STEM CELL AGREEMENT
Exhibit
10.37
This Stem Cell Agreement (“Agreement”)
is made and entered into as of the 23rd day of February, 2009 (the “Effective
Date”), by and between Reproductive
Genetics Institute, an Illinois corporation with offices located at 0000
Xxxxx Xxxxxxx Xx., Xxxxxxx, XX 000000 (“RGI”), Embryome
Sciences, Inc., a California corporation (“ES”), with offices located at
0000 Xxxxxx Xxx Xxxxxxx, Xxxxx 000, Xxxxxxx, Xxxxxxxxxx 00000. RGI and ES are
sometimes hereinafter referred to as the “Parties”.
WITNESSETH
WHEREAS, RGI owns or has licensed with
a sublicensable interest the CELLS, CELL LINES, and KNOW-HOW; and
WHEREAS, ES desires to obtain a license
from RGI to use, reproduce, market, and sell the CELLS upon the terms and
conditions set forth in this Agreement; and
WHEREAS, RGI is willing to provide the
CELLS and grant such a license to ES upon the terms and conditions set forth in
this Agreement;
NOW, THEREFORE, in consideration of the
premises and the mutual covenants contained herein, the Parties hereto agree as
follows:
ARTICLE 1 -
DEFINITIONS
For the purposes of this Agreement, the
following words and phrases shall have the following meanings:
1.1 “ACCEPTABLY
DERIVED” has the meaning defined in Section 3.2.
1.2 “AFFILIATE”
means any corporation, limited liability company, limited partnership or other
entity in control of, controlled by, or under common control with
ES.
1.3 “CELLS”
means the cells ACCEPTABLY DERIVED from the CELL LINES identified in Exhibit A attached
hereto (the “CELL LINES”), and additional cell lines derived from
preimplantation embryos during the term of this Agreement, that are covered by
(i.e., made or developed using) the KNOW-HOW and/or are provided to ES by RGI in
accordance with the provisions of Articles 2 or 3, as applicable, of this
Agreement. The CELL LINES will include, but not be limited to, those
made animal product free and those with defined HLA types and determined to
carry disease gene alleles.
1.4 “COMBINATION
PRODUCT” means a product that contains a CELLS component and at least one other
component that has independent research, diagnostic or therapeutic utility,
could reasonably be sold separately and has economic value of its
own.
1.5 “COMMERCIAL
USE” means a use of CELLS or CELL LINES for any use other than a NON-COMMERCIAL
USE.
1.6 “CONFIDENTIAL
INFORMATION” means confidential or proprietary information of RGI or ES relating
to the KNOW-HOW, CELLS and/or CELL LINES. CONFIDENTIAL INFORMATION may be in
written, graphic, oral or physical form and may include scientific knowledge,
know-how, processes, inventions, techniques, formulae, products, business
operations, customer requirements, designs, sketches, photographs, drawings,
specifications, reports, studies, findings, data, plans or other records,
biological materials, and/or software. CONFIDENTIAL INFORMATION shall
not include: (a) information which is, or later becomes, generally
available to the public through no fault of the recipient; (b) information which
is provided to the recipient by an independent third party having no obligation
to keep the information secret; (c) information which the recipient can
establish by written documentation was previously known to it; or (d)
information which the recipient can establish by written documentation was
independently developed by it without reference to the CONFIDENTIAL
INFORMATION.
1.7 “KNOW-HOW”
means all compositions of matter, techniques and data and other know-how and
technical information including inventions (whether or not patentable),
improvements and developments, practices, methods, concepts, trade secrets,
documents, computer data, computer slide illustrations, computer code,
apparatus, test data, analytical and quality control data, formulation,
manufacturing, patent data or descriptions, development information, drawings,
specifications, designs, plans, proposals and technical data and
manuals, all of which may constitute CONFIDENTIAL
INFORMATION, that is owned or controlled by RGI as of the Effective Date or that
is developed or acquired by RGI in the future, and that specifically relates
to the growth, development, reproduction, or characterization of the
CELLS acquired by ES from RGI.
1.8 “NET
SALES” means the amounts received by ES from sales or other disposition for
value of CELLS and CELL LINES or COMBINATION PRODUCTS by ES or its AFFILIATES to
any third party (excluding any disposition transaction involving a merger or
consolidation of ES or a sale of all or part of ES’s business where the
purchaser assumes ES’s rights and obligations under this Agreement), less (to
the extent applicable and appropriately documented) (i) sales, tariff and import
duties, use and other taxes directly imposed with reference to particular sales,
(ii) discounts, rebates, and similar credits and chargebacks actually allowed
and taken (regardless of whether taken or paid at the time of sale or paid or
credited to the buyer at a subsequent date), (iii) amounts allowed or credited
on returns; provided, any such allowed deductions shall be listed on the
applicable sales invoice or otherwise documented in the ordinary course of
business, and (iv) in the case of sales of CELLS for NON-COMMERCIAL USE,
royalties payable to any third party for the use of any patent or other
technology in connection with the growth, reproduction, or characterization of
CELLS.
In the
case of NET SALES of COMBINATION PRODUCTS, NET SALES means the total invoice
amount collected of COMBINATION PRODUCTS by ES or its AFFILIATES to any third
party, less, to the extent applicable, the deductions set forth above,
multiplied by a proration factor that is determined as follows:
(i) If
all components of the COMBINATION PRODUCT were sold separately during the same
or immediately preceding calendar quarter, the proration factor shall
be
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determined
by the formula [A/(A+B)], where A is the average invoice amount earned on the
CELLS during such period when sold separately in finished form, and B is the
average invoice amount earned on all other active components of the COMBINATION
PRODUCT during such period when sold separately in finished form;
or
(ii) if
all components of the COMBINATION PRODUCT were not sold separately during the
same or immediately preceding calendar quarter, the proration factor shall be
determined by the formula [C/(C+D)], where C is the average fully absorbed cost
of the CELLS component during the prior quarter and D is the average fully
absorbed cost of all other active components of the COMBINATION PRODUCT during
the prior quarter.
1.9 “NONCOMMERCIAL
USE” means the use of CELLS as research tools, including but not limited to use
in the discovery and development of drugs and other products for the treatment
or diagnosis of disease; provided, however, that the use of CELLS directly in
the treatment or diagnosis of disease in humans shall be deemed a COMMERCIAL
USE.
