Exhibit
10.1
Confidential
AMENDED AND RESTATED
MANUFACTURING TECHNOLOGY TRANSFER AND
SUPPLY AGREEMENT
BY AND BETWEEN
ANTIGENICS, INC., A MASSACHUSETTS
CORPORATION
AND
GLAXOSMITHKLINE BIOLOGICALS
SA
Confidential
AMENDED AND RESTATED
MANUFACTURING TECHNOLOGY TRANSFER AND SUPPLY
AGREEMENT
This Amended and Restated
Manufacturing Technology Transfer and Supply Agreement (this
“ Agreement ”) is made effective this 16th day
of January, 2009 (“ Effective Date ”) by and
between Antigenics Inc., a Massachusetts corporation and wholly
owned subsidiary of Antigenics Inc., a Delaware corporation, having
offices at 3 Forbes Road, Lexington, MA 02421 (“
Antigenics MA ”), and GlaxoSmithKline Biologicals SA,
a Belgian company, having an address at 89 rue de l’Institut,
1330 Rixensart, Belgium (“ GSK ”) (each
singularly a “ Party ” and collectively the
“ Parties ”).
WHEREAS, Antigenics MA and GSK were
parties to that certain License, Development, and Supply Agreement
entered into effective September 11, 1992 between Cambridge
Biotech Corporation (predecessor to Antigenics MA) and Smithkline
Beecham p.l.c. (predecessor to GlaxoSmithKline plc an Affiliate of
GSK) (as amended, the “ 1992 Agreement ”);
and
WHEREAS Antigenics MA and GSK
terminated and superceeded the 1992 Agreement with that certain
Manufacturing Technology Transfer and Supply Agreement entered into
effective July 6, 2006 between the Parties (the “
2006 Supply Agreement ”) and the License Agreement (as
defined below);
WHEREAS, the Parties entered into
that certain Binding Letter of Intent dated July 20, 2007 (the
“ Letter ”) to accelerate GSK’s
manufacturing rights for QS-21 under the 2006 Supply Agreement;
and
WHEREAS, GSK and Antigenics MA now
desire to memorialize their understanding as described in the
Letter and supercede and amend and restate the 2006 Supply
Agreement with this Agreement;
NOW, THEREFORE, in consideration of
the premises and the mutual covenants and agreements herein
contained, and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the
Parties do hereby agree as follows:
1. Definitions .
The following terms, whether used in
the singular or the plural, shall have the following meanings for
purposes of this Agreement:
1.1 Affiliate ” means
any corporation, firm, partnership or other entity, which controls,
is controlled by or is under common control with a Party. For
purposes of this Section 1.1, “control” means
direct or indirect ownership of fifty percent (50%) or more,
or such lesser percentage which is the maximum allowed to be owned
by a foreign corporation in a particular jurisdiction, of the
outstanding stock or other voting rights entitled to elect
directors thereof or the ability to otherwise control the
management of the corporation, firm, partnership or other
entity.
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1.2 “ BMF ” means
(a) Antigenics MA’s FDA biologics master file(s) for
QS-21 and (b) GSK’s and/or its Affiliate’s and/or
[**] biological master file(s) for QS-21, existing now or at any
time in the future, as the case may be.
1.3 “ Business Day
” means a day on which banking institutions in both Brussels,
Belgium and Boston, Massachusetts are open for business.
1.4 “ cGMP ”
means the current European Guidelines, ICH Guidelines and United
States Good Manufacturing Practices for Finished Pharmaceuticals
pursuant to 21 C.F.R. 210 et seq., as amended from time to
time.
1.5 “ cGMP Consistency
Lots ” means minimum of [**] commercial grade process
validation runs for Antigenics MA’s facility, Manufactured in
accordance with the Specifications.
1.6 “ Completion of the
Transfer of the Manufacturing Technology Package ” means
(a) transfer of all documents of the Manufacturing Technology
Package by Antigenics MA to GSK and (b) performance of a [**]
in accordance with [**] and [**] of [**] at [**] in accordance with
[**] and [**] of [**] at [**], of one (1) [**] of [**] (which
[**] is [**] without any [**] from the [**] which would [**] and
[**]), in accordance with the Manufacturing Technology Transfer
Plan, which [**] shall be [**] the [**] to [**] in [**] with [**],
for the [**] of [**] and [**] the transfer of the Manufacturing
Technology Package. For avoidance of doubt, Completion of the
Transfer of the Manufacturing Technology Package does not require
[**] and [**] of [**].
1.7 “ Confidential
Information ” has the meaning set forth in Article 9
hereof.
1.8 “ Customer ”
means (a) Antigenics MA, in the case where GSK is
Manufacturing and supplying for Antigenics MA hereunder, or
(b) GSK, in the case where Antigenics MA is Manufacturing and
supplying for GSK hereunder.
1.9 “ FDA ” means
the United States Food and Drug Administration or any successor
entity thereto.
