Contract
EXHIBIT 10.23
Contents
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Section
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Content
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Page
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1.
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Interpretation
and Definitions
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2
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2.
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The
License
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5
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3.
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Term
of the License
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5
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4.
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Sub-Licenses
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5
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5.
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Considerations
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6
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6.
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Reports
and Accounting
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7
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7.
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Development
and Commercialization
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8
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8.
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Ownership
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9
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9.
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Patents
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9
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10.
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Patent
Rights Protection
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10
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11.
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Confidentiality
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11
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12.
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Publications
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11
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13.
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Liability
and Indemnity
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12
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14.
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Termination
of the Agreement
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13
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15.
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Law
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14
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16.
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Arbitration
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14
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17.
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Miscellaneous
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15
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18.
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Notices
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16
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Appendices
Appendix
A – The Registered Patents and the Scope
Appendix
B – License Fee
Appendix
C - Consultancy Agreements
Appendix
D - Consultancy Fee Payment Schedule
Appendix
E - The Development Plan
Appendix
F – Exercise Notice
Appendix
G – Explanation of the Company’s Expected Investment Rounds
Appendix
H – Consultancy Fees
AGREEMENT
Made in
Jerusalem this 23rd day of
November, 2005, by and between:
YISSUM RESEARCH DEVELOPMENT COMPANY
OF THE HEBREW UNIVERSITY OF JERUSALEM, of Hi Tech Park, Xxxxxx X. Xxxxx
Xxxxxx, Xxxxx Xxx, Xxxxxxxxx 00000, Israel, Fax: x000-0-000 6689; email: __________________ (the “Licensor”) of the one part; and
Medgenics, Inc., of Shorashim D.N. Xxxxxx 00000
Xxxxxx
fax: 00-
000-0000, email: xxxx@xxxxxxxxx.xxx Attention: Xx. Xxxxxx Xxxxxxxx (the “Company”);
of the second part
Recitals:
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WHEREAS
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The
Parties entered into a Research and License agreement, which is no longer
in force, whereby, inter
alia, the Company obtained a license from Licensor for the
commercial development, production and marketing of products based on the
technology owned by the Licensor (hereinafter: the “Former License”) and pursuant to which the
Licensor performed Research between the dates of August 1, 2000 and May
31, 2001; and
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WHEREAS
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The
Parties wish to enter into a new License Agreement in respect of the
Registered Patents, this wish having been set out in the Memorandum of
Understanding entered into between the Parties and dated May 23, 2005;
and
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WHEREAS
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This
Agreement shall replace the Former License which shall be considered null
and void, including those provisions of the Former License that according
to the terms of the Former License survive termination thereof;
and
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WHEREAS
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The
Company declares that as stated in the Exercise Notice (attached hereto as
Appendix F), it has reviewed the Registered Patents that it has had the
opportunity to acquire independent advice as to the Registered Patents,
their protection, validity and coverage in specific geographical areas and
that it is satisfied with the information and data it
received.
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WHEREAS
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The
Licensor hereby agrees to grant the Company a license with respect to the
Registered Patents, in accordance with the terms and conditions of this
Agreement and subject to the full performance by the Company of its
obligations in accordance with this Agreement;
and
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NOW THEREFORE THE PARTIES DO HEREBY
AGREE AS FOLLOWS:
Interpretation
and Definitions
| 1. |
(a)
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The
recitals and appendixes annexed hereto constitute an integral part hereof
and shall be read jointly with its terms and
provisions.
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(b)
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In
this Agreement, unless otherwise required or indicated by the context, the
singular shall include the plural and vice-versa, the masculine gender
shall include all other
genders.
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(c)
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The
headings to the sections in this agreement are for the sake of convenience
only and shall not serve in the Agreement’s
interpretation.
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Page 2 of
24
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(d)
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In
this agreement the following capitalized terms shall have the meanings
appearing alongside them, unless provided otherwise
herein:
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“Affiliate” – means a Related Entity in which the
percentage of control is more than 75%.
“Agreement” – means this agreement together with all the
appendices and annexes hereto.
“Development Plan” – As defined in section 7.
“Development
Results” – means the Development
Plan, any information, material, results, devices, know-how, data, which does
not form part of the License or Further Research, discovered in the course of
performance by the Company of the development work pursuant to section 7,
including any regulatory filing or approval, filed or obtained by the Company in
relation to the Product.
“Distributor” – means any distributor or marketer who
engages, inter alia, in any one of the following activities: makes any payment
to the Company which is not considered as Net Sales; undertakes to advertise the
Product at its own expense; undertakes to obtain relevant authorities’ approval
for the sale of the Product and is liable for costs incurred in gaining such
approval.
“First Commercial
Sale” – means the selling of an
aggregated amount of the Product by the Company and/or by a Sub-Licensee or
sub-sub-licensee in a single transaction or a series of related transactions
with a third party whom is not a Related Entity, which commences an ongoing
stream of sales subject to payment of Royalties. For the avoidance of doubt
sales of the product for the purposes of clinical trials prior to the First
Commercial Sale shall not entitle the Licensor to payment of consideration in
accordance with this Agreement and shall not be considered a First Commercial
Sale.
“Scope” – as defined in Appendix A.
“Indemnitees” – as defined in Section 13
“License” – as defined in Section 2 herein.
“Net Sales” - means all amounts in respect whereof invoices
are issued by the Company, a Related Entity, and/or Distributors in connection
with the sale of Products in an “arm’s length” transaction, after deduction of:
(i) all discounts and returns given in respect of such sales; and (ii) sales
taxes, including VAT. Such deductions shall be directly related to the sale of
Products that were awarded within the regular running of the business of the
Company and made at “arms length”. For the sake of clarity, any payment or
rebate received by the Company from any governmental agency directly in relation
to sales shall be considered as Net Sales.
Sales at
discounts between Related Entities and/or where the parties share a significant
trading interest – such as preferred customers or suppliers – shall not be
considered “arm’s length” transactions. In any transfers of Products between the
Company and Related Entities and Related Entities and their respective Related
Entities, Net Sales shall be equal to the higher of (i) fair market value of the
Products assuming an arm’s length transaction made in the ordinary course of
business and (ii) the total amount invoiced by such Related Entity on resale to
an independent third party purchaser; in each case after deducting discounts and
sales taxes as set forth above.
In the
event of sales not made at “arms length”, Net Sales shall be calculated in
accordance with arm’s length prices determined by the current market conditions,
or in the absence of such conditions, according to the assessment of an
independent valuer to be selected by the parties.
