Confidential Treatment Requested. Confidential portions of this document have been redacted and separately filed with the Commission. LICENSE AGREEMENT
Confidential
Treatment Requested. Confidential portions of this document have been redacted
and separately filed with the Commission.
This
LICENSE
AGREEMENT
(this
“Agreement”),
effective as of June 2, 2004 (the “Effective
Date”),
is
between CUBIST
PHARMACEUTICALS, INC.,
a
corporation organized and existing under the laws of Delaware (together with
its
Affiliates referred to herein as “CUBIST”)
and
XTL
BIOPHARMACEUTICALS LTD.,
a
corporation organized and existing under the laws of Israel (together with
its
Affiliates referred to herein as “XTL”).
XTL
and CUBIST are sometimes hereinafter referred to each as a “Party”
and
collectively as the “Parties.”
Background
XTL
has
developed monoclonal antibodies that are active against Hepatitis B using XTL
Know-How and has rights to XTL Patent Rights. CUBIST desires to obtain a license
under the XTL Patent Rights and XTL Know-How upon the terms and conditions
set
forth herein in order to Obtain Regulatory Approval and commercialize such
monoclonal antibodies, and XTL desires to grant such a license. In consideration
of the foregoing premises and the mutual covenants herein contained, the Parties
hereby agree as follows:
Terms
Section
1. DEFINITIONS.
1.1 Defined
Terms.
Unless
specifically set forth to the contrary herein, the following terms, whether
used
in the singular or plural, shall have the respective meanings set forth
below:
“Additional
HBV Products”
shall
mean any and all compounds, products, methods or systems, other than a Product
or a Directly Competitive Product, in any formulation for the treatment or
prevention of Hepatitis B, that is Controlled by XTL as of the Effective Date
or
at any time during the term of this Agreement.
“Affiliate”
shall
mean, with respect to any Person, (a) any other Person of which fifty percent
(50%) or more of the securities or other ownership interests representing the
equity, the voting stock or general partnership interest are owned, controlled,
or held, directly or indirectly by, or under common ownership or control with,
such Person; or (b) any other Person that, directly or indirectly, owns,
controls, or holds fifty percent (50%) or more of the securities or other
ownership interests representing the equity, the voting stock or, if applicable,
the general partnership interest, of such Person.
“Aggregate
Designated Costs”
shall
have the meaning set forth in Section 7.4.
“Approved
Third Party Licenses”
shall
have the meaning set forth in Section 12.10(c).
“Change
of Control”
shall
mean, with respect to either Party, that a Third Party shall have become the
beneficial owner of securities representing at least fifty percent (50%) or
more
of the aggregate voting power of the then outstanding voting securities of
such
Party, or any sale by such Party of all or substantially all of such Party’s
assets; provided
that in
no event shall the sale by a Party of securities in connection with a financing
or offering undertaken to raise working capital be deemed to be a Change of
Control unless, as a result of such financing or offering, a Person owns 50%
or
more of the voting power of the Party.
“Code”
shall
have the meaning set forth in Section 13.6(d).
“Combination
Product”
shall
mean (a) any product, or biologic or pharmaceutical composition comprising,
among other things, at least two distinct active ingredients, one of which
shall
be a Product and at least one of the other active ingredients is not a Product,
or (b) two or more products, or biologic or pharmaceutical compositions that
are
marketed and sold together in the same package, where at least one of such
products, or biologic or pharmaceutical compositions is a Product and at least
one of the other products, or biologic or pharmaceutical compositions are not
Products (including, without limitation, (i) a pharmaceutical or biologic
composition containing an active ingredient distinct from the active ingredient
of such Product, (ii) a delivery device or (iii) a delivery system).
“Commercialize”
shall
mean all activities relating to the commercialization of a Product including,
without limitation, promotion, marketing, sales and distribution, whether
conducted by a Party or for such Party by another, and “Commercialization”
shall
be interpreted accordingly.
*****
Confidential material redacted and filed separately with the
Commission.
“Commercially
Reasonable Efforts”
means
(a) with respect to any objective by any Party, commercially reasonable,
diligent, good faith efforts to accomplish such objective as such Party would
normally use to accomplish a similar objective under similar circumstances;
and
(b) with respect to any CUBIST objective to Obtain Regulatory Approval of or
Commercialize any Product, efforts and resources normally used by such Party
with respect to a product owned by such Party or to which such Party has similar
rights which is of similar market potential at a similar stage in the
development or life of such product, taking into account all relevant factors
in
all relevant jurisdictions, taken as a whole, including, but not limited to,
issues of safety, efficacy, product profile, the competitiveness of the
marketplace, the proprietary position of the product (including whether the
Product is reasonably likely to infringe the intellectual property or other
proprietary rights of a Third Party in any jurisdiction), the regulatory
structure involved and the Regulatory Approval for the Product in each
jurisdiction (including but not limited to, the extent of the indications for
such Product has been approved), the level of reimbursement available for the
Product in each jurisdiction, and the perceived market potential of the Product
(including the anticipated profitability of the Product).
“Consent
Agreement”
shall
mean that certain Consent and Amendment Agreement by and among CUBIST, XTL,
and
Yeda executed on or about the Effective Date.
“Contract
Year”
shall
mean each twelve month period during the term of this Agreement commencing
on
January 1, and ending on December 31; provided
that the
first Contract Year during the term of this Agreement will commence on the
Effective Date and end on December 31 and the last Contract Year during the
term
of this Agreement will commence on January 1 and end upon expiration or
termination of this Agreement.
“Control”
shall
mean with respect to (a) any item of information or (b) any intellectual
property right or (c) any HBV Antibody (including any intellectual property
or
other proprietary right embodied therein or related thereto, including without
limitation any method or process of manufacturing thereof or any use thereof),
the possession of the right (whether directly or indirectly and whether by
ownership, license or otherwise, other than pursuant to this Agreement) by
a
Party to grant to the other Party access or a license as provided in this
Agreement under such item of information or intellectual property right without
violating the terms of any agreement or other arrangements existing before
or
after the Effective Date between such Party and any Third Party, and the term
“Controlled”
shall be
interpreted accordingly.
“Coordinator”
shall
have the meaning set forth in Section 3.2.
“CUBIST
Designated Costs”
shall
mean, with respect to any period, the Designated Costs attributed to
CUBIST.
“CUBIST
Indemnitees”
shall
have the meaning set forth in Section 11.3(b).
“CUBIST
Inventions”
shall
have the meaning set forth in Section 12.1.
“CUBIST
Know-How”
shall
mean all inventions (including without limitation all CUBIST Inventions),
discoveries, improvements, methods, processes, formulas, materials, data,
know-how, technology, trade secrets and information, whether or not patentable,
that (a) are owned or Controlled by CUBIST as of the Effective Date or at any
time during the term of this Agreement, (b) are not, as of the Effective Date
or
at any time thereafter, in the public domain or generally known or available
to
the public or disclosed in any CUBIST Patents, and (c) are necessary or useful
to Obtain Regulatory Approval, manufacture, market, promote, sell, import or
export Products in the Territory.
“CUBIST
Patents”
shall
mean any and all Patents that: (a) are owned or Controlled by CUBIST as of
the
Effective Date or at any time during the term of this Agreement; and (b) claim
or cover any invention (including, without limitation, any CUBIST Invention),
discovery, improvement, method, process, formula, material, trade secret,
technology, data or information, solely to the extent necessary or useful to
Obtain Regulatory Approval, manufacture, market, promote, sell, import or export
Products in the Territory; provided,
however, that the CUBIST Patents are all to the extent and only to the extent
that CUBIST has the right to grant licenses or sublicenses
thereunder.
“CUBIST
Trademark”
shall
mean any Trademark Controlled by CUBIST.
2
*****
Confidential material redacted and filed separately with the
Commission.
“Designated
Costs”
shall
mean the direct costs and expenses, in Dollars, excluding any general and
administrative
overhead costs and expenses, actually incurred from and after the Effective
Date
in performing those activities that are necessary or advisable to Obtain
Regulatory Approval for a commercially viable formulation of HepeX-B for the
prevention of recurrent Hepatitis B infections in liver transplant patients
in
the Territory. Subject to the foregoing provisions of this definition,
Designated Costs shall include: internal human resources costs of either Party
(calculated using actual local salary and employee benefit rates for
each
Full Time Equivalent), expenses paid to contractors, consultants or other third
parties (such as testing laboratories, clinical consultants, clinical research
organizations, contract manufacturing organizations and preclinical
laboratories), including costs and expenses associated with regulatory fees
(such as PDUFA fees), laboratory supplies, office supplies, travel expenses,
and
reasonable allocations of facility and information technology costs. Designated
Costs shall not include expenses for corporate overhead, profit margin, expenses
for market research, manufacture or supply for commercial use, commercial launch
and other Commercialization activities, post-marketing studies not required
as a
condition to Obtaining Regulatory Approval in the Territory, or participation
on
the Joint Alliance Team. If the Parties are unable to agree whether a particular
cost or expense is a Designated Cost, either Party may submit the matter to
the
dispute resolution procedures set forth in Section 14.
“Directly
Competitive Product”
shall
mean any pharmaceutical or biologic composition (other than a Product
Commercialized by or for CUBIST or its Affiliates or Sublicensees) that contains
an HBV Antibody in any formulation for the treatment or prevention of Hepatitis
B.
“Disagreement
Notice”
shall
have the meaning ascribed to it in Section 2.2.
“Dollars”
shall
mean U.S. dollars.
“ECACC”
shall
mean the European Collection of Cell Cultures.
“FDA”
shall
mean the United States Food and Drug Administration and any successor
agency.
“First
Commercial Sale”
shall
mean, with respect to a Product, any transfer for value in an arm’s-length
transaction to a Third Party distributor, agent or end user in a country or
jurisdiction after obtaining all necessary Regulatory Approvals as may be
necessary for such transfer in such country or jurisdiction.
“HBIg”
shall
mean the immunoglobulin product containing polyclonal antibodies (derived from
human plasma) to hepatitis B surface antigen, and occasionally referred to
as
“HBIg”.
“HBV
Antibody”shall
mean any and all human or humanized monoclonal immunoglobulins, including intact
immunoglobulin molecules and any portion or fragment of an immunoglobulin
molecule, *****, that is directed to and binds to the Hepatitis B virus or
any
portion of the Hepatitis B virus.
“HepeX-B”
shall
mean, without regard to the actual trade name used, any Product containing
the
human monoclonal antibody *****,
and the
human monoclonal antibody *****,
and no
other antibodies or fragments of other antibodies.
“HepeX-B
Plan”
shall
have the meaning set forth in Section 5.2.
“ICC”
shall
have the meaning set forth in Section 14.2(a).
“ICC
Rules”
shall
have the meaning set forth in Section 14.2(a).
“IND”
shall
mean an Investigational New Drug Application, or its foreign equivalent,
regarding Product filed with a Regulatory Authority.
“Joint
Alliance Team”
shall
have the meaning set forth in Section 3.1.
“Joint
Invention”
shall
have the meaning set forth in Section 12.1.
“Joint
Patent”
shall
have the meaning set forth in Section 12.2.
3
*****
Confidential material redacted and filed separately with the
Commission.
“Know-How
Royalty Rate”
shall
have the meaning set forth in Section 10.2.
“Legal
Opinion”
shall
mean a legal opinion that satisfies each of the following conditions: (a) is
addressed to CUBIST for CUBIST’s benefit, (b) provides that CUBIST’s exercise of
its rights and licenses under, and its activities under and pursuant to, this
Agreement, to Obtain Regulatory Approval, make, have made, use, promote, market,
sell, have sold, offer to sell, import, export, and Commercialize HepeX-B,
would
not infringe or misappropriate the intellectual property rights addressed in
that opinion (including by literal infringement and infringement under the
doctrine of equivalents and/or other applicable legal standards), or that such
intellectual property rights are invalid or unenforceable, (c) is provided
by a
nationally recognized United States law firm reasonably acceptable to both
Parties, and (d) was obtained in connection with a joint defense agreement
pursuant to which such nationally recognized law firm enters into an
attorney-client relationship with both XTL and CUBIST for the purpose of
providing such legal opinion.
“Losses”
shall
have the meaning set forth in Section 11.3(a).
“Marketing
Inquiry”
shall
have the meaning ascribed to it in Section 2.2.
“Major
Markets” shall
mean the United States of America, the United Kingdom, Spain, Italy, France,
Germany and Japan.
“Milestone
Event”
shall
have the meaning set forth in Section 9.2(a).
“Net
Sales”
shall
mean the aggregate gross sales actually received by CUBIST from sales of a
Product sold directly by CUBIST or its Affiliate to a Third Party (that is
not
an Affiliate or Sublicensee of CUBIST unless the Affiliate or Sublicensee is
the
end user of the Product) after deducting, if not previously deducted, from
the
amount received the following amounts related specifically to such sales and
not
otherwise recovered or reimbursed to CUBIST or its Affiliate: (a) trade and
quantity discounts in amounts customary in the trade and actually allowed and
taken; (b) returns, rebates, credits and allowances in amounts customary in
the
trade; (c) chargebacks paid on sale or dispensing of Product; and (d) sales
or
excise taxes, freight, postage, transportation, insurance charges, custom duties
and other governmental charges.
For
purposes of clarification, sales of a Product sold directly by a Sublicensee
shall not be included in the calculation of Net Sales, and amounts
received by CUBIST and its Affiliates for the sale of Products among CUBIST
and
its Affiliates for resale shall not be included in the computation of Net Sales
hereunder.
In
the
event that a Product is sold as a component of a Combination Product, then
Net
Sales shall be determined by multiplying the Net Sales of the Combination
Product by the fraction A/(A+B) where A
equals
the
average selling price of such Product sold separately in finished form and
B
equals
the
aggregate average selling price of the relevant other product sold separately
in
finished form, in
each case
in the
relevant country in which sales were made. In the event that no separate sale
of
either Product or the relevant other product is made during the applicable
royalty reporting period and in the relevant country in which the sale of the
Combination Product was made, then Net Sales shall be determined by multiplying
the Net Sales of the Combination Product by a fraction (C/(C+D)), where
C
equals
CUBIST’s
standard fully-absorbed cost of Product and D
equals
the
standard fully-absorbed cost of the relevant other product, in
each case
determined in accordance with United States generally accepted accounting
principles for the relevant country in which sales were made. If the relevant
other product is sold separately in finished form and Product is not, then
Net
Sales shall be determined by multiplying the Net Sales of the Combination
Product by the fraction (E - B)/E, where E
equals
the
average selling price of the Combination Product for the country in which sales
were made.
“Obtain
Regulatory Approval”
shall
mean those actions required or advisable to prepare and submit commercially
viable Products for Regulatory Approval as soon as reasonably practicable,
including without limitation formulation, modification and refinement
activities, determination of dosage, conducting clinical trials, and labeling
the Products.
“OCS”
shall
have the meaning set forth in Section 11.2(h).
“OCS
Technology”
shall
have the meaning set forth in Section 12.1.
“Patent
Royalty Rate”
shall
have the meaning set forth in Section 10.1.
4
*****
Confidential material redacted and filed separately with the
Commission.
“Patents”
shall
mean (a) unexpired letters patent (including inventor’s certificates) which have
not been revoked or cancelled by a government agency or held invalid or
unenforceable by a court of competent jurisdiction, from which no appeal can
be
taken or has been taken within the required time period, including without
limitation any substitution, extension, registration, confirmation, reissue,
re-examination, renewal or any like filing thereof; (b) pending applications
for
letters patent, including without limitation any provisional application,
utility application, continuing prosecution or continuation application,
divisional application, reissue application and/or continuation in part thereof
and (c) any foreign or international equivalents or counterparts of such
unexpired letters patent and pending applications for letters
patent.
“Person”
shall
mean any individual, entity, association, corporation, partnership, limited
liability company, government (or agency or subdivision thereof), trust, joint
venture, or proprietorship.
“Product(s)”
shall
mean any or all pharmaceutical or biological composition(s) containing an HBV
Antibody Controlled by XTL as of the Effective Date or any time thereafter
during the term of this Agreement, alone or in combination with another
antibody, antibody fragment or other active compound, for all indications,
in
any formulation, by any route of administration, including without limitation,
HepeX-B. Each distinct formulation of any of the items referred to in the
foregoing sentence shall be treated as a separate Product.
“Proprietary
Information”
shall
mean all inventions, discoveries, improvements, processes, formulas, materials,
know-how and trade secrets, and all other scientific, clinical, regulatory,
marketing, financial and commercial information or data, whether communicated
in
writing or orally or by sensory detection, which is provided by, or on behalf
of, one Party to the other Party in connection with this Agreement.
“Recalculated
Royalties”
shall
have the meaning set forth in Section 10.1.
“Regulatory
Approval”
shall
mean any approvals (including supplements, variations, amendments, pre- and
post-approvals), licenses, registrations or authorizations of any national,
state or local regulatory agency, department, bureau, commission, council or
other governmental entity, necessary for the sale, import or Commercialization
of Products in the Territory.
“Regulatory
Authority” shall
mean the FDA or any foreign counterpart of the FDA, as applicable.
“Retroactive
Payment Quarter”
shall
have the meaning set forth in Section 10.1.
“Retroactive
Royalty Country”
shall
have the meaning set forth in Section 10.1.
“Retroactive
Royalty Year”
shall
have the meaning set forth in Section 10.1.
“Retroactive
Valid Claim”
shall
have the meaning set forth in the definition of Valid Claim.
“Sublicensee”
shall
mean, without derogating from the Consent Agreement, any Person (other than
an
Affiliate of CUBIST) to whom CUBIST
grants a
sublicense to the license rights granted by XTL to CUBIST
hereunder.
“Sublicensee
Revenues”
shall
mean the aggregate upfront, milestone, royalty and other payments actually
received by CUBIST or its Affiliates from each of its Sublicensees (other than
XTL, if applicable) with respect to XTL Technology or Products, excluding
payments made to reimburse CUBIST for any verifiable costs actually incurred
by
CUBIST in connection with (a) activities to Obtain Regulatory Approval,
manufacture, market, promote, sell, offer to sell, import or export Product
and
(b) the transaction contemplated between CUBIST and such
Sublicensee.
“Territory”
shall
mean all countries of the world.
“Third
Party” shall
mean a Person other than CUBIST or XTL or an Affiliate of either
Party.
“Third
Party Infringement Claim”
shall
have the meaning set forth in Section 12.6(a).
“Third
Party Transaction”
shall
have the meaning set forth in Section 2.3.
5
*****
Confidential material redacted and filed separately with the
Commission.
“TM
Infringement”
shall
have the meaning set forth in Section 12.5.
"Trademark"
shall
mean any word, phrase, slogan, design, symbol or product packaging used or
intended to be used to identify the Products or distinguish them from
competitive or related products, and shall include any application to register
or registration of or common law rights of the foregoing.
“Unlicensed
Product”
shall
mean, with respect to any given country or jurisdiction within the Territory,
any pharmaceutical or biological composition containing an HBV Antibody (except
for HBIg), for sale or use for the treatment or prevention of Hepatitis B
infection or re-infection in such country within the Territory, other
than
as a result of any license, sublicense, distribution or
other arrangement
with respect to a Product or the rights or licensees granted by XTL to CUBIST
hereunder granted or entered into by CUBIST or any of its Affiliates or
distributors.
“Valid
Claim”
shall
mean an unexpired claim of an issued patent within XTL Patents which has not
been found to be invalid or unenforceable by a court or other competent
authority in the subject country, from which decision no appeal is taken or
can
be taken. In the event a claim in a pending patent application Controlled by
XTL
issues in a country and such issued claim has not been found to be invalid
or
unenforceable by a court or other competent authority in the subject country,
from which decision no appeal is taken or can be taken, such claim shall
retroactively be deemed a Valid Claim in such country for the purposes of
royalty and Sublicensee Revenues payments under Section 10.1(b) and Section
10.3(e) as of the date the applicable patent application was filed in such
country (a “Retroactive
Valid Claim”).
“XTL
Activities”
shall
have the meaning set forth in Section 5.1(b).
“XTL
Designated Costs”
shall
mean, with respect to any period, the Designated Costs attributed to
XTL.
“XTL
Indemnitees”
shall
have the meaning set forth in Section 11.3(a).
“XTL
Inventions”
shall
have the meaning set forth in Section 12.1.
“XTL
Know-How”
shall
mean all inventions (including without limitation all XTL Inventions),
discoveries, improvements, methods, processes, formulas, materials, data,
know-how, technology, trade secrets and information, whether or not patentable,
that (a) are owned or Controlled by XTL as of the Effective Date or at any
time
during the term of this Agreement, (b) are not, as of the Effective Date or
at
any time thereafter, in the public domain or generally known or available to
the
public or disclosed in any XTL Patents, and (c) are necessary or reasonably
useful to Obtain Regulatory Approval, manufacture, market, promote, sell, import
or export Products in the Territory.
“XTL
Licensor Payments”
shall
mean any amounts that are required to be paid to Yeda pursuant to the XY
Agreement as supplemented by the Consent Agreement, or any amounts that XTL
is
required to pay to any other Third Party licensors pursuant to written
agreements entered into prior to the Effective Date which are identified on
Exhibit
E
to the
extent that such payments are required (a) with respect to sales of Product,
or
(b) with respect to milestone or royalty payments that XTL receives, or is
deemed to have received under XTL’s agreements with such Third Parties, from
CUBIST.
“XTL
Patents”
shall
mean any and all Patents that: (a) are owned or Controlled by XTL as of the
Effective Date or at any time during the term of this Agreement; and (b) claim
or cover any invention (including, without limitation, any XTL Invention),
discovery, improvement, method, process, formula, material, trade secret,
technology, data or information, solely to the extent necessary or reasonably
useful to Obtain Regulatory Approval, manufacture, market, promote, sell, import
or export Products in the Territory (including, without limitation, those
Patents listed on Exhibit
A);
provided,
however, that the XTL Patents are all to the extent and only to the extent
that
XTL has the right to grant licenses or sublicenses thereunder.