1.10 “ First Commercial
Sale ” means the date of first commercial sale of a QS-21
Vaccine by GSK or its Affiliates or Third Party Sublicensees or
distributors anywhere in the Territory.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.11 “ Fully Burdened
Costs ” means: (a) in the case where [**]
Manufactures QS-21 for supply to [**] hereunder, the total cost to
Manufacture by [**] and/or its Affiliates hereunder, which total
cost shall include direct and indirect labor costs, direct material
costs (including without limitation, raw materials, lab supplies
and other materials used directly in Manufacturing QS-21) and
indirect material costs (including without limitation shipping
materials (driven by shipments not batches), stability materials,
batch record materials, sundry supplies to support QS-21
Manufacture, record keeping, stationary, incidental supplies etc.)
calculated in accordance with Generally Accepted Accounting
Principles (“GAAP”), and Other Overhead Costs
calculated in accordance with GAAP [**]; or (b) in the case
where [**] engages a Third Party to Manufacture QS-21 on its behalf
for supply to [**] hereunder, the actual cost to [**] to have QS-21
Manufactured and supplied by such Third Party, including without
limitation, direct and indirect costs borne by [**] for any
internal quality assurance, quality control, fill/finish,
packaging, shipping, and/or delivery, in each case as duly
documented by [**]. In the case [**] is [**]of the [**] (both [**]
and [**]) to meet it supply obligations under this Agreement, the
[**] of the [**] shall be added to the [**]to [**] and/or the
[**]by [**] as appropriate, however, in no event shall any [**] be
included as part of the Fully Burdened Costs. [**] In the event
that [**] Manufactures QS-21 for [**] and/or other customers of
[**] during this period, [**] and these other customers will bear
their appropriate proportionate share of the [**]. For the
avoidance of doubt, in no event shall any of the cost components
exclusive of the Manufacturing direct labor and direct material
costs exceed [**].
For either (a) or
(b) above, Fully Burdened Costs shall also include direct and
indirect costs incurred by [**] as a result of [**] fulfilling its
Manufacturing and supply obligations pursuant to this Agreement,
but shall specifically exclude any costs or expenses otherwise
payable or reimbursable by [**] hereunder, if applicable. Upon [**]
by [**] to [**],[**] estimated Fully Burdened Cost details shall be
updated annually (or semi-annually upon the request of Customer) by
Supplier and shall be [**].
1.12 “ Gross Sales
” has the meaning set forth in Section 1.26
below.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.13 “ GSK Capacity
Date” means the date upon which GSK has commercial grade
QS-21 Manufacturing capabilities such that it is capable of
supplying Antigenics MA with QS-21 in accordance with this
Agreement, but in no event later than [*].
1.14 “ Letter ”
has the meaning set forth in the third Whereas clause.
1.15 “ License
Agreement ” means the license agreement by and between
Antigenics MA and GSK entered into contemporaneously with the 2006
Supply Agreement and providing GSK with license rights under
certain intellectual property to use QS-21 (as defined below) to
develop, make, have made, use, sell, offer for sale and import
certain products containing QS-21.
1.16 “ Licensed
Indications ” means the Vaccine indications licensed to
GSK pursuant to the License Agreement.
1.17 “ Licensed
Vaccines ” means the Vaccines for which GSK has license
rights under the License Agreement.
1.18 “ Manufacture or
Manufacturing ” means the storage, production,
purification, handling, materials procurement, processing, testing,
packaging and release of QS-21 in accordance with this
Agreement.
1.19 “ Manufacturing
Capacity ” means (a) in the case where Antigenics MA
is the Supplier, the amounts of QS-21 binding on GSK as set forth
on Exhibit B attached hereto and incorporated herein, or
such higher capacity as Antigenics MA may advise GSKin accordance
with Exhibit B, and (b) in the case where GSK is the Supplier,
[**] of QS-21 per [**], provided that in the event that
Antigenics MA requests more than [**] of QS-21 per [**], GSK
will reasonably consider any such requests for increased capacity,
such agreement not to be unreasonably withheld if it would not
interfere with GSK’s own QS-21 supply needs.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.20 “ Manufacturing
Improvements ” means any development, enhancement,
improvement, invention, modification, or derivative (whether or not
patentable) necessary for or actually applied to the Manufacture of
QS-21 that is made, discovered, conceived or reduced to practice by
or on behalf of GSK or its Affiliates in the course of the further
development or Manufacturing of QS-21 at any time during the term
of the [**], or the [**] of this Agreement or by Antigenics MA or
its Affiliates in the course of the further development or
Manufacture of QS-21 at any time during the term of the [**], or
the [**] of this Agreement. For the avoidance of doubt,
Manufacturing Improvements specifically exclude any development,
enhancement, improvement, invention, modification, or derivative
(whether or not patentable) relating to [**] (as opposed to [**])
or [**] or [**] or [**] of [**] with a [**] other [**] or any other
[**] of a [**].
1.21 “ Manufacturing
Technology ” means (i) United States Patent No. [**]
(the “‘[**] Patent”), together with any patents
issuing from any continuations, continuations-in-part (to the
extent that the claims therein are directed to subject matter
disclosed in the ‘[**] Patent), divisionals, substitutions,
reissues, reexaminations or extensions of the ‘[**] Patent,
and any foreign counterparts or equivalents of the foregoing, and
(ii) the technical and regulatory information contained in the
Manufacturing Technology Package, and (iii) any know-how owned
or controlled by Antigenics MA (with the right to grant licenses or
sublicenses hereunder) existing as of the effective date of the
2006 Supply Agreement that are necessary or reasonably useful for
the Manufacture of QS-21 and (iv) any Manufacturing
Improvements owned or controlled by Antigenics MA or its Affiliates
(with the right to grant licenses or sublicenses hereunder) whether
or not claimed by a patent filed by Antigenics MA.