1.10 “STEERING
COMMITTEE” means a committee of four people, two being appointed by ES and two
being appointed by RGI that will decide on behalf of the two companies
commercial strategies for jointly developing, marketing, and selling CELLS for
COMMERCIAL USE. The STEERING COMMITTEE shall not make decisions on
pricing of sales of CELLS by ES.
For
purposes of this Agreement, except as otherwise expressly provided herein or
unless the context otherwise requires: (a) the use herein of the
plural shall include the single and vice versa and the use of the
masculine shall include the feminine; (b) unless otherwise set forth herein, the
use of the term “including” or “includes” means “including [includes] but [is]
not limited to”; and (c) the words “herein,” “hereof,” “hereunder” and other
words of similar import refer to this Agreement as a whole and not to any
particular provision. Additional terms may be defined throughout this
Agreement.
ARTICLE 2 – LICENSE
GRANT
2.1 Grant of
Rights. RGI hereby grants to ES, and ES accepts, subject to
the terms and conditions of this Agreement, a royalty-bearing, worldwide,
non-exclusive license during the term of this Agreement only, to use the
KNOW-HOW to research, develop, make, have made, use, sell, have sold, offer for
sale, have offered for sale, import, have imported, export and have exported
CELLS and CELL LINES. The KNOW-HOW shall not be sublicensed by ES
without RGI’s written consent.
2.2 Knowledge
Transfer. Within sixty (60) days of the Effective Date, RGI
shall provide and deliver to ES, on a non-exclusive basis, copies of all
information and data relating to the KNOW-HOW as may be reasonably necessary to
allow ES to exploit the licenses granted hereunder and to reproduce the CELLS
acquired from RGI. If after the Effective Date RGI develops or
obtains any new or additional KNOW-HOW pertaining the CELLS acquired by ES from
RGI, RGI shall provide, deliver, and transfer copies of such KNOW-HOW and other
information to ES, on a non-exclusive basis, promptly after such KNOW-HOW is
developed or obtained. Such deliveries shall be made free and clear
of all liens, security interests, encumbrances, and claims of any kind by any
third party. RGI shall bear all costs of so delivering the KNOW-HOW
to ES.
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2.3 Regulatory
Approvals. ES acknowledges and agrees that the CELLS have not
been approved by the United States Food and Drug Administration or by any
similar regulatory agency of any other country for use as drug or medical
device.
2.4 New Patents, Inventions, and
Discoveries. ES shall have the right to file and prosecute new
patent applications (and to obtain new patents) with respect to any technology,
invention, or discovery made by ES or any of its AFFILIATES using CELLS and
KNOW-HOW. RGI shall acquire no right, title or interest with respect
to such new patents, inventions, discoveries, or technology not included within
the KNOW-HOW licensed to ES by RGI, except that in the case of any product or
treatment for COMMERCIAL USE developed by ES using CELLS otherwise than in
accordance with plans approved by the STEERING COMMITTEE, RGI shall be granted a
non-exclusive, perpetual, royalty free license to make, use and sell such
products and treatments covered by such patents.
2.5 Sales of ES CELLS to
RGI. ES agrees that to the extent RGI desires to purchase
CELLS of any type from ES for NON-COMMERCIAL USE, ES will sell such CELLS to RGI
for a price per ampule equal to fifty percent (50%) of the lowest price offered
by ES to any other Customer for NON-COMMERCIAL USE during the
immediately-preceding twenty-four (24) month period.
ARTICLE 3 – MATERIAL
TRANSFER
3.1 Delivery of CELLS and CELL
LINES. In consideration of the issuance and delivery of the
License Fee Shares under Section 5.1, RGI hereby sells, transfers and assigns to
ES ten (10) of the CELLS from ten (10) CELL LINES chosen by ES listed on EXHIBIT
A. Within fifteen (15) business days after the Effective Date, RGI
shall deliver to ES a quantity of ampules containing CELLS, sufficient to enable
ES to reproduce in commercial quantities the 10 different types of
CELLS. Should ES elect to market additional types of CELLS, ES shall
give RGI written notice of the additional cell types chosen by ES from the CELL
LINES listed on Exhibit A and within fifteen (15) business days of such notice,
RGI shall sell, transfer, assign, and deliver to ES a quantity of ampules
containing such additional CELLS, sufficient to enable ES to reproduce the
additional types of CELLS in commercial quantities. Such transfer and
assignment is made free and clear of all liens, security interests,
encumbrances, and claims of any kind by any third party. RGI shall
bear all costs of delivering the CELLS to ES. All CELLS shall be
delivered to ES between the hours of 9:00 a.m. and 5:00 p.m. on a weekday (other
than a Federal or California state holiday) at the address shown in Article 10
of this Agreement, upon twenty-four hours oral or written notice to
ES. All CELLS shall be contained in cryovials and packaging suitable
for the purpose of storage and delivery. If ES elects to acquire
additional CELLS after the initial ten (10) CELLS are delivered to ES by RGI,
and RGI requires more than fifteen (15) business to deliver all of the
additional CELLS requested by ES due to the number of CELLS so requested, ES
shall allow RGI such additional time as RGI may reasonably require to complete
the delivery of all of the additional CELLS, and RGI shall use commercially
reasonably efforts and diligence to complete the delivery of such additional
CELLS, including making such deliveries in installments as sufficient CELLS of
each CELL LINE become available.
3.2 Acceptably
Derived. All human pluripotent stem cells and cell lines
comprising CELLS provided to ES under this Agreement must be ACCEPTABLY
DERIVED. RGI will provide ES with documentation verifying that all
CELLS of each CELL LINE delivered to ES were ACCEPTABLY
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DERIVED. If
so requested by ES, RGI will take all such actions as are necessary to have the
CELLS deposited in the United Kingdom Stem Cell Bank. In order to be
ACCEPTABLY DERIVED human pluripotent stem cells must have:
(a) Been
listed on the National Institutes of Health Human Embryonic Stem Cell Registry,
or
(b) Been
deposited in the United Kingdom Stem Cell Bank, or
(c) Been
derived by, or approved for use by, a licensee of the United Kingdom Human
Fertilisation and Embryology Authority, or
(d) Been
derived in accordance with the Canadian Institutes of Health Research
Guidelines for Human Stem Cell Research under an application approved by the
National Stem Cell Oversight Committee, or
(e) Been
derived under the following conditions:
(i) Donors
of gametes, embryos, somatic cells or human tissue gave voluntary and informed
consent.