“XTL
Technology”
shall
mean XTL Patents and XTL Know-How.
“XTL
Trademarks”
shall
mean the trademarks Controlled by XTL as of the Effective Date and set forth
on
Exhibit
B
hereto.
6
*****
Confidential material redacted and filed separately with the
Commission.
“XY
Agreement”
shall
mean that certain Research and License Agreement between Xenograft Technologies
Ltd. (now known as XTL Biopharmaceuticals Ltd.) and Yeda Research and
Development Company Ltd. (hereinafter “Yeda”)
executed on or about April 7, 1993, as amended on or about August 31, 1995,
January 25, 1998, and January 26, 2003 and as further amended as of the
Effective Date.
“Yeda
Technology”
shall
have the meaning set forth in Section 12.1.
Section
2. LICENSE;
DILIGENCE; RIGHT OF FIRST NEGOTIATION.
2.1 License
Grant.
Subject
to the terms and conditions of this Agreement and the provisions of the Consent
Agreement, XTL hereby grants to CUBIST the
exclusive right and license (even as to XTL), including the right, subject
to
the Consent Agreement, to sublicense (which includes the sublicense to XTL
under
Section 2.5 below), under the XTL Technology and XTL Trademarks to Obtain
Regulatory Approval, make, have made (including under Section 3.3 below), use,
promote, market, sell, have sold, offer to sell, import or export Products
in
the Territory. CUBIST (excluding Cubist Affiliates) may grant sublicenses of
the
rights licensed to CUBIST pursuant to this Section 2.1 (subject to the
limitations and obligations imposed pursuant to the Consent Agreement). Any
sublicense by CUBIST to a Sublicensee of the rights licensed by XTL to CUBIST
hereunder shall be consistent with the terms and conditions of this Agreement
and the Consent Agreement, and shall include an obligation for the Sublicensee
to comply with the obligations of this Agreement applicable to Sublicensees,
including, without limitation, the applicable obligations contained in Section
4.1(b) pertaining to reports, Section 8.1 pertaining to confidentiality and
Section 8.5 pertaining to records and audits. CUBIST hereby agrees to remain
liable for performance under this Agreement by all Sublicensees (including
CUBIST Affiliates).
2.2 CUBIST
Diligence. (a)
Subject
to, and in accordance with, the terms and conditions of this Agreement and
all
requirements of applicable laws, rules and regulations, CUBIST shall use
Commercially Reasonable Efforts to Obtain Regulatory Approval for HepeX-B in
each of the Major Markets, and subsequent to obtaining Regulatory Approval
in a
Major Market, to Commercialize HepeX-B in such Major Market. The sole remedy
of
XTL for any breach by CUBIST of its obligations under this Section 2.2 with
respect to any Major Market is to terminate CUBIST’s rights and licenses under
this Agreement with respect to such Major Market pursuant to Section 13.4.
In
the event CUBIST breaches its obligations under Section 2.2 with respect to
***** or more Major Market countries, XTL shall also have the right pursuant
to
Section 13.4 to terminate CUBIST’s rights and licenses under this Agreement with
respect to each country that is not a Major Market country in which CUBIST
is
not then using Commercially Reasonable Efforts to Obtain Regulatory Approval
for
HepeX-B, and subsequent to obtaining Regulatory Approval in such country, to
Commercialize HepeX-B in such country. For the avoidance of doubt, CUBIST shall
not be considered to be in violation of its diligence obligations under this
Section 2.2 if the failure to use Commercially Reasonable Efforts as required
under this Section 2.2 is caused in material part by the wrongful acts or
omissions of XTL or any breach of this Agreement by XTL.
(b) CUBIST
shall be deemed to have used Commercially Reasonable Efforts for all purposes
of
this Section 2.2 at all times following such time as CUBIST (and its Affiliates
and Sublicensees) has achieved worldwide Net Sales and Sublicensee Revenues
which, combined, exceed the aggregate amount of $50,000,000. Notwithstanding
anything to the contrary in this Agreement, the “safe harbor” provisions of this
Section 2.2(b) are not intended to set minimum standards of performance by
CUBIST, and CUBIST shall be entitled to demonstrate that other efforts with
respect to the Product should be deemed to be Commercially Reasonable
Efforts.
(c) As
set
forth in Section 2.2(a), the parties agree that XTL’s sole and exclusive remedy
with respect to a material breach by CUBIST of its obligations set forth in
Section 2.2(a) shall be to terminate the rights and licenses granted by XTL
to
CUBIST under this Agreement with respect to those jurisdictions within the
Territory in which CUBIST shall have failed to use Commercially Reasonable
Efforts; provided
that
within sixty (60) days after receipt of any report provided by CUBIST under
Section 4.1(b), XTL shall have delivered to CUBIST written notice (a
“Disagreement
Notice”)
of
such failure, which notice shall set forth in reasonable detail the nature
of
the alleged failure; provided
further
that such failure has not been cured or waived within 60 calendar days following
delivery of such notice. If XTL does not deliver a Disagreement Notice under
this Section 2.2(c) within such sixty (60) day period, CUBIST shall
be
deemed to be in full compliance with the terms of Section 2.2(a) with
respect to the time period covered by such CUBIST report. XTL shall not bring,
commence, continue or prosecute any claim, legal action or proceeding under,
in
relation to, arising out of or in connection with a breach of Section 2.2(a),
except as set forth in Section 2.2(d).
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(d) If
XTL
and CUBIST are not able to resolve their disagreement with respect to CUBIST’s
compliance with Section 2.2(a) within sixty (60) days after CUBIST’s
receipt of a Disagreement Notice, then either XTL or CUBIST, acting alone,
may
at any time following receipt of such Disagreement Notice by delivery to the
other party of a written notice indicating such party’s election to have the
disagreement resolved by arbitration (a “Marketing
Inquiry”),
cause
the matter to be submitted to binding arbitration under Section 14.2;
provided
that (i)
the
arbitrators shall be entitled to review and resolve only whether or not CUBIST
failed to materially comply with its obligations under Section 2.2(a) during
the
applicable reporting period of time that is the subject of the Marketing
Inquiry, and (ii) the arbitrators shall be individuals who are knowledgeable
in
the field of the development, manufacture, and sale of drugs and drug products,
and shall have no current or prior business relationships with any of XTL,
CUBIST, or any of their respective Affiliates.
2.3 Rights
to Additional HBV Product.
Subject
to the limitation set forth below in this Section 2.3, in the event that XTL
intends to grant a license or sublicense (or to otherwise transfer rights other
than pursuant to a Change of Control of XTL) to a Third Party to obtain
regulatory approval or commercialize Additional HBV Products (a "Third
Party Transaction"),
XTL
shall so notify CUBIST (and shall provide together with such notice all such
information necessary or useful to CUBIST to determine whether to exercise
its
rights under this Section 2.3 with respect to the Additional HBV Products as
is
in XTL’s possession or control) prior to entering into negotiations or
discussions with such Third Party Transaction. If, within *****
days
after CUBIST has received such notice (and information) from XTL, CUBIST
notifies XTL in writing that it wishes to negotiate to obtain a license or
sublicense (or otherwise acquire rights to) such Additional HBV Products, then
the Parties shall negotiate in good faith for a period of *****
days to
see if the Parties can reach agreement on commercially reasonable terms pursuant
to which XTL would license or sublicense (or otherwise transfer rights to)
such
Additional HBV Products to CUBIST. During the *****
day
period in which CUBIST and XTL are negotiating pursuant to this Section 2.3,
such negotiations shall be exclusive and XTL cannot carry on discussions or
negotiations with any Third Party regarding the grant of a license or sublicense
(or other transfer of rights) to such Third Party to obtain regulatory approval
or commercialize Additional HBV Products in any country or jurisdiction within
the Territory. If XTL and CUBIST cannot reach agreement on such terms within
such *****
days,
then XTL shall be free to enter into negotiations and discussions with such
Third Party, and enter into a Third Party Transaction; provided,
however, in no event will XTL enter into an agreement with such Third Party
to
obtain regulatory approval or commercialize such Additional HBV Products on
terms, considered in the totality of the circumstances, any less favorable
than
the terms last offered or proposed by CUBIST pursuant to the preceding
provisions of this Section 2.3 without providing CUBIST with written notice
of
such terms and giving CUBIST *****
days to
accept them. Notwithstanding anything expressed or implied in the foregoing
provisions of this Section 2.3, in the event of a Change of Control of XTL,
CUBIST’s rights under this Section 2.3 shall terminate with respect to any
Additional HBV Product of which CUBIST was informed by XTL in writing pursuant
to Section 15.4 (without copies to legal counsel) at least thirty (30) days
prior to the Change of Control of XTL; provided
that if
CUBIST notifies XTL in writing that it wishes to negotiate to obtain a license
or sublicense (or otherwise acquire rights to) such Additional HBV Product
within *****
days
after XTL informed CUBIST of such Additional HBV Product, CUBIST’s rights under
this Section 2.3 shall not terminate with respect to such Additional HBV Product
unless and until XTL has negotiated in good faith for a period of up to
*****
days and
has failed to reach agreement on commercially reasonable terms pursuant to
which
XTL would license or sublicense (or otherwise transfer rights to) such
Additional HBV Product to CUBIST.
2.4 Directly
Competitive Product.
During
the term of this Agreement and until the earlier to occur of (a) the first
anniversary of the effective date of expiration or termination of this Agreement
in its entirety, and (b) the effective date of *****;
XTL
shall not develop, research, market, sell, distribute or otherwise Commercialize
a Directly Competitive Product in the Territory, nor will XTL provide any
services, data or information to any Third Party in the furtherance of, or
with
respect to, any of the foregoing; provided,
however, that the restrictions in this Section 2.4 shall not apply in any
jurisdictions with respect to which Cubist’s rights and licenses granted by XTL
under this Agreement have been terminated pursuant to Section 2.2.
2.5 Sublicensing. (a)
If
CUBIST proposes to sublicense to a Third Party any rights to distribute promote,
market or sell Product in the United States and/or in more than *****
Major
Markets in the European Union, then CUBIST will notify XTL in writing thereof.
If, within thirty (30) days after XTL has received such notice from XTL, XTL
notifies CUBIST in writing that it wishes to negotiate to become CUBIST’s
Sublicensee with respect to the activities to distribute, promote, market or
sell Product described in CUBIST’s notice with respect to such countries, then
the Parties shall negotiate in good faith for a period of *****
days to
see if the Parties can reach agreement on commercially reasonable terms pursuant
to which XTL would serve as such Sublicensee. During the *****
day
period in which CUBIST and XTL are negotiating pursuant to this Section 2.5,
such negotiations shall be exclusive and CUBIST cannot carry on discussions
or
negotiations with any Third Party regarding the opportunity to serve as such
Sublicensee in such countries. If XTL and CUBIST cannot reach agreement on
such
terms within such *****
days,
then CUBIST shall be free to enter into negotiations and discussions with such
Third Party, and grant such a sublicense to such Third Party; provided,
however, in no event will CUBIST grant such a sublicense to such Third Party
on
terms, considered in the totality of the circumstances, any less favorable
to
CUBIST than the terms last offered or proposed by XTL pursuant to the preceding
provisions of this Section 2.5 without providing XTL with written notice of
such
terms and giving XTL *****
days to
accept them.
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(b) Without
limiting clause (a) above, if CUBIST proposes to sublicense to a Third Party
any
rights to distribute promote, market, and sell Product *****,
then
CUBIST will notify XTL in writing thereof and thereafter, XTL, to the extent
that it remains so interested, shall be included among the interested parties
with whom CUBIST holds discussions for such rights until such time as CUBIST
selects the party with whom it wishes to enter into negotiations for a
definitive agreement for such rights. XTL acknowledges that beyond inclusion
and
participation in the discussions for such rights, XTL has no additional right
or
expectation whatsoever, and CUBIST has no additional obligation to XTL in
respect of such rights under this Section 2.5(b).
(c) Notwithstanding
anything expressed or implied in this Section 2.5, in the event of a Change
of
Control of CUBIST, XTL’s rights under this Section 2.5 shall terminate
(except
with respect to any separate written agreement entered into between CUBIST
and
XTL prior to the effective date of such Change of Control;
provided
that
CUBIST has promptly complied with the notice provisions set forth in this
Section 2.5 prior to such Change of Control).
2.6 Trademarks.
XTL
hereby grants CUBIST an exclusive, royalty-free license under its entire right,
title and interest in and to the XTL Trademarks, if any, to use and display
the
XTL Trademarks in connection with the Commercialization of Product within the
Territory. CUBIST shall not be obligated to use XTL Trademarks, and shall be
free to select, create and use its own trade names and marks for its use, in
connection with the Commercialization of Product in the Territory.
Section
3. COORDINATION.
3.1 Joint
Alliance Team.
(a) Within
thirty (30) days after the Effective Date, CUBIST and XTL shall establish
a
committee to exchange information regarding, and to discuss activities to Obtain
Regulatory Approval and manufacture and supply of Product in the Territory
(the
“Joint
Alliance Team”),
which
shall (i) monitor activities to Obtain Regulatory Approval under the
HepeX-B Plan, (ii) discuss, formulate, and recommend proposed modifications
to
the HepeX-B Plan for review by CUBIST and XTL, (iii) serve as a forum for the
review and discussion of the Parties’ efforts to Obtain Regulatory Approval and
efforts to manufacture Product, (iv) serve as a vehicle to facilitate the
transfer to CUBIST of certain information, data and technology related to
Products, and (v) serve as a forum for the discussion of disputes between the
Parties before resorting to the dispute resolution mechanism in Section 14
of
this Agreement.
(b) The
Joint
Alliance Team shall be composed of named representatives of CUBIST and named
representatives of XTL. Each Party shall appoint its respective representatives
to the Joint Alliance Team from time to time, and may substitute one or more
of
its representatives, in its sole discretion, effective upon notice to the other
Party of such change. Of the initial representatives to be designated by each
Party, there shall be expertise in preclinical development, process development,
regulatory activities, clinical development, and manufacturing and supply
matters. The Parties shall be free to change their representatives from time
to
time and at any time. Each representative serving on the Joint Alliance Team
shall have appropriate technical credentials, experience and knowledge, and
ongoing familiarity in the specific area of such representative’s expertise. The
chief business officer, or his/her designee, of each Party shall serve as
co-chair to the Joint Alliance Team. Additional representatives or consultants
may from time to time, by mutual consent of the Parties, be invited to attend
Joint Alliance Team meetings, subject to compliance with the provisions of
Section 8.1 of this Agreement. The co-chairpersons shall be responsible for
calling meetings, preparing and circulating an agenda in advance of each
meeting, and preparing and issuing minutes of each meeting within thirty (30)
days thereafter.
(c) The
Joint
Alliance Team shall hold meetings at such times as it elects to do so, but
in no
event shall
such meetings be held less frequently than once every three (3) months unless
otherwise agreed by the Parties. The first meeting of the Joint Alliance Team
shall be held no later than sixty (60) days after the Effective Date. Meetings
of the Joint Alliance Team may be held by audio or video teleconference with
the
consent of each Party; provided
that at
least two (2) meetings per year shall be held in person, one (1) per year at
the
location of each party or such other location as the Parties may mutually agree.
Each Party shall be responsible for all of its own expenses of participating
in
the Joint Alliance Team. The co-chairpersons will alternate responsibility
for
preparing minutes of each meeting of the Joint Alliance Team, which minutes
will
not be finalized until the co-chairperson that did not prepare such minutes
reviews and confirms the accuracy of such minutes in writing.
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(d) The
Joint
Alliance Team shall operate by consensus. If the Joint Alliance Team is unable
to reach consensus on any particular issue, CUBIST shall have the right in
its
sole discretion to make the final decision. The Joint Alliance Team shall not
have the power resolve any disputes concerning the validity, interpretation
or
construction of, or the compliance with or breach of, this Agreement, which
disputes shall be resolved pursuant to Section 14. The rights and
responsibilities of each Party shall be governed by this Agreement, including
the exhibits hereto, and the Joint Alliance Team shall not have any power to
amend, modify or waive compliance with this Agreement.
(e) Notwithstanding
anything express or implied to the contrary in this Agreement, CUBIST may
terminate the Joint Alliance Team and its functions hereunder, in whole or
in
part, in its sole discretion upon thirty (30) days’ prior written notice to XTL.
Upon termination of the Joint Alliance Team, CUBIST shall assume sole
responsibility to update the HepeX-B Plan from time to time in accordance with
Section 5.2.
3.2 Coordinators. Each
Party shall appoint a designee (a “Coordinator”)
to
coordinate its activities under this Agreement. The Coordinators shall serve
as
primary contacts between the Parties with respect to this Agreement. Each Party
shall notify the other Party within thirty (30) days of the date of this
Agreement of the appointment of its Coordinator and shall notify the other
Party
as soon as practicable upon changing such appointment. The Coordinator appointed
by each Party shall be responsible for (a) preparing such Party’s
representatives serving on the Joint Alliance Team for meetings of the Joint
Alliance Team, (b) coordinating the distribution and exchange of
information to, from and among such Party’s representatives serving on the Joint
Alliance Team, and (c) assisting in the coordination of the day-to-day
activities of such Party’s representatives serving on the Joint Alliance Team so
that the Joint Alliance Team can function effectively and such representatives
can more effectively discharge their responsibilities as members of the Joint
Alliance Team.
3.3 Non-exclusive
Right of Negotiation for Manufacturing Rights.
Subject
to the provisions of this Section 3.3, CUBIST hereby grants XTL a non-exclusive
right of negotiation during the term of this Agreement to obtain all or any
portion of the rights to manufacture and supply Product in the Territory. In
the
event that CUBIST proposes to engage a Third Party manufacturer to manufacture
and supply Product in the Territory, then CUBIST will notify XTL in writing
thereof and thereafter, XTL, to the extent that it remains so interested, shall
be included among the interested parties with whom CUBIST holds discussions
for
the right to manufacture Products in the Territory until such time as CUBIST
selects the party with whom it wishes to enter into negotiations for a
definitive agreement for such rights. XTL acknowledges that beyond inclusion
and
participation in the discussions for such rights, XTL has no additional right
or
expectation whatsoever, and CUBIST has no additional obligation to XTL in
respect of such non-exclusive negotiation rights. CUBIST shall consider
commercially reasonable criteria in selecting its Third Party manufacturers,
including without limitation, the Product specifications, the cost of goods
sold, regulatory requirements and prior experience and performance. Without
limiting the generality of the foregoing, XTL acknowledges that CUBIST shall
have complete liberty to select its manufacturing partners, and to determine
all
manufacturing activities, as CUBIST, in its sole discretion, sees fit, but
consistent with CUBIST’s obligations to use Commercially Reasonable Efforts as
set forth in Section 2.2. Notwithstanding anything expressed or implied to
the
contrary in this Section 3.3, XTL shall be afforded the opportunity to
participate in such negotiations only once during the term of this Agreement
and
in the event that XTL foregoes its non-exclusive right of negotiation for the
manufacture and supply of a particular Product, or if XTL participates in such
negotiations but is not selected by CUBIST, then XTL’s non-exclusive rights
under this Section 3.3 shall terminate. XTL’s
rights under this Section 3.3 will terminate upon a Change of Control of CUBIST
(except
with respect to any separate written manufacturing agreement entered into
between CUBIST and XTL prior to the effective date of such Change of
Control;
provided
that
CUBIST has promptly complied with the notice provisions set forth in this
Section 3.3 prior to such Change of Control).
3.4 Independence. Subject
to the terms of this Agreement, the activities and resources of each Party
shall
be managed by such Party, acting independently and in its individual capacity.
The relationship between CUBIST and XTL is that of independent contractors,
and
neither Party shall have the power to bind or obligate the other Party in any
manner, other than as is expressly set forth in this Agreement.
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Section
4. INFORMATION
SHARING.
4.1 Product
Information.
(a) During
the term of this Agreement, XTL shall have an ongoing obligation to transfer
to
CUBIST all information, including technical data, in XTL’s possession or Control
and related to the Product as CUBIST may reasonably require; provided
that in
the event that XTL is unable to transfer any information or technology to CUBIST
required to be transferred under this Agreement, upon CUBIST’s written request,
XTL shall arrange for the prompt transfer of such information or technology
to
an Israeli subsidiary of CUBIST at XTL’s expense. On the first business day of
each quarter during the term of this Agreement, XTL shall provide CUBIST with
a
written report detailing the activities undertaken by XTL under the HepeX-B
Plan
and the results obtained from such activities. At any time during the term
of
this Agreement, upon reasonable request by CUBIST, XTL shall deliver to CUBIST
or its designee copies of all files in the possession or control of XTL or
its
agents that relate to the Product or activities undertaken by XTL under the
HepeX-B Plan. During
the term of this Agreement and for one (1) year thereafter, XTL shall maintain
all data and other records in XTL’s possession that are obtained or generated by
XTL, its Affiliates or its Third Party service providers in the course of
providing services under the HepeX-B Plan (collectively, “Records”)
in a
safe and secure manner and in accordance with all applicable laws and
regulations. XTL shall make available all Records to CUBIST for examination
and
duplication, during normal business hours and at mutually agreeable times.
During
the term of this Agreement, XTL shall provide CUBIST with reasonable access
to
pertinent XTL employees or members of Third Party contractors that are engaged
in the activities undertaken by XTL under the HepeX-B Plan or have experience
with or information related to any Products. For the purposes of calculating
Designated Costs, XTL’s activities under this Section 4.1(a) (with the exception
of XTL’s obligation to transfer information or technology to an Israeli
subsidiary of CUBIST) in connection with HepeX-B shall be considered to be
activities necessary or advisable to Obtain Regulatory Approval for a
commercially viable formulation of HepeX-B for the prevention of recurrent
Hepatitis B infections in liver transplant patients in the
Territory.