Page 3 of
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“Product” - means any product and/or product component
and/or production supplement and/or process directly and/or indirectly based on
and/or related to the Registered Patents and/or the Development Results or any
part thereof, or any other product not licensed from a third party, which is
sold by the Company within the Scope.
“Registered
Patents” - means all patent
applications and/or registered patents detailed in Appendix A (except for Yissum
File No. 2610, which Licensor agreed to assign to Company), any patent
application that claims priority therefrom; all divisions, continuations,
continuations-in-part, re-examinations, reissues, substitutions, or extensions –
including European Special Protection Certificates (“SPCs”) – and any and all
patents issuing from, and inventions, methods, processes, and other patentable
subject matter disclosed or claimed in, any and all of the
foregoing.
“Related Entity” – means any person or organization controlling,
controlled by or under common control with the Company, including any parent,
subsidiary or affiliate company. The term “control” shall mean direct or
indirect ownership of more than 10% (ten percent) of the outstanding stock or
other voting interest, entitled to vote for the election of directors or to
direct the management and policies of any party, directly or
indirectly.
“Research” - means the research related to the Registered
Patents carried out and conducted in the University under the supervision of the
Researchers between August 1, 2000 and May 31, 2001.
“Researcher” - means Xxxxxxxxx Xx Xxxxxxx and Xxxxxxxxx Xxxx
Panet, or such other person as determined and appointed from time to time by the
Licensor to supervise and to perform the Research, if applicable.
“Research Results” - means the Research, including any Registered
Patents, information, material, results, devices and/or Registered Patents
arising therefrom.
“Royalties” – means royalties calculated on the basis of
Net Sales at the rate set forth in Section 5.
“Sub-License” - As defined in section 4.
“Sub-License
Considerations” – means any proceeds
and/or consideration and/or benefit of any kind whatsoever that the Company may
receive from a Sub-Licensee or distributor as a direct or indirect result of the
grant of an option or a right to sub-license, manufacture, market or distribute
the Registered Patents and/or the Product.
“Sub-License Fees” - means fees calculated on the basis of
Sub-License Considerations at the rates set forth in Section 5.
“Sub-Licensee” – means any third party to whom the Company
shall transfer any right or option of a right to sub-license, manufacture,
market or distribute the Registered Patents and/or the Product, or any other
right granted under the License. For the sake of clarity, Sublicensee shall
include sub-sub-licensees, if permitted hereunder, and any other third party to
whom such rights shall be transferred, assigned, or who may assume control
thereof by operation of law or otherwise, but shall not include Subcontractors
(as defined below). Sublicensees shall also include Distributors, as defined
hereinabove.
“Subcontractors” - means any third party, who does not pay any
type of consideration to the Company and/or Related Entities and/or
Sub-licensees, who is engaged by the Company, to perform services on behalf of
the Company and/or its Sub-licensee or and/or sub-sub-licensee and the Company
continues to maintain control and responsibility over the performance of the
services.
“Territory” - means worldwide.
“University” - means the Hebrew University of Jerusalem
and/or each of its branches.
Page 4 of
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The
License
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2.
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Subject
to the full performance by the Company of its obligations in accordance
with this Agreement, the Licensor shall grant the Company an exclusive
license to make commercial use of the Registered Patents, in order to
develop, manufacture and/or market a Product, all within the Scope and the
Territory only, subject to the terms and conditions
hereof.
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Nothing
in the above License shall derogate from the Licensor’s right to continue to use
the Registered Patents, for non-commercial, academic (research and education)
purposes only.
Term of
the License
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3.
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The
License shall end, if not ended or terminated prior thereto pursuant to
the provisions hereof, upon the later of: (i) the date of expiration of
the last valid Registered Patent, in the Territory, upon which the Product
is partially based; or (ii) the end of a period of 20 years from the date
of making the First Commercial
Sale.
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Sub-Licenses
| 4. |
(a)
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The
Company shall be entitled to sub-license the rights granted in the
License, or any part thereof, (herein referred to as “Sub-License”) to
third parties after obtaining Licensors written approval to the identity
of the intended sub-licensee (the “Sublicensee”) and the Licensor’s
consent to all the material terms and conditions of the Sublicense, which
shall not be unreasonably withheld. The Sublicense shall not derogate from
Yissum’s rights or Licensee’s obligations under this Agreement. The
Licensor shall make best efforts to provide the Licensee with an answer in
relation to the Sublicense no later than 30 days from the date of receipt
of the request by the Licensee. The Company hereby warrants that all
Sub-Licenses shall be granted at “arms-length”
terms.
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(b)
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The
Company shall fully disclose and submit to the Licensor all documentation
relating directly and indirectly to the Sub-License, and adequately
disclose to the Licensor any other business connection which it now has or
is in the process of forming with the Sub-Licensee which may reasonably
effect the Company’s decision regarding the Sub-Licenses’ Terms and
Conditions; and shall notify the Licensor in writing, whether a proposed
Sub-Licensee is a Related Entity and/or
Affiliate.
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(c)
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Subject
to subsection (g), any Sub-License shall be dependent on the validity of
the License and shall terminate in whole or in part upon termination of
the License or any part thereof.
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(d)
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Subject
to subsection (g), the Company shall ensure that all Sublicense agreements
shall include terms that bind the Sub-Licensee to observe the terms of
this Agreement, the breach of which shall be a fundamental breach
resulting in the prompt termination of the Sub-License. In such an event,
the Company undertakes to take all reasonable steps to enforce such terms
upon the Sub-Licensee, including the termination of the Sub-license. In
all cases, the Company shall immediately notify the Licensor of any breach
of the terms of a Sub-License, and shall copy the Licensor on all
correspondence with regard thereto.
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(e)
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Any
act or omission of the Sub-Licensee which is not promptly remedied by the
Company or the Sub-Licensee and which would have constituted a breach of
this Agreement by the Company had it been an act or omission of the
Company, and which the Company has not made best efforts to promptly cure,
including termination of the sublicense, shall constitute a breach of this
Agreement by the Company.
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(f)
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For
the avoidance of any doubt it is hereby declared that under no
circumstance whatsoever shall a Sub-Licensee be entitled to grant the
Sub-License or any part thereof to any third party without the prior
consent of both the Company and the Licensor, not to be unreasonably
withheld.