(ii) Donors
of gametes, embryos, somatic cells or human tissue did not receive valuable
consideration. This provision does not prohibit reimbursement for
permissible expenses as determined by an Institutional Review Board
(IRB).
(iii) Not
been derived from gametes, embryos, somatic cells, or human tissue knowingly
purchased or sold for valuable consideration for research
purposes. This provision does not prohibit reimbursement for
permissible expenditures as determined by an IRB or a Stem Cell Research
Oversight Committee. APermissible
expenditures@
means necessary and reasonable costs directly incurred as a result of persons,
not including human subjects or donors, providing gametes, embryos, somatic
cells, or human tissue for research purposes. Permissible
expenditures may include but are not limited to costs associated with
processing, quality control, storage, or transportation of
materials.
(iv) Donation
of gametes, embryos, somatic cells or human tissue was overseen by an IRB (or,
in the case of foreign sources, an IRB-equivalent).
(v) Individuals
who consented to donate stored gametes, embryos, somatic cells or human tissue
were not reimbursed for the cost of storage prior to the decision to
donate.
3.3 Non-Exclusive
Rights. ES acknowledges and agrees that its right to acquire
CELLS from RGI is on a non-exclusive basis, and that RGI shall be entitled to
make, use, sell, market, distribute, and transfer identical or other CELLS and
CELL LINES to third parties, or otherwise use same, for RGI’s own account, on
such terms and conditions as RGI may determine, in its sole and absolute
discretion.
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3.4 ES
agrees that to the extent it desires to purchase CELLS which are available for
purchase from RGI, ES will purchase its requirements of such CELLS from RGI and
will not purchase such requirements for any third party unless RGI shall be
unable to timely provide same.
ARTICLE 4 –
COMMERCIALIZATION
4.1 ES
intends to use, or to cause its AFFILIATES to use, commercially reasonable
efforts to bring one or more CELL LINES developed from the CELLS acquired
hereunder to market for NON-COMMERCIAL USE during the term of this
Agreement. ES makes no representation, guaranty, or warranty that it
or its AFFILIATES will be successful in reproducing, marketing, selling, or
distributing any CELLS or CELL LINES.
ARTICLE 5 -
CONSIDERATION
5.1 License
Fee. In partial consideration of the rights and licenses
granted to ES by RGI in this Agreement, ES shall cause its parent BioTime, Inc.
to issue to RGI, as a license fee for the KNOW-HOW related to the first 10 cell
types chosen by ES from the list in Exhibit A, a number of BioTime common shares
determined by dividing Fifty Thousand Dollars ($50,000) by the closing price of
BioTime common shares on the OTC-BB market on the Effective Date of this
Agreement (or the closing price on the most recent date on which BioTime shares
traded before the Effective Date if BioTime common shares did not trade on the
OTC-BB market on the Effective Date) (the “License Fee Shares”). For each
additional cell type chosen by ES from the list in Exhibit A and as it is
updated in the future, a number of BioTime common shares determined by dividing
Five Thousand Dollars ($5,000) by the closing price of BioTime common shares on
the OTC-BB market on the date of such written notice to RGI from ES (or the
closing price on the most recent date on which BioTime shares traded before the
date of written notice if BioTime common shares did not trade on the OTC-BB
market on the date of notice) shall be issued to RGI as a license fee for the
KNOW-HOW related to CELLS derived from those additional CELL LINES (the
“Additional License Fee Shares”). The License Fee Shares and
Additional License Fee Shares are not refundable and the value of the License
Fee Shares and Additional License Fee Shares are not creditable against other
payments due to RGI under this Agreement. The License Fee Shares and
Additional License Fee Shares shall be issued to RGI within ten (10) business
days after RGI’s delivery of the KNOW-HOW and CELLS pursuant to Section 2.2 and
Section 3.1; provided, that ES shall not be in breach of this Agreement for any
delay in delivery of the License Fee Shares resulting from the time required by
the transfer agent and registrar of such shares to make a certificate of such
shares available for delivery.
(a) Investment
Representations. RGI represents and warrants to ES and BioTime
that:
(i) RGI
has received a copy of BioTime’s Annual Report on Form 10-K for the year ended
December 31, 2007 and its Quarterly Report on Form 10-Q for the three months
ended September 30, 2008 (the “Disclosure Documents”) and is relying on the
information provided therein in determining to acquire the License Fee
Shares. RGI has had a reasonable opportunity to ask questions of and
receive answers from the executive officers and directors of BioTime or one or
more of its officers, concerning BioTime and to obtain additional information,
to the extent possessed or obtainable
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without
unreasonable effort or expense, necessary to verify the information in the
Disclosure Documents. All such questions have been answered to RGI’s
satisfaction;
(ii) RGI
understands that the License Fee Shares are being offered and sold without
registration under the Securities Act of 1933, as amended (the “Act”) or
qualification under the California Corporate Securities Law of 1968, or under
the laws of other states, in reliance upon the exemptions from such registration
and qualification requirements for non-public offerings. RGI
acknowledges and understands that the availability of the aforesaid exemptions
depends in part upon the accuracy of certain of the representations,
declarations and warranties contained herein, which RGI hereby makes with the
intent that they may be relied upon by BioTime and its officers and directors,
and by ESI and its officers and directors, in determining RGI’s suitability to
acquire the License Fee Shares. RGI understands and acknowledges that
no federal, state or other agency has reviewed or endorsed the offering of the
License Fee Shares or made any finding or determination as to the fairness of
the offering or completeness of the information in the Disclosure
Documents;
(iii) RGI
understands that the License Fee Shares may not be offered, sold, or transferred
in any manner unless subsequently registered under the Act, or unless there is
an exemption from such registration available for such offer, sale or
transfer;
(iv) RGI
has such knowledge and experience in financial and business matters to enable
RGI to utilize the information contained in the Disclosure Documents, or
otherwise made available to RGI to evaluate the merits and risks of an
investment in the License Fee Shares, and to make an informed investment
decision with respect thereto.