(b) On
or
before February 1st and August 1st of each Contract Year, CUBIST shall provide
to XTL written progress reports summarizing in reasonable detail CUBIST’s
activities to Obtain Regulatory Approval during the six- (6) month period ending
on the preceding December 31st and June 30th,
respectively, as well as anticipated activities to be undertaken during the
subsequent six-month period. CUBIST shall also notify XTL in writing of any
material developments as a result of CUBIST’s activities to Obtain Regulatory
Approval within thirty (30) days thereafter.
4.2 Pre-Clinical
and Clinical Data; Regulatory Filings.
XTL
will
provide to CUBIST
all
relevant pre-clinical or clinical information (including without limitation
that
with respect to Product safety) relating to or in connection with Product in
a
timely fashion and to permit CUBIST to comply with any applicable law or
regulation. No
later
than five (5) days after the Effective Date, XTL will provide CUBIST copies
of
all regulatory filings, INDs, and orphan drug designations, and the results
of
all pre-clinical and clinical testing of Products performed by or on behalf
of
XTL. On an ongoing basis during the term of this Agreement, XTL will provide
to
CUBIST (i) all information in XTL’s possession or control regarding pre-clinical
testing and clinical testing performed or to be performed by or on behalf of
XTL
with respect to the Products (including, without limitation, information
concerning the design and plans with respect to such pre-clinical testing or
clinical testing) as such information becomes available, (ii) the results of
all
pre-clinical and clinical testing performed by or on behalf of XTL with respect
to the Products as such information becomes available, (iii) all information
in
XTL’s possession regarding Products necessary or useful for making regulatory
filings in the Territory with respect to Products as such information becomes
available, and (iv) copies of all regulatory filings made by or on behalf of
XTL
with respect to Products promptly after such regulatory filings are made. CUBIST
shall have a right of access, a right of reference and the right to use and
incorporate all information provided to it pursuant to this Section 4.2 in
its
applications for Regulatory Approval of Products within the Territory and for
all other purposes related to Obtaining Regulatory Approval, manufacture and
Commercialization of Products. For the purposes of calculating Designated Costs,
XTL’s activities under this Section 4.2 in connection with HepeX-B shall be
considered to be activities necessary or advisable to Obtain Regulatory Approval
for a commercially viable formulation of HepeX-B for the prevention of recurrent
Hepatitis B infections in liver transplant patients in the
Territory.
4.3 No
Retained Rights.
Notwithstanding
anything expressed or implied in the foregoing provisions of this Section 4
to
the contrary, nothing in this Section 4 or elsewhere in this Agreement is
intended to diminish the scope of the exclusive rights licensed by XTL to CUBIST
pursuant to Section 2 or to suggest that, from and after the Effective Date,
XTL
retains any rights to Obtain Regulatory Approval for, manufacture, use or
Commercialize any Product for the prevention or treatment of Hepatitis B, except
to the extent necessary for XTL to perform its obligations under the HepeX-B
Plan in accordance with the provisions of this Agreement.
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Section
5. REGULATORY
APPROVAL ACTIVITIES.
5.1 Regulatory
Approval Activities. (a) Subject
to, and in accordance with, the terms and conditions of this Agreement and
all
requirements of applicable laws, rules, and regulations, XTL shall use
Commercially Reasonable Efforts to conduct its activities to Obtain Regulatory
Approval set forth in the HepeX-B Plan; provided,
however, that subject to Section 5.1(b), XTL shall not have any obligation
to
perform activities to Obtain Regulatory Approval under the HepeX-B Plan or,
prior to the first iteration of the HepeX-B Plan, under the guidelines attached
as Exhibit
C
(other
than the XTL Activities and such other XTL obligations as are expressly set
forth in this Agreement) to which XTL has not consented if (i) prior to the
first iteration of the HepeX-B Plan, CUBIST attempts to impose obligations
that
materially deviate in scope from the guidelines set forth in Exhibit
C,
(ii)
the initial HepeX-B Plan materially deviates in scope from the guidelines
attached in Exhibit
C,
and/or
(iii) material changes are made to the HepeX-B Plan without XTL’s prior written
consent; provided
that in
all cases, XTL may not refuse to provide any data or information pursuant to
Sections 4.1(a) or 4.2. XTL hereby acknowledges and agrees that it shall not
be
entitled to engage in any activities to Obtain Regulatory Approval with respect
to any Product intended for treatment or prevention of Hepatitis B, unless
and
until such activities have been incorporated into the HepeX-B Plan and CUBIST
shall have provided written consent to XTL engaging in such development
activities. The Parties shall use Commercially Reasonable Efforts to minimize
the costs and expenses incurred by them as a result of the performance of their
obligations under this Section 5. Notwithstanding anything in this Section
5 or
elsewhere in this Agreement to the contrary, XTL shall cease any activities
to
Obtain Regulatory Approval, including any pre-clinical and clinical activity
for
Products, upon receipt of written notice from CUBIST to cease such activity,
or
as soon as practicable thereafter.
(b) If
and to
the extent requested by CUBIST and included in the HepeX-B Plan, XTL shall
use
Commercially Reasonable Efforts to deliver to CUBIST the following
(collectively, as described in Exhibit
D
and as
revised from time to time by mutual written consent of the Parties, the
“XTL
Activities”):
(i) a
commercially viable method to manufacture Product using *****,
including development and implementation of a testing plan to demonstrate
comparability to Products produced from *****;
(ii) a
commercially viable, concentrated parenteral formulation of Product for both
intravenous and subcutaneous injection; (iii) complete the phase 2b study and
the PK/PD bridging study for HepeX-B undertaken by XTL and underway as of the
Effective Date.
5.2. HepeX-B
Plan.
All
activities of the Parties (including allocation of responsibilities of each
Party or its designee) contemplated under this Agreement to Obtain Regulatory
Approval, including without limitation, pre-clinical and clinical Product
activities, any XTL Activities requested by CUBIST, and all scientific,
clinical, manufacturing, regulatory and other activities to be undertaken for
a
commercially viable Product, and a budget for the foregoing, shall be set forth
in a plan, as modified from time to time (the “HepeX-B
Plan”).
In
addition, the HepeX-B Plan will indicate whether any budgeted costs are
Designated Costs. Within *****
days
after the Effective Date, the Joint Alliance Team shall propose a detailed
initial HepeX-B Plan for each Party’s review. An initial guideline identifying
major concepts for inclusion in the HepeX-B Plan is attached as Exhibit
C;
if
requested by CUBIST, any or all of the XTL Activities shall also be included
in
the HepeX-B Plan. The Joint Alliance Team will propose recommended changes
to
the HepeX-B Plan at least *****.
No
modification to the HepeX-B Plan will be effective unless and until approved
by
CUBIST and provided to XTL pursuant to Section 15.4 (without copies to legal
counsel). CUBIST will have the sole right to determine whether to *****
CUBIST’s
sole discretion, but subject to *****.
XTL has
the right to review *****
to the
HepeX-B Plan for the purpose of (a) *****
under
the HepeX-B Plan should constitute *****;
and (b)
to *****
under
the modified HepeX-B Plan (other than XTL Activities) as contemplated in Section
5.1(a). XTL shall have *****
days
from receipt of any proposed modified HepeX-B Plan pursuant to Section 15.4
(without copies to legal counsel) to inform CUBIST whether it disputes the
categorization of any such costs as Designated Costs. If XTL timely informs
CUBIST that *****,
the
Parties shall then have *****
business
days to discuss *****,
and if
the Parties cannot agree after good faith discussions whether any *****,
the
matter shall be resolved in accordance with the dispute resolution process
set
forth in Section 14. If XTL does not inform CUBIST within *****
days
after receipt of any proposed modified HepeX-B Plan that it agrees to
*****
proposed
under the modified HepeX-B Plan as contemplated in Section 5.1(a), XTL will
be
deemed to have elected *****.
5.3 Use
of Data by XTL.
All
data generated by XTL from any activities engaged in by XTL pursuant to, and
in
accordance with, the provisions of this Section 5 shall not be used by XTL
and
its Affiliates, except to support Regulatory Approval in the Territory of
Product or to Commercialize Product in the Territory without the prior written
consent of CUBIST, which shall not be unreasonably withheld.
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5.4 Costs
and Expenses.
The
costs and expenses incurred by both Parties in connection with any and all
activities engaged in pursuant to, and in accordance with, the provisions of
this Section 5, shall be allocated in the manner set forth in Section
7.
5.5 Health
Hazards.
Each
Party will notify the other Party of any material health hazards with respect
to
Products that may impact employees involved in the activities to Obtain
Regulatory Approval, manufacture, production or supply of Products as soon
as
practicable, and in any event within forty-eight (48) hours, after such Party
becomes aware of such hazards.
5.6 XTL
Compliance.
In
connection with any activities undertaken by XTL to Obtain Regulatory Approval
in connection with any Product, XTL shall comply with all applicable laws,
rules
and regulations regarding such activities, as such laws, rules and regulations
are in effect where such activities are undertaken.
5.7
No
Debarred Personnel. In
the course of the development of Product or any component thereof, XTL has
not
used prior to the Effective Date, and neither XTL nor CUBIST shall not use
during the term of this Agreement, the services of any employee, consultant,
contractor, or clinical investigator that has been debarred by the FDA or any
other Regulatory Authorities or that is the subject of debarment proceedings
by
the FDA or any other Regulatory Authority.
Section
6. REGULATORY
ACTIVITIES
6.1 Regulatory
Activities.
Subject
to, and in accordance with, the terms and conditions of this Agreement
(including Section 6.3), and all requirements of applicable laws, rules, and
regulations, CUBIST shall be responsible for filing and obtaining Regulatory
Approvals for Products in the Territory. XTL shall not be entitled to engage
in
any regulatory activities with respect to any Product without the prior written
consent of CUBIST. XTL shall use Commercially Reasonable Efforts to assist
CUBIST in complying with all requirements of applicable laws, rules, and
regulations related to Regulatory Approval of Product in the Territory.
Notwithstanding anything in this Section 6 or elsewhere in this Agreement to
the
contrary, XTL shall cease any regulatory activity and all attempts to Obtain
Regulatory Approval with respect to any Product upon receipt of written notice
from CUBIST to cease such activity, or as soon as practicable
thereafter.
6.2 Regulatory
Approvals. To
the extent permitted by applicable laws, rules and regulations, CUBIST
shall file in its own name, and own, all drug, biologic and device approval
applications and Regulatory Approvals for Products in the Territory, and shall
be solely responsible for all communications with Regulatory Authorities in
such
countries relating thereto. Upon CUBIST’s reasonable request, XTL shall
cooperate with and assist CUBIST in the communication with any Regulatory
Authority or in the preparation and submission of any regulatory filing
regarding Product, and will provide such information and data in XTL’s
possession or control that is necessary to Obtain Regulatory Approval. If XTL
is
required by applicable laws or regulations or a Regulatory Authority having
jurisdiction in the Territory to disclose information directly to such
Regulatory Authority relating to Product, XTL shall notify CUBIST in writing
of
the requirement and the particulars of the information required to be disclosed,
and XTL shall coordinate with CUBIST in making any such disclosure. Further,
with respect to any such required disclosures, CUBIST shall have the right
to be
present and to participate at all face-to-face meetings and scheduled conference
calls between XTL and such Regulatory Authority with respect to Product and
CUBIST shall have the right to lead any such face-to-face meetings or scheduled
conference calls. Promptly after the Effective Date, XTL shall transfer and
assign to CUBIST any and all such drug, biologic and device approval
applications, INDs, orphan drug designations or Regulatory Approvals held by
XTL
as of the Effective Date.
6.3 Costs
and Expenses.
The
costs and expenses incurred by both Parties in connection with any and all
regulatory activities engaged in pursuant to, and in accordance with, the
provisions of this Section 6, shall be allocated in the manner set forth in
Section 7.
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Section
7. PRODUCT
COSTS AND EXPENSES.
7.1 Collaboration
Support.
The
Parties acknowledge that XTL will incur costs from and after the Effective
Date
in furtherance of its activities set forth in the HepeX-B Plan. Subject to
the
last sentence of this Section 7.1, CUBIST shall pay XTL $2,000,000 in
contemplation of costs, of which (a) *****
after
the Joint Alliance Team’s initial presentation of the HepeX-B Plan for approval,
unless CUBIST dissolves the Joint Alliance Team prior to such initial
presentation, in which case, CUBIST will pay such amount within *****
days
after *****;
(b)
*****
shall be
paid on or prior to *****;
and (c)
*****
shall be
paid on the last business day of *****.
Notwithstanding anything to the contrary express or implied in this Section
7.1,
CUBIST shall have no obligation to make any payment under this Section 7.1
if
XTL is in material breach of its obligations under this Agreement.
7.2 Overall
Designated Costs.
The
Parties shall use Commercially Reasonable Efforts to minimize the Designated
Costs. It is the intent of the Parties, to the extent practicable, to endeavor
to limit the Designated Costs to not more than $33,900,000.
7.3 Designated
Costs. (a)
In
addition to the payments under Section 7.1, and subject to Section 7.4, CUBIST
shall bear all Designated Costs; provided
that any
XTL Designated Costs are incurred in the performance of activities that are
set
forth in an approved HepeX-B Plan in effect as of the time XTL incurred such
Designated Costs or became obligated to incur such Designated Costs. XTL shall
submit quarterly invoices in Dollars to CUBIST no later than *****
after
the end of each quarter which set forth in reasonable detail the XTL Designated
Costs for the immediately preceding quarter. If not previously approved by
CUBIST in writing, CUBIST shall inform XTL within *****
days of
receipt of an invoice whether it disputes the categorization of any such costs
listed in such invoice as Designated Costs. The Parties shall have *****
business
days to discuss such costs, and if the Parties cannot agree after good faith
discussions whether any itemized costs listed in such invoice are Designated
Costs, the matter shall be resolved in accordance with the dispute resolution
process set forth in Section 14. CUBIST shall not be responsible for any costs
set forth in an invoice that are not Designated Costs. Subject to the
immediately preceding sentence and Section 7.4 below, CUBIST shall reimburse
Designated Costs that are not subject to a good faith dispute within
*****
days
after receipt of such invoice.
(b) CUBIST
shall provide to XTL, no later than *****
days
after the end of each quarter, a report which sets forth in reasonable detail
the CUBIST Designated Costs for the immediately preceding quarter. XTL shall
inform CUBIST within *****
days of
receipt of any such report whether it disputes the categorization of any such
costs listed in such invoice as Designated Costs. The Parties shall have
*****
business
days to discuss such costs, and if the Parties cannot agree after good faith
discussions whether any itemized costs listed in such report are Designated
Costs, the matter shall be resolved in accordance with the dispute resolution
process set forth in Section 14.
7.4 CUBIST
Designated Costs Cap.
Notwithstanding
anything express or implied to the contrary contained herein, CUBIST shall
be
responsible for up to $33,900,000 of the Designated Costs (whether incurred
by
CUBIST or XTL). Thereafter, the Parties shall each bear fifty percent (50%)
of
the Designated Costs in excess of $33,900,000. From and after the date that
the
aggregate amount of undisputed Designated Costs is equal to or greater than
$33,900,000, after receipt of each invoice from XTL, CUBIST shall determine
the
aggregate Designated Costs for such quarter by adding the undisputed XTL
Designated Costs for such quarter (to the extent such Designated Costs are
in
excess of the aggregate Designated Costs of $33,900,000) plus the undisputed
CUBIST Designated Costs for such quarter (to the extent such Designated Costs
are in excess of the aggregate Designated Costs of $33,900,000) (the sum of
the
XTL Designated Costs and the CUBIST Designated Costs for such quarter referred
to herein as the “Aggregate
Designated Costs”).
If
the undisputed XTL Designated Costs for such quarter are greater than fifty
percent (50%) of the Aggregate Designated Costs for such quarter, then CUBIST
shall pay to XTL an amount equal to (i) the XTL Designated Costs for such
quarter minus (ii) the result of the Aggregate Designated Costs for such quarter
divided by two (2). CUBIST shall pay such amount within *****
days of
receipt of the invoice for XTL Designated Costs for such quarter. If the
undisputed CUBIST Designated Costs for such quarter are greater than fifty
percent (50%) of the Aggregate Designated Costs for such quarter, then XTL
shall
pay to CUBIST an amount equal to (I) the CUBIST Designated Costs for such
quarter minus (II) the result of the Aggregate Designated Costs for such quarter
divided by two (2). CUBIST shall deliver an invoice to XTL for such amount,
which invoice shall set forth in reasonable detail the CUBIST Designated Costs
for the immediately preceding calendar quarter. XTL may either make such payment
within *****
days
of
receipt of the invoice or *****
under
*****
hereunder such that the *****
are no
less than the *****,
until
XTL’s share of Designated Costs is offset in full. A one-time fee of
*****
shall be
assessed on every amount that *****
pursuant
to this Section 7.4. In addition, interest shall accrue pursuant to Section
10.8
on all *****
that XTL
*****
pursuant
to this Section 7.4 beginning *****
months
after XTL’s receipt of CUBIST’s invoice therefor. XTL shall have no obligation
to pay any Designated Costs that have not been *****
as of
the termination or expiration of this Agreement. XTL shall have no obligation
to
share in any Designated Costs incurred *****,
and
interest shall cease to accrue with respect to any previously incurred
Designated Costs. For the avoidance of doubt, XTL’s obligation to share in any
Designated Costs under this Section 7.4 shall be limited to HepeX-B, unless
otherwise agreed by the Parties in writing.
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Commission.
7.5 Practices.
XTL will
perform its activities under the HepeX-B Plan in accordance with then current
Good Laboratory Practices, Good Clinical Practices (as required of a sponsor
of
a clinical trial), and Good Manufacturing Practices, if and to the extent
required by the HepeX-B Plan, and in such event, XTL will include in each
agreement with each of its subcontractors, if any, performing any such
activities contemplated under the HepeX-B Plan a requirement that such
subcontractors perform its activities in accordance with then current Good
Laboratory Practices, Good Clinical Practices, and Good Manufacturing Practices,
as and if applicable.
Section
8. CONFIDENTIALITY;
PUBLICATION; RECORDS.
8.1 Nondisclosure
Obligation.
All
Proprietary Information disclosed by or on behalf of one Party to the other
Party under this Agreement that is marked “confidential” or “proprietary”, and
in the case of oral information, is summarized in a writing that is marked
“confidential” or “proprietary” and delivered to the other Party within thirty
(30) days of disclosure of such information, shall be maintained in confidence
by the receiving Party and shall not be disclosed to a non-Party or used for
any
purpose whatsoever without the prior written consent of the other Party, except
to the extent that such Proprietary Information:
(a) is
known
by recipient at the time of its receipt, and not through a prior disclosure
by
or on behalf of the disclosing Party, as documented by contemporaneous business
records;
(b) is
properly in the public domain through no fault of the recipient;
(c) is
subsequently disclosed to a receiving Party by a Third Party who may lawfully
do
so and is not directly or indirectly under an obligation of confidentiality
to
the disclosing Party, as documented by written business records in existence
prior to the receipt of such information from the disclosing Party;
(d) is
developed by the recipient independently of, and without reference to or use
of,
Proprietary Information received from the disclosing Party;
(e) is
required to be disclosed to governmental or other regulatory agencies in order
to obtain patents, to obtain approval to conduct clinical trials or to market
Products, or to comply with applicable governmental or stock exchange or
quotation system regulations; provided,
however, that such disclosure may be only to the extent reasonably necessary
to
obtain patents or approval, or to comply with laws or regulations as appropriate
and that confidential treatment will be sought to the extent reasonably
practicable;
(f) is
disclosed to actual or potential permitted sublicensees or permitted assignees
and/or other third parties (1) for the purpose of conducting activities under
this Agreement (or for such actual or potential permitted sublicensees or
permitted assignees and/or other third parties to determine their interest
in
performing such activities) in accordance with this Agreement or (2) for the
purpose of allowing the Party making such disclosure to effectively exploit
its
rights under this Agreement and obtain all of the benefits under this Agreement
to which such Party is entitled as contemplated by this Agreement; provided,
however, that such actual or potential permitted sublicensees or permitted
assignees and/or other third parties have agreed to be bound by confidentiality
obligations substantially equivalent to the terms herein for no less than five
years from the date of disclosure;
(g) is
disclosed to employees, officers, directors, consultants, agents, investors
or
potential investors of, or lenders or potential lenders to, the Party making
such disclosure; provided,
however, that such employees, officers, directors, consultants, agents,
investors, potential investors, lenders and potential lenders have agreed to
be
bound by confidentiality obligations substantially equivalent to the terms
herein for no less than five years from the date of disclosure; and provided
further
that notwithstanding the provisions set forth above in this subsection (g),
neither Party shall disclose Proprietary Information of the other Party to
potential investors or potential lenders except to the extent that such
disclosure is made in the context of such potential investors’ or potential
lenders’ due diligence
investigation of the Party making such disclosure;
(h) is
used
by the receiving Party for the purpose of conducting activities under this
Agreement in accordance with its respective terms or is used by the receiving
Party for the purpose of allowing the receiving Party to effectively exploit
its
rights under this Agreement and obtain all of the benefits under this Agreement
to which such receiving Party is entitled as contemplated by this Agreement;
or
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Commission.
(i) is
required to be disclosed by law, regulation or court order; provided
that
notice is promptly delivered to the other Party in order to provide an
opportunity to challenge or limit the disclosure obligations; and provided further
that
such disclosure may be only to the extent reasonably necessary to comply with
the applicable law, regulation or court order.
The
disclosing Party shall identify any Proprietary Information delivered to the
receiving Party that is confidential information of a Third Party and the
disclosing Party shall inform the receiving Party of any restrictions,
limitations and qualifications imposed on such Proprietary Information by such
Third Party. XTL agrees that with respect to any CUBIST Proprietary Information
disclosed to Yeda as contemplated by the XY Agreement and the Consent Agreement,
that XTL shall ▇▇▇▇ all such CUBIST Proprietary Information as “confidential” or
“proprietary”, and in the case of oral information, XTL shall summarize such
CUBIST Proprietary Information in a writing that is marked “confidential” or
“proprietary” and deliver such summary to Yeda within thirty (30) days of
disclosure of such CUBIST Proprietary Information.