1.22 “ Manufacturing
Technology Package ” means all relevant technical and
regulatory information on QS-21 and the QS-21 Manufacturing process
owned and/or controlled by Antigenics MA (with the right to
transfer to GSK BIO), as listed under the heading “Phase 1:
Transfer of Enabling Technology (Manufacturing Technology
Package)” in the Manufacturing Technology Transfer
Plan.
1.23 “ Manufacturing
Technology Transfer Royalty ” has the meaning set forth
in Section 5.3 hereof.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.24 “ Manufacturing
Technology Transfer Plan ” means the written transfer
plan agreed to between the Parties pursuant to the 2006 Supply
Agreement and to be updated by mutual written agreement of the
Parties within a reasonable time after execution of this Agreement,
which forms an integral part hereof, which will set forth the
activities of each Party relating to the objectives, criteria,
milestones and timelines relating to each Party’s
Manufacturing activities hereunder including without limitation,
cooperation of the Parties to ensure [**] between the Parties and
timelines for [**] of QS-21 as further described therein, and as
may be updated from time to time until completion of all
contemplated activities.
1.25 “ Marketing
Approval ” means approval received from the FDA or any
comparable approval in any non-US jurisdiction with any relevant
Regulatory Authority granting the right to commercialize QS-21
Vaccines (but specifically independent of pricing or reimbursement
considerations, where applicable).
1.26 “ Net Sales
” means the amount billed or invoiced on arms length sales of
QS-21 Vaccines by GSK, its Affiliates or Third Party Sublicensees
to Third Parties including its distributors (“ Gross
Sales ”) less deductions duly documented for
(i) normal and customary trade, quantity and cash discounts
and non-affiliated broker’s, distributor’s or
agent’s commissions actually allowed and taken;
(ii) amounts repaid or credited by reason of rejection or
return or retroactive price reduction; (iii) to the extent
separately stated on purchase or sales orders, invoices, or other
documents of sale, sales and excise taxes and duties levied on
and/or other governmental charges made as to production, sale,
importation, transportation, delivery or use paid by or on behalf
of GSK or its Affiliates or Third Party Sublicensees;
(iv) transportation costs including insurance; and
(v) the [**] determined as [**] of [**] and other special [**]
and/or [**] and [**] with Licensed Vaccines; (vi) any [**] to
[**] on [**], provided however that deductions under this
subparagraph (vi) shall not exceed [**] of [**]; and
(vii) contributions and payments required by the United States
Government to be made pursuant to the [**], specifically with
respect to any of [**], and which [**] and [**] have been [**] on
to the [**] and are [**] in the [**] of [**] and which are not
[**], provided however that deductions under this subparagraph
(vii) and subparagraph (v) shall not exceed [**] of [**]
in the [**]. Sales between or among GSK and its Affiliates or Third
Party Sublicensees shall be excluded from the computation of Net
Sales except where the Affiliates or Third Party Sublicensees are
end users, but Net Sales shall include the subsequent final sales
to Third Parties by the Affiliates or Third Party
Sublicensees.
For the avoidance of doubt, in the
event GSK gets any indirect financial interest, income or other
consideration back from the subsequent QS-21 Vaccines sales of GSK
distributors to Third Parties, such financial interest, income or
consideration shall be included as Net Sales.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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In addition, in the event that GSK has entered
into a distribution agreement with a Third Party and which
distribution agreement is in a form that is in economic and
business substance a sublicense relationship and not a traditional
distribution relationship in such country or countries, then such
distributor shall be treated as a Sublicensee for purposes of
calculating Net Sales and royalties hereunder.
If GSK or any of its Affiliates or
Third Party Sublicensees makes any transfer of QS-21 Vaccines to
Third Parties for consideration other than monetary value or as
part of a multi-product transaction, such transfer will be
considered a sale hereunder for Net Sales, accounting and royalty
purposes. Net Sales for any such transfers will be determined on a
country by country basis and will be the average price of
“arms length” sales of QS-21 Vaccines by GSK or its
Affiliates or Third Party Sublicensees in such country during the
royalty reporting period in which such transfer occurs or, if no
such “arms length” sales occurred in such country
during such period, during the last period in which such
“arms length” sales occurred. If no “arms
length” sales have occurred in a particular country, Net
Sales for any such transfer in such country will be the average
price of “arms length” sales of QS-21 Vaccines in all
countries in the Territory by GSK, its Affiliates or Third Party
Sublicensees.
If QS-21 Vaccine(s) is (are) sold as
part of a Combination Vaccine (as hereinafter defined), Net Sales
for purposes of determining royalties on QS-21 Vaccine(s) in the
Combination Vaccine shall be calculated by [**] of the [**] (as
determined in accordance with the provisions of this Section) by
the [**], where [**] is the [**] of the QS-21 Vaccine(s) [**] in
the [**] and [**]) and [**] is the [**] of the [**] in the [**] in
the [**] and [**]).