(v) RGI
is acquiring the License Fee Shares for RGI’s own account and for long-term
investment purposes, and not with a view to, or for sale in connection with, any
distribution of the License Fee Shares; and
(vi) RGI
is an “accredited investor,” as such term is defined in Regulation D promulgated
under the Act.
5.2 Royalties and other
Consideration. As additional consideration of the license
granted to ES from RGI in Article 2 of this Agreement, ES shall pay to RGI
royalties as follows:
(a) A
royalty equal to seven percent (7%) of the collections of Net Sales received by
ES and its AFFILIATES for each ampule of CELLS sold or otherwise disposed of for
NONCOMMERCIAL USE only. ES agrees not to sell CELLS for less than
Seven Thousand Five Hundred Dollars ($7,500) per ampule.
(b) In
the case of sales or other dispositions of CELLS by ES or any AFFILIATE for
COMMERCIAL USE, a royalty on Net Sales of an amount equal to (A) 50% of Net
Sales, minus one-half of any other royalties paid or required to be
paid by ES or its AFFILIATES to third parties on such Net Sales or (B) such
other amount as a majority of the members of the Steering Committee may approve
in writing.
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5.3 Payment
Method. All payments due under this Agreement shall be paid to
RGI in Chicago, Illinois, U.S.A., and shall be made in United States currency
without deduction for taxes, assessments, exchanges, collection or other charges
of any kind. Conversion of foreign currency to U.S. dollars shall be
made at the conversion rate reported in The Wall Street Journal on the last
working day of the calendar quarter to which the payment relates.
5.4 Late
Fee. ES shall pay RGI interest on any overdue amounts at the
rate of one percent (1%) per month (twelve percent (12%) per annum), from the
date when such payment should have been made.
ARTICLE 6 - REPORTS AND
RECORDS
6.1 ES
shall maintain complete and accurate records of CELLS that are sold by ES or its
AFFILIATES under this Agreement. ES shall keep, and shall cause its
AFFILIATES to keep, full, true and accurate books of account containing all
particulars that may be necessary for the purpose of showing the amounts payable
to RGI hereunder and ES’s compliance with the terms and conditions of this
Agreement. Said books of account shall be kept at ES’s principal
place of business or at such other location as may be agreed upon by the
parties. Said books and the supporting data shall be open for
inspection and audit by RGI upon reasonable advance notice for three
(3) years following the end of the calendar year to which they pertain, to the
inspection of RGI or its agents for the purpose of verifying ES’s royalty
statement or compliance in other respects with this Agreement. If any
such audit determines that the reported payments to RGI were less than ninety
percent (95%) of the actual amount due to RGI for the period in question, ES
shall bear the cost of such audit (without limiting RGI’s other remedies with
respect thereto). RGI may inspect and audit such books and records no
more frequently than twice per calendar year, except that if payments reported
to RGI in any calendar year were less than 95% of the actual amount due, RGI may
inspect and audit the books and records not more than four times during that
calendar year and the following calendar year.
6.2 After
the first sale or other disposition of any CELLS for COMMERCIAL USE by ES or any
AFFILIATE, ES, within forty-five (45) days after March 31, June 30, September 30
and December 31, of each year, shall deliver to RGI a true and accurate report
of all NET SALES during the preceding three-month period under this Agreement as
shall be pertinent to a royalty accounting hereunder. Each such
report shall include at least the following:
(a) number(s)
and type(s) of CELLS sold by ES and/or its AFFILIATES;
(b) total
xxxxxxxx and payments received for CELLS sold by ES and itsAFFILIATES;
and
(c) deductions
applicable as provided in Section 1.8;
6.3 With
each such report submitted, ES shall pay to RGI the royalties and other payments
due and payable under this Agreement. If no royalties or other
payments shall be due, ES shall so report.
6.4 ES’s
reporting obligations hereunder shall terminate when ES’S obligation to pay
royalties to RGI has been fully satisfied.
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ARTICLE 7 –
INDEMNIFICATION,
7.1 RGI
shall at all times during the term of this Agreement and thereafter, indemnify,
defend and hold harmless ES and its AFFILIATES, successors, assigns, agents,
officers, directors, shareholders and employees (each, an “Indemnified Party”),
at RGI’s sole cost and expense, against all liabilities of any kind whatsoever,
including legal expenses and reasonable attorneys’ fees, arising out of or
arising from a breach of any representation or warranty of RGI hereunder,
excepting only claims that result from (a) the willful misconduct or negligence
of ES or its AFFILIATES, and (b) claims alleging that the use of any of the
KNOW-HOW, or the use, reproduction, sale, transfer, or distribution of CELLS
infringes upon any patent, or trade secret of any third party. The
indemnification obligations set forth herein are subject to the following
conditions: (i) the Indemnified Party shall notify RGI in writing promptly upon
learning of any claim or suit for which indemnification is sought; (ii) RGI
shall have control of the defense or settlement, provided that the
Indemnified Party shall have the right (but not the obligation) to participate
in such defense or settlement with counsel at its selection and at its sole
expense; and (iii) the Indemnified Party shall reasonably cooperate with the
defense, at RGI’s expense.
7.2 EXCEPT
AS OTHERWISE EXPRESSLY SET FORTH IN THIS AGREEMENT, RGI, ITS DIRECTORS,
OFFICERS, AGENTS, SHAREHOLDERS, EMPLOYEES, AND AFFILIATES MAKE NO
REPRESENTATIONS AND EXTEND NO WARRANTIES OF ANY KIND, EXPRESSED OR IMPLIED, AND
EXPRESSLY DISCLAIM ALL WARRANTIES OF MERCHANTABILTY
AND FITNESS
FOR A PARTICULAR PURPOSE.
7.3 ES
shall at all times during the term of this Agreement and thereafter, indemnify,
defend and hold harmless RGI and its AFFILIATES, successors, assigns, agents,
officers, directors, shareholders and employees (each, an “Indemnified Party”),
at ES’s sole cost and expense, against all liabilities of any kind whatsoever,
including legal expenses and reasonable attorneys’ fees, arising out of or
arising from a breach of any representation or warranty of ES hereunder,
excepting only claims that result from (a) the willful misconduct or negligence
of RGI or its AFFILIATES, and (b) claims for which RGI is liable pursuant to the
indemnity set forth in Section 7.1 above, , and (c) claims that the use of any
KNOW-HOW licensed by ES to RGI hereunder infringes upon any patent or trade
secret of any third party. The indemnification obligations set forth
herein are subject to the following conditions: (i) the Indemnified Party shall
notify ES in writing promptly upon learning of any claim or suit for which
indemnification is sought; (ii) ES shall have control of the defense or
settlement, provided
that the Indemnified Party shall have the right (but not the obligation)
to participate in such defense or settlement with counsel at its selection and
at its sole expense; and (iii) the Indemnified Party shall reasonably cooperate
with the defense, at ES’s expense.