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Page 5 of
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(g)
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Notwithstanding
anything to the contrary set forth herein, if the License is lawfully
terminated by Licensor in accordance with the provisions hereof, Yissum
agrees, if so requested by a Sub-Licensee within 30 days from date of
termination of the License, to grant to such a Sublicensee (other than
Related Entities of the Company) a direct license under the same terms and
conditions of this Agreement, provided that such Sublicensee (1) agrees to
be bound to Yissum under the same terms and conditions of this Agreement,
including to render direct payment to Licensor of any consideration that
would have been payable to Licensor by Licensee (such direct license with
a Sublicensee shall not impose any obligations or liabilities on Yissum
which are not included in this Agreement or which are in any way more
onerous than those included in this Agreement); (ii) Sub-License pays to
Yissum any amount due and owing under this Agreement at time of
termination that has not been paid by the Company;, and (iii) the
Sublicensee is not in breach of its Sub-License Agreement with the
Company. In such instance, such Sub-licensee shall become obligated
directly towards Licensor on all terms set forth in such Sub-License
Agreement.
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Considerations
| 5. |
(a)
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In
consideration for the grant of the License, the Company shall pay the
Licensor the following
considerations:
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(a)
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a
non-refundable License Fee to be paid as detailed in Appendix
B.
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(b)
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Royalties
at a rate of 5% of Net Sales of the Product.
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(c)
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Sub-License
Fees at a rate of 9% of Sublicense
Considerations.
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Notwithstanding
sub-sections (b) and (c) above, the total aggregate payment of Royalties and
Sub-License Fees from the Company to Licensor shall not exceed US
$10,000,000.
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(b)
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The
Company acknowledges that pursuant to the Former License, it owes the
Licensor certain License Fees as well as accumulated patent expenses with
respect to the Registered Patents up to May 23, 2005, the date of
execution of the Memorandum of Understanding , in the total amount of
$128,000 (hereinafter: “License and Patent Fees Debt”).
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No later
than March 31, 2006, the Company shall issue the Licensor shares in the company
constituting 5% of the issued and outstanding share capital of the Company, post
the initial expected investment in the Company of $750,000 USD (“Initial
Investment Round”), all as set forth in the Appendix G for no additional
consideration (hereinafter: the “Equity”), the Company shall forgive the
payment of the outstanding License and Patent Fees Debt. The Company warrants
that the Licensor and the Licensor’s Equity shall benefit from the same terms
provided to the other shareholders in the Company, who shall be investing in the
Company in the Initial Investment Round and that shares issued to the Licensor
shall be of the same type and class as shares issued to the other shareholders
investing in the Initial Investment Round, all as shall be defined and detailed
in the Stock Purchase Agreement and the Shareholders Agreement to which the
Licensor shall be signatory. The Company shall provide the Licensor with all
relevant documentation evidencing such issue, including but not limited to a
share certificate in the name of the Licensor.
Upon the
issuance of the Equity and provision of documentation in respect of same as set
forth herein, the License and Patent Fees Debt shall be deemed to be paid in
full and the Licensor to have waived any claim in respect thereof. In the event
the Company shall not be able to issue the Equity by March 31, 2006, the Company
shall be obligated to pay the Licensor the License and Patent Fees Debt plus all
accrued interest until date of actual payment or in the alternative the Licensor
shall be entitled to terminate this Agreement in accordance with section
14(b)(3).
Page 6 of
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For the
sake of clarity, all new patent expenses incurred in relation to the
registration or maintenance of the Registered Patents as of May 23, 2005, the
date of execution of the Memorandum of Understanding and until date of execution
of this Agreement, will be paid by the Company, as follows: (i) $10,000 USD no
later than January 31, 2006 upon receipt of Yissum’s invoice and (ii) the
remaining balance within 10 days following the closing of the Initial Investment
Round, but in any event no later than March 31, 2005.
It is
further hereby agreed that upon the date of signature hereof, the Licensor shall
be entitled to appoint an observer (hereinafter: the “Observer”), at its sole discretion, to the
Board of the Company, for a period of three years. The Observer shall be invited
to attend the Board of the Company, at no expense to the Company, all meetings
of the Board of Directors of the Company, and shall receive copies of all
reports distributed to members of the Board of Directors. The Observer shall not
have any voting rights. The Company hereby undertakes to take any actions or
issue any decisions necessary to enable the appointment of the Observer, in
accordance with the terms herein, including but not limited to amendment of the
incorporation documents of the Company.
Reports
and Accounting
| 6. |
(a)
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The
Company shall give the Licensor written notice of the First Commercial
Sale or Sub-License, of the Product by itself or by any Sub-Licensee
within 30 days thereof. This provision is a fundamental term of the
Agreement. The breach thereof shall constitute a fundamental breach of the
Agreement, and the Licensor, at its sole discretion, shall have the right
to terminate the Agreement immediately under terms and conditions as
stated in section 14.
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(b)
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Thirty
days after the end of each calendar quarter (January 1, April 1, etc.)
commencing from the date of the First Commercial Sale of the Product, the
Company shall furnish the Licensor with a quarterly report (“Periodic
Report”) detailing the total sales effected and Sublicense Consideration
received during the preceding quarter and the total Royalties and
Sublicense Fees due to the Licensor in respect of that
period.
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(b)
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The
Periodic Reports shall contain full particulars of all sales made by the
Company and/or Sub-Licensees and all of the proceeds obtained by the
Company in respect of granting Sub-Licenses pursuant to section 5 above,
including sales broken down according to countries, a breakdown of the
number of Products sold, discounts, returns, the currency in which the
sales were made, invoice date and all other data enabling the Royalties
and Sub-License Fees payable to be calculated. The Periodic Reports shall
also specify any Net Sale to a Related Entity and shall set forth full
details thereof.
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(c)
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On
the date prescribed for the submission of each Periodic Report, the
Company shall pay the Royalties and Sub-License Fees due to the Licensor
for the period reported on.
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(d)
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The
value of each sale shall be computed on the date of sale in US Dollars
based on the rates published in the Wall Street Journal. The Royalties
shall be computed and paid in US dollars. Payment of Value Added Tax (if
charged) shall be added to each payment in accordance with the statutory
rate in force at such time. In event that the Company is prohibited under
applicable foreign currency laws to transact in US Dollars, payment shall
be made in New Israeli shekels according to the representative rate of
exchange prevailing on the date of
payment.
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Page 7 of
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(e)
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The
Company shall keep full and correct books of accounts in accordance with
General Accepted Accounting Procedures as required by international
accounting standards enabling the Royalties and Sub-License Fees to be
calculated. The Company shall procure that Sub-Licensees, if any, also
keep such books of accounts as aforesaid. The CEO of the Company shall
certify in writing that all the particulars mentioned in each Periodic
Report are correct and accurate. Starting from the date of the First
Commercial Sale, or the date a Sub-License is granted, whichever occurs
first an annual report, authorized by a certified public accountant, shall
be submitted at the end of each year, detailing Net Sales and Sub-License
Considerations, Royalties and Sub-License Fees, both due and paid (the
“Annual Reports”).
