
(ii) Royalties for Product-Kits governed by non-exclusive licenses to
Genetronics Core Technology:
[...***...] on Net Sales; the price paid by BII for any components purchased
from Genetronics that are incorporated into the Product-Kit shall be subtracted
from the amount of Net Sales before calculating any royalties.
The [...***...] royalty rate for each Product-Kit shall be diminished by
[...***...] for each additional delivery-related license BII obtains for that
Product-Kit and by [...***...] for the first license BII obtains for a BII
Product within that Product-Kit and by [...***...] for the second and each
additional license BII obtains for a BII Product that constitutes part of that
Product-Kit. Each such decrease in royalty rate shall be made only if BII is
obligated to pay a royalty to the respective third party licensor that is
[...***...] the rate of the decrease contemplated by this Clause 3 (ii). By way
of example, in the event BII is obligated to pay a royalty for a
delivery-related license for a BII Product that is at least [...***...] of Net
Sales, then the present [...***...] royalty shall be decreased by [...***...].
Alternatively, in the event BII is obligated to pay a royalty for a
delivery-related license for a BII Product that is less than [...***...] of Net
Sales, then the present [...***...] royalty shall not be decreased by
[...***...] in recognition of that third party license. In no case shall the
royalty rate paid to Genetronics under a non-exclusive license be
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less than [...***...].
(iii) Transfer price of disposable delivery device (e.g., electrodes)
for a Product-Kit:
The purchase price BII shall pay Genetronics for the single use
disposable delivery device which is presently envisioned to be a
component of a Product-Kit shall be the higher of (i)[...***...]
for each single use disposable delivery device suitable for one
vaccination (one "shot") per person, or (ii) a price [...***...]
in excess of Genetronics manufacturing costs for such device,
(allowing a [...***...] gross profit) but, in the event
[...***...] of the weighted average retail price of the
respective Product-Kit is greater than the higher of (i) or (ii),
the purchase price for the single use disposable delivery device
shall not exceed [...***...] of the weighted average retail price
of the respective Product-Kit. The [...***...] upper cap may be
revised by mutual written agreement of the parties depending on
the progress in Product-Kit development and projected market
conditions. BII will use, and will require its sublicensees to
use, Genetronics disposables exclusively. In all cases
Genetronics will use best efforts to provide BII with the
economically best transfer price.
(iv) Marketing of pulse generators:
Pulse generators shall be developed and tested in consultation
with BII and manufactured, distributed and serviced by
Genetronics or its Affiliates. BII shall require the exclusive
use of Genetronics pulse generators with Genetronics'
disposables. Pricing of pulse generators shall be the sole
responsibility of Genetronics; however, input from BII market
research will be welcomed in reaching a pricing decision.
(v) By virtue of the Agreement, Genetronics shall not acquire any
ownership in future inventions or intellectual property rights to
any of BII's existing or future intellectual property regarding
gene transfer systems, except for such future inventions and/or
intellectual property rights that fall under Genetronics Core
Technology as defined in Clause 1.16 of the Research and Option
Agreement.
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