As used herein, “
Combination Vaccine ” means QS-21 Vaccines formulated
in combination with one or more Other Vaccine Product(s). As used
herein, “ Other Vaccine Product ” means a
vaccine product, other than a QS-21 Vaccine, which is [**] with
[**] and [**] when [**] with the [**] as [**] by [**] to
[**].
In the event that no such separate
sales are made of the QS-21 Vaccine or Other Vaccine Product(s) in
such Combination Vaccine in the relevant country during the royalty
period in question, then by [**] of the [**] (as determined in
accordance with the provisions of this Section) by the [**], where
[**] is the [**] of the [**] in [**] within the [**] and [**] and
[**] is the [**] of the [**] in such [**] within the [**] and
[**].
In the event that no such separate
sales are made of the QS-21 Vaccines or any of the Other Vaccine
Products in such Combination Vaccine in the relevant countries
within the same geographical region and similar economic profile
during the royalty period in question, Net Sales, for the purposes
of determining royalty payments, shall be calculated as [**] in
[**] the [**], provided that in the event the Parties are [**] to
[**] to [**] on [**] after [**], then [**] shall be [**] for [**]
to an [**] to the [**] shall be [**].
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.27 “ Other Overhead
Costs ” for purposes of determining Fully Burdened Costs,
means appropriate [**] and [**] of [**] related to QS-21
Manufacturing activities
1.28 [**] has the meaning set forth
in Section [**] of this Agreement.
1.29 “ Quality
Agreement ” means (i) the Quality Agreement entered
into between the Parties contemporaneously with the 2006 Supply
Agreement, and (ii) the Quality Agreement to be entered into
between the Parties as soon as reasonably possible after the
execution of this Agreement, each as may be revised by the Parties
from time to time and which form an integral part
hereof.
1.30 “ QS-21 ”
means all adjuvant isolated from Quillaja saponaria tree
extract, or any structural equivalents thereof, manufactured by or
on behalf of Customer. For purpose of clarification GSK has no
obligation to Manufacture or have Manufactured any other saponin
outside the agreed Specifications for QS-21, unless otherwise
agreed between the Parties.
1.31 “ QS-21 Vaccine(s)
” means, during the term of the License Agreement, the
Licensed Vaccines, and after expiration of a Valid Claim of the
Licensed Patent Rights covering the applicable Vaccine product,
QS-21 Vaccines means any Vaccine product of GSK or its Affiliates
or Third Party Sublicensees formulated using QS-21.
1.32 “ Regulatory
Authority ” means the U.S. or foreign government agency
or health authority that regulates and grants recommendations for
approvals for the manufacture and sale of pharmaceutical
products.
1.33 “ Release ”
has the meaning set forth in Section 4.1 hereof.
1.34 “ Specifications
” means the applicable release specifications for QS-21
agreed to by the Parties and set out in Exhibit A attached
hereto and incorporated herein, as may be amended from time to time
by mutual agreement of the Parties.
1.35 “ Steering
Committee ” means the Steering Committee maintained in
accordance with this Agreement.
1.36 “ Sublicensee
” means any Affiliate or Third Party to whom GSK grants a
sublicense of any of the license rights granted to GSK pursuant to
the terms and conditions of the License Agreement.
1.37 “ Supplier ”
means (a) Antigenics MA, in the case where Antigenics MA is
Manufacturing and supplying for GSK hereunder, or (b) GSK, in
the case where GSK is Manufacturing and supplying for Antigenics MA
hereunder.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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1.38 “ Term ” has
the meaning set forth in Section 8.1 hereof.
1.39 “ Territory
” means the world.
1.40 “ Third Party
” means any entity other than the Parties to this Agreement
or their respective Affiliates.
1.41 “ Vaccine ”
means a preparation in finished form (not requiring any further
processing or packaging prior to sale to the end user).
1.42 “ 2006 Supply
Agreement ” has the meaning set forth in the second
whereas clause.
2. Steering Committee,
Manufacturing Technology Transfer, Cooperation and License
Rights .
2.1 General . The Parties
acknowledge that Antigenics MA transferred the Manufacturing
Technology Package to GSK in accordance with the Manufacturing
Technology Transfer Plan. Both Parties will perform their remaining
respective activities under and in accordance with the
Manufacturing Technology Transfer Plan in order to facilitate
consistency in QS-21 Manufacturing between the two
Parties.
2.2 Steering Committee
.