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(f)
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Upon
reasonable notice, the Licensor and its authorized representatives may
examine the Company’s and Sub-Licensees’ books of accounts and any report
or information relating to the manufacture and marketing of the Product in
order to verify the calculation of the Royalties and Sub-License Fees and
the accuracy of the information given to The Licensor in the Period and
Annual Reports. If an error greater than 2% in the reports of the Company
will be found the Company will bear the full cost of the
examination.
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(g)
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Any
sum of money due to the Licensor which is not duly paid shall bear
interest from the due date of payment until the actual date of payment at
the maximum rate of interest for the time-being prevailing in respect of
unauthorized withdrawals on a credit line at Bank Leumi Le-Israel
Ltd.
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(h)
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All
payments required to be made in accordance with the provisions of this
Agreement shall be made with the addition of any taxes assessable upon the
Licensor (excluding income taxes) such that all payments shall be free and
clear of any taxes or withholding of any
kind.
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Development
and Commercialization
| 7. |
(a)
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The
Company undertakes, at its own expense, to carry out the development
(including clinical trials) and manufacturing work (including regulatory
approval) necessary to develop the Product in accordance with the written
plan and timetable for the development of the Product (herein “Development
Plan”) as approved by the Company’s Board of Directors and updated from
time to time, a copy of which is attached hereto as Appendix
E.
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(b)
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The
Company shall provide the Licensor on no less frequent basis than twice
per year, with the same reports, which have been submitted to the
Company’s Board of Directors, and which shall detail the material
Development Results and other related work effected by the Company or by
any Sub-Licensee during the period since the previous such report
(“Development Reports”). Development Reports shall also set forth a
general assessment regarding the status of the development of the Product
and the marketing thereof and detail all material proposed changes to the
Development Plan.
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(c)
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Upon
completion of the development of the Product, the Company undertakes to
perform all actions necessary to seek effective commercialization in terms
of strategic partnerships, alliances or other corporate deals, as well as
maximize Net Sales.
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(d)
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The
Licensor shall first offer the Company the opportunity to fund any further
research by the Researchers regarding the Registered Patents in the Scope
(“Further Research”), upon terms to be negotiated between the parties in
good faith, before allowing any other third party to fund the Further
Research. If the Company does fund the Further Research, then any Further
Research Results or other intellectual property deriving therefrom shall
belong to the Licensor and shall be licensed to the Company under the same
terms and conditions set forth herein. If the Company does not positively
indicate its desire to fund the Further Research within sixty (60)
calendar days of being offered same, and agree upon terms with Yissum
within sixty (60) calendar days thereafter, Yissum shall be free to
contract with a third party for the funding of such Further Research.
Ownership.
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Page 8 of
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8.
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Ownership
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8.
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Except
for Yissum File No. 2610 in Appendix A, all rights in the Registered
Patents listed in Appendix A, shall be solely owned by the Licensor, and
the Company shall hold the rights granted pursuant to the License as
trustee for the Licensor and make use of them solely in accordance with
the terms of this Agreement.
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In
addition, all intellectual property, including all know-how and/or patents
developed during the course of the Further Research, conducted in accordance
with section 7(d), shall solely owned by Yissum and licensed to the Company
under the terms and conditions of this Agreement.
The
Parties agree that the Development Results (as defined above) developed solely
by or on behalf of the Company, without the involvement of the Licensor and/or
Xxxx. Xxxxxxx and/or Prof. Panet or other researcher of the Hebrew University,
and which do not form part of the License or Further Research shall belong
solely to the Company.
The
Company is free at its sole discretion to prepare, file, and otherwise manage
any patents related to the Development Results, without any approval or
involvement of the Licensor, and for such patents sections 9 (a) – (e) below do
not apply.
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9.
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Patents
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| 9. |
(a)
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With
regard to the Registered Patents or any Further Research, the Licensor,
following consultation with the Company, shall proceed in registering
patents in all the states and countries of the Territory, at the Company’s
expense. Each application and every patent registration as aforesaid shall
be made by the Licensor and registered in the name of the Licensor at the
Company’s expense. The Company shall reimburse the Licensor for all
documented costs and expenses the Licensor shall incur with regard to the
aforesaid application, registrations and maintenance and for all future
documented costs and expenses the Licensor shall incur with regard to the
aforesaid application, registrations and maintenance of the Registered
Patents or any patents resulting from the Further Research within 21 days
of invoice by the Licensor.
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(b)
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Subject
to the above, the parties shall consult and make every effort to reach
agreement in all respects relating to the manner of making applications
and registering said Registered Patents and other patents that may arise
from the Further Research, including the time of making the applications,
the countries where applications will be made and all other particulars
relating to patent registration as
aforesaid.
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(c)
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In
regard to the above, in the event that the Company is not willing to fund
the registering or maintenance of a patent in a certain state or country,
solely on the basis of reasonable commercial considerations to be provided
in writing by the Company to the Licensor, the Company will not be
required to reimburse the Licensor for expenses relating to the
registration and maintenance of the patent in such state or country.
However, thereafter and notwithstanding the terms of this Agreement, in
the event that the Licensor effects the application and/or registration of
a patent in the said state or country at its own cost, the License with
respect to such state or country shall revert back to the Licensor and the
Licensor shall be free to sub-license such rights to any other third
party, at its discretion.
|
|
|
(d)
|
The
aforegoing does not constitute an obligation on the part of the Licensor
that any patent or patent registration applications will indeed be made
and/or registered and/or registerable in respect of the Further Research
and/or any part thereof, nor shall such constitute an obligation,
warranty, or declaration on the part of the Licensor that a patent
registered as aforesaid will afford due
protection.
|
Page 9 of
24
For the
avoidance of doubt, the provisions of this Agreement and of Appendix “A” do not
constitute confirmation and/or representation by the Licensor in connection with
the validity and/or applicability of any of the patents and/or patent
registration applications detailed in Appendix “A”, and the Licensor hereby
expresses that it made no representation as to the validity of the patents
and/or patent applications as aforesaid before the submission thereof for
registration. The Company affirms that it has reviewed the Registered Patents,
that it has had the opportunity to acquire independent advice as to Registered
Patents, including their protection, validity and coverage in specific
geographical areas and that it is satisfied with the information and data it
received.