8.2 No
Disclosure of Terms.
Either
Party may disclose the existence of this Agreement, but, except to the extent
otherwise provided below in this Section 8.2, neither Party shall disclose
the
terms of this Agreement without the prior written consent of the other Party.
Notwithstanding the foregoing, either Party may disclose the terms of this
Agreement pursuant to the provisions of subparagraphs (b), (e), (f) (with
financial terms redacted), (g), or (i) of Section 8.1 to the same extent as
if
the terms of this Agreement were Proprietary Information of the non-disclosing
Party.
8.3 No
Publication.
XTL
shall not publish or publicly present any information (a) relating to this
Agreement, (b) any activities conducted under or in relation to this Agreement,
or (c) relating to any Product, in all cases without the prior written consent
of CUBIST. Neither Party shall make public use of the other Party’s name or
identifying marks except as otherwise permitted under this Agreement, with
the
prior written consent of the other Party or as required by applicable law or
regulation. CUBIST shall not use the names of Yeda, the Weizmann Institute
of
Science, Rehovot, or ▇▇▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇▇▇ in any advertising, sales
literature, or promotional material unless (i) the prior written approval of
Yeda thereto has been obtained or (ii) such use or disclosure is to governmental
authorities for the purposes of obtaining approval or permission for the
exercise of its license rights to any XTL Technology licensed to XTL pursuant
to
the XY Agreement or is in the fulfillment of any legal duty owed to any
governmental authority or is required by applicable law. Nothing in this Section
8.3 shall limit XTL’s ability to apply for any patent protection.
8.4 Press
Releases, Etc.
Notwithstanding anything set forth in Section 8.1, 8.2 or 8.3 above to the
contrary, XTL may not issue any news release or other public announcement
relating to this Agreement or to the Parties’ performance hereunder, without the
prior written consent of CUBIST, which shall not be unreasonably withheld or
delayed, except to the extent required by applicable law, regulation or stock
exchange or quotation system requirement; provided
that XTL
uses Commercially Reasonable Efforts to submit to CUBIST a draft of such news
release or public announcement at least five (5) days prior to the date of
planned issuance thereof and shall review and consider in good faith any
comments provided by CUBIST. CUBIST may issue any news release or other public
announcement relating to Product without the prior written consent of XTL,
subject to the confidentiality provisions of Sections 8.1, 8.2 and 8.3;
provided,
however, that CUBIST may not issue any news release or other public announcement
relating to this Agreement or to XTL’s performance hereunder, without the prior
written consent of XTL, which shall not be unreasonably withheld or delayed,
except to the extent required by applicable law, regulation or stock exchange
or
quotation system requirement; and provided further that, unless precluded by
applicable law, regulation or stock exchange or quotation system requirement,
CUBIST will use Commercially Reasonable Efforts to submit to XTL a draft of
such
news release or public announcement at least five (5) days prior to the date
of
planned issuance thereof so as to afford XTL the opportunity to object if such
proposed press release would violate applicable Israeli law, regulation or
stock
exchange or quotation system requirement. In the event of such objection, the
parties will diligently cooperate to arrive at a revised draft of such proposed
press release that does not so violate such applicable Israeli law, regulation
or stock exchange or quotation system requirement.
8.5 Records;
Audit Rights.
Each
Party shall keep or cause to be kept full and accurate books of account and
records containing all particulars that may be necessary to determine, in a
manner consistent with generally accepted accounting principles in the United
States, the sums or credits due under this Agreement, including, but not limited
to Designated Costs, Net Sales and Sublicensee Revenues. At the written request
(and expense) of either Party, the other Party and its Affiliates, and in the
case of CUBIST, its licensees and sublicensees shall permit an independent
certified public accountant appointed by such Party and reasonably acceptable
to
the other Party, accompanied by representatives of the financial department
of
the audited Party at reasonable times, upon reasonable notice and no more
frequently than once per Contract Year, to examine only those records as may
be
necessary to determine the correctness or completeness of any report or payment
made under this Agreement, including but not limited to Designated Costs, Net
Sales and Sublicensee Revenues (including a breakdown of the components thereof
so as to enable calculation of royalties payable to Yeda under the XY
Agreement), with respect to any Contract Year ending not more than *****
prior to
such Party’s request. Results of any such examination shall be (i) made
available to both Parties, (ii) limited to information necessary to report
any
error in any payment or report made under this Agreement and (iii) subject
to
the provisions of this Section 8. The Party requesting the audit shall bear
the
full cost of the performance of any such audit, unless such audit discloses
a
variance of more than *****
from the
amount of the original report, royalty or payment calculation. In such case,
the
Party being audited shall bear the full cost of the performance of such
audit.
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Section
9. LICENSE
AND MILESTONE PAYMENTS.
9.1 Consideration
for License.
In
consideration for the licenses granted to CUBIST under Section 2, CUBIST shall
make a cash payment to XTL of USD $1,000,000 within three (3) business
days
after the Effective Date of this Agreement.
9.2 Milestones.
(a)
Subject
to the terms and conditions in this Agreement (including, without limitation,
the provisions of Sections 9.2(b), 9.2(c) and 9.3 below), CUBIST shall make
cash
payments to XTL in the respective amounts set forth below upon attainment of
the
milestones events (each a “Milestone
Event”)
set
forth below:
|
Milestone
Event
|
Payment
Amount
|
|
|
*****
|
USD
$*****
|
|
|
*****
|
USD
$*****
|
(b) CUBIST
shall promptly notify XTL in writing upon the achievement of any of the
milestones set forth above in Section 9.2(a) and CUBIST shall have *****
days
after the occurrence of the Milestone Event to make the corresponding milestone
payment due. All milestone payments shall be in Dollars.
(c) CUBIST
shall make only one of the payments set forth in Section 9.2(a) and only upon
the first achievement of the applicable Milestone Event by the first iteration
of HepeX-B to achieve such milestone. After the achievement of a given Milestone
Event and the payment required to be made by CUBIST pursuant to Section 9.2(a),
no further payment shall be due or owed by CUBIST in connection with any
Milestone Event, regardless of how many times the same Milestone Event is
achieved by different or multiple Products. If the first achievement of the
Milestone Event occurs after December 31, 2008, then no payment shall be due
or
owed by CUBIST pursuant to Section 9.2(a).
9.3 Reduction
of Milestone Payments.
Notwithstanding
any provision in this Section 9 or elsewhere in this Agreement to the contrary,
CUBIST shall be entitled to reduce payments required pursuant to Section 9.2
above as set forth in Section 7.4, Section 11.3, or Section 12.10, or pursuant
to the Consent Agreement, as further contemplated under Section
10.4.
Section
10. ROYALTIES.
10.1 Royalties
on Net Sales of HepeX-B covered by a Valid Claim. (a) For
each
Contract Year during the term of this Agreement, CUBIST shall pay to XTL,
subject to the terms and conditions of this Agreement (including, without
limitation, the provisions of Sections 10.2, 10.4, 10.5 and 10.9), a royalty
with respect to Net Sales of HepeX-B sold by CUBIST or its Affiliates, in any
and all countries where the manufacture, use or sale of HepeX-B are covered
by a
Valid Claim in such country (each a “Patent
Country”),
equal
to:
(i) if
Net
Sales of HepeX-B in Patent Countries during such Contract Year are equal to
or
less than *****,
ten
percent (10%) of the aggregate Net Sales for HepeX-B sold in Patent Countries
during such Contract Year, and
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Commission.
(ii) if
Net
Sales of HepeX-B in Patent Countries during such Contract Year are greater
than
*****,
then
the lesser of (A) the Patent Royalty Rate, and (B) seventeen percent (17%);
multiplied by the aggregate Net Sales for HepeX-B sold in Patent Countries
during such Contract Year.
For
purposes of this Section 10, the “Patent
Royalty Rate”
shall
equal:
For
purposes of illustration only, if aggregate Net Sales of HepeX-B in Patent
Countries during a Contract Year is equal to *****,
then
the Patent Royalty Rate shall equal to *****,
or
*****.
(b) In
the
event of the issuance of a Retroactive Valid Claim in a country that was not
a
Patent Country prior to such filing (the “Retroactive
Royalty Country”),
for
each Contract Year during which the application for the Retroactive Valid Claim
was pending (but in no event more than *****
prior to
the date of issuance of such Retroactive Valid Claim in the Retroactive Royalty
Country), through the date of issuance (each such Contract Year, a “Retroactive
Royalty Year”),
CUBIST shall recalculate the aggregate royalties payable under Sections 10.1(a)
and 10.2 for each such Retroactive Royalty Year by including the Net Sales
of
such Retroactive Royalty Country in the calculations for Patent Countries under
Section 10.1(a), and reducing by such amount the Net Sales in the calculations
for Know-How Countries under Section 10.2 (collectively the “Recalculated
Royalties”).
CUBIST will pay to XTL, subject to the terms and conditions of this Agreement
(including, without limitation, the provisions of Sections 10.2, 10.4, 10.5
and
10.9), a retroactive royalty with respect to each Retroactive Royalty Year
in an
amount equal to (i) the Recalculated Royalties, minus
(ii) any
amounts paid or payable to XTL under Section 10.1(a) and Section 10.2 for such
Retroactive Royalty Year prior to effecting any setoffs or offsets under this
Agreement. For the first Retroactive Royalty Year, such retroactive payment
will
only apply for Net Sales effected after the effective date of filing of the
application for the Retroactive Valid Claim. Such retroactive royalty payments
will be paid in *****,
each
*****
after
each of the next *****
(each a
*****;
provided
that if
such aggregate payment together with amounts payable under Section 10.3(e)
for
the same Retroactive Valid Claim(s) exceeds *****
of the
royalties paid or payable prior to effecting any setoffs or offsets under this
Agreement for the Contract Year immediately preceding the Contract Year in
such
Retroactive Valid Claim issued, then CUBIST may elect to pay such retroactive
royalty payments in *****
after
each of the next *****.
If
CUBIST elects to pay in *****,
interest shall accrue pursuant to Section 10.8 on all such retroactive royalty
payments beginning on the thirty-first (31st)
day
after the *****
that are
then unpaid.
10.2 Know-How
Royalties.
Notwithstanding
any provision in this Section 10 or elsewhere in this Agreement to the contrary
but subject to Section 10.4(a), for each Contract Year during the term of this
Agreement, CUBIST shall pay to XTL a royalty with respect to annual Net Sales
of
HepeX-B sold by CUBIST or its Affiliates in any country where the manufacture,
use or sale of HepeX-B is not covered by a Valid Claim in such country (each
a
“Know-How
Country”)
in an
amount equal to:
(a) if
Net
Sales of HepeX-B in the Territory during such Contract Year are equal to or
less
than *****
of the
aggregate Net Sales for HepeX-B sold in Know-How Countries during such Contract
Year, and
(b) if
Net
Sales of HepeX-B in the Territory during such Contract Year are greater than
$*****,
then
the lesser of (i) the Know-How Royalty Rate, and (ii) *****;
multiplied by the aggregate Net Sales for HepeX-B sold in all Know-How Countries
during such Contract Year.
For
purposes of this Section 10, the “Know-How
Royalty Rate”
shall
equal:
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Commission.
For
purposes of illustration only, if aggregate Net Sales of HepeX-B by CUBIST
or
its Affiliates during a Contract Year in the Territory is equal to *****
(representing *****
of
aggregate Net Sales in Patent Countries and $*****
of
aggregate Net Sales in Know-How Countries), then the Know-How Royalty Rate
under
this Section 10.2 shall equal *****,
or
*****.
10.3 Royalties
on Net Sublicensee Revenues. (a)
Subject
to Sections 10.3(b), (c) and (d), for each Contract Year during the term of
this
Agreement, CUBIST shall pay to XTL, subject to the terms and conditions of
this
Agreement, an amount equal to *****
of the
aggregate annual Sublicensee Revenues for such Contract Year.
(b) Notwithstanding
anything to the contrary in Section 10.3(a) above, but subject to the other
terms and conditions of this Agreement, for each Contract Year during the term
of this Agreement, CUBIST shall pay to XTL an amount equal to (i)
*****
of the
aggregate annual Sublicensee Revenues for such Contract Year with respect to
rights to Commercialize Product in the United States of America, and (ii)
if
CUBIST sublicenses rights to Commercialize Product in more than *****
European
Major Markets, CUBIST shall pay to XTL *****
of the
aggregate annual Sublicense Revenues for such Contract Year with respect to
rights to Commercialize Product in the *****
European
Major Market country in which CUBIST has sublicensed rights to Commercialize
Product. In the event it is not clear which of several countries are the
*****
European
Major Market countries in which CUBIST has sublicensed rights to Commercialize
Product, CUBIST shall have the right in its sole discretion to identify which
*****
of those
countries are the *****
European
Major Market countries; provided
that
such determination may not be subsequently changed by CUBIST without XTL’s prior
written consent. To the extent that Sublicensee Revenues are applicable to
more
than one country listed above, the percentage of such Sublicensee Revenues
that
CUBIST shall be required to pay to XTL shall be calculated based on an
appropriate weighted average of the applicable countries.
(c) With
respect to Sublicensee Revenues that relate solely to Know-How Countries in
a
particular Contract Year, the amount payable by CUBIST to XTL under Sections
10.3(a) or 10.3(b) will be reduced by *****.
(d) With
respect to Sublicensee Revenues (other than Sublicensee Revenues based on sales)
from a particular Sublicensee that relate to both Patent Countries and Know-How
Countries in a particular Contract Year, the amount payable by CUBIST to XTL
under Sections 10.3(a) and 10.3(b) will be reduced by a percentage between
*****
(in the
event that all countries are Know-How Countries) calculated using a weighted
average. The weighted average shall be based on the reasonable estimate provided
in good faith by CUBIST to XTL within thirty (30) days after execution of the
underlying sublicense agreement of *****.
If XTL
disputes such good faith estimate, then XTL may submit the matter to the dispute
resolution procedures set forth in Section 14.
(e) For
each
Retroactive Royalty Year applicable for a particular country that was not a
Patent Country during such Retroactive Royalty Year absent such Retroactive
Valid Claim, CUBIST will pay to XTL, subject to the terms and conditions of
this
Agreement (including, without limitation, the provisions of Sections 10.2,
10.4,
10.5 and 10.9), a retroactive royalty in an amount equal to (i) the amounts
that
would have been payable with respect to such country under Sections 10.3(a),
(b), or (d), minus (ii) any amounts paid or payable to XTL under Section 10.3
with respect to such country prior to effecting any setoffs or offsets. For
the
first Retroactive Royalty Year, such retroactive payment will only apply for
Sublicensee Revenues received after the effective date of filing of the
application for the Retroactive Valid Claim. Such retroactive royalty payments
will be paid in *****
after
each of the next *****;
provided
that if
such aggregate payment together with amounts payable under Section 10.1(b)
for
the same Retroactive Valid Claim(s) exceeds *****
of the
royalties paid for the Contract Year immediately preceding the Contract Year
in
such Retroactive Valid Claim issued, then CUBIST may elect to pay such
retroactive payments in *****.
If
CUBIST elects to pay in *****,
interest shall accrue pursuant to Section 10.8 on all such retroactive royalty
payments beginning on the thirty-first (31st)
day
after the *****
that are
then unpaid.
10.4 Setoffs
and Offsets. (a)
Notwithstanding
any provision in this Section 10 or elsewhere in this Agreement to the contrary
but subject to Section 10.4(b), CUBIST shall be entitled to reduce payments
otherwise required pursuant to this Section 10 pursuant to Section 7.4, 11.3,
or
12.10, or pursuant to the Consent Agreement. In addition, notwithstanding any
provision in this Agreement to the contrary except Section 10.4(b), for any
given country within the Territory, CUBIST shall have no obligation to make
payments to XTL under Section 10.2 or 10.3 for any Contract Year with respect
to
a country where Product is not covered by a Valid Claim, if the aggregate unit
sales of Unlicensed Products during such Contract Year by all Third Parties
in
such country constitute more than ***** of the market share on a per unit basis
with respect to all unit sales of both such Unlicensed Products and HepeX-B
in
such country. CUBIST shall have no obligation to make payments to XTL under
Section 10.2 or Section 10.3 for any Contract Year in any country within the
Territory: (i) that is not a *****; (ii) where HepeX-B is *****; and (iii)
where
unit sales of Unlicensed Product that is also covered
by a Valid Claim by all Third Parties in such country constitute more than
*****
of the
market share on a per unit basis with respect to all unit sales of both such
Unlicensed Product and HepeX-B.
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(b) With
respect to any amount payable by CUBIST to XTL under Section 9 or Section 10,
in
no event may CUBIST setoff or offset amounts under Section 7.4, Section 11.3,
or
Section 12.10 or pursuant to the Consent Agreement against such payment in
an
amount exceeding such amount payable. Setoffs and offsets permitted pursuant
to
Section 9.3, Section 11.3, and Section 10.4 will be applied in the following
order: (i) first to reductions pursuant to *****;
and
(ii) second to reductions pursuant to *****;
(iii)
third to reductions pursuant to *****;
and
(iv) fourth to reductions pursuant to *****;
provided
that in
no event will such offsets or setoffs reduce any such payment to an amount
less
than the amount of the XTL Licensor Payment applicable for such payment period.
Any amounts setoff or offset amounts that are not actually setoff or offset
against a particular payment amount, will be carried forward to the next
milestone or royalty payment period.
(c) XTL
shall
use any XTL Licensor Payment amount received under this Section 10.4 for the
sole and exclusive purpose of paying such Third Parties; if XTL fails to use
such amounts for such purpose, and does not remedy such failure as soon as
reasonably practicable, and in any event no later than *****
days
after receipt of written notice from CUBIST, and except as otherwise agreed
in
the Consent Agreement with respect to Yeda, CUBIST may withhold XTL Licensor
Payment amounts from subsequent payments under Section 9 or Section 10 to apply
against any setoffs or offsets under Section 7.4, Section 11.3, or Section
12.10.
(d) It
is
agreed that the references to the Consent Agreement in the definition of the
XTL
Licensor Payments and in Sections 9.3 and 10.4(a) and (b) shall not derogate
from the rights of Yeda under the Consent Agreement, and for the purpose of
those rights, shall be deemed not to have been made.
10.5 Term
of Royalties.
XTL’s
right to receive (and CUBIST’s obligation to pay) royalties under this Section
10 with respect to any country in the Territory shall expire (and Net Sales
in
such country after expiration will not be applied in the calculation of any
royalty rates hereunder) upon the later of (a) ten (10) years from the First
Commercial Sale of HepeX-B in such country, or (b) the expiration of the last
to
expire Valid Claim, if any, covering the manufacture, use, or sale of HepeX-B
in
such country;
provided
that if
there is no such Valid Claim in such country, then the period described in
clause (a) above shall control;
and
further provided that if clause (a) controls and if the XY Agreement requires
XTL to pay royalties with respect to sales of HepeX-B under this Agreement
for
up to an additional two (2) years after such ten (10) year period, then during
such additional period, CUBIST will pay directly to Yeda on behalf of XTL,
such
royalty amount to which Yeda is entitled under the XY Agreement and the Consent
Agreement, calculated as if CUBIST were to continue to pay to XTL the amounts
due to XTL under this Agreement and the Consent Agreement during the said two
(2) year period. In the event that, in accordance with the provisions of this
Section 10.5, the right of XTL to receive (and CUBIST’s obligation to pay)
royalties under this Section 10 in connection with sales of HepeX-B in any
country in the Territory expires, CUBIST shall nevertheless remain obligated
to
pay accrued royalties to XTL in connection with all sales of HepeX-B in such
country that occurred prior to the effective date of such expiration.
10.6 Royalty
Payments and Reports.
Royalties shall be calculated by converting all applicable Net Sales and
Sublicensee Revenues into Dollars in accordance with the provisions of Section
10.8 below and applying the appropriate royalty percentages set forth in, or
determined in accordance with, Section 10.1 or Section 10.2 or Section 10.3,
as
applicable. During the term of this Agreement, royalties accrued to XTL pursuant
to this Section 10 shall be paid within *****
days
after the close of each Contract Year. Royalty payments shall be made in
Dollars. Within *****
days of
the end of each Contract Year, CUBIST shall furnish to XTL a report showing:
(i)
the calculation of Net Sales for HepeX-B that were sold in the Territory on
a
country-by-country basis during such Contract Year, (ii) the calculation of
Sublicensee Revenues attributed to HepeX-B that was sold in the Territory on
a
country-by-country basis during such Contract Year, (iii) royalties accrued
to
XTL pursuant to Section 10.1 and pursuant to Section 10.2 during such Contract
Year, and (v) the currency exchange rates used in determining the amount of
Dollars payable to XTL. If no royalty payments are due for any Contract Year
hereunder, CUBIST shall so report. All reports delivered pursuant to this
Section 10.6 and any information that can be derived therefrom shall constitute
Proprietary Information of CUBIST for purposes of Section 8.1.
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10.7 Exchange
Rate.
The rate
of exchange to be used in computing Designated Costs, Net Sales and Sublicensee
Revenues in each country within the Territory shall be made at the average
rate
of exchange for such country’s currency published in the Wall
Street Journal
(New
York Edition) for the last business day of each month in the applicable
period.
10.8 Interest
on Overdue Payments.
Any
amounts not paid by CUBIST or XTL when due under this Agreement shall be subject
to interest from and including the date payment is due through and including
the
date upon which CUBIST or XTL has made such payment calculated at the annual
rate equal to the prime rate plus *****
percent,
as prime is reported in the Wall
Street Journal (New
York
Edition), as determined for each month on the last business day of the previous
month. For the avoidance of doubt, this Section 10.8 shall not apply to amounts
XTL has elected to have CUBIST offset against future payments pursuant to
Section 7.4.