ARTICLE 8 –
TERMINATION
8.1 Subject
to the other termination provisions of this Article 8, this Agreement shall be
effective on the Effective Date and shall continue in effect until December 31,
2039 (the “Original Expiration Date”). The term of this
Agreement shall be automatically extended beyond the Original Expiration Date
for a period of ten years (the “First Extension Period”), unless either party
gives the other party notice of non-extension not less than 120 days prior to
the Original Expiration Date, and thereafter shall be automatically extended
beyond the First Extension Period for an additional period
of
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ten years
(the “Second Extension Period”), unless either party gives the other party
notice of non-extension not less than 120 days prior to the expiration of the
First Extension Period.
8.2 In
addition to any other rights that RGI may have, RGI may terminate this Agreement
and the rights, privileges and license granted hereunder by written notice upon
a breach or default of this Agreement by ES, as follows:
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(i)
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non-payment
of any amounts due which is not cured within thirty (30) days of receipt
of written notice of such non-payment;
or
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(ii)
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breach
of any obligation which is not cured within thirty (30) days of a written
request to remedy such breach wherein said request is delivered by
registered mail, or if the breach cannot be cured within said thirty (30)
day period, despite ES’s best efforts to do so, failure of ES within said
thirty (30) day period to proceed with reasonable promptness thereafter to
cure the breach.
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Such
termination shall become effective upon notice from RGI thereof, unless ES shall
have cured any such material breach or default prior to the expiration of the
applicable cure period.
8.3 ES
shall have the right to terminate this Agreement at any time on thirty (30) days
prior notice to RGI provided, that ES shall discontinue sales of CELLS upon such
termination of this Agreement. Notwithstanding such termination, ES
shall pay RGI any royalties due with respect to the sale of CELLS that occurred
prior to the date of termination.
8.4 Upon
termination of this Agreement for any reason, nothing herein shall be construed
to release either party from any obligation that matured prior to the effective
date of such termination; and Sections 6.1, Article 7, Article 9, and Article
11, and any other Sections or provisions which by their nature are intended to
survive termination, shall survive any such termination.
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ARTICLE 9 -
CONFIDENTIALITY
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9.1 During
the course of this Agreement, RGI and ES may provide each other with
CONFIDENTIAL INFORMATION. CONFIDENTIAL INFORMATION may be disclosed
in oral, visual or written form, and includes such information that is
designated in writing as such by the discloser at the time of disclosure, orally
disclosed information that is designated in writing as confidential within 30
days after such oral disclosure, or information which, under all of the given
circumstances ought reasonably be treated as CONFIDENTIAL INFORMATION of the
disclosing party. RGI and ES each intend to maintain the confidential or trade
secret status of their CONFIDENTIAL INFORMATION. Each shall exercise
reasonable care to protect the CONFIDENTIAL INFORMATION of the other from
disclosure to third parties; no such disclosure shall be made without the
other’s written permission. Upon termination or expiration of this
Agreement, RGI and/or ES shall comply with the other’s written request to return
all CONFIDENTIAL INFORMATION that is in written or tangible
form. Except as expressly provided herein, neither RGI nor ES is
granted any license to use the other’s CONFIDENTIAL INFORMATION. The
obligations of RGI and ES under this Article 9 shall survive
10
any
expiration or termination of this Agreement. Notwithstanding the
preceding provisions of this Section 9.1, until such time as this Agreement is
terminated: ES shall have the right to disclose KNOW-HOW to third
parties who purchase CELLS on a need-to-know basis, provided that such third
parties sign confidentially and non-disclosure agreements recognizing the
proprietary rights of RGI thereto in form and substance satisfactory to
RGI.
ARTICLE 10 - PAYMENTS,
NOTICES, AND OTHER COMMUNICATIONS
Any payment, notice or other
communication required to be given to any party will be deemed to have been
properly given and to be effective (a) on the date of delivery if delivered by
hand, recognized national next business day delivery service, confirmed
facsimile transmission, or confirmed electronic mail, or five (5) days after
mailing by registered or certified mail, postage prepaid, return receipt
requested, to the respective addresses given below, or to another address as it
shall designate by written notice given to the other party in the manner
provided in this Section.
In the case of RGI: | Reproductive Genetics Institute |
|
0000
Xxxxx Xxxxxxx Xxxxxx
|
|
Xxxxxxx,
XX 000000
|
|
Attention: Xxxx
Xxxxxxxxx
|
With a copy to: | Xxxxx X. Xxxxxx, Esq. |
|
Deutsch,
Levy & Xxxxx, Chtd.
|
|
000
X. Xxxxxxxxxx Xxxxxx, Xxxxx
0000
|
|
Xxxxxxx,
XX 00000
|
In the case of ES | Embryome Sciences, Inc. |
|
0000
Xxxxxx Xxx Xxxxxxx, Xxxxx 000
|
|
Xxxxxxx,
Xxxxxxxxxx 00000
|
|
Attention: Xxxxxxx
X. Xxxx
|
With
a copy to:
|
Xxxxxxx
X. Xxxxxx, Esq.
|
|
Lippenberger,
Thompson, Welch, Xxxxxx & Xxxxxxx
LLP
|
|
000
Xxxxx Xxxxx Xxxx.
|
|
Xxxxx
Xxxxxx, Xxxxxxxxxx 00000
|
11
ARTICLE 11 - REPRESENTATIONS
AND WARRANTIES
11.1 ES
represents and warrants that it has full corporate power and authority to enter
into this Agreement, that this Agreement constitutes the binding legal
obligation of ES, enforceable in accordance with its terms, and that the
execution and performance of this Agreement by ES will not violate, contravene
or conflict with any other agreement to which ES is a party or by which it is
bound or with any law, rule or regulation applicable to ES, and that any
permits, consents or approvals necessary or appropriate for ES to enter into
this Agreement have been obtained.