(a) Antigenics MA and GSK will
maintain a steering committee (the “ Steering
Committee ”) to oversee the activities to be undertaken
pursuant to this Agreement. The Steering Committee will facilitate
communication between the Parties and provide a forum to review any
technology transfer, supply and Manufacturing matters pertaining to
QS-21. The Steering Committee shall consist of three
(3) individuals appointed by each Party or such other number
of representatives the Parties may mutually agree upon and may also
include additional representatives from the Parties, as mutually
agreed, on an ad-hoc basis and shall be co-chaired by GSK and
Antigenics MA. The co-chairs will coordinate agendas and
minute-taking for meetings of the Steering Committee. Each Party
may replace its Steering Committee representatives at any time upon
written notice to the other Party provided that, the Party
intending to change its representative(s) will [**] and will [**]
to any [**]. The Steering Committee may establish certain ad hoc
sub-committees which consider certain matters, including without
limitation, one or more sub-committees (consisting of at least one
(1) individual from each Party) to address (i) technical
matters in dispute that have not been resolved under the Quality
Agreement and (ii) repetitive, specific cGMP
issues.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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(b) The Steering Committee shall
meet (in person, or by teleconference or videoconference as agreed
by the Parties) at least [**] during the [**] and thereafter [**]
(or more frequently as the Parties mutually agree is appropriate,
or on such dates and at such times as the Parties shall agree. The
Steering Committee (itself or through one or more sub-committees as
contemplated in Section 2.2(a) above) will, among other
things: (i) oversee the disclosure of Manufacturing
Improvements in accordance with this Agreement; (ii) review
and manage the Manufacturing relationship hereunder, including
without limitation, review the Manufacturing requirements for QS-21
for Customer, (iii) discuss and review for Supplier’s
reasonable consideration, the [**], discuss and review validation
plans for Manufacturing, QC testing and facilities, and coordinate
efforts to ensure [**] between the two Parties; and
(iv) address such other matters as may be agreed to between
the Parties, including open matters that may exist at the level of
the sub-committees. In addition and without limiting the foregoing,
the Steering Committee shall meet [**] starting [**] to discuss
[**] and [**], with respect to QS-21 Manufacturing to ensure that
GSK will meet the Capacity Date deadline of [**]. In such meetings,
GSK shall provide the Steering Committee with detailed summaries
and updates with respect to the foregoing. All information provided
to Antigenics MA pursuant to this Section shall be considered the
Confidential Information of GSK in accordance with Article 9;
provided, however , that GSK grants permission to Antigenics
MA to disclose such information as may be necessary or reasonably
useful: (i) to comply with any applicable laws, rules,
regulations, or guidelines, including to reference and submit any
such information to the FDA and other relevant Regulatory
Authorities and (ii) for Antigenics MA and its Affiliates and
QS-21 licensees and customers to [**] with respect to [**], and
(ii) for inclusion in the QS-21 BMF or comparable filing,
subject to GSK’s confidential obligations to Third Parties.
All information provided to GSK pursuant to this Section shall be
considered the Confidential Information of Antigenics MA in
accordance with Article 9, provided however that Antigenics
MA grants permission to GSK to disclose such information as may be
necessary or reasonably useful: (i) to comply with any
applicable laws, rules, regulations, or guidelines, including to
reference and submit any such information to the FDA and other
relevant Regulatory Authorities, and (ii) for securing product
license with respect to QS-21 Vaccines, subject to Antigenics
MA’s confidential obligations to Third Parties. For the
avoidance of doubt, nothing in this subsection shall extend the
limitation on Antigenics MA’s right to grant sublicenses to
practice Manufacturing Improvements to Manufacture QS-21 as set
forth in Section 2.6 below.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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(c) Subject to Section 10.1
below, the Steering Committee will operate by consensus, and each
Party will consider the other Party’s input in good faith,
provided however that [**] shall [**] in [**] on the [**] with [**]
with respect to [**], provided that (x) [**] shall not [**] in
[**] that [**] in [**] to a [**] or other [**], or [**] in [**]
between (i) [**] and [**] (or, in the case of [**], its [**])
[**], or (ii) each [**], or [**] hereunder); and
(y) without in any way limiting (x), Customer shall indemnify
and hold harmless Supplier from any liability incurred by Supplier
as a result of [**].
2.3 Manufacturing Technology
Transfer Plan, Manufacturing Technology Transfer Team and
Manufacturing Technology Package .
(a) Manufacturing Technology
Transfer Plan . The Parties will use commercially reasonable
efforts to update the Manufacturing Technology Transfer Plan and
perform their respective activities thereunder, in an efficient and
timely manner and in accordance with any schedule that may be set
forth in the Manufacturing Technology Transfer Plan. The Parties
acknowledge that Antigenics MA has transferred to GSK all documents
under the Manufacturing Technology Package and the Parties have
completed the Phase 1 of the Manufacturing Technology Transfer Plan
in accordance with the timelines set forth in the 2006 Supply
Agreement. The Parties shall use commercially reasonable efforts to
complete their obligations under the Manufacturing Technology
Transfer Plan.
(b) Establishment of
Manufacturing Technology Transfer Team . Until completion of
the Manufacturing Technology Transfer Plan (as shall be amended by
the Parties in accordance with this Agreement), GSK and Antigenics
MA shall maintain a Manufacturing Technology Transfer Team
comprised at least of four (4) representatives designated by
GSK and at least four (4) representatives designated by
Antigenics MA; provided that GSK and Antigenics MA may
designate an equal number of additional representatives from time
to time. Either Party may change its designees to the Manufacturing
Technology Team at any time upon written notice to the other Party.
Each representative shall have appropriate skills and competencies
for its role on the team.
(c) Contact Persons . The
Parties will identify contact persons to serve as the primary
contacts for and day-to-day management of the disclosure of the
Manufacturing Improvements under the Manufacturing Technology
Transfer Plan and this Agreement.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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(d) Transfer of the Manufacturing
Technology Package . The Parties acknowledge that Antigenics MA
has accomplished the Completion of the Transfer of the
Manufacturing Technology Package and GSK has made the payment
described in Sections 5.2 (a) and (b) below in accordance
with the provisions of Section 5.2.