10.9 Taxes.
If
CUBIST is required by law, rule or regulation to withhold taxes from any
payments due to XTL from CUBIST hereunder, CUBIST will (i) deduct those taxes
from the remittable amount, (ii) pay the taxes to the proper taxing authority,
and (iii) send evidence of the obligation together with proof of payment to
XTL
within thirty (30) business days following that payment. CUBIST will provide
to
XTL such assistance as XTL may reasonably require at XTL’s expense (including
without limitation submission of documents to relevant revenue authorities)
in
claiming exemption from any such withholding requirements or seeking deductions
under any double taxation or other similar treaty or agreement from time to
time
in force. In the event that XTL delivers to CUBIST an opinion from legal counsel
reasonably acceptable to CUBIST that tax withholding is not
required, CUBIST
shall not make such withholding, in which case, XTL shall, pursuant to the
procedures in Section 11.3, indemnify, defend and hold harmless the CUBIST
Indemnitees with respect to any Losses resulting from a Third Party claim
arising out of CUBIST’s not making such withholding. Without limiting the
generality of the foregoing provisions of this Section 10.9, but subject to
the
immediately preceding sentence, CUBIST shall be responsible for all taxes
imposed on or attributable to it under applicable law, and XTL shall be
responsible for all taxes imposed on or attributable to it under applicable
law.
10.10 Products
other than HepeX-B. (a)
If, at
any time during the term of this Agreement before sales of HepeX-B are being
made by CUBIST or a Sublicensee, CUBIST ceases to conduct any material
activities to Obtain Regulatory Approval for HepeX-B, CUBIST shall be obligated,
at all times during the remainder of the term of this Agreement, under the
diligence requirements under Section 2.2 with respect to at least one other
Product.
(b) Prior
to
Commercializing any Product other than HepeX-B (irrespective of whether sales
of
HepeX-B are made or not): (i) by written notice to XTL, CUBIST may elect to
abide by the royalty provisions of this Section 10 with respect to such Product,
and references to “HepeX-B” in Section 10, except with respect to this Section
10.10, will be deemed to include such Product, except that CUBIST shall have
the
right to make setoffs and offsets
pursuant to Section 10.4 only with respect to Designated Costs, infringement
claims and payments pursuant to Third Party licenses in connection with HepeX-B,
which CUBIST could not setoff or offset against royalties or milestones
otherwise payable to XTL with respect to HepeX-B; or (ii) if requested by
CUBIST, the Parties agree to negotiate in good faith the financial terms and
diligence obligations associated with such Product to account for any material
increases in costs and expenses with respect to such Product.
(c) In
the
event CUBIST invokes clause (ii) of Section 10.10(b), if after good faith
negotiation, the Parties are unable to mutually agree upon financial terms
for
such Product, then the matter shall be submitted to the dispute resolution
procedures set forth in Section 14. In the event of arbitration, the arbitrator
will determine commercially reasonable financial terms in light of (i) any
additional costs required to Obtain Regulatory Approval for such new Product,
(ii) the anticipated market for such new Product, (iii) the commercial viability
of HepeX-B and the respective investment of the Parties in HepeX-B, and (iv)
financial and due diligence terms for other similarly situated products in
the
marketplace.
Section
11. RISK
ALLOCATION.
11.1 Mutual
Representations and Warranties.
Each
Party hereby represents and warrants to the other Party
that:
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Commission.
(a) it
is a
corporation duly organized, validly existing and in good standing under the
laws
of the jurisdiction in which it is incorporated, and has full corporate power
and authority and the legal right to own and operate its property and assets
and
to carry on its business as it is now being conducted and as contemplated in
this Agreement;
(b) it
has
the corporate power and authority and the legal right to enter into this
Agreement and perform its obligations hereunder; it has taken all necessary
corporate action on its part required to authorize the execution and delivery
of
this Agreement and the performance of its obligations hereunder; and this
Agreement has been duly executed and delivered on behalf of such Party, and
constitutes a legal, valid and binding obligation of such Party that is
enforceable against it in accordance with its terms;
(c) it
has
not entered, and will not enter, into any agreement with any Third Party that
is
in conflict with the rights granted to the other Party under this Agreement,
and
has not taken and will not take any action that would in any way prevent it
from
granting the rights granted to the other Party under this Agreement, or that
would otherwise materially conflict with or adversely affect the rights granted
to the other Party under this Agreement; and
(d) its
performance and execution of this Agreement will not result in a breach of
any
other contract to which it is a party.
11.2 XTL
Representations and Warranties.
XTL
represents and warrants that:
(a) XTL
has
not taken any action or omission to encumber any of its right, title and
interest in and to the XTL Technology in the Territory in any way that would
have a material adverse effect on the rights and licenses granted to CUBIST
hereunder;
(b) XTL
has
sufficient rights in and to the XTL Patents and XTL Know-How to grant the rights
set forth in this Agreement to CUBIST, and XTL will do all such things and
take
all such actions as may be necessary to maintain such sufficient rights in
good
standing during the term of this Agreement, including the payment of any amounts
and the performance of any obligations to any Third Party licensor of XTL
Technology as required under any agreement or arrangement with any such Third
Party (including without limitation the XY Agreement);
(c) XTL
has
not misappropriated the trade secrets (or, to XTL’s knowledge after due and
reasonable investigation, infringed) the intellectual property rights of any
other Person in its activities to Obtain Regulatory Approval hereunder, and,
to
XTL’s knowledge after due and reasonable investigation, the exercise of the
licenses granted to CUBIST under the XTL Patents and XTL Know-How, including
to
Obtain Regulatory Approval, Commercialize, or manufacture Products in the
Territory do not infringe any patent rights Controlled by any Third Party which
such patent is granted or published as a patent application on or prior to
the
Effective Date;
(d) XTL
is
unaware of any activities by any Third Party that would constitute infringement
of any XTL Patents or misappropriation of any XTL Know-How;
(e) XTL
is
not aware of any claims, judgments or settlements against or owed by XTL and
has
not received notice of any pending or threatened claims or litigation relating
to Product, the XTL Patents or XTL Know-How;
(f) to
XTL’s
knowledge, after due and reasonable investigation, XTL has not used, prior
to
the Effective Date, in connection with HepeX-B, the services of any employee,
consultant or clinical investigator that has been debarred by the FDA or any
other regulatory authority or is the subject of debarment proceedings by the
FDA
or any other regulatory authority;
(g) XTL
has
obtained the consent of the Office of the Chief Scientist of Israel (the
“OCS”)
to the
transfer out of Israel of manufacturing rights as detailed under this Agreement
by XTL and no provision of this Agreement, including the license grant set
forth
in Section 2.1, or the performance by either Party of their respective
obligations hereunder will violate or be in conflict with any statute,
regulation, rule, judgment, order, decree or injunction of any governmental
agency or body of
Israel;
(h) CUBIST
is
not and will not be liable to OCS for any loan or obligation incurred by XTL
without CUBIST’s prior express, written consent;
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(i) neither
the execution and delivery of this Agreement by XTL nor the performance of
its
obligations hereunder will constitute a violation of, or be in conflict with,
or
constitute or create a default or accelerate or adversely affect any obligations
under, any agreement or commitment to which XTL is a party or by which any
XTL
Patent or XTL Know-How is subject, including without limitation the XY
Agreement;
(j) there
is
no fact known to XTL that has not been disclosed in writing to CUBIST (i) that
could reasonably be expected to have a material adverse effect upon the right
to
the XTL Patents or the XTL Know-How granted hereunder, or (ii) that could
reasonably be expected to materially and adversely affect the ability of XTL
to
perform its obligations under this Agreement;
(k) XTL
owns
or Controls the human monoclonal antibody *****,
as
referred to and described in *****,
and the
human monoclonal antibody *****,
as
referred to and described in *****;
and
(l) to
XTL's
actual knowledge, (i) any clinical studies of HepeX-B undertaken by or on behalf
of XTL complied with applicable then current Good Clinical Practices, (ii)
any
HepeX-B manufactured by or on behalf of XTL for use in humans complied with
applicable then current Good Manufacturing Practices and (iii) any pre-clinical
activities undertaken by or on behalf of XTL and intended by XTL for inclusion
in an application for Regulatory Approval complied with applicable then current
Good Laboratory Practices.
11.3
Indemnity.
(a)
CUBIST
hereby agrees to defend, hold harmless and indemnify XTL and its agents,
directors, officers and employees (the “XTL
Indemnitees”)
from
and against any and all suits, claims, actions, demands, liabilities, expenses
and/or losses, including, without limitation, reasonable legal expenses and
attorneys’ fees (collectively “Losses”)
resulting directly or indirectly from a claim of a Third Party with respect
to:
(i) the manufacture, handling, storage, use, promotion, sale, offer for sale,
distribution, importation or exportation of Products by or on behalf of CUBIST
or its Sublicensees (other
than by XTL or other than such Losses that result from claims arising out of
an
XTL indemnification obligation under Section 11.3(b)),
(ii) a
material breach of any of the provisions of this Agreement by CUBIST or any
of
its agents or employees; or (iii) the negligence, recklessness, or willful
misconduct by CUBIST or any of its agents or employees in the performance of
any
obligations of CUBIST under this Agreement. The
foregoing indemnification obligations will not apply in the event and to the
extent that such Losses arose as a result of any XTL Indemnitee’s negligence,
willful misconduct, or breach of this Agreement.
(b) XTL
hereby agrees to defend, hold harmless and indemnify CUBIST and its agents,
directors, officers, employees, Sublicensees and distributors (the “CUBIST
Indemnitees”)
from
and against any and all Losses resulting directly or indirectly from a claim
of
a Third Party with respect to: (i) a material breach of any of the provisions
of
this Agreement by XTL or any of its agents or employees; (ii) the negligence,
recklessness, or willful misconduct by XTL or any of its agents or employees
in
the performance of any obligations of XTL under this Agreement; (iii) the
infringement of any Third Party intellectual property right which such
intellectual property is issued or published prior to the Effective Date caused
by Obtaining Regulatory Approval, Commercialization, or the manufacture, use,
promotion, marketing, sale, offer for sale, importation or exportation of
HepeX-B in the Territory by CUBIST and its sublicensees or distributors; or
(iv)
the misappropriation of any Third Party intellectual property right by XTL
or
any of its agents or employees which is known after due and reasonable
investigation as of the Effective Date.
(c) XTL
hereby agrees to defend, hold harmless and indemnify CUBIST Indemnitees from
and
against fifty percent (50%) of any and all Losses resulting directly or
indirectly from a claim of a Third Party with respect to: (i) the infringement
of any Third Party intellectual property right which such intellectual property
is not issued or published prior to the Effective Date caused by Obtaining
Regulatory Approval, Commercialization, and the manufacture, use, promotion,
marketing, sale, offer for sale, importation or exportation of HepeX-B in the
Territory by CUBIST and its Sublicensees or distributors; and (ii) the
misappropriation of any Third Party intellectual property right by XTL or any
of
its agents or employees which is not known or knowable as of the Effective
Date.
(d) If
either
Party is seeking indemnification under this Section 11.3 in connection with
a
Third Party claim: (i) it shall inform the indemnifying Party of such Third
Party claim giving rise to the obligation to indemnify as soon as reasonably
practicable after receiving notice of the claim; (ii) except as provided in
Section 11.3(d)(iii) with respect to claims under Section 11.3(b)(iii), Section
11.3(b)(iv) or Section 11.3(c), the indemnifying Party shall have the right
to
assume the defense of, and take control of, any such Third Party claim for
which
it is obligated to indemnify the indemnified Party under this Section 11.3,
the
indemnified Party shall cooperate with the indemnifying Party (and its insurer)
as the indemnifying Party may reasonably request, the indemnified Party shall
have the right to participate, at its own expense and with counsel of its
choice, in the defense of any claim or suit that has been assumed by the
indemnifying Party, and neither Party shall have any obligation to indemnify
the
other Party in connection with any settlement made without the indemnifying
Party’s written consent, provided that the indemnifying Party does not
unreasonably withhold or delay any such written consent; and (iii) with respect
to claims under Section 11.3(b)(iii), Section 11.3(b)(iv) or Section 11.3(c),
CUBIST shall have the right to assume the defense of, and take control of,
any
such claim, XTL will cooperate with CUBIST as CUBIST may reasonably request,
XTL
shall have the right to participate, at its own expense and with counsel of
its
choice, in the defense of any such claim or suit that has been assumed by
CUBIST, and XTL shall not have any obligation to indemnify CUBIST in connection
with any settlement made without XTL’s written consent, provided that XTL does
not unreasonably withhold or delay any such written consent.
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Commission.
(e) Notwithstanding
anything expressed or implied to the contrary in this Section 11, the amount
of
any Losses subject to indemnification shall be reduced by the amount of any
insurance proceeds received by the indemnified Party with respect to such
Losses; and there shall be no obligation under this Agreement to indemnify
such
indemnified Party for the amount of Losses so reduced.
(f) XTL
*****
under
its indemnification obligations as set forth in Section 11.3(b)(iii) and (iv)
and under Section 11.3(c), or *****
such
that the *****
are no
less than the *****,
until
XTL’s indemnification payment obligations under Section 11.3(b)(iii) and (iv)
and under Section 11.3(c) are *****.
Interest shall begin to accrue on any such XTL payment obligations commencing
as
of the date first due at a rate determined in accordance with Section 10.8
on
any such amounts *****.
XTL
shall have no obligation to pay any amounts under its indemnification
obligations as set forth in Section 11.3(b)(iii) and (iv) and under Section
11.3(c) that have not been *****
as of
the termination or expiration of this Agreement.
11.4 Limitation
of Liability.
EXCEPT
(i) AS A RESULT OF ANY INFRINGEMENT BY A PARTY OF THE INTELLECTUAL PROPERTY
RIGHTS OF THE OTHER PARTY, (ii) AS A RESULT OF THE FAILURE OF SUCH PARTY TO
PERFORM AND OBSERVE ITS CONFIDENTIALITY OBLIGATIONS TO THE OTHER PARTY UNDER
THIS AGREEMENT OR (iii) PURSUANT TO A PARTY’S INDEMNIFICATION OBLIGATIONS UNDER
SECTION 11.3, NEITHER PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR LOST PROFITS
OR FOR ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, PUNITIVE OR EXEMPLARY
DAMAGES OF THE OTHER PARTY IN CONNECTION WITH THIS AGREEMENT OR THE TRANSACTIONS
CONTEMPLATED BY THIS AGREEMENT, HOWEVER CAUSED, UNDER ANY THEORY OF
LIABILITY.
11.5 Insurance.
XTL and
CUBIST shall each procure and maintain insurance, including product liability
insurance, adequate to cover its obligations hereunder and that are consistent
with normal business practices of prudent companies similarly situated. It
is
understood that such insurance shall not be construed to create a limit of
the
Parties’ liability with respect to its indemnification obligations under this
Section 11. CUBIST and XTL shall provide each other with written evidence of
such insurance upon request (which evidence need not necessarily be insurance
certificates). CUBIST and XTL shall provide the other with written notice at
least ten (10) days prior to the cancellation, non-renewal or material change
in
such insurance that materially adversely affects the other Party’s rights
hereunder.
Section
12. INTELLECTUAL
PROPERTY.
12.1 Inventions.
(a) The
entire right, title and interest in and to all discoveries, improvements,
processes, formulas, data, inventions, enhancements, know-how and trade secrets,
patentable or otherwise, that arise from activities under this Agreement or
that
are necessary or useful in connection with Obtaining Regulatory Approval,
manufacture, marketing, promotion, sale, import or export of Products, and
that
were or are developed or invented: (i) solely by employees of CUBIST
(“CUBIST
Inventions”)
shall
be owned solely by CUBIST; (ii) solely by employees of XTL (“XTL
Inventions”)
shall
be owned solely by XTL; and (iii) jointly by employees of CUBIST and XTL
(“Joint
Inventions”)
shall
be owned jointly by CUBIST and XTL; provided,
however, that if the joint ownership by CUBIST and XTL of any Joint Invention
conceived using technology funded in whole or in part by OCS (“OCS
Technology”)
would
result in the transfer of any rights outside of Israel in breach or violation
of
Section 19b1 of the Israeli Encouragement of Development and Research in
Industry Law, 1984, then such Joint Invention shall be solely owned by XTL,
and
XTL hereby grants to CUBIST, for any such Joint Invention: (A) an exclusive,
perpetual, worldwide, irrevocable, fully paid up license (with the right to
sublicense) to Obtain Regulatory Approval, make, have made, use, promote,
market, sell, have sold, offer to sell, import or export Products, and (B)
a
co-exclusive perpetual, worldwide, irrevocable, fully paid up license (with
each
Party having the right to sublicense) for any and all other purposes.
Notwithstanding anything to the contrary above, none of the foregoing shall
serve to or require (x) CUBIST to assign or transfer, or otherwise relinquish,
any of CUBIST’s right, title or interest in or to any CUBIST Invention, Joint
Invention, CUBIST Patent, Joint Patent or CUBIST Know-How without the prior
written consent of CUBIST, or (y) XTL to assign or transfer, or otherwise
relinquish, any of XTL’s right, title or interest in or to any XTL Invention,
Joint Invention, XTL Patent, Joint Patent or XTL Know-How without the prior
written consent of XTL. Commencing as of the Effective Date, XTL shall not
use
any OCS Technology in the performance of its obligations under this Agreement
unless prior to such use (1) XTL notifies CUBIST in writing of XTL’s intent to
use OCS Technology, (2) XTL specifically identifies the OCS Technology
contemplated to be used and the purpose for which XTL intends to use it, and
(3)
CUBIST gives its prior written consent to such use of such OCS Technology.
Inventorship shall be determined in accordance with U.S. patent law. All
clinical data collected pursuant to services paid for in whole or in part by
CUBIST will be owned by CUBIST.
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(b) Notwithstanding
anything to the contrary in this Agreement, in the case any CUBIST Invention,
XTL Invention or Joint Invention is conceived through the use of the Licensed
Technology or Licensed Patents (as such terms are defined under the XY
Agreement) (excluding
the human monoclonal antibody *****,
as
referred to and described in *****,
and the
human monoclonal antibody *****,
as
referred to and described in *****,
including any portions or fragments thereof)
(collectively the “Yeda
Technology”),
the
parties shall not *****,
which
shall include the terms and conditions for such registration or use of the
CUBIST Invention, XTL Invention or Joint Invention and relating to the ownership
thereof. It is agreed, without derogating from the Consent Agreement, that
commencing as of the Effective Date, XTL shall not use any Yeda Technology
in
the performance of its obligations under this Agreement unless prior to such
use
(i) XTL notifies CUBIST in writing of XTL’s intent to use Yeda Technology (in
which case XTL shall also deliver a copy of such notice to Yeda), (ii) XTL
specifically identifies the Yeda Technology contemplated to be used and the
purpose for which XTL intends to use it, and (iii) CUBIST gives its prior
written consent to such use of such Yeda Technology.
12.2 Filing,
Prosecution and Maintenance of Patents. (a)
CUBIST
shall be entitled to file, prosecute and maintain in the Territory all patent
applications and patents that claim any CUBIST Inventions at its sole expense.
(b) XTL
agrees to file, prosecute and maintain the XTL Patents at its sole expense,
provided,
however,
that
XTL shall (i) use outside counsel reasonably acceptable to CUBIST, (ii)
provide CUBIST with all material documentation and correspondence from, sent
to
or filed with patent offices in the Territory regarding any XTL Patent,
(iii) provide CUBIST with a reasonable opportunity to review and comment
upon all filings with such patent offices in advance of submissions to such
patent offices, and (iv) shall consider, in good faith, incorporating any
comments provided by CUBIST. In the event that XTL is unwilling, unable or
otherwise fails to file or prosecute any XTL Patent in any country in the
Territory, CUBIST shall have the right, but not the obligation, and XTL
shall
provide CUBIST with thirty (30) days written notice to permit CUBIST to, file,
prosecute and/or maintain such XTL Patent in such country, and XTL shall execute
such documents and perform such acts as may be reasonably necessary to allow
CUBIST to file, prosecute and maintain such XTL Patent in such country in a
timely manner; provided
that in
any event any such XTL Patents shall always be registered in XTL’s name or in
the name of the relevant licensor of XTL as identified in writing to CUBIST
by
XTL.
(c) With
respect to all filings, prosecution and maintenance of any Patent pursuant
to
this Section 12.2, the filing Party shall be responsible for payment of all
costs and expenses related to such Patent filing, prosecution or maintenance.
(d) With
respect to any Joint Inventions, CUBIST shall have the first right to file,
prosecute and maintain in the Territory, upon appropriate consultation with
XTL,
Patents that claim or cover any Joint Invention (a “Joint
Patent”);
however,
in the
event that CUBIST elects not to file any patent application in the Territory
with respect to any Joint Invention, XTL shall have such right and upon exercise
by XTL of such right, XTL shall have the right to prosecute and maintain in
the
Territory, upon appropriate consultation with CUBIST, the Joint Patents to
which
such Joint Invention relates. Each of XTL and CUBIST shall execute such
documents and perform such acts as may be reasonably necessary to allow CUBIST,
in the first instance, and XTL, in the second instance, to file, prosecute
and
maintain Joint Patents in any country within the Territory in a timely basis.
CUBIST shall promptly give notice to XTL of the grant, lapse, revocation,
surrender, invalidation or abandonment in the Territory of any Joint Patent
being prosecuted by CUBIST. XTL shall promptly give notice to CUBIST of the
grant, lapse, revocation, surrender, invalidation or abandonment of any Joint
Patent being prosecuted by XTL.
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12.3 Option
of the Parties to Prosecute and Maintain Patents.
Each
Party shall give notice to the other Party of any desire to cease prosecution
of
patent applications and/or maintenance in the Territory of XTL Patents that
such
Party is then prosecuting or maintaining, and, in such case, shall permit the
other Party, in its sole discretion, to continue such prosecution or maintenance
in the Territory at its own expense. If the other Party then elects to continue
prosecution or maintenance in the Territory, each Party shall execute such
documents and perform such acts as may be reasonably necessary to allow
continuation of such prosecution or maintenance in the Territory.