|
|
(e)
|
The
Parties shall assist each other in all respects relating to the
preparation of documents for the registration of any patent or any
patent-related right forthwith upon the other’s request. Towards this end,
the Licensor shall promptly notify the Company regarding any application,
documentation, communication and/or “office action” received or required
to be filed relating to any Registered Patent. In addition, the Company
undertakes to take all appropriate action in order to assist the Licensor
to extend the period of the duration of the patent or any other extension,
granted by the law, to enable maximum extension of the time in which the
Registered Patents are protected.
|
Patent
Rights Protection
| 10. |
(a)
|
To
the extent commercially reasonable as mutually agreed between the Parties,
the Company undertakes to act forthwith at its own expense to provide full
protection against a third party’s infringement of the Registered Patents,
in connection to the Scope, and/or any other right therein and forthwith
to advise the Licensor upon learning of the infringement. The Company
shall give the Licensor immediate notice of any approach made to it by a
patent examiner and/or attorney in connection with the subject matter of
this Agreement. The Company shall only reply to such approaches after
consultation with the Licensor and subject to its consent. In the event
the Parties mutually agree as to the lack of commercially reasonable
grounds to commence infringement proceedings, the Licensor shall be free
to take said legal action, at its sole expense. In such an event the
Licensor shall be entitled to the entire award, which may be granted as a
result of such legal action.
|
|
|
(b)
|
The
Company shall use its best efforts at its own expense to defend any
action, claim or demand made by any entity in connection with rights in
the Registered Patents, in connection to the Scope, and shall give notice
to the Licensor immediately upon learning of any such action, claim or
demand as aforesaid. Notwithstanding the aforementioned, nothing in this
Section 10(b) requires the Company so defend, should both Parties
determine, that there are valid commercial or other reasons not to do so,
in which the Licensor shall be free to take said action. In such an event
the Licensor shall be entitled to the entire award, which may be granted
as a result of such legal action.
|
|
|
(c)
|
Subject
to reimbursement of documented and reasonable out-of-pocket expenses
incurred by the Company in relation to any legal action contemplated under
the provisions of sub-sections (a) and (b) above and initiated by the
Company, any award in favor of the Licensor and/or the Company resulting
from such legal action shall be deemed to be a fee received by the Company
from a Sub-Licensee.
|
Page 10
of 24
Confidentiality
| 11. |
(a)
|
The
Company warrants and undertakes that it shall maintain full and absolute
confidentiality and shall also be liable for its employees and/or
representatives and/or persons acting on its behalf
maintaining absolute confidentiality concerning, confidential information
which is in and/or comes to its knowledge and/or that of its employees,
representatives and/or any person acting on its behalf directly or
indirectly, and relating to the Registered Patents, the Licensor, the
University, the Researchers and their employees. For confidential
information received up to the date of signature of this Agreement, said
undertaking shall apply for 5 years from date of signature of this
Agreement, and for confidential information received after signature of
Agreement said undertaking shall apply for the duration of the term of
this Agreement and subsequent thereto. The Company undertakes not to
convey or disclose said confidential information in connection with the
aforegoing to any entity unless said entity executes a confidential
disclosure agreement with the Company having terms similar in content to
this section. Notwithstanding the above, the Parties acknowledge that as
of the date of this Agreement,, there is no confidential information
pertaining or belonging to Licensor or its employees that is subject to
the terms of this
Agreement.
|
|
(b)
|
The
obligation contained in this section shall not apply to information which
is in the public domain as at the date hereof or to information which
hereafter comes into the public domain, unless the Company breaches its
obligations pursuant to this Agreement and as a result thereof the
information comes into the public
domain.
|
|
(c)
|
Notwithstanding
the above, the Company may disclose details and information to its
employees and Sub-Licensees, as necessary for the performance of its
obligations pursuant to this Agreement, provided that it procures that its
employees and Sub-Licensees execute a confidentiality agreement
substantially similar in content to this section
11.
|
|
(d)
|
Without
prejudice to the aforegoing, and except for the purposes of fundraising,
the Company shall not mention the University’s and/or the Licensor’s name,
unless required by law, in any manner or for any purpose in connection
with this Agreement, or any matter relating to the Registered Patents,
without obtaining the Licensor’s prior written
consent.
|
|
(e)
|
As
a precondition to any Sub-License, the Company shall ensure that in
regards to any then applicable confidential information of the Licensor to
be disclosed in the Sub-License, the Sub-Licensee procure that the
employees and persons engaged thereby execute a confidentiality agreement
substantially similar in content to this Section
11.
|
|
(g)
|
This
section 11 shall survive expiry or termination of this
Agreement.
|
|
(i)
|
The
provisions of this section shall be subject to permitted publications
pursuant to section 12 herein.
|
Publications
| 12. |
(a)
|
The
Parties hereby agree to co-ordinate with each other regarding publications
involving the work of the Researchers, related to the Registered Patents,
but otherwise the Company shall be free to publicize as it sees fit. The
Company thus undertakes not to publish any information involving work
performed by the Researchers, including the Development Results, if
applicable, thereof without obtaining the Licensor’s prior written consent
to the publication and the manner of making such
publication.
|
|
|
(b)
|
The
Licensor shall ensure that no publications in writing, in scientific
journals or orally at scientific conventions relating to the results of
any Further Research, are published by it or its Researchers, without the
Company’s consent.
|
|
|
(c)
|
The
Company undertakes to reply to such any request for publication by the
Licensor within 30 days of application. The Company may only decline such
an application upon reasonable grounds which shall be fully detailed in
writing.
|
|
|
(d)
|
Should
the Company decide not to allow publication as provided in sub-section (b)
above for reasons which in the Licensor’s opinion are unreasonable,
publication shall be postponed for a period of not more than 3 months to
enable for the registration of
patents.
|
Page 11
of 24
|
(e)
|
The
provisions of this section shall not prejudice any other right which the
Licensor has pursuant to this Agreement and at
law.
|
|
(f)
|
For
the avoidance of doubt, the provisions of this section in connection with
the prohibition against publication shall not apply whatsoever to internal
publication by the Licensor made in the University for the Researchers and
employees.