11.2 ES
is an entity duly incorporated or otherwise organized, validly existing and in
good standing under the laws of the jurisdiction of its incorporation or
organization, with the requisite power and authority to own and use its
properties and assets and to carry on its business as currently
conducted.
11.3 RGI
represents and warrants that (a) it owns the KNOW-HOW, (b) it has the full legal
right and power to grant the licenses granted hereunder, (c) that this Agreement
constitutes the binding legal obligation of RGI, enforceable in accordance with
its terms, (d) the execution, delivery, and performance of this Agreement by RGI
will not violate, contravene or conflict with any other agreement to which RGI
is a party or by which it is bound or with any law, rule or regulation
applicable to RGI, and (e) any permits, consents or approvals necessary or
appropriate for RGI to enter into this Agreement have been
obtained.
11.4 RGI
represents and warrants that, to the best of its knowledge, the use of the KNOW-
HOW and CELLS by ES or any of ES’s AFFLIATES for any purposes contemplated or
permitted by this Agreement, will not infringe in any way any claim under any
patent held by any third party.
11.5 RGI
represents and warrant that the use of the KNOW-HOW and the CELLS by ES or any
of ES’s AFFLIATES for any purposes contemplated or permitted by this Agreement,
will not infringe in any way any claim under any patent held by RGI or under any
patent that may issue from any RGI patent application now pending, or any other
intellectual property rights of RGI.
11.6 RGI
further represents, warrants and agrees, that it shall not make any claim or
demand, or commence any lawsuit or other proceeding, alleging that use of the
KNOW-HOW or CELLS by ES or any Sublicensee during the term of this Agreement for
any purpose contemplated or permitted by this Agreement infringes in any way any
claim under any patent that RGI may in the future obtain, or any other
intellectual property rights that RGI may obtain in the future. The
provisions of this Section 11.6 shall pertain as well to all subsidiaries of RGI
and all patents and patent applications of RGI subsidiaries. RGI and its
subsidiaries shall cause the provisions of this Section 11.6, as they pertain to
refraining from asserting claims and demands or commencing lawsuits and
proceedings, to be including in all licenses and assignments of RGI’s patents
and patent applications.
11.7 RGI
represents and warrants that all CELLS and CELL LINES have been ACCEPTABLY
DERIVED.
12
ARTICLE 12 - MISCELLANEOUS
PROVISIONS
12.1 Nothing
herein shall be deemed to constitute either party as the agent or representative
of the other party.
12.2 To
the extent commercially feasible, and consistent with prevailing business
practices, all products manufactured or sold under this Agreement will be marked
with the number of each issued patent that applies to such product.
12.3 This
Agreement shall be construed, governed, interpreted and applied in accordance
with the laws of Illinois, without regard to principles of conflicts of law
thereof, except that questions affecting the construction and effect of any
patent shall be determined by the law of the country in which the patent was
granted.
12.4 The
parties hereto acknowledge that this Agreement (including the Exhibits hereto)
sets forth the entire Agreement and understanding of the parties hereto as to
the subject matter hereof, and shall not be subject to any change or
modification except by the execution of a written instrument subscribed to by
the parties hereto.
12.5 The
provisions of this Agreement are severable, and in the event that any provisions
of this Agreement shall be determined to be invalid or unenforceable under any
controlling body of the law, such invalidity or unenforceability shall not in
any way affect the validity or enforceability of the remaining provisions
hereof.
12.6 The
failure of either party to assert a right hereunder or to insist upon compliance
with any term or condition of this Agreement shall not constitute a waiver of
that right or excuse a similar subsequent failure to perform any such term or
condition by the other party.
12.7 Licenses of Intellectual
Property; Bankruptcy Code. The parties agree that the licenses
granted by the parties to the other to use KNOW-HOW constitute licenses of
“intellectual property” as defined in the United States Bankruptcy Code (the
“Bankruptcy Code”) and as used in Section 365(n) of the Bankruptcy
Code. The parties agree that the KNOW-HOW includes trade
secrets. The parties also agree that the payments of royalties on Net
Sales required to be paid by ES to RGI under this Agreement constitute
“royalties” under Section 365(n) of the Bankruptcy Code.
ARTICLE 13—XXXX
SUBLICENSE
13.1 XXXX
Sublicense. ES grants RGI a non-exclusive royalty-free
sublicense to use XXXX Technology solely for the purpose of developing,
producing, making, and providing to ES CELLS and CELL LINES under this
Agreement. Except as required for such purpose, no other license or
sublicense of XXXX Technology is granted or shall be implied by this
Agreement. RGI agrees that (a) XXXX Technology may be used by RGI
only for the purpose of producing, making, and providing to ES CELLS and CELL
LINES under this Agreement; (b) RGI shall not sell, use, or transfer any CELLS
or CELL LINES produced using XXXX Technology to any third party other than ES;
(c) RGI shall not use XXXX Technology or CELLS or CELL LINES created, produced,
or developed using XXXX Technology in any
13
manner
not permitted by the XXXX license, (d) RGI shall not grant any sublicense or
assign any of its rights to use XXXX Technology, and (e) RGI’s right to use XXXX
Technology shall terminate upon the termination of the XXXX license or this
Agreement, whichever first occurs.
13.2 Certain
Definitions. “XXXX” means Wisconsin Alumni Research
Foundation. “XXXX Technology” means technology under patents licensed
by BioTime from XXXX and sublicensed by BioTime to ES.
[The next
page is the signature page]
14
IN WITNESS WHEREOF, the parties have
duly executed this Agreement as of the Effective Date set forth
above.
REPRODUCTIVE
GENETICS INSTITUTE
By: /s/ Xxxx
Xxxxxxxxx
Printed
Name: Xxxx Xxxxxxxxx
Title: Chief
Executive Officer
By: /s/
Xxxx
Xxxxxxxxx
Printed
Name: Xxxx Xxxxxxxxx
Title: COO
EMBRYOME
SCIENCES, INC.
By: /s/ Xxxxxxx X.