12.4 Legal
or Administrative Proceedings.
(a) Each
Party shall, within ten (10) days of learning of such event, inform the other
of
any request for, or filing or declaration of, any interference, opposition,
reexamination, revocation, nullity proceeding or declaration of non-infringement
and/or invalidity, whether by administrative or legal proceeding, sounding
in
equity or in law (or the equivalent of any of the foregoing), whether initiated
by a Third Party or any patent office, in the Territory relating to any XTL
Patent. XTL and CUBIST shall thereafter consult and cooperate fully to determine
a course of action with respect to any such proceeding. Each Party shall have
the right to review and comment upon any submission to be made in connection
with such proceeding and the Party responsible for prosecuting or maintaining
the Patent at issue in such proceeding shall consider, in good faith,
incorporating any comments provided by the other Party.
(b) Neither
Party shall initiate any reexamination, interference, reissue, revocation,
nullity or declaration of non-infringement proceeding in the Territory with
respect to XTL Patents or Joint Patents without the prior written consent of
the
other Party.
(c) In
connection with any interference, opposition, reexamination, revocation, nullity
proceeding or declaration of non-infringement and/or invalidity, whether by
administrative or legal proceeding, sounding in equity or in law (or the
equivalent of any of the foregoing), whether initiated by a Third Party or
any
Patent Office, in the Territory relating to any XTL Patent or Joint Patent,
XTL
and CUBIST will cooperate fully and will provide each other with any information
or assistance that either may reasonably request. The Parties shall keep each
other informed of developments in any such action or proceeding, including
to
the extent permissible by law and contracts, the status of any settlement
negotiations and the terms of any offer related thereto.
(d) XTL,
in
the case of XTL Patents, shall bear the expense of any interference, opposition,
reexamination, revocation, nullity proceeding or declaration of non-infringement
and/or invalidity, whether by administrative or legal proceeding, sounding
in
equity or in law (or the equivalent of any of the foregoing), whether initiated
by a Third Party or any Patent Office, relating thereto. The expenses of any
interference, opposition, reexamination, revocation, nullity proceeding or
declaration of non-infringement and/or invalidity, whether by administrative
or
legal proceeding, sounding in equity or in law (or the equivalent of any of
the
foregoing), whether initiated by a Third Party or any Patent Office, with
respect to Joint Patents shall be shared equally by the Parties.
(e) This
Section 12.4 applies to any proceeding before the United States Patent and
Trademark Office or
similar patent authority in the Territory and to any proceeding before a court,
arbitration panel or similar body of competent jurisdiction.
12.5 Enforcement.
(a) Either
Party shall give written notice to the other Party of (i) any actual, alleged
or
threatened infringement of any XTL Trademark or CUBIST Trademark or of any
unfair trade practices, trade dress imitation, passing off of counterfeit goods,
or like offenses, or any such claims brought by a Third Party against a Product
(hereinafter “TM
Infringement”),
(ii)
any infringement of any XTL Patent and/or CUBIST Patent, and/or Joint Patent,
and (iii) any misappropriation or misuse of XTL Know-How and/or CUBIST Know-How
and/or Joint Inventions; in each case that such Party has knowledge of. XTL
and
CUBIST shall thereafter consult and cooperate fully to determine a course of
action, including but not limited to the commencement of legal action by either
or both XTL and CUBIST, to terminate any infringement of XTL Patents Joint
Patents, or Joint Inventions or to terminate any misappropriation or misuse
of
XTL Know-How. CUBIST shall have the first right to initiate and prosecute legal
action anywhere in the Territory, at CUBIST’s expense and in its own name, and,
as necessary, in the name of XTL, with respect to XTL Patents, XTL Know-How,
Joint Patents, and Joint Inventions. Subject to the provisions of this Section
12.5, CUBIST shall control and conduct such legal action in its sole discretion,
including without limitation, the terms and conditions of any settlement. In
the
event that CUBIST notifies XTL in writing that it elects not to initiate and/or
prosecute any such legal action, or if CUBIST does not take material action
to
▇▇▇▇▇ any such actual, alleged or threatened infringement within ninety (90)
days after the date of notice to CUBIST of such actual, alleged or threatened
infringement, XTL shall thereafter have the right to initiate and prosecute
such
action in the Territory in its own name.
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Commission.
(b) For
any
infringement action concerning XTL Patents or Joint Patents or any
misappropriation or misuse of XTL Know-How or Joint Inventions, in the event
that CUBIST elects to initiate or prosecute such action but is unable to do
so
solely in its own name, XTL will join such action voluntarily, and at CUBIST’s
expense, will execute all documents necessary for CUBIST to initiate, prosecute
and/or maintain such action. In the event that XTL elects to be represented
by
its own counsel in connection with any matter pertaining to such action, XTL
shall pay all of the costs and expenses of its own counsel. In connection with
any such action, XTL and CUBIST will cooperate fully and will provide each
other
with any information or assistance that either may reasonably request,
provided,
however,
CUBIST
shall control and conduct such legal action in its sole discretion, including
without limitation, the terms and conditions of any settlement. The Parties
shall keep each other informed of developments in any such action or proceeding,
including to the extent permissible by law and contracts, the status of any
settlement negotiations and the terms of any offer related thereto.
(c) Any
recovery of damages or an award received by either or both of XTL and CUBIST
in
connection with or as a result of any action contemplated by this Section 12.5
or Section 12.6 below, whether by settlement or otherwise, shall be shared
in
order as follows:
(i) the
Party
or Parties that prosecuted the action shall recoup all of its or their costs
and
expenses incurred in connection with the action;
(ii) the
other
Party (to the extent that it did not prosecute the action) shall then, from
funds remaining, recover its costs and expenses incurred in connection with
the
action to the extent that such costs and expenses are reasonably incurred to
comply with such Party’s obligations under Section 12.5 or to the extent that
such other Party participates in the prosecution of such action but not as
a
party thereto; and
(iii) any
amount remaining shall be included for royalty payment purposes under Section
10.1 within Net Sales in Patent Countries for the royalty period in which such
amount was received.
12.6 Avoidance
of Third Party Infringement Claims.
If
a
Product becomes the subject of a claim by a Third Party that the activities
undertaken to Obtain Regulatory Approval, manufacture, use, sell, Commercialize
or export or import Product constitutes, causes or results in infringement
of
any patent rights of such Third Party or other related intellectual property
rights (any such claim, a “Third
Party Infringement Claim”),
the
Party first having notice of such Third Party Infringement Claim shall promptly
notify the other Party. In the event that there is a Third Party Infringement
Claim that arises from the use or practice of any XTL Patents or XTL Know-How
in
connection or associated with the activities undertaken to Obtain Regulatory
Approval, manufacture, use, sell, offer for sale, Commercialize, export or
import Product, the Parties shall confer in good faith as promptly as
practicable after both Parties become aware of such Third Party Infringement
Claim as to whether it is feasible to alter their approach to their activities
with respect to the Product so as to avoid such Third Party Infringement Claim
without adversely affecting their rights under this Agreement. In the event
the
Parties determine in good faith that it is feasible to alter their approach
to
such activities without adversely affecting their rights under this Agreement,
the Parties shall implement such alternative approach to such activities.
12.7 Patent
Term Restoration and Regulatory Data Exclusivity.
The
Parties shall cooperate with each other in obtaining patent term restoration
or
extension, supplementary protection certificates, or their equivalents, with
respect to XTL Patents, CUBIST Patents, Joint Patents, and regulatory data
exclusivity and the like, with respect to HepeX-B, in the
Territory.
12.8 Patent
Marking.
CUBIST
shall ▇▇▇▇ all Products sold with appropriate patent numbers or indicia at
XTL’s
request to the extent required and/or permitted by law.
12.9 Trademarks. (a)
CUBIST
shall have the right to determine appropriate trademark, trade dress and other
related intellectual property usage in connection with marketing Products under
this Agreement. CUBIST shall have the exclusive right to use any trademarks
in
connection with marketing Products under this Agreement in the Territory.
(b) XTL
agrees to file, prosecute and maintain the XTL Trademarks at its sole expense,
provided,
however,
that
XTL shall (i) use outside counsel reasonably acceptable to CUBIST, (ii)
provide CUBIST with all material documentation and correspondence from, sent
to
or filed with trademark offices in the Territory regarding any XTL Trademark,
(iii) provide CUBIST with a reasonable opportunity to review and comment
upon all filings with such trademark offices in advance of submissions to such
patent offices, and (iv) shall consider, in good faith, incorporating any
comments provided by CUBIST. In the event that XTL is unwilling, unable or
otherwise fails to file or prosecute any XTL Trademark in any country in the
Territory, XTL shall provide CUBIST with thirty (30) days notice to permit
CUBIST to file, prosecute and/or maintain such XTL Trademark in such country,
and XTL shall execute such documents and perform such acts as may be reasonably
necessary to allow CUBIST to file, prosecute and maintain such XTL Trademark
in
such country in a timely manner.
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Commission.
(c) With
respect to all filings, prosecution and maintenance of any Trademark pursuant
to
this Section 12.9, the filing Party shall be responsible for payment of all
costs and expenses related to such Trademark filing prosecution or
maintenance.
12.10 Third
Party Licenses. (a)
The
Parties shall confer and discuss whether any license from a Third Party is
necessary or advisable to avoid, settle, resolve or satisfy any claim that
the
activities to Obtain Regulatory Approval, make, have made, use, promote, market,
sell, have sold, offer to sell, import or export HepeX-B by CUBIST or its
Sublicensees in any country within the Territory infringes or misappropriates
any intellectual property rights of such Third Party. Prior to September 30,
2004, the Parties shall confer and agree upon a strategy as to how to address
any Third Parties, if any, then known to the Parties from whom it would be
necessary or advisable to obtain a license to avoid, settle resolve, or satisfy
any claim that the activities to Obtain Regulatory Approval, Commercialize,
manufacture, use, promote, market, sell, offer, import or export of HepeX-B
by
CUBIST or its Sublicensees in any country within the Territory infringes or
misappropriates any intellectual property rights of such Third Party (the
“Strategy”).
To
assist in devising the Strategy, CUBIST shall engage the services of a
nationally recognized law firm with sufficient knowledge and expertise in the
field of patent rights. If the parties, after good faith discussion and due
consideration of the input of such law firm, are unable to mutually agree upon
the Strategy, then CUBIST may, acting in good faith, make final decisions with
respect to devising the Strategy. The Strategy may be modified from time to
time
pursuant to the mutual agreement of the Parties; provided
that if
the parties, after good faith discussion and due consideration of the input
from
the above-referenced law firm, are unable to mutually agree, then CUBIST may,
acting in good faith, make final decisions with respect to revising the
Strategy.
(b) CUBIST
shall be responsible for obtaining licenses identified in the Strategy on
commercially reasonable terms. CUBIST will provide XTL with five (5) business
days to review and *****
the
scope of such license is reasonably limited to permit CUBIST to exercise its
rights and licenses under, and its activities under and pursuant to, this
Agreement to Obtain Regulatory Approval, make, have made, use, promote, market,
sell, have sold, offer to sell, import, export, and Commercialize HepeX-B,
and
whether such license contains commercially reasonable terms; such *****.
If XTL
does not *****
within
such *****,
XTL
will be deemed to have *****.
CUBIST
shall pay all amounts required to be paid to the Third Parties pursuant to
such
licenses described in Section 12.10(b). If and to the extent practicable, CUBIST
shall endeavor to use reasonable efforts to obtain a clause in any such license
permitting assignment of such license to XTL; provided
that in
no event shall CUBIST be in breach of this Agreement or in any way otherwise
liable for any failure to obtain any such assignment clause in any such license;
and further
provided
that
CUBIST will have no obligation to include or accept an assignment clause that
requires CUBIST to retain or incur any further liability under such license
subsequent to such assignment. XTL may not reject any such license due to the
failure of such license to contain such assignment clause as contemplated under
this Section 12.10(b).
(c) With
respect to licenses obtained pursuant to Section 12.10(b) which were
*****,
or with
respect to which *****
(“Approved
Third Party Licenses”)
wherein the intellectual property rights were described in an issued patent
or
published in a patent application as of the Effective Date, unless with respect
to any such licenses that were not mutually agreed-upon in the Strategy, XTL
obtains a Legal Opinion, at XTL’s expense, that is in form and substance
reasonably acceptable to CUBIST (provided
that
CUBIST must notify XTL within thirty (30) days after receipt of the executed
Legal Opinion if CUBIST deems such Legal Opinion to not be reasonably
acceptable), CUBIST shall have the right to reduce milestone and royalty
payments otherwise owed to XTL pursuant to Sections 9 and 10 by the amounts
paid
to such Third Parties for such licenses such that the reduced milestone and
royalty payments are no less than the *****.
In the
event that CUBIST cannot fully offset such amounts against milestone and royalty
payments otherwise owed to XTL, unless paid by XTL, interest shall begin to
accrue as of the date CUBIST first makes such payment to such Third Party at
a
rate determined in accordance with Section 10.8 on any such amounts not able
to
be offset. CUBIST will reasonably cooperate with the law firm agreed to by
the
Parties to provide such information as may be reasonably necessary to enable
the
law firm to render its opinion.
After
a
Change of Control of CUBIST, (i) amounts previously paid by CUBIST with respect
to the licenses described under this Section 12.10(c), plus any accrued interest
through the date of the Change of Control, and not yet paid by XTL or offset
pursuant to this Section 12.10(c), will continue to be offset against milestone
and royalty payments otherwise owed to XTL pursuant to Sections 9 and 10 before
any other offsets pursuant to this Agreement; provided
that
such milestones and royalties shall not be reduced by more than fifty percent
(50%), (ii) only fifty percent (50%) of amounts required to be paid by CUBIST
pursuant to such licenses after a Change of Control of CUBIST shall be offset
against milestone and royalty payments otherwise owed to XTL pursuant to
Sections 9 and 10 before any other offsets pursuant to this Agreement;
provided
that
such milestones and royalties shall not be reduced by more than fifty percent
(50%), and (iii) interest shall cease to accrue on all amounts paid by CUBIST
pursuant to the licenses obtained or to be obtained under this Section 12.10(c)
but not otherwise offset as permitted under this Agreement.
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(d) With
respect to Approved Third Party Licenses wherein the intellectual property
rights were neither described in an issued patent nor published in a patent
application as of the Effective Date, unless with respect to any such licenses
that were not mutually agreed-upon in the Strategy, XTL obtains a Legal Opinion,
at XTL’s expense, that is in form and substance reasonably acceptable to CUBIST
(provided
that
CUBIST must notify XTL within thirty (30) days after receipt of the executed
Legal Opinion if CUBIST deems such Legal Opinion to not be reasonably
acceptable), CUBIST shall have the right to reduce milestone and royalty
payments otherwise owed to XTL pursuant to Sections 9 and 10 by fifty percent
(50%) of the amounts paid to such Third Parties for such licenses such that
the
reduced milestone and royalty payments are no less than the XTL Licensor
Payments. In the event that CUBIST cannot fully offset such amounts against
milestone and royalty payments otherwise owed to XTL, unless paid by XTL,
interest shall begin to accrue as of the date CUBIST first makes such payment
to
such Third Party at a rate determined in accordance with Section 10.8 on any
such amounts not able to be offset. CUBIST will reasonably cooperate with the
law firm agreed to by the Parties to provide such information as may be
reasonably necessary to enable the law firm to render its opinion.
After
a
Change of Control of CUBIST, (i) amounts previously paid by CUBIST with respect
to the licenses described under this Section 12.10(d), plus any accrued interest
through the date of the Change of Control, and not yet paid by XTL or offset
pursuant to this Section 12.10(d), will continue to be offset against milestone
and royalty payments otherwise owed to XTL pursuant to Sections 9 and 10 before
any other offsets pursuant to this Agreement; provided
that
such milestones and royalties shall not be reduced by more than fifty percent
(50%), and (ii) interest shall cease to accrue on all amounts paid by CUBIST
pursuant to the licenses obtained or to be obtained under this Section 12.10(d)
but not otherwise offset as permitted under this Agreement.
(e) XTL
shall
have no obligation to pay any amounts incurred by CUBIST pursuant to the Third
Party licenses obtained under this Section 12.10, which amounts have not been
offset against milestone and royalty payments as of the termination or
expiration of this Agreement.
12.11 Limitation.
Notwithstanding
any other provision in this Section 12, except with respect to the Patents
listed in Exhibit
A,
(a)
neither Party shall be obligated to prepare, file, prosecute and maintain
Patents, or to bring or pursue
enforcement proceedings or defend declaratory judgment actions under this
Section 12 if, and to the extent that, such Party is not entitled to do so
under
its licenses from Third Parties, and (b) any rights conveyed under this Section
12 permitting a Party to prepare, file, prosecute and maintain certain Patents,
or to bring and pursue enforcement proceedings, or defend declaratory judgment
actions shall be subject to all applicable licenses from Third Parties, and
are
conveyed only to the extent permitted under such agreements. With respect to
Patents Controlled by XTL after the Effective Date, XTL shall promptly notify
CUBIST in writing if XTL is not entitled under its licenses to such Patents
from
Third Parties to perform the activities listed in (a) above, or if any rights
listed in (b) above that have been conveyed to CUBIST are restricted by XTL’s
licenses from Third Parties to such Patents.
Section
13. TERM
AND TERMINATION.
13.1 Term.
This
Agreement shall be effective as of the Effective Date and remain in effect
until
the earlier of (a) the effective date of termination pursuant to Section 13.2
or
Section 13.3 below, and (b) the expiration of the term of this Agreement on
the
date on which CUBIST is no longer obligated, pursuant to this Agreement, to
make
payment to XTL of any royalties in connection with sales of Products in the
Territory. In the event that the term of this Agreement expires pursuant to
clause (b) of this Section 13.1, then the licenses granted by
XTL to
CUBIST shall survive such expiration and shall be fully paid-up, royalty-free,
perpetual and irrevocable licenses.
13.2 Termination
by CUBIST. (a)
This
Agreement may be terminated by CUBIST at any time during the term of this
Agreement for any reason or no reason if CUBIST gives at least one hundred
and
eighty (180) days prior written notice of termination to XTL.
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(b) CUBIST
may terminate this Agreement upon twenty (20) days’ prior written notice to XTL
if (i) in CUBIST’s judgment continuation of the activities contemplated
hereunder is inappropriate, impractical, or inadvisable either for reasons
of
safety or efficacy; or (ii) the emergence of any adverse event or side effect
with the Product is of such magnitude or incidence in the opinion of CUBIST
to
support termination. Upon CUBIST’s delivery of such notice to XTL, CUBIST shall
have no further obligations under this Agreement except as provided under
Section 13.5.
(c) CUBIST
may terminate this Agreement pursuant to this Section 13.2 on a Product by
Product or country by country basis.
13.3 Termination
By Either Party Upon Bankruptcy or Insolvency.
This
Agreement may be terminated in its entirety by either Party by giving written
notice of termination to the other Party in the event that such other Party
files or institutes any bankruptcy, liquidation or receivership proceedings,
or
in the event that such other Party makes an assignment of a substantial portion
of the assets of such other Party for the benefit of its creditors; provided,
however, that, in the case of any involuntary bankruptcy proceeding such right
to terminate shall only become effective if such other Party consents to the
involuntary bankruptcy or such proceeding is not dismissed within sixty (60)
days after the filing thereof.
13.4 Termination
for Breach. (a)
If either Party (the “Non-Breaching
Party”)
believes that the other Party (the “Breaching
Party”)
is in
material breach of this Agreement with respect to one or more Products, then
the
Non-Breaching Party may deliver notice of such breach to the Breaching Party.
The Breaching Party shall have thirty (30) days to cure such breach;
provided
that, if
cure cannot be reasonably effected within such thirty (30) day period, the
Breaching Party may elect to deliver to the Non-Breaching Party within such
thirty (30) day period a plan to cure such breach within a timeframe that is
reasonably prompt in light of the circumstances then prevailing, and the
Non-Breaching Party shall have the right to approve or reject in writing such
proposed plan in its absolute discretion. If the Non-Breaching Party approves
in
writing such proposed plan, then the cure period will be extended in accordance
with the terms of such plan and the Breaching Party shall use Commercially
Reasonable Efforts to carry out such plan and cure the breach in
accordance with the provisions of such plan.
(b)
If the Breaching Party fails to cure such breach as provided for in
Section 13.4(a), the Non-Breaching Party may terminate this Agreement
either in its entirety or with respect to one or more Products upon written
notice to the Breaching Party; provided
that,
the Non-Breaching Party gives such written notice of termination within six
(6)
months after the Breaching Party has failed to cure such breach as provided
for
in Section 13.4(a).
(c)
If the Non-Breaching Party gives notice of termination under this
Section 13.4 and the Breaching Party disputes whether such termination
is
proper under this Section 13.4, then the issue of whether this Agreement
may properly be terminated upon expiration of the notice period (unless such
breach is cured as provided in Section 13.4(a)) shall be resolved in
accordance with Section 14 (Dispute Resolution). If as a result of such
dispute resolution process it is determined that the notice of termination
was
proper, then such termination shall be deemed to have been effective thirty
(30)
days following the date of the notice of termination. If as a result of such
dispute resolution process it is determined that the notice of termination
was
improper, then no termination shall have occurred and this Agreement shall
remain in effect.
13.5 Effect
of Expiration or Termination of this Agreement.
(a)
In the
event of termination or expiration of this Agreement, then, except to the extent
otherwise provided in this Section 13.5(a) and Section 13.5(f) below, neither
Party shall have any liability or obligation to the other Party under this
Agreement. Notwithstanding the foregoing sentence, the licenses granted to
CUBIST under Section 2 shall survive expiration of this Agreement pursuant
to
Section 13.1(b), and in such event, such licenses shall be deemed to be fully
paid up, irrevocable and perpetual.