|
Liability
and Indemnity
| 13. |
(a)
|
THE
LICENSOR MAKES NO WARRANTIES OF ANY KIND WITH RESPECT TO THE REGISTERED
PATENTS. IN PARTICULAR, THE LICENSOR MAKES NO EXPRESS OR IMPLIED
WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE NOR IS
THERE A WARRANTY THAT THE USE OF THE REGISTERED PATENTS WILL NOT INFRINGE
ANY PATENT, COPYRIGHT, TRADEMARK OR OTHER RIGHTS. IN ADDITION, NOTHING IN
THIS AGREEMENT MAY BE DEEMED TO BE A REPRESENTATION OR WARRANTY BY THE
LICENSOR OF THE VALIDITY OF ANY OF THE PATENTS OR THEIR REGISTRABILITY OR
THE ACCURACY, SAFETY, EFFICACY, OR USEFULNESS, FOR ANY PURPOSE, OF THE
REGISTERED PATENTS. THE LICENSOR HAS NO OBLIGATION, EXPRESS OR IMPLIED, TO
SUPERVISE, MONITOR, REVIEW OR OTHERWISE ASSUME RESPONSIBILITY FOR THE
PRODUCTION, MANUFACTURE, TESTING, MARKETING OR SALE OF ANY PRODUCT OR
SERVICE. THE LICENSOR HAS NO LIABILITY WHATSOEVER TO THE COMPANY OR ANY
THIRD PARTIES FOR OR ON ACCOUNT OF ANY INJURY, LOSS, OR DAMAGE, OF ANY
KIND OR NATURE, SUSTAINED BY, OR ANY DAMAGE ASSESSED OR ASSERTED AGAINST,
OR ANY OTHER LIABILITY INCURRED BY OR IMPOSED UPON COMPANY OR ANY OTHER
PERSON OR ENTITY, ARISING OUT OF OR IN CONNECTION WITH OR RESULTING FROM
(i) the production, use, practice, lease, or sale of any Product or
service; the use of the Registered Patents; or (ii) any advertising or
other promotional activities with respect to any of the
foregoing.
|
The
Company acknowledges, declares and represents that nothing in this Agreement may
be deemed to be a representation or warranty by Yissum of the validity of any of
the Registered Patents detailed herein, or their registrability or of their
accuracy, efficacy, or usefulness, safety for any purpose. Other than normal
patent maintenance detailed in section 9 hereinabove, Yissum bears no
responsibility whatsoever in relation to patent coverage in specific
geographical areas, including the patent protection afforded therein. The
Company waives all claims and/or demands of Yissum in relation
thereto.
|
|
(b)
|
The
Company shall be liable for any loss, injury and/or damage whatsoever
caused to its employees and/or any person acting on its behalf and/or to
the employees of the Licensor and/or any person acting on its behalf
and/or the Researcher and his/her team, and/or to any third party by
reason of the Company’s acts and/or omissions pursuant to this Agreement
and/or by reason of any use made of the Registered Patents, the Further
Research Results, the Development Plan, the Development Results, Product,
License and/or anything connected therewith by any third party
whatsoever.
|
|
|
(c)
|
The
Company undertakes to compensate, indemnify, defend and hold harmless the
Licensor and/or any person acting on its behalf and/or any of its
employees and/or representatives and/or the University and/or the
Researcher and his/her team (herein referred to as “Indemnitees”) against
any liability including product liability, damage, loss or expenses
including reasonable legal fees and litigation expenses incurred by or
imposed upon the Indemnitees by reason of the Company’s acts and/or
omissions and/or which derive from its use, development, manufacture,
marketing, sale and/or sub-licensing of the Product and/or Registered
Patents. Notwithstanding the foregoing, this indemnity shall not apply to
liability arising out of claims by third parties for infringement of
intellectual property rights.
|
Page 12
of 24
|
(d)
|
During
the Development Period the Company shall procure and maintain, at its own
cost and expense, comprehensive general liability insurance in amounts as
are industry standard for similar circumstances. Beginning at the time as
any Product shall be commercially distributed or sold by the Company or by
a Sub-Licensee, but in any event no later than the First Commercial Sale,
the Company and its Sub-License (if applicable) shall procure and
maintain, at their own cost and expense, comprehensive general liability
insurance in amounts that are standard in the industry for similar
products. The minimum amounts of insurance coverage required shall not be
construed to create a limit of the Company’s liability with respect to its
indemnification under this
Agreement.
|
Such
comprehensive general liability insurance shall provide: (i) product liability
coverage; (ii) contractual liability coverage for the Company’s indemnification
under this Agreement and in particular as stated above in sub-section (c); and
(iii) name the Licensor as an additional insured without any right of
subrogation against the Licensor.
|
(e)
|
The
Company shall provide the Licensor with written evidence of such insurance
upon request of the Licensor. The Company shall provide the Licensor with
written notice at least fifteen days prior to the cancellation,
non-renewal or material change in such insurance; if the Company does not
obtain replacement insurance providing comparable coverage within such
fifteen day period, this shall constitute a breach of this Agreement, and
the Licensor shall have the right at the end of such fifteen day period to
apply the procedure and provisions of termination section
14.
|
|
(f)
|
The
Company shall maintain, at its own expense, comprehensive general
liability insurance beyond the expiration or termination of this Agreement
during the period that a Product relating to and/or developed pursuant to
this Agreement is being commercially distributed or sold by the Company
and/or Sub-Licensee.
|
Termination
of the Agreement
| 14. |
(a)
|
Without
prejudice to either party’s rights pursuant to this Agreement or at law
and subject to Section 4(g) of this Agreement, either Party may terminate
this Agreement by written notice to the other only in the following
cases:
|
|
(1)
|
Breach
of this Agreement, including Fundamental Breaches, and such breach is not
remedied within 45 days of written
notice;
|
|
(2)
|
If
any of the following occur (i) the other Party passes a resolution for
voluntary winding up or a winding up application is made against it and
not set aside within 60 days; and/or (ii) a receiver or liquidator is
appointed for the other Party; and/or (iii) the other Party enters into
winding up or insolvency or bankruptcy proceedings, and the affected Party
fails within 90 days to demonstrate substantive evidence that it will be
able to reverse said event and continue operations. Each of the Parties
undertakes to notify the other within seven days if any of the
abovementioned events occur.
|
|
(b)
|
The
following shall be deemed breaches of this Agreement, entitling the
Licensor to terminate the Agreement and the License granted
hereunder:
|
|
(1)
|
Failure
by the Company to fulfill its obligation to make good faith efforts to
develop a Product in accordance with Section 7 hereinabove;
or
|
|
(2)
|
Non-performance
or delay of over than 180 days in the performance of the then applicable
approved Development Plan.
|
|
(3)
|
In
the event the Company fails to issue the Equity or fails to pay the past patent
expenses, as set forth in section 5(b), by March 31,
2006.
|
Page 13
of 24
|
|
(c)
|
Upon
termination of this Agreement and termination of the License, or upon this
Agreement ending for any reason, the License shall revert to the Licensor,
and the Licensor shall be free to enter into agreements with any other
third parties for the granting of the License and/or any other right
regarding the Registered Patents.
|
The
Company shall return and/or transfer to the Licensor, within 30 days of
termination, all material, in soft or hard copy, relating to the Registered
Patents and/or results of the Further Research and/or Development Results and/or
Product connected with the License, and it may not make any further use thereof.