Xxxx
Printed
Name: Xxxxxxx X. Xxxx
Title:
Chief Executive Officer
By: /s/ Xxxxxx
Xxxxxx
Printed
Name: Xxxxxx Xxxxxx
Title:
Secretary
15
EXHIBIT
A
List of
ES-cell lines with cytogenetic disorders Updated 11/07/2008
1
|
hESC-104
|
69,XXY
|
2
|
hESC-145
|
47,XXY
|
3
|
hESC-168
|
46,XX
der(4) t(4;13)
|
4
|
hESC-184
|
47,XX
+13
|
5
|
hESC-208
|
47,XX
+14
|
6
|
hESC-245
|
47,XXY
|
7
|
hESC-252
|
47,XXX
|
8
|
hESC-257
|
47,XY
+12
|
9
|
hESC-267
|
45,XX
-22
|
10
|
hESC-278
|
47,XY
+der(21)t(2,21)
|
11
|
hESC-300
|
46,X
+MAR
|
12
|
hESC-310
|
46,XX
t(14;17)
|
13
|
hESC-321
|
47,XX
+21
|
14
|
hESC-339
|
46,XX
iso(17q)
|
15
|
hESC-359
|
47,XX
+12
|
16
List of
ES-cell lines with genetic disorders Updated 10/29/2008
Cell
Line ID
|
Genetic
Disorder
|
hESC-201
|
ADRENOLEUKODYSTROPHY;
ALD; affected (I801 del AG)
|
hESC-279
|
ALBINISM,
OCULAR, TYPE I; OA1, affected, male (c.25ldel C)
|
hESC-285
|
ALBINISM,
OCULAR, TYPE I; OA1, carrier (N / c.251del C)
|
hESC-414
|
BREAST
CANCER, FAMILIAL (BRCA2); affected (N/IVS7 GT
del)
|
hESC-413
|
BREAST
CANCER, FAMILIAL (BRCA2); affected (N/IVS7 GT del) & MULTIPLE
ENDOCRINE NEOPLASIA, TYPE I; MEN1 affected (N/3036 4bp
del)
|
hESC-416
|
CYSTIC
FIBROSIS; affected (AF508/1717-1 G>A)
|
hESC-417
|
CYSTIC
FIBROSIS; affected (AF508/ 17-17-1 G-A)
|
hESC-288
|
CYSTIC
FIBROSIS; affected (AF508/AFSfl8)
|
hESC-289
|
CYSTIC
FIBROSIS; affected (AF508/AF508)
|
hESC-411
|
CYSTIC FIBROSIS affected
(AF508/AF508)
|
hESC-412
|
CYSTIC
FIBROSIS,
affected (AF508/AF508)
|
hESC-410
|
CYSTIC
FIBROSIS, affected (N1303K/AF508)
|
hESC-257
|
CYSTIC
FIBROSIS, affected (W1282X/R117C)
|
hESC-148
|
DYSTROPHIA MYOTONICA
1, affected
|
hESC-153
|
DYSTROPHIA MYOTONICA
1, affected
|
hESC-246
|
XXXXX-XXXXXXXX
MUSCULAR DYSTROPHY, X-LINKED; EDMD, affected (XY)
|
hESC-357
|
XXXXX-XXXXXXXX
MUSCULAR DYSTROPHY, X-LINKED; EDMD, affected (XY)
|
hESC-358
|
XXXXX-XXXXXXXX
MUSCULAR DYSTROPHY, X-LINKED; EDMD, affected (XY)
|
hESC-245
|
XXXXX-XXXXXXXX
MUSCULAR DYSTROPHY, X-LINKED; EDMD, carrier (XXY)
|
hESC-328
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A, affected
|
hESC-330
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A, affected
|
hESC-333
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A, affected
|
hESC-399
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A, affected
|
hESC-401
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A, affected
|
hESC-402
|
FACIOSCAPULOHUMERAL
MUSCULAR DYSTROPHY 1A; FSHMD1A,
affected
|
00
xXXX-000
|
XXXXXXXXXXXXXXXXXXX
XXXXXXXX XXXXXXXXX 0X; FSHMD1A, affected
|
hESC-128
|
FANCONI
ANEMIA, COMPLEMENTATION GROUP A; FANCA, carrier (N/14bp
del)
|
hESC-214
|
FRAGILE
SITE MENTAL RETARDATION 1, affected male
|
hESC-125
|
FRAGILE
SITE MENTAL RETARDATION 1, carrier
|
hESC-356
|
HEMOGLOBIN-ALPHA LOCUS;
HBA, affected (-- /--)
|
hESC-164
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (cd39 / IVS1-110)
|
hESC-418
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (cd8+G/619del)
|
hESC-233
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (HbS/HbS - sickle cell
anemia)
|
hESC-405
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (lVSI-5/Cd8+G)
|
hESC-223
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (IVSI-6/IVSI-6)
|
hESC-254
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (Unknown / IVSII-1)
|
hESC-277
|
HEMOGLOBIN-BETA
LOCUS; HBB, affected (Unknown/IVSII-1)
|
hESC-158
|
HEMOGLOBIN-BETA
LOCUS; HBB, carrier (N/IVS 1-1)
|
hESC-213
|
HEMOGLOBIN-BETA
LOCUS; HBB, carrier (N/IVSl-1l0)
|
hESC-186
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-187
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-194
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-218
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-396
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-397
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-415
|
HUNTINGTON
DISEASE; HD, affected
|
hESC-154
|
MARFAN
SYNDROME; MFS, affected (N/G7712A )
|
hESC-414
|
MULTIPLE
ENDOCRINE NEOPLASIA, TYPE I; MEN1 affected (N/3036 4bp
del)
|
hESC-170
|
MUSCULAR
DYSTROPHY, XXXXXX TYPE; BMD, affected male
|
hESC-283
|
MUSCULAR
DYSTROPHY, DUCHENNE TYPE; DMD, affected male
|
hESC-301
|
MUSCULAR
DYSTROPHY, DUCHENNE TYPE; DMD, affected male
|
hESC-180
|
MUSCULAR
DYSTROPHY, DUCHENNE TYPE; DMD, carrier
|
hESC-302
|
MUSCULAR
DYSTROPHY, DUCHENNE TYPE; DMD,
carrier
|
18
hESC-137
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (EXON 29 TGG-TGA)
|
hESC-138
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (EXON 29 TGG-TGA)
|
hESC-139
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (EXON 29 TGG-TGA)
|
hESC-140
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (EXON 29 TGG-TGA)
|
hESC-141
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (EXON 29 TGG-TGA)
|
hESC-235
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (N/e.750-75I insT)
|
hESC-315
|
NEUROFIBROMATOSIS,
TYPE I; NF;laffected (R19 47X/N)
|
hESC-326
|
POPLITEAL
PTERYGIUM SYNDROME; PPS; affected (R84H/N)
|
hESC-323
|
SANDHOFF
DISEASE; affected (II20V/5’end l6 kb DEL)
|
hESC-324
|
SANDHOFF
DISEASE; affected (II20V/5' end 16 kb DEL)
|
hESC-395
|
SANDHOFF
DISEASE; affected (II20V/5' end l6 kbDEL)
|
hESC-274
|
SPINAL
MUSCULAR ATROPHY, TYPE I; SMA1, affected
|
hESC-404
|
SPINAL
MUSCULAR ATROPHY, TYPE I; SMA1, affected
|
hESC-271
|
TORSION
DYSTONIA 1, AUTOSOMAL DOMINANT; DYT1, affected (N/ GAG
del)
|
hESC-386
|
TORSION
DYSTONIA 1, AUTOSOMAL DOMINANT; DYT1, affected (N/ GAG
del)
|
hESC-406
|
TORSION
DYSTONIA 1, AUTOSOMAL DOMINANT; DYT1, affected (N/ GAG
del)
|
hESC-407
|
TREACHER
XXXXXXX-XXXXXXXXXXXXX SYNDROME; TCOF (Nt. 4374 ins.