2.4 Regulatory Cooperation
.
(a) Access to Regulatory
Documents and Communications . GSK will have the right to
cross-reference Antigenics MA’s BMF, and Antigenics MA has
provided GSK with a redacted copy of such BMF. GSK shall also have
the right to file or have filed its own BMF, and shall provide and
hereby provides Antigenics MA (and its Third Party manufacturer,
Affiliates, and QS-21 licensees and customers) with an automatic,
blanket right to cross-reference such BMF for all indications. GSK
shall provide Antigenics MA with a redacted copy of any such BMF.
In addition, each Party shall provide the other Party with relevant
sections of its BMF upon update, and shall maintain its BMF for a
period of [**] from the Effective Date of this Agreement, unless
otherwise agreed to between the Parties. In addition, GSK shall
promptly cooperate with Antigenics MA and provide Antigenics MA
with any necessary additional documentation to effectuate the
foregoing. In addition, each Party shall promptly send the other
Party a copy of any material notices, material reports, and other
material communications it has received from any Regulatory
Authority or other governmental entity concerning QS-21. Antigenics
MA will discuss with GSK any material documents relating to
Manufacturing matters for the QS-21 Vaccines pertaining to the
QS-21 that Antigenics MA receives from, or intends to submit to,
the Regulatory Authorities in the Territory in line with
Section 5.8 of the License Agreement and GSK will discuss with
Antigenics MA any material documents relating to Manufacturing
matters for QS-21 or QS-21 Vaccines pertaining to the QS-21 that
GSK receives from, or intends to submit to, the Regulatory
Authorities in the Territory in line with Section 5.8 of the
License Agreement. Upon one Party’s reasonable request, the
other Party will reasonably cooperate with the requesting Party in
support of all regulatory filings involving QS-21, including
participation in meetings with Regulatory Authorities as
appropriate. In addition, Supplier will authorize and reasonably
cooperate with Customer to prepare any visit or inspection
requested by Regulatory Authorities.
(b) Changes to Manufacturing
Processes . Any changes to Manufacturing processes shall be
handled pursuant to the provisions of the Quality Agreement and
Section 2.8 of this Agreement.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
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Confidential
(c) Adverse Events Reporting
. GSK shall be responsible for reporting all safety related events
from studies of QS-21 Vaccines to the appropriate Regulatory
Authorities and agencies according to the applicable local
regulations, including without limitation, the regulations outlined
in 21 CFR 312.32 (and other applicable international regulations).
GSK and Antigenics MA shall keep each other informed of any serious
adverse reactions, or other significant, unusual or unexpected
safety findings related to QS-21 as provided for in
Section 5.8 of the License Agreement.
(d) Compliance .
Notwithstanding the foregoing and for the avoidance of doubt,
(i) GSK shall comply, and shall cause its Sublicensees to
comply, with the Specifications, the cGMP and all applicable
federal and state laws, rules, regulations and guidelines in
connection with its performance under this Agreement, the
Manufacture of QS-21, and the development and commercialization of
QS-21 Vaccines; and (ii) Antigenics MA shall comply, and shall
cause its Affiliates and Third Party Manufacturer (other than the
contract manufacturer selected by the Steering Committee, whose
compliance shall be the joint responsibility of Antigenics MA and
GSK) to comply, with the Specifications, the cGMP and other
applicable federal and state laws, rules and regulations in
connection with its performance under this Agreement and the
Manufacture of QS-21. Without limiting the generality of the
foregoing, GSK shall use Commercially Reasonable Efforts (as such
term is defined in the License Agreement) to ensure compliance with
all applicable product safety, product testing, product labeling,
package marking, and product advertising laws and regulations and
International Conference on Harmonisation (ICH) Guidelines. As
between the Parties, GSK shall be solely responsible for diligently
obtaining all required and/or necessary Regulatory Authority
authorizations and approvals to develop, Manufacture and
commercialize QS-21 Vaccines hereunder and under the License
Agreement.
(e) Product Recalls . Any
products recalls will be handled pursuant to the terms of the
Quality Agreement.
2.5 License Grant to GSK
.
(a) Subject to the terms and
conditions of this Agreement (including without limitation, the
provisions of Article 4 below and the retained rights of Antigenics
MA set forth in Section 2.5(b) below), Antigenics MA hereby
grants to GSK a [**], right and license (with the right to grant
sublicenses to its Affiliates and Sublicensees as defined in the
License Agreement, subject to the provisions of Section 2.5(c)
below) to the Manufacturing Technology for the sole purpose of
Manufacturing QS-21: (i) to supply Antigenics MA (and its
Affiliates and QS-21 licensees and customers) in accordance with
this Agreement, and (ii) to develop, make, have made, use,
sell, offer for sale and import QS-21 Vaccines. To the extent that
Antigenics MA
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
13
Confidential
subcontracts or sublicenses with its
Affiliates or Third Parties to Manufacture for GSK hereunder,
Antigenics MA shall obtain the right under the intellectual
property rights of such Affiliate or Third Party related to the
Manufacture of QS-21, with the right to grant sublicenses to GSK
and its Affiliates (and such license shall be further sublicensable
by GSK to its Affiliates and Sublicensees, subject to the
provisions of Section 2.5(c) below), to use any such
intellectual property necessary for or actually applied to the
Manufacture of QS-21 that is discovered or developed by such
Affiliate or Third Party to preserve the license granted to GSK and
its Affiliates in this Section.