In case of termination as set out herein, the Company will not be entitled to
any reimbursement of any amount paid to the Licensor in terms of this Agreement.
The Licensor shall be entitled to conduct an audit in order to ascertain
compliance with this provision and the Company agrees to allow access to the
Licensor and/or its representatives for this purpose.
|
|
(d)
|
Notwithstanding
the aforesaid, the end or termination of this Agreement shall not release
the Company from its obligation to carry out any financial or other
obligation which it was liable to perform prior to the Agreement’s end or
termination. Sections 8, 11, 12, 13, 15 and 16 shall survive termination
of this Agreement.
|
|
|
(e)
|
For
the sake of clarity, failure to comply with the terms and conditions of
sections 2, 3, 4, 5, 7, 8, 9, 10, 11, 12 and 13 shall constitute a
fundamental breach hereunder (“Fundamental
Breaches”).
|
Law
|
15.
|
The
provisions of this Agreement and everything concerning the relationship
between the parties in accordance with this Agreement shall be governed by
Israeli law and jurisdiction shall be granted only to the appropriate
court in Jerusalem.
|
Notwithstanding
the above, the Company hereby agrees that, in the event that no treaty exists
upholding the enforceability of temporary orders or decisions issued by Israeli
courts in the foreign jurisdiction in which the Licensor may require such an
order or decision to be upheld, the Licensor may, at its own discretion, elect
the place of jurisdiction for the obtaining of writs against the Company. The
Company undertakes not to object to the enforcement against it of writs and
decisions issued by any aforesaid jurisdiction under such circumstances. The
Company hereby waives any immunity it may have against enforcement of any
judgment obtained against it by the Licensor.
Arbitration
| 16. |
(a)
|
All
differences and disputes arising between the parties in connection with
the Agreement and/or its interpretation and/or its performance and/or
breach, shall be referred for the decision of a single arbitrator, whose
identity shall be determined by mutual consent of the
parties.
|
|
|
(b)
|
Should
the parties not reach agreement as to the arbitrator’s identity, the
arbitrator shall be appointed by the President of the Jerusalem district
of the Israeli Bar Association on the application of either of the
parties.
|
|
|
(c)
|
The
arbitration shall be held in Israel. The arbitrator shall not be bound by
the civil procedure regulations and laws of evidence but shall be bound by
the substantive law of Israel and be liable to give grounds for his
decision. The Arbitrator shall be empowered to grant temporary injunctions
and orders, which shall be enforceable in foreign jurisdictions, as per
Section 16 above.
|
|
|
(d)
|
The
arbitrator’s decision shall be final and binding upon the parties, and
shall be enforceable in foreign jurisdictions, as per Section 16
above.
|
|
(e)
|
The
execution of this Agreement shall constitute the execution of an
arbitration deed.
|
Page 14
of 24
Miscellaneous
| 17. |
(a)
|
Relationship of the
Parties. It is hereby agreed and declared between the parties that
they shall act in all respects relating to this Agreement as independent
contractors and there neither is nor shall be any employer-employee or
principal-agent relationship and/or partnership relationship between the
Company and/or any of its employees and the Licensor. Each party will be
responsible for payment of all salaries and taxes and social welfare and
benefits and any other payments of any kind in respect of their employees
and office holders, regardless of the location of the performance of their
duties, or the source of the directions for the performance
thereof.
|
|
|
(b)
|
Assignment.
Except for a transfer or assignment in connection with a merger,
acquisition or other change of control, the Company shall not be entitled
to transfer and/or assign and/or endorse its rights and/or duties and/or
any of them pursuant to this Agreement, to a third party, without the
prior written consent of the Licensor, which shall not be unreasonably
withheld by Licensor. In the event Licensor does not consent to the
assignment, it shall provide the Company with a detailed explanation
within 30 days after receiving written notice from Company about the
proposed transfer of rights.
|
In the
event of assignment in connection with a merger, acquisition or other change of
control, the Company undertakes to ensure that it successors shall be bound by
the terms and conditions of this Agreement as if they were a party to this
Agreement. Failure to do so shall entitle the Licensor to terminate this
Agreement under section 14 (a).
|
|
(c)
|
No waiver. The
failure or delay of a party to the Agreement to claim the performance of
an obligation of the other party shall not be deemed a waiver of the
performance of such obligation.
|
|
|
(d)
|
Linkage. All
payments to be effected in accordance with the terms of this Agreement
shall be linked to the Israeli Consumer Price Index, and the month of the
signing of this Agreement shall serve as the base for all
calculations.
|
|
|
(e)
|
Legal Costs.
Each party shall bear its own legal expenses involved in the making of
this Agreement.
|
|
|
(f)
|
Entire
Agreement. This Agreement constitutes a full and complete Agreement
between the parties and may only be amended by a document signed by both
parties.
|
|
|
(g)
|
Disclosure of
Agreements with Researcher. The Company shall disclose to the
Licensor any existing agreement and/or arrangement of any kind with the
Researcher and or any representative thereof, and shall not enter any
agreement and/or arrangement of any kind with the Researcher or
representative thereof, without the prior written consent of the
Licensor.
|
Non-compliance
with this sub-section constitutes a fundamental breach of this agreement and the
Licensor, at its sole discretion, shall have the right to terminate the
Agreement under terms and conditions as stated in section 14.
The
Company acknowledges that pursuant to the Consultancy Agreements with the Xxxx.
Xx Xxxxxxx, the Company owes Consultancy Fees to the Xxxx. Xxxxxxx, in the total
amount detailed in Appendix H, (hereinafter: “Unpaid
Consultancy Fees”). The Company
hereby agrees to make full payment of the Unpaid Consultancy Fees, in accordance
with the agreed payment Schedule detailed in Appendix H.
|
|
(h)
|
Taxes. Prices
mentioned in this agreement do not include Value Added Tax (VAT). All
taxes and duties to be paid in connection with this agreement, including
any VAT (if applicable), shall be borne by the Company. Any duties or
taxes paid by the Licensor in connection with this contract shall be
reimbursed by the Company.
|
Page 15
of 24
Notices
|
18.
|
All
notices and communications pursuant to this Agreement shall be made in
writing and sent by registered mail to or served at the following
addresses:
|
The
Licensor:
Yissum
Research Development Company
of the
Hebrew University of Xxxxxxxxx,
X.X. Xxx
00000,
Xxxxxxxxx
00000
Xxxxxx
The
Company –________________________________
or such
other address furnished in writing by one party to the other. Any notice sent as
aforesaid shall be deemed to have been received seven days after being posted by
registered mail with copy by receipted fax or email with written
confirmation.