(b) In
the
event that CUBIST terminates this Agreement pursuant to Section 13.4, then
this
Agreement shall terminate, and, except to the extent otherwise provided in
Section 13.5(f) below, neither Party shall have any liability or obligation
to
the other Party under this Agreement.
(c) In
the
event that CUBIST terminates this Agreement pursuant to Section 13.2, or in
the
event that XTL terminates this Agreement pursuant to Section 13.4, then this
Agreement shall terminate, and, except to the extent otherwise provided in
this
Section 13.5(c), Section 13.5(d) and Section 13.5(f) below, neither Party shall
have any further liability or obligation to the other Party under this
Agreement, including with respect to Section 9 and Section 10. The licenses
granted to CUBIST under Section 2 shall terminate. Notwithstanding anything
to
the contrary in this Section 13.5(c), in the event that CUBIST terminates this
Agreement pursuant to Section 13.2 or XTL terminates this Agreement pursuant
to
Section 13.4, CUBIST shall have the right to sell in the Territory all of its
inventory of Products for a period of twelve (12) months from the effective
date
of termination, subject to CUBIST’s payment obligations under Section
10.
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(d) If
requested by XTL within ten (10) days after the effective date of a termination
pursuant to Section 13.2 or a termination by XTL pursuant to Section 13.4,
either with respect to this Agreement in its entirety, or with respect to a
particular Product in one or more countries, CUBIST will: (i) transfer to XTL
all INDs, Regulatory Approval applications, Regulatory Approvals and orphan
drug
designations for such terminated Products in the terminated countries in effect
as of the time of any such termination, (ii) subject to the scope of use
limitations described in clause (iii) below, provide to XTL a copy of all
information, data, records and reports (but specifically excluding know-how
of
CUBIST and CUBIST Patents) in Cubist's Control created or obtained in the
performance of CUBIST's or XTL’s activities under this Agreement that are
directly related to the Products (or in the event of a termination with respect
to a particular Product, such terminated Product) and necessary or reasonably
useful for XTL to
Obtain
Regulatory Approval and Commercialize the
Products (or in the event of a termination with respect to a particular Product,
such terminated Product) in the terminated countries (collectively, the
“Data”),
and
(iii) grant to XTL a non-exclusive license in the terminated countries in and
to
the Data solely for the purpose of using and incorporating the Data in its
applications for and in the maintenance of Regulatory Approval of Products
(or
in the event of a termination with respect to a particular Product, such
terminated Product) within the terminated countries and to Obtain Regulatory
Approval, manufacture and Commercialize Products (or in the event of a
termination with respect to a particular Product, such terminated Product)
in
the terminated countries, and (iv) if permitted under any Third Party licenses
obtained by CUBIST after the Effective Date pursuant to the Strategy, CUBIST
will assign to XTL such licenses, or if any such license covers countries other
than the terminated countries will grant to XTL a sublicense under such license
with respect to the terminated countries, to Obtain Regulatory Approval, make,
have made, use, promote, market, sell, have sold, offer to sell, import
or export HepeX-B in the terminated countries; provided
that if
any such license requires consents of the Third Party licensor to effect such
assignment, CUBIST will request such consent and if such consent is not provided
or is otherwise qualified, CUBIST will have no obligation to assign such
license. In addition, upon any such termination, CUBIST shall either (y)
negotiate in good faith with XTL to enter into an agreement to supply such
terminated Product to XTL on commercially reasonable terms, or (z) if such
termination terminated this Agreement in its entirety, provide to XTL all
biological materials in CUBIST’s Control created or obtained under this
Agreement with respect to Products (subject to CUBIST’s sell-off rights with
respect to inventory under Section 13.5(c)), and a copy of all information,
data, records and reports (but specifically excluding know-how of CUBIST and
CUBIST Patents) in Cubist's Control created or obtained in the performance
of
CUBIST's or XTL’s activities under this Agreement that are directly related to
the terminated Products and necessary or reasonably useful for XTL to
manufacture such terminated Products, and such data and information shall be
deemed to be included within the Data. Notwithstanding
the foregoing, CUBIST will have no obligation to assign or otherwise transfer
to
XTL any INDs, Regulatory Approval applications, Regulatory Approvals or orphan
drug designations if any of the foregoing are in effect with respect to any
country other than the terminated countries. XTL and CUBIST will negotiate
in
good faith with respect to mutually agree upon reasonable and appropriate
compensation to CUBIST for the commercial value received as a result of the
transfers and licenses provided as set forth in this Section 13.5(d); if the
Parties are unable to so mutually agree within ninety (90) days after the
effective date of termination of this Agreement the Parties shall refer the
matter to the dispute resolution process set forth in Section 14, and in any
arbitration, the arbitrator will take into consideration, among other factors,
the investment of CUBIST in creating or obtaining the Data and the Parties’
investment in obtaining such transferred INDs, Regulatory Approval applications,
Regulatory Approvals and orphan drug designations, and amounts paid by CUBIST
but offset under Section 10.4 with respect to any assigned Third Party licenses.
(e) In
the
event this Agreement is terminated due to the rejection of this Agreement by
or
on behalf of a Party under ▇▇▇▇▇▇▇ ▇▇▇ ▇▇ ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇ Bankruptcy Code
(the
“Code”),
and
the equivalent provisions, if any, of the bankruptcy laws of other countries
in
which CUBIST exercises the license granted hereunder, all licenses and rights
to
licenses granted under or pursuant to this Agreement by one Party to the other
are, and shall otherwise be deemed to be, for purposes of Section 365(n) of
the
Code, and any such equivalent law, licenses of rights to “intellectual property”
as defined under Section 101(35A) of the Code. The Parties agree that the
licensed Party, as a licensee of such rights under this Agreement, shall retain
and may fully exercise all of its rights and elections under the Code, and
any
such equivalent law, and that upon commencement of a bankruptcy proceeding
by or
against a Party under the Code, the other Party shall be entitled to a complete
duplicate of or complete access to, any such intellectual property and all
embodiments of such intellectual property. Such intellectual property and all
embodiments thereof shall be promptly delivered to the other Party (i) upon
any
such commencement of a bankruptcy proceeding upon written request therefor
by a
Party, unless the Party elects to continue to perform all of its obligations
under this Agreement or (ii) if not delivered under (i) above, upon the
rejection of this Agreement by or on behalf of the Party upon written request
therefor. The foregoing is without prejudice to any rights either Party may
have
arising under the Code or other applicable law.
31
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Confidential material redacted and filed separately with the
Commission.
(f) Termination
of this Agreement shall not relieve either Party of any obligation of such
Party
accruing prior to such termination. Any termination of this Agreement shall
be
without prejudice to the rights of either Party against the other accrued or
accruing under this Agreement prior to termination. The provisions of Section
1,
Section 8.2, Section 8.3, Section 8.4, Section 11.3, Section 11.4, Section
12.1,
Section 13, Section 14 and Section 15 shall survive the termination of this
Agreement. Section 8.1 and Section 8.5 shall survive termination of this
Agreement for a period of five (5) years.
(g) CUBIST
shall reimburse XTL for all non-cancelable out-of-pocket expenses XTL incurs
after a termination of this Agreement (by CUBIST pursuant to Section 13.2,
or by
XTL pursuant to Section 13.4) with respect to Third Party service providers
contracted by XTL to assist in the performance of XTL’s obligations hereunder;
provided
that (i)
such obligations are set forth in a written agreement between XTL and such
Third
Party service provider, (ii) the terms and provisions of such written agreement,
including those relating to such non-cancelable expenses, are commercially
reasonable, (iii) XTL has used commercially reasonable efforts to minimize
such
non-cancelable expenses; and (iv) such non-cancelable expenses relate solely
and
directly to the performance of XTL obligations under this
Agreement.
Section
14. DISPUTE
RESOLUTION.
14.1 Escalation.
The
Parties recognize that disputes as to certain matters may from time to time
arise during the term of this Agreement which relate to either Party’s rights
and/or obligations hereunder. It is the objective of the Parties to establish
procedures to facilitate the resolution of disputes arising under this Agreement
in an expedient manner by mutual cooperation and without resort to litigation.
To accomplish this objective, the Parties agree to follow the procedures set
forth in this Section 14.1 if and when a dispute arises under this Agreement.
Any dispute arising under this Agreement shall, by either Party providing
written notice to the other Party, be referred to the respective chief executive
officers of the Parties for attempted resolution by good faith negotiations
within fourteen (14) days after such notice is received. In the event that
the
designated officers are not able to resolve such dispute within such fourteen
(14) day period, and do not agree to extend the time period for resolving the
dispute, or if the terms and conditions of the resolution or settlement of
the
dispute are breached, the dispute shall be submitted for mediation by a mutually
acceptable Third Party within thirty (30) days after expiration of the previous
fourteen (14) day period, unless the Parties agree to extend the period for
submitting the dispute for mediation. In the event that such dispute is not
resolved within thirty (30) days after such dispute is submitted for mediation,
unless the parties otherwise agree to extend the time period for resolving
the
dispute, then such dispute shall be resolved by arbitration pursuant to the
provisions of Section 14.2. Pending resolution of any dispute covered by this
Section 14.1, both Parties will continue their performance under this Agreement
of any obligations (including, without limitation, payment obligations) that
are
not the subject of such dispute.
14.2 Arbitration.
(a)
Any
claim, dispute, or controversy arising out of or relating to this Agreement
that
is not resolved in accordance with the provisions of Section 14.1 and that
the
Parties agree to submit to binding arbitration pursuant to this Section 14.2
will be submitted by the parties to arbitration under rules then in effect
(“ICC
Rules”)
of the
International Chamber of Commerce (“ICC”)
in New
York City, New York, U.S.A. as modified herein or by agreement of the Parties.
Any such arbitration shall be conducted in New York City, New York, U.S.A.
by
three (3) arbitrators. Each Party shall select one (1) arbitrator and such
arbitrators shall jointly appoint the third arbitrator who shall act as the
chairman. If either Party fails to appoint an arbitrator within thirty (30)
days
of a request by the other Party, or if the arbitrators selected by the parties
cannot agree on a chairman within thirty (30) days after they have been
selected, then either Party may request the ICC to appoint such co-arbitrator
(for the non-responsive Party) or the chairman. Such appointment shall be
binding on the Parties. Each Party irrevocably and unconditionally (i) consents
to the jurisdiction of any such proceeding and waives any objection that it
may
have to personal jurisdiction or the laying of venue of any such proceeding;
and
(ii) knowingly and voluntarily waives its rights to have disputes tried and
adjudicated by a judge and jury except as otherwise expressly provided herein.
The Parties will cooperate with each other in causing the arbitration to be
held
in as efficient and expeditious a manner as practicable. Unless the Parties
agree otherwise, they shall be limited in their discovery to directly relevant
documents. Responses or objections to a document request shall be served twenty
(20) days after receipt of the request. The arbitrators shall resolve any
discovery disputes. Nothing herein shall prevent the Parties from settling
any
dispute by mutual agreement at any time.
32
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Confidential material redacted and filed separately with the
Commission.
(b) The
arbitration shall be of each Party’s individual claims only, and no claim of any
other Party shall be subject to arbitration in such proceeding. Except as
otherwise required by law, the Parties and the arbitrator(s) shall maintain
as
confidential all information or documents obtained during the arbitration
process, including the resolution of the dispute. The arbitration shall be
conducted in English language.
(c) The
arbitrator(s) shall not have the authority to award any injunctive relief or
to
award exemplary or punitive damages, and the Parties expressly waive any right
to such damages. The arbitrator(s) shall have the authority to award actual
money damages (including interest on unpaid amounts from the date due). The
costs and expenses of the arbitration, but not the costs and expenses of the
Parties, shall be shared equally by the Parties; provided
that the
non-prevailing Party in any arbitration shall pay the other Party’s costs and
expenses (including travel expenses) and reimburse such Party for its portion
of
the arbitration costs. In the event that neither Party wins totally,
reimbursement shall be made proportionally in accordance with the ICC Rules.
Any
award rendered by the arbitrator(s) shall be final and binding upon the Parties.
Judgment upon the award may be entered in any court of competent jurisdiction.
If a Party fails to proceed with arbitration, unsuccessfully challenges the
arbitration award, or fails to comply with the arbitration award, the other
Party is entitled to costs, including reasonable attorneys’ fees, for having to
compel arbitration or defend or enforce the award.
Section
15. MISCELLANEOUS.
15.1 Force
Majeure.
Neither
Party shall be held liable or responsible to the other Party nor be deemed
to
have defaulted under or breached the Agreement for failure or delay in
fulfilling or performing any term of the Agreement when such failure or delay
is
caused by or results from causes beyond the reasonable control of the affected
Party including, but not limited to, earthquakes, fire, floods, embargoes,
insurrections, riots, civil commotions, strikes, lockouts or other labor
disturbances, acts of God, acts of war or terrorism, or acts, omissions or
delays in acting by any governmental authority or the other Party. The affected
Party shall notify the other Party of such force majeure circumstances as soon
as reasonably practical.
15.2 Assignment. Neither
party may assign its rights or obligations hereunder without the prior written
consent of the other party which will not be unreasonably withheld or delayed;
provided
that
either may assign this Agreement to one of its Affiliates, or pursuant to a
merger, consolidation or sale of substantially all of its assets or stocks
or
other ownership interests without such prior written consent. The Parties agree
that the issue of whether prior written consent to an assignment was
unreasonably withheld or delayed by a Party shall be governed by the laws of
the
Commonwealth of Massachusetts without reference to any rules of conflicts of
laws. This Agreement will bind and inure to the benefit of the parties hereto
and their respective successors and permitted assigns.
15.3 Severability.
In the
event any one or more of the provisions contained in this Agreement should
be
held invalid, illegal or unenforceable in any respect, the validity, legality
and enforceability of the remaining provisions contained herein shall not in
any
way be affected or impaired thereby, unless the absence of the invalidated
provision(s) adversely affect the substantive rights of the Parties. The Parties
shall in such an instance use their best efforts to replace the invalid, illegal
or unenforceable provision(s) with valid, legal and enforceable provision(s)
that, insofar as practical, implement the purposes of this
Agreement.
15.4 Notices.
All
notices or other communications that are required or permitted hereunder shall
be in writing and sufficient if delivered personally, sent by telecopier (and
promptly confirmed by personal delivery, registered or certified mail or
overnight courier), sent by internationally-recognized overnight courier,
addressed as follows:
|
If
to CUBIST, to:
|
If
to XTL, to:
|
|
|
CUBIST
Pharmaceuticals, Inc.
▇▇
▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇,
▇▇ ▇▇▇▇▇
Attention:
Chief Executive Officer
Telecopier
No.: (▇▇▇) ▇▇▇-▇▇▇▇
|
▇▇▇▇▇▇▇▇
▇
▇▇▇▇▇▇
▇▇▇▇▇▇▇▇
▇▇▇▇▇▇▇
▇▇▇▇▇
▇▇▇▇▇▇
Attention:
Chief Executive Officer
Telecopier
No.: (▇▇▇) ▇.▇▇▇.▇▇▇▇
|
33
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Confidential material redacted and filed separately with the
Commission.
|
With
a copy to:
|
With
a copy to:
|
|
|
CUBIST
Pharmaceuticals, Inc.
▇▇
▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇,
▇▇ ▇▇▇▇▇
Attention:
General Counsel
Telecopier
No.: (▇▇▇) ▇▇▇-▇▇▇▇
And
▇▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇ LLP
▇▇▇
▇▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇,
▇▇ ▇▇▇▇▇
Attention:
▇▇▇▇▇ ▇. ▇▇▇▇, Esq.
Telecopier
No.: (▇▇▇) ▇▇▇-▇▇▇▇
|
▇▇▇▇▇▇
▇▇▇▇▇▇ White & ▇▇▇▇▇▇▇▇▇ LLP
▇▇▇▇
▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇ ▇▇▇▇▇
▇▇▇
▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Attention:
▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇
Telecopier
No.: (▇▇▇) ▇▇▇-▇▇▇▇
|
or
to
such other address as the Party to whom notice is to be given may have furnished
to the other Party in writing in accordance herewith. Any such communication
shall be deemed to have been given when delivered if personally delivered or
sent by telecopier on a business day, on the business day after dispatch if
sent
by internationally-recognized overnight courier.
15.5 English
Language.
All
notices, disclosures or information delivered or made available by either Party
or its employees and agents to the other Party and its employees or agents
pursuant to this Agreement shall be made in English. The English language
version of this Agreement shall control notwithstanding the translation of
this
Agreement into any other language.
15.6 Applicable
Law.
Except
as otherwise expressly set forth in Section 15.2, this Agreement shall be
governed by and construed in accordance with the laws of the United States
and
the State of New York without reference to any rules of conflict of laws. The
Parties irrevocably consent to the exclusive personal jurisdiction (except
as to
actions for the enforcement of a judgment, in which case such jurisdiction
shall
be non-exclusive) of the federal and state courts located in New York, New
York,
and venue in New York, New York.
15.7 Entire
Agreement.
The
Agreement contains the entire understanding of the Parties with respect to
the
subject matter hereof. All express or implied agreements and understandings,
either oral or written, heretofore made are expressly merged in and made a
part
of the Agreement. Except as expressly set forth in this Agreement, the Agreement
may be amended, or any term hereof modified, only by a written instrument duly
executed by both Parties.
15.8 Headings.
The
captions to the several sections hereof are not a part of the Agreement, but
are
merely guides or labels to assist in locating and reading the several sections
hereof.
15.9 Independent
Contractors.
It is
expressly agreed that CUBIST and XTL shall be independent contractors and that
the relationship between the two Parties shall not constitute a partnership,
joint venture or agency. Neither CUBIST nor XTL shall have the authority to
make
any statements, representations or commitments of any kind, or to take any
action, which shall be binding on the other, without the prior consent of the
other Party.
15.10 Waiver.
The
waiver by either Party hereto of any right hereunder or the failure to perform
or of a breach by the other Party shall not be deemed a waiver of any other
right hereunder or of any other breach or failure by said other Party whether
of
a similar nature or otherwise.
15.11 Counterparts.
The
Agreement may be executed in two or more counterparts, each of which shall
be
deemed an original, but all of which together shall constitute one and the
same
instrument.
15.12 Waiver
of Rule of Construction.
Each
Party has had the opportunity to consult with counsel in connection with the
review, drafting and negotiation of this Agreement. Accordingly, the rule of
construction that any ambiguity in this Agreement shall be construed against
the
drafting Party shall not apply.
15.13 Third
Party Beneficiaries.
Except
as otherwise expressly provided in this Agreement, nothing herein expressed
or
implied is intended or shall be construed to confer upon or to give to any
Third
Party any rights or remedies by reason of this Agreement. Except as otherwise
expressly provided in this Agreement, there are no intended Third Party
beneficiaries under or by reason of this Agreement.
[The
remainder of this page is intentionally left blank.]
34
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Confidential material redacted and filed separately with the
Commission.
IN
WITNESS WHEREOF, the Parties have executed this License Agreement as of the
Effective Date.
| XTL BIOPHARMACEUTICALS LTD. | CUBIST PHARMACEUTICALS, INC. | ||
| By: | /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ | By: | /s/ ▇▇▇▇▇▇ ▇▇▇▇▇▇ |
|
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇ |
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇ |
||
| Title: CEO and President | Title: SVP, Corporate Development and CBO |
[SIGNATURE
PAGE TO LICENSE AGREEMENT]
35
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Confidential material redacted and filed separately with the
Commission.
Exhibit
A
(XTL
Patents as of the Effective Date)
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Antibody
17 Patents
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Antibody19
[Combination]
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Note
that
confidential
treatment has been requested and one (1) page of material from this Exhibit
B
has been omitted and filed separately with the Commission.
36
*****
Confidential material redacted and filed separately with the
Commission.
Exhibit
B
(XTL
Trademarks)
Note
that
confidential
treatment has been requested and one (1) page of material from this Exhibit
B
has been omitted and filed separately with the Commission.
|
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37
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Confidential material redacted and filed separately with the
Commission.
Exhibit
C
(HepeX-B
Plan Guidelines)
Note
that
confidential
treatment has been requested and one (1) page of material from this Exhibit
C
has been omitted and filed separately with the Commission.
Exhibit
C
provides guidelines for developing the detailed HepeX-B Plan. The Guidelines
outline the scientific, clinical, regulatory and manufacturing activities that
are currently contemplated to be required
to
Obtain
Regulatory Approval for a commercially viable formulation of HepeX-B for the
prevention of recurrent Hepatitis B infections in liver transplant patients
in
the US and the EU. A preliminary budget for 2004 and 2005 is included and
subject to change as the detailed HepeX-B Plan is developed. These guidelines
are subject to section 5.2 of the Agreement. Activities include:
| 1. |
*****
|
| 2. |
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| 3. |
*****
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| 4. |
*****
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| 5. |
*****
|
| 6. |
*****
|
It
is
contemplated that the HepeX-B Plan will also *****. However, the Parties
recognize that additional activities ***** may also be required, and cannot
be
specified at this stage.
*****
Note:
There might be some redundancy in costs identified in *****. The preliminary
budget does not include costs of *****
38
*****
Confidential material redacted and filed separately with the
Commission.
Exhibit
D
(XTL
Obligations)
Specific
XTL obligations are identified in the following
activities:
| 1. |
Complete
production of material for *****
|
| 2. |
Complete
the development of an ***** of
HepeX-B]
|
| 3. |
Complete
the following clinical studies
|
| a. |
*****
|
| i. |
*****
to be completed by April 2005
|
| ii. |
*****
to be completed by April 2006
|
| b. |
*****
to be completed by January 2005]
|
Complete
production of material for *****
*****
*****
clones ***** and for ***** were selected and adapted to ***** produced were
***** and found similar to the ***** produced in *****.
*****
for
each ***** was produced by *****
*****:
Preparation of a ***** consisting of ***** was completed. The ***** was tested
by *****, and passed all ***** required by*****; however, a ***** result was
obtained by ***** with the *****. ***** will perform necessary testing to
demonstrate that the results do not represent an ***** (e.g., ***** of three
***** to a study using *****. ***** will deliver a ***** that is fully compliant
with ***** and is acceptable for entry to ***** (i.e., must pass ***** testing)
by *****. Additionally, ***** will provide ***** with all reports and data
associated with the *****.