(b) Notwithstanding the provisions
of Section 2.5(a) above, Antigenics MA hereby retains the
right and has the obligation to Manufacture QS-21 for GSK as set
forth in Section 3.1 below, and any other parties. For the
avoidance of doubt, nothing in this Section 2.5 shall be
construed to prevent Antigenics MA from Manufacturing or having
Manufactured QS-21 for itself or any other parties. For the Term of
this Agreement, GSK agrees to Manufacture or have Manufactured
QS-21 solely in accordance with this Agreement, and for the term of
the License Agreement and thereafter to use QS-21 solely to
develop, make, have made, use, sell, offer for sale and import
QS-21 Vaccines.
(c) GSK may grant sublicenses to
Sublicensees provided that:
(i) the Sublicensee will practice
the Manufacturing Technology only to the extent granted to GSK
under this Agreement;
(ii) GSK and each Affiliate
Sublicensee will sign a side letter under which the Affiliate
Sublicensee will agree to be bound by the terms of this
Agreement;
(iii) GSK and each Third Party
Sublicensee shall enter into a written agreement subject to,
consistent with, and not to extend beyond the scope of GSK’s
rights under, and the terms and conditions of, this Agreement, or
provide for Sublicensee obligations inconsistent with or less than
GSK’s obligations under this Agreement, and which written
agreement shall require the Third Party Sublicensee to agree to be
bound by and comply with provisions that are consistent with the
provisions of this Agreement;
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
14
Confidential
(iv) GSK shall remain responsible
for compliance by any Sublicensee receiving a sublicense hereunder
with all terms and conditions of this Agreement relevant to such
Sublicensee. GSK shall promptly provide Antigenics MA with a copy
of the relevant provisions of such agreement entered into with any
Third Party Sublicensee redacted as may be deemed appropriate by
GSK for confidentiality or legal reason; and
(v) in addition and notwithstanding
the foregoing, GSK may grant sublicenses to Affiliate subsidiaries
controlled by GSK without entering into a written side letter or
sublicense agreement with such subsidiaries, provided that GSK
shall and hereby guarantees and remains primarily responsible for
the performance of such subsidiaries in accordance with this
Agreement.
Should this Agreement terminate for
any reason, at GSK’s request (or Antigenics MA’s
election in the event this Agreement and the licenses granted to
GSK hereunder are terminated by Antigenics MA for GSK’s
material breach in accordance with Section 8.4(c)), and
provided that GSK’s Third Party Sublicensee continues to
comply with the provisions of the written agreement to be entered
into pursuant to this Section, the Third Party Sublicense shall
survive, provided that Antigenics MA shall be substituted for GSK
and become the direct licensor of GSK’s Third Party
Sublicensee, provided that Antigenics MA has approved or has not
reasonably objected to such written agreement. However, Antigenics
MA shall assume no obligations of GSK under such written agreement,
other than the obligation to grant the Manufacturing rights
contemplated in this Section 2.5, unless Antigenics MA
otherwise agrees.
2.6 License Grant to Antigenics
MA . Subject to the terms and conditions of this Agreement, GSK
shall grant and hereby grants to Antigenics MA and its Affiliates a
[**], right and license, with the right to grant sublicenses, to
any Manufacturing Improvement (whether or not patented or
patentable) to make or have made QS-21. For the avoidance of doubt,
nothing in this Section 2.6 shall be construed as granting
Antigenics MA any right to [**] or to [**]. To the extent that GSK
subcontracts or sublicenses with its Affiliates or Third Parties
for the performance of GSK’s rights or obligations hereunder
in accordance with this Agreement, GSK shall obtain the right under
the intellectual property rights of such Affiliate or Third Party
related to the Manufacture of QS-21, with the right to grant
sublicenses to Antigenics MA and its Affiliates (and such license
shall be further sublicensable by Antigenics MA), to use any such
intellectual property necessary for or actually applied to the [**]
that is discovered or developed by such Affiliate or Third Party to
preserve the license granted to Antigenics MA and its Affiliates
in
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
15
Confidential
this Section. Notwithstanding the
foregoing, Antigenics MA’s right to grant sublicenses to any
Manufacturing Improvements of GSK to [**] conceived and reduced to
practice after the effective date of the Letter shall be limited to
[**] of [**] provided that such [**] may in no event be a party
listed on Exhibit C-1. In the event that GSK identifies a party not
listed on Exhibit C-1 for whom GSK does not want Antigenics MA to
grant sublicense rights hereunder in the future, and such third
party is a GSK Direct Competitor (as hereinafter defined), such
party may be added to Exhibit C-1 upon mutual agreement of the
Parties. In such an event, GSK shall notify Antigenics MA and shall
provide Antigenics MA with reasonable basis for identifying such
party as a GSK Direct Competitor. In the event that Antigenics MA
disagrees with GSK’s determination, then the matter shall be
resolved in accordance with Section 10.1. A GSK Direct
Competitor shall be defined as any company active in [**] and/or
[**] of [**] and/or [**]. For the avoidance of doubt, not all
parties listed in Exhibit C-1 as of the effective date of the
Letter were Direct Competitors of GSK. For further clarification,
for purpose of this Section the following entities are not to be
regarded as a GSK Direct Competitor: (a) [**] or its [**], or
(b) Third Party contract manufacturers whose primary business
is contract manufacturing, including without limitation, the
parties listed on Exhibit C-2.