******
IN
WITNESS THE HANDS OF THE PARTIES
|
THE
LICENSOR
|
THE
COMPANY
|
||||
|
By:
|
By:
|
||||
|
Name:
|
Name:
|
||||
|
Title:
|
Title:
|
||||
|
Date:
|
Date:
|
||||
We the
undersigned, Xxxx. Xxxxxxx and Xxxx Xxxxx, have reviewed, are familiar with and
agree to all of the above terms and conditions. We hereby undertake to fully
cooperate with the Licensor in order to ensure its ability to fulfill its
obligations hereunder, as set forth herein.
|
Prof.
|
Date
signed
|
||
|
Prof.
|
Date
signed
|
||
Page 16
of 24
Appendix
A
The
Registered Patents and the Scope
DEFINITIONS OF TECHNOLOGY
AND SCOPE:
Yissum has patent/s rights developed
by Prof./Xx. Xx Xxxxxxx in the field of exploitation of Micro Organ and the
micro-organ technologies (MO) described in the Registered Patents and Patent
Applications and know how and technical data developed by Prof./Xx.
Xx Xxxxxxx and Prof./Xx. Xxxx Panet in the field of exploitation of
Micro Organ and the micro-organ technologies (MO) (“Technology”) for
production and use of:
MO whose
genetic material has been modified from its natural state by transfection using
any transfection technique (viral or other means), or are derived from
transgenic animals altered by genetic engineering methods and are used
exclusively in,
a.) In
developing or implementing gene therapy, i.e., the introduction to the body of
genes (whether foreign or modified autologous) for the purpose of producing
recombinant proteins used in the prevention, treatment, diagnosis or curing
disease.
b) In the
development, in vitro testing and in vivo production of recombinant proteins or
nucleic acids including DNA and RNA, whether sense RNA or antisense
RNA.
c) Using
MOs whose genetic material has not been modified or that are derived from non
transgenic animals, solely and exclusively for testing the safety, efficacy and
quality assurance of the MOs whose genetic material has been modified or that
are derived from transgenic animals, as aforesaid, whether in vitro or in vivo,
whether in the recipient or in another body. (“Scope”)
The Scope
will NOT include:
a) Use of
liver MO;
b) Use of
kidney MO;
c) Use of
pancreas MO;
d) Uses
of MO for the purpose of inducing angiogenesis, which includes stimulating
and/or promoting the growth or formation of new and/or nascent blood vessels,
and/or the maintenance of said affected blood vessels.
For the
sake of clarity uses of MO as defined in a) through c) above, for the induction
of physiological vasoconstriction and vasodilatation and to the extent that they
are not for the purpose of inducing angiogenesis as therapeutic, as aforesaid,
are not excluded.
Page 17
of 24
Page 18
of 24
Page 19
of 24
Page 20
of 00
Xxxxxxxx
X
License
Fee
The
Company hereby undertakes to pay the Licensor a License Fee in the amount of
Four Hundred Thousand US Dollars (US$400,000), in the following
manner;
|
|
(i)
|
Installment
1 in the amount of Fifty Thousand US Dollars (US$50,000) shall be paid
when the accrued investments in the Company by any third party, from the
date of the MOU (23rd
of May 2005), amount to at least
$3,000,000
|
|
|
(ii)
|
Installment
2 in the amount of One Hundred and Fifty Thousand US Dollars (US$150,000)
shall be paid when the accrued investments in the company by any third
party, from the date of the MOU (23rd
of May 2005), amount to at least
$12,000,000
|
|
(iii)
|
Installment
3 in the amount of Two Hundred Thousand US Dollars (US$200,000) shall be
paid when the accrued investments in the company by any third party, from
the date of the MOU (23rd
of May 2005), amount to at least
$18,000,000
|
Page 21
of 24
Appendix
C
Consultancy
Agreements
Page 22
of 24
Appendix
D
Consultancy
Fee Payment Schedule
Page 23
of 24
Appendix
E
The
Development Plan
APPENDIX E: Initial
Development Plan DRAFT Nov. 23, 2005
Subject
to approval by the Company’s Board of Directors, the following summarizes the
key elements of the Development plan.
Objectives
of the development plan are to achieve a clinical BP-EPO version with protein
production profile judged likely to be capable of successfully providing at
least 4-6 months’ elevated hematocrit in CKD patients. The key challenge is to
demonstrate that at least one of the new, custom vectors (currently comprising
varieties of AAV vectors, and gutless Adeno vectors) yield the required
quantities of EPO production per Biopump for several months in vitro and in SCID
mice. Based on the preliminary results before operations shut down, this appears
achievable through optimization work typical of what the company has done to
date. This would be followed in the next stage, with further funding, by a
proof-of-concept clinical trial similar to the proof-of-principle trial, but one
which Medgenics believes has high likelihood to demonstrate clinically useful
performance.
Stage
1: the first
stage of the restart plan is designed to achieve the key performance milestone
within 12 months of new funding: clear in-vitro and in-vivo evidence of the
requisite long lasting Biopump performance for EPO, with clear path to clinical
trial approval. This will be accomplished using manual biopump preparation, not
using the Bioreactor. The Bioreactor is to be operated and tested on a modest
scale during the latter part of Stage 1, as a benchmark prior to optimization to
proof of concept as part of Stage 2. The new vectors will be tested and
optimized using human skin microogans obtained from freshly removed skin slabs
in abdominoplasty procedures, as was done previously. Several aspects of the
processing protocol, shown to optimize results in previous testing with the
original vectors, will be tested for best results using the new vectors in
Biopumps. Steps towards key milestone include:
|
|
1.
|
Demonstration
of significant EPO secretion from each of the new, completed
vectors
|
|
|
2.
|
Demonstration
of requisite sustained levels for at least 2 months, without signs of
imminent decline, from at least one of the
vectors
|
|
|
3.
|
Key
Milestone: reproducible demonstration from at least one of the vectors, of
requisite sustained EPO levels for 4-6 months in vitro and in SCID mice,
projected to be capable of elevating hematocrit in patients for at least
4-6 months
|
In
parallel:
|
|
·
|
Key
patents will be maintained and national phase filings
pursued
|
|
|
·
|
Preparations
for potential GMP production of the selected
vector.
|
In
addition, the selected vector will also be prepared with the gene for an
additional, commercially attractive protein, with feasibility demonstrated in
vitro and in mice by month 15.
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