A/N)
|
hESC-408
|
TREACHER
XXXXXXX-XXXXXXXXXXXXX SYNDROME; TCOF (Nt. 4374 ins,
A/N)
|
hESC-316
|
TUBEROUS
SCLEROSIS TYPE 1, affected (N/IVS+1 G ¦^)
|
hESC-320
|
TUBEROUS
SCLEROSIS TYPE 1, affected (N/ IVS7+1 G¦^)
|
19
ID
|
Karyotype
|
Type
|
XXXX0
|
XXXX0
|
XXX00
|
XXX00
|
XXX00
|
Oct4
|
AP
|
FL
|
|||||||||
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-17
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-18
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-21
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-24
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-27
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-31
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-53
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-60
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-63
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-73
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-79
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-80
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-8I
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-00
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-95
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
||
SI-96
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-97
|
46,XY
|
M
|
+
|
||||||
SI-98
|
pending
|
M
|
+
|
4-
|
4-
|
+
|
+
|
||
SI-99
|
46,XY
|
M
|
+
|
4-
|
4-
|
+
|
+
|
00
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
||
SI-101
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-102
|
46,XX
|
M
|
+
|
+
|
|||||
SI-103
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-105
|
46,XX
|
M
|
+
|
+
|
|||||
SI-106
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-107
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-108
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-109
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-110
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-111
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-114
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-115
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-122
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-123
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-124
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-126
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-131
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-132
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-133
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-134
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-135
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-144
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-146
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-149
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-150
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
21
SI-151
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-155
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-156
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-157
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-159
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-160
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-161
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-162
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-163
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-165
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-167
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-169
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-171
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-172
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-174
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-175
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
||
SI-176
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-177
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-178
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-179
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-182
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-183
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-185
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-188
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-189
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-191
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
22
SI-192
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-193
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-195
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-196
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-197
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-198
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-199
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-200
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-202
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-203
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-204
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-205
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-206
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-209
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-210
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-211
|
pending
|
VI
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-215
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-216
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI
217
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-219
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-221
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-222
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-224
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-226
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-227
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-228
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
00
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-231
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-232
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-234
|
45X?
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-236
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-237
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-238
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-239
|
pending
|
M
|
|||||||
SI-240
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-241
|
pending
|
M
|
|||||||
SI-242
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-243
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-244
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-247
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-248
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-249
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-250
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-251
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-253
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-255
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-256
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-258
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-259
|
46XX
|
M
|
|||||||
SI-260
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-261
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
xxxxxxx
|
X
|
00
XX-000
|
00XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-264
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-265
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-266
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
|
SI-268
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-269
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-270
|
46,XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-272
|
46XX
|
H
|
|||||||
SI-273
|
46XX
|
H
|
|||||||
SI-275
|
46XX
|
H
|
|||||||
SI-276
|
pending
|
H
|
|||||||
SI-280
|
46XX
|
H
|
|||||||
SI-281
|
46
XX
|
X
|
|||||||
XX-000
|
00XX
|
X
|
|||||||
XX-000
|
00XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00XX
|
X
|
|||||||
XX-000
|
pending
|
H
|
|||||||
SI-290
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-291
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-292
|
46XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-293
|
46XY
|
free
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-294
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-295
|
46XX
|
M
|
|||||||
SI-296
|
pending
|
M
|
|||||||
SI-297
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-298
|
46XY
|
M
|
00
XX-000
|
00XX
|
X
|
|||||||
XX-000
|
00XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-304
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-305
|
46XY
|
X
|
|||||||
XX-000
|
00XX
|
X
|
|||||||
XX-000
|
00XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-308
|
46XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00XX
|
X
|
|||||||
XX-000
|
00XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-313
|
46XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-322
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-325
|
46,XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-327
|
46XX
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-331
|
46XY
|
M
|
|||||||
SI-334
|
46XX
|
M
|
|||||||
SI-335
|
pending
|
X
|
|||||||
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-337
|
46XX
|
M
|
|||||||
SI-338
|
46XY
|
M
|
|||||||
SI-340
|
46XX
|
M
|
|||||||
SI-341
|
46XY
|
M
|
|||||||
SI-342
|
pending
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-343
|
46XY
|
M
|
|||||||
SI-344
|
pending
|
M+H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-345
|
46XX
|
M
|
|||||||
S1-349
|
46,XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
26
SI-3
50
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-351
|
46XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-352
|
46XX
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-353
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-354
|
46,XY
|
M+H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-0
00
|
00XX
|
XxX
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-357
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-358
|
46XY
|
M
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
XX-000
|
00,XX
|
X
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-363
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-364
|
46XY
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-3
65
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-366
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-367
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-368
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-369
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-370
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
S1-371
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-372
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-373
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-3
74
|
pending
|
H
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
SI-375
|
pending
|
H
|
|||||||
SI-390
|
pending
|
M
|
27