2.7 No Other Rights . Except
for the express licenses granted pursuant to this Article 2, no
license, express or implied, is granted by either Party to the
other Party under any intellectual property or other rights owned
or controlled by such Party pursuant to this Agreement.
2.8 Disclosure of Manufacturing
Improvements . For the avoidance of doubt, no obligations on
either Party to disclose Manufacturing Improvements (and in the
case of Antigenics MA, [**]) are implied by the license grants set
forth herein, and the only Manufacturing Improvements (and in the
case of Antigenics MA, [**]) disclosure obligations under this
Agreement are the specific disclosure and reporting obligations
expressly set forth in this Agreement, the Quality Agreement or the
Manufacturing Technology Transfer Plan. The Parties agree that each
Party will promptly disclose to the other Party those Manufacturing
Improvements that are modifications, alternatives, improvements or
other changes to the Manufacturing process that may reasonably
affect the yield, scale, cost, purity, or efficiency of the
Manufacturing process, or the Specifications and shall cooperate
with the other Party for a period not to exceed [**] from the last
supply to the other Party hereunder to enable the other Party to
practice such modifications, improvements or other changes in its
Manufacturing processes in accordance with such other Party’s
rights under this Agreement. For the avoidance of doubt Antigenics
MA shall be entitled to share Manufacturing Improvements conceived
by GSK to its [**] and applicable Regulatory Authorities, but shall
not be entitled to disclose such Manufacturing Improvements to
[**]. In the event that either Party requires the other Party to
Manufacture a batch of QS-21 not otherwise to be produced by such
Party, in furtherance of this provision, the requesting Party
agrees to purchase
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
16
Confidential
such batch at a transfer price of
[**] of the [**]. In addition, in the event that either Party
requires the other Party to perform any analytical testing outside
of the Manufacture of QS-21 in accordance with the provisions of
Article 3 in furtherance of this provision and not otherwise to be
performed by such Party, the Parties shall negotiate in good faith
a [**] to be paid by the requesting Party for such
services.
3. Manufacture and Supply
Obligations .
3.1 Supply Obligations of
Antigenics MA . The Parties acknowledge and agree that, subject
to the terms and conditions contained in the 2006 Supply Agreement,
until the Manufacturing Transition Date (as defined under the 2006
Supply Agreement), GSK agreed to purchase solely from Antigenics MA
or it Affiliates (or [**] or another Third Party manufacturer
approved by GSK, such approval not to be unreasonably withheld or
delayed), and Antigenics MA or its Affiliates (or a Third Party
manufacturer approved by GSK, such approval not to be unreasonably
withheld or delayed) agreed to supply GSK and its Sublicensees with
one hundred percent (100%) of their initial requirements of
QS-21 (subject to the Manufacturing Capacity) for use solely in the
development, marketing and sale of QS-21 Vaccines in the Territory.
However, after the effective date of the Letter, GSK had and shall
have no further obligation to purchase QS-21 from Antigenics MA (or
its Affiliates or Third Party designee), and Antigenics MA (or its
Affiliates or Third Party designee) shall have no further
obligation to supply GSK and its Sublicensees QS-21, subject to the
remaining provisions of this Section 3.1. Subject to the terms
and conditions contained in this Agreement, GSK shall purchase from
Antigenics MA (or its approved Third Party manufacturer) and
Antigenics MA (or its approved Third Party manufacturer) shall
supply to GSK, pre-commercial grade QS-21 in the amounts and
timelines set forth on Exhibit B.
3.2 Supply Obligations of GSK
. At and upon Antigenics MA’s election but not before the GSK
Capacity Date, and subject to the terms and conditions contained in
this Agreement, GSK shall supply Antigenics MA (and Antigenics
MA’s Affiliates and QS-21 licensees and customers) with up to
[**] per [**] of commercial grade QS-21 for up to [**] from the
[**] of [**] from Antigenics MA to GSK. GSK shall reasonably
consider any request by Antigenics MA or its Affiliates or [**] to
extend the [**] supply term if such request will not unreasonably
interfere with GSK’s business or QS-21 supply needs. GSK
shall keep Antigenics MA informed as to its timelines for having
commercial grade QS-21 Manufacturing capabilities. In the event
that GSK determines that there is a possibility that it will not be
able to supply QS-21 to Antigenics MA by [**], or thereafter have
an inability to supply Antigenics MA with quantities requested by
Antigenics MA, GSK shall immediately notify Antigenics MA and
cooperate with Antigenics MA to address such inability. For the
avoidance of doubt, Antigenics MA has no obligation to purchase
QS-21 from GSK.
[**] = Portions of this exhibit have
been omitted pursuant to a confidential treatment request. An
unpredicted version of this exhibit has been filed separately with
the Commission.
17
Confidential
3.3 Supply to GSK’s
Sublicensees . Prior to supplying any Sublicensee under the
License Agreement with QS-21 supplied to GSK hereunder, GSK shall
enter into a written agreement with such Subl