*****:
Preparation of a ***** consisting of ***** was completed. The ***** was tested
by *****, and passed all ***** required by *****; *****, in light of the *****
test result obtained above, ***** will perform all tests that may be necessary
(in the same manner as is being done for the *****) should the ***** in any
relevant *****. ***** will deliver a ***** that is fully compliant with
*****-required tests and is acceptable for entry to ***** (i.e., must pass
*****
testing) by *****. Additionally, ***** will provide ***** with all reports
and
data associated with the *****.
39
*****
Confidential material redacted and filed separately with the
Commission.
*****
About
***** was produced in *****. Material was ***** is stored until *****. The
*****
described above must be complete prior to release of this material *****, which
is to be completed by *****. If the ***** does not meet the requirements
described above, this lot of ***** (i.e. the lot produced from the *****) must
be rejected. ***** will provide ***** with the ***** and all ***** associated
with its production (e.g., batch records, results of in-process testing).
Production
of ***** is expected to start during *****. The retesting of the ***** described
above must be complete prior to ***** of this *****, which is to be completed
by
*****. If the ***** does not meet the requirements described above, ***** (i.e.
the lot produced from the *****) must be *****. ***** will provide ***** with
the ***** associated with its *****.
Purified
***** will be formulated in the same***** and will be vialed in the *****.
Because the ***** studies are not ***** and ***** must be done with the *****
formulated in *****, as was done in earlier studies.
*****
will have completed real ***** for each ***** produced at *****.
*****
will provide to ***** all records and data in ***** possession or control that
are associated with the ***** work to enable ***** to continue *****, including
***** and full *****.
The
material manufactured at ***** is intended for use in the ***** referenced
below
and this ***** must be comparable (based upon acceptance criteria) ***** must
so
that the ***** may be included in this *****.
*****
*****
*****
will develop an ***** to ***** the ***** for the HepeX-B ***** (based on *****.
***** will provide ***** with all ***** reports and data related to this *****,
as well as ***** and subsequent technical support.
In
addition to performing ***** on the ***** will also aid in ***** for all other
***** previously developed for and relevant to the HepeX-B program.
Complete
development of an *****
for HepeX-B
*****
studies were performed at ***** to develop a ***** at a high concentration
*****. ***** was completed. Three lead ***** were selected in which the *****.
***** will provide ***** with all records, including final study reports,
relating to the ***** and the *****. ***** development for ***** will be
completed by *****. ***** will provide ***** with all records, including final
study reports, relating to the ***** and the *****. Until further testing to
***** is completed, the ***** must be ***** separately for *****.
By
*****,
***** will complete an ***** on the ***** in combination at one ***** in the
same *****.
40
*****
Confidential material redacted and filed separately with the
Commission.
Complete
the following clinical studies:
Clinical
Activities - *****
-
Synopsis
|
Name
of Sponsor:
*****
|
Name
of Active Ingredient:
HepeX-BÔ
|
Study
number:
*****
|
|
Title
of study:
A
***** Study to Compare the ***** of HepeX-BÔ,
a
Mixture of Two Monoclonal Antibodies, as Compared to ***** for
Treatment
of *****
|
||
|
Investigators:
Approximately
***** investigators in *****
Study
centers: *****
|
||
|
Study
period: Approximately *****
(***** weeks of recruitment
+ *****
weeks treatment in the *****, with the possibility of enrolling
in the
***** of the trial for an additional ***** weeks of treatment.
All
patients will be observed for ***** after completion of treatment).
|
Phase
of development:
*****
|
|
|
Objectives:
The primary objective will be to compare the ***** of HepeX-BÔ to
***** as measured by *****, in patients who have received *****
for
treatment of *****. ***** is the primary measure of ***** and
is defined
as ***** measured on two consecutive assessments ***** days apart.
Secondary objectives will be to compare the ***** concentrations
and to
describe the safety of the reference and test agents.
|
||
|
Methodology:
This is a ***** study of the ***** of HepeX-BÔ as
compared to standard ***** in patients who have received *****
for
treatment of ***** and who are currently receiving ***** and
concomitant
treatment with an *****. Up to ***** patients may be enrolled
in order to
achieve at least ***** evaluable patients (***** patients per
treatment
group). Eligible patients will be *****. Patients will receive
an ***** of
study medication every ***** for ***** in the *****, with the
possibility
of an additional ***** all patients enrolled in the ***** of
the trial.
All patients will be observed for ***** after completion of treatment.
Periodic ***** will be collected for determination of *****.
***** will be
monitored by a Data and Safety Monitoring Board (DSMB). After
successful
completion of this study, patients may be eligible for participation
in a
12-month follow-on study to examine *****.
|
||
|
Number
of subjects:
Up
to ***** patients may be enrolled in order to obtain ***** evaluable
patients *****. To be considered evaluable, patients must either
receive
***** and complete the ***** follow-up visit, or must have met
the
criteria for treatment failure. Patients who terminate the study
prematurely for reasons other than treatment failure will be
replaced.
|
||
|
Main
Inclusion Criteria:
Patients who are at least ***** post first ***** for treatment
of *****,
who have received ***** from the time of ***** through the time
of entry
into the study, who have received an ***** for at least the *****
immediately prior to entry into the study, and who have undetectable
*****
on two consecutive tests within the ***** screening period, are
eligible
for the study.
|
||
|
Main
Exclusion Criteria: Patients
who are *****, or who have received other ***** are ineligible
to
participate.
|
||
41
*****
Confidential material redacted and filed separately with the
Commission.
|
Test
product, dose and mode of administration:
HepeX-BÔ will
be *****.
·
HepeX-BÔ *****
every ***** for ***** for all patients enrolled in the *****,
with the
possibility of an additional ***** for all patients enrolled
in the *****
of the trial. All patients will be observed for ***** after completion
of
treatment.
·
HepeX-BÔ *****
every ***** for***** for all patients enrolled in the *****,
with the
possibility of an additional ***** for all patients enrolled
in the *****
of the trial. All patients will be observed for ***** after completion
of
treatment.
|
||
|
Reference
therapy, dose and mode of administration:
*****.
·
***** for all patients enrolled in the *****, with the possibility
of an
additional ***** for all patients enrolled in the ***** of the
trial. All
patients will be observed for ***** after completion of treatment.
|
||
|
Duration
of treatment and observation:
***** for all patients enrolled in the *****, with the possibility
of an
additional ***** for all patients enrolled in the ***** phase
of the
trial. All patients will be observed for ***** after completion
of
treatment.
|
||
|
Anti-viral
assessments:
***** will be determined prior to and ***** following each *****.
*****
results will be confirmed by repeat testing at least *****.
*****
assessments:
***** will be determined immediately prior to each *****, at
the end of
each *****, ***** after the completion of each *****, and at*****
after
each *****. The ***** determined immediately prior to each *****
will be
considered the *****.
Safety
assessments:
Safety will be evaluated by periodic ***** and reported and observed
*****. Emergence of ***** (as indicated by detectable *****)
will also be
reviewed as a safety measure. Selected safety measures, including
*****
status, will be reviewed periodically by an independent Data
Safety
Monitoring Board (DSMB). Criteria will be prospectively established
to
terminate one or both of the experimental arms in the event of
unacceptable risk to study participants.
|
||
|
Criteria
for Evaluation:
The primary
endpoint will be the ***** in each treatment regimen without
*****. *****
is defined as the ***** of detectable ***** measured on two consecutive
assessments ***** apart. Secondary endpoints will be a comparison
of
*****, including the proportion of subjects in each arm of the
study with
*****, and a description of safety (i.e., *****) throughout the
study.
|
||
|
Statistical
Methods: Hypothesis
testing will be done for the primary endpoint using a ***** approach
at an
alpha of *****.
*****:
HepeX-BÔ
is
not inferior to the active comparator, *****, using a maximum
delta of
*****
To
test the null hypothesis, the lower bound of the two-sided 95%
confidence
interval (CI) of the difference between the proportions of response
in
HepeX-BÔ
and the active comparator will be compared to the pre-set threshold
(*****
difference). The difference will be calculated HepeX-BÔ
minus active comparator.
Categorical
variables (nominal or ordinal) will be summarized by sample size,
number
(frequency), and percentage of subjects at each level of the
variable.
Continuous variables will be summarized by sample size, mean,
median,
standard deviation (SD), minimum, and maximum values.
For
the efficacy analyses, the proportion of patients without *****
breakthrough will be presented by treatment regimen for each
analysis
population. Summaries of ***** will be presented for the evaluation
of
safety. Listings of ***** will be provided as well as summaries
of the
*****.
The primary analysis for the study will be conducted when the
last patient
enrolled has received ***** and completed ***** of follow-up.
At this
time, the ***** data for all patients will be analyzed. A secondary
analysis will be performed when ***** has been completed by *****
patients
and will include all of the data accumulated during the
*****,
|
42
*****
Confidential material redacted and filed separately with the
Commission.
*****
Study
- Synopsis
It
is
understood that Cubist will determine the precise timing and scope of
*****
prior
to their start, and that *****
will
be responsible for study execution.
|
1.1.1.1.1
Name of Sponsor
*****
|
Name
of Active Ingredient
*****
|
Study
number:
|
|
Title
of study:
*****
|
||
|
Investigator:
|
||
|
Study
center:
|
||
|
Study
period: *****
|
Phase
of development:
*****
|
|
|
Objectives:
The primary objectives of this study are to
· assess
the *****, as determined from ***** administered by *****
(prepared from
*****) administered by *****
· assess
the relative *****, as determined from *****, of single doses
of *****
(prepared from *****) administered by ***** (prepared from
*****)
administered by *****
The
secondary objectives of this study are to
· assess
the relative *****, as determined from *****, of single doses
*****
(prepared from *****) administered by ***** (prepared from
*****)
administered by *****
· evaluate
the safety of the ***** of single doses of ***** (prepared
from *****)
compared to ***** (prepared from *****)
|
||
|
Methods:
This study will be conducted in *****. Subjects will be screened
for
eligibility. Subjects will be randomly assigned to receive
a
*****:
Group
1: ***** subjects will receive a ***** prepared from *****
Group
2: ***** subjects will receive a ***** prepared from *****
and
administered over *****.
Group
3: ***** subjects will receive a ***** prepared from *****
and
administered over *****.
Subjects
will remain at the study center for at least ***** after the
***** for
collection of ***** and safety monitoring. Subjects will return
to the
study center on Study Days ***** for collection of ***** and
safety
monitoring. Subjects will return to the study center on Study
Day *****
for collection of ***** and completion of a Follow-up
visit].
|
||
43
*****
Confidential material redacted and filed separately with the
Commission.
|
[Population:
***** volunteers, *****, who are *****, and who have a body mass
index
(BMI) between *****. Subjects who received ***** and those who
use any
concomitant medications that may impact ***** within 30 days prior
to
study entry are not eligible to participate.
|
|
Number
of subjects:
***** volunteers will be entered randomly into one of three dose
groups
(*****). Subjects who terminate prematurely before completing the
sample
collections through Study Day ***** will be replaced.
|
|
Test
product, dose and mode of administration:
***** (prepared from *****) administered as a *****
· *****
· *****
(the route of administration, *****, will be based on the results
of *****
efforts currently ongoing).
|
|
Reference
therapy, dose and mode of administration:
***** (prepared from *****) administered as a *****
|
|
Duration
of treatment and observation:
On
Study Day ***** subjects will receive a *****. Subjects will remain
at the
study center for at least ***** hours after commencement of the
*****.
***** will be collected at intervals while the subjects remain
at the
study center, and the subjects will be monitored regularly for
safety.
Subjects will return to the study center on Study Days ***** for
collection of ***** and safety monitoring. Subjects will return
to the
study center on Study Day ***** for collection of ***** and for
completion
of a Termination Visit.
|
|
*****
assessments: *****
concentrations will be determined in ***** collected at the following
times:
§ Study
Day *****: immediately prior to commencement of the *****, and
at
approximately Hours *****
§ Study
Day *****: at approximately *****
§ Study
Day *****: at approximately *****
§ Study
Day *****: at approximately *****
§ Study
Days *****
Safety
assessments:
Safety will be evaluated by periodic
*****.
|
44
*****
Confidential material redacted and filed separately with the
Commission.
|
Statistical
Methods:
*****:
The
***** analysis will be based on all subjects who have evaluable
*****. The
individual concentration-time profiles of ***** will be evaluated
using
*****. Data permitting, the following pharmacokinetic parameters
will be
determined:
*****
Descriptive
statistics (N, mean, standard deviation, CV, median, minimum,
and maximum)
will be used to summarize ***** concentration data at each planned
sampling time point for each treatment. ***** parameters calculated
from
the concentrations will also be summarized by treatment using
descriptive
statistics.
Bioequivalence
will be evaluated for ***** (prepared from *****) compared to
*****
(prepared from *****) with an analysis of their log-transformed
*****.
***** with terms for subject and treatment will be performed
for the
parameters ***** From these analyses, 90% confidence intervals
(CIs) for
the geometric test/reference mean ratios will be obtained. Group
1 will be
compared with Group 2, with Treatment Group 2 as the reference.
Bioequivalence will be declared if the 90% confidence limits
for the test
to reference ratios fall within *****.
Bioeavailability
will be evaluated for ***** (prepared from *****) compared to
both *****
(prepared from *****) ***** (prepared from *****) using the same
*****
model described above. Group 3 will be compared with Group 1
as well as
Group 2, with Treatment Group 1 and Treatment Group 2 as the
reference,
respectively. For these comparisons, the bioavailability ratio
and 95%
C.I. will be calculated using the difference between the
*****
A
sample size of ***** per group has been calculated to provide
greater than
90% power to demonstrate equivalence using a CV of *****. The
CV of *****
was the largest CV calculated for the log transformed ***** parameters
using data from the following study: *****
Safety:
Descriptive summaries will be provided by treatment group for
demographics. The frequency of adverse events will be tabulated.
Baseline,
within study and end-of-study, and change from baseline clinical
laboratories, and ▇▇▇▇▇ ▇▇▇▇▇ will be summarized. Descriptive
statistics
will be computed for safety parameters as appropriate. Further
statistical
evaluations will be applied for select endpoints, if warranted.
All
baseline data and safety data collected during the study will
be listed
for each subject and dose group].
|
45
*****
Confidential material redacted and filed separately with the
Commission.
*****
Study
- Synopsis
|
1.1.1.1.2
[Name of
Sponsor
*****
|
Name
of Active Ingredient
*****
|
Study
number:
|
|
Title
of study:
*****
|
||
|
Investigator:
*****
|
||
|
Study
center: *****
|
||
|
Study
period: *****
|
Phase
of development:
*****
|
|
|
Objectives:
The primary objectives of this study are to
· Compare
the *****, as determined by the relative changes in ***** in
response to a
***** (prepared from *****) administered by ***** (prepared
from *****)
*****.
· Compare
the *****, as determined by the relative changes in ***** in
response to a
***** (prepared from *****) administered by ***** (prepared
from *****)
administered by *****.
The
secondary objectives of this study are to
· Compare
the *****, as determined by the relative changes in ***** in
response to a
***** (prepared from *****) administered by ***** (prepared
from *****)
administered by *****.
· Evaluate
the safety of the ***** (prepared from *****) compared to *****
(prepared
from *****).
|
||
|
Methods:
This study will be conducted in an *****. Subjects will be screened
for
eligibility and randomly assigned to receive each of the following
treatments on Study Day *****. ***** washout period between study
doses
will separate each treatment period.
Treatment
A: *****
prepared from *****
Treatment
B: *****
prepared from ***** and administered over *****.
Treatment
C: ***** prepared from ***** and administered over *****.
During
each treatment period, subjects will remain at the study center
for at
least ***** after the administration of study medication for
collection of
***** and safety monitoring. Following period *****, subjects
will return
to the study center on Study Day ***** for completion of a Follow-up
visit].
|
||
46
*****
Confidential material redacted and filed separately with the
Commission.
|
Population:
Eligible patients will be *****, with
a minimum *****
at screening for subject inclusion to allow better cross-over
comparison.
|
||
|
Number
of subjects:
***** subjects will be entered into the study. Subjects who
terminate
prematurely before completing the ***** will be replaced.
|
||
|
Test
product, dose and mode of administration:
***** (prepared from *****) administered as *****
· *****
· *****
(the route of administration, *****, will be based on the
results of *****
efforts currently ongoing).
|
||
|
Reference
therapy, dose and mode of administration:
*****
|
||
|
Duration
of treatment and observation:
The study duration will be approximately ***** for each subject.
Subjects
will be screened within ***** of administration of *****. During
each
treatment period, subjects will receive *****. Subjects will
remain at the
study center for at least ***** after commencement of *****.
Subjects will
check out on Day ***** following the ***** and return on Day
***** for the
*****. Subjects will be monitored regularly for safety. A washout
of *****
between doses will separate each treatment period. Following
period *****,
subjects will return to the study center between Day *****
for completion
of a Follow-up visit.
|
||
|
*****
and
*****
assessments:
*****
concentrations and***** concentrations will be determined in
*****
collected at screening and at the following times during each
treatment
period:
§ Study
Day *****: immediately prior to commencement of *****, and
at
approximately *****
commencement
§ Study
Day *****: ***** commencement
§ Study
Day *****: ***** commencement
Safety
assessments:
Safety will be evaluated by periodic *****.
|
||
|
Criteria
for evaluation:
*****:
The primary variable for comparison of the ***** is the change
in *****
(in percent) following ***** administration compared to the
concentration
immediately prior to administration on Day ***** of each treatment
period.
*****:
As
secondary variable for comparison, ***** concentration-time
data will be
compared for the *****. ***** in healthy normal volunteers
has been
previously evaluated. However, the ***** has not been previously
evaluated
in patients with *****. ***** are expected to be highly variable
between
patients due to the complex relationship to ***** concentration,
changes
in ***** over time will be evaluated for each treatment.
*****.
|
47
*****
Confidential material redacted and filed separately with the
Commission.
|
Statistical
Methods:
Pharmacodynamics:
The
pharmacodynamic analysis will be based on all subjects who
have evaluable
change in ***** For each concentration-time point, a change
from baseline
value (in percent) will be calculated as follows: ***** The
individual
percent change from baseline values of ***** will be evaluated
using
model-independent methods as implemented in *****. Data permitting,
the
following pharmacodynamic parameters will be determined:
*****
The
rational for deriving partial average changes from baseline
for select
time intervals is the *****:
a)
***** concentrations appears to be correlated to the baseline
*****
concentration which could affect interpretation of the changes
in ***** in
the later portion of the concentration-time profile
b)
Intersubject variability due to the severity of the disease
state is
likely to affect the rate of ***** which could affect interpretation
of
the changes in ***** in the later portion of the concentration-time
profile
c)
The potential of differences in ***** may affect the *****
Descriptive
statistics (N, mean, standard deviation, CV, median, minimum,
and maximum)
will be used to summarize the percent change from baseline
concentration
data at each planned sampling time point for each treatment.
Change from
baseline pharmacodynamic parameters will also be summarized
by treatment
using descriptive statistics.
Similarity
in ***** will be evaluated for the percent change from baseline
pharmacodynamic parameters for ***** (prepared from *****)
relative to
***** (prepared from *****)] with an analysis of their pharmacodynamic
parameters. An ***** with terms for subject, period, sequence,
and
treatment will be performed for the parameters ***** above.
One-sided 95%
confidence intervals (CI) for the test/reference mean ratios
will be
estimated from the ***** to assess ***** of the test treatments
using
*****. The test treatment will be compared with the reference
treatment
and ***** will be declared if the 95% confidence limit for
the test to
reference ratios are greater than ***** for all of the identified
parameters.
Similarity
in ***** be evaluated for the percent change from baseline
pharmacodynamic
parameters for ***** (prepared from *****) relative to both
*****
(prepared from *****) and ***** (prepared from *****)] using
the same
***** model described above. One-sided 95% confidence intervals
(CIs) for
the test/reference mean ratios will be estimated from the *****
to assess
***** of the test treatments using *****. Treatment A will
be compared to
Treatment C and to Treatment B, with Treatments C and B treated
as
reference. Non-inferiority will be declared if the 95% confidence
limit
for the test to reference ratios are greater than ***** for
all of the
identified parameters.
A
sample size of *****
yields just over 80% power to show *****
in
the cross-over design using the following assumptions.
·
There is no difference between the *****.
*****
defined as the test treatment yielding responses no less than
*****
of
the reference treatment. The intra-patient CV is at most *****.
*****
one-sided significance level.
Pharmacokinetics:
Descriptive
statistics (N, mean, standard deviation, CV, median, minimum,
and maximum)
will be used to summarize ***** concentration data at each
planned
sampling time point for each treatment. An attempt will be
made to perform
a pharmacokinetic analysis for those subjects who have *****
that follow a
traditional pattern of *****. The individual concentration-time
profiles
of ***** will be evaluated using model-independent methods
as implemented
in *****. Data permitting, the following pharmacokinetic parameters
will
be determined:
*****
*****
pharmacokinetic parameters calculated from the concentrations
will also be
summarized by treatment using descriptive statistics. Differences
in
concentration-time data and/or pharmacokinetic parameters will
be
evaluated graphically.
Safety:
Descriptive summaries will be provided by treatment group for
demographics. The frequency of adverse events will be tabulated.
Baseline,
within study and end-of-study, and change from baseline clinical
laboratories, and ▇▇▇▇▇ ▇▇▇▇▇ will be summarized. Descriptive
statistics
will be computed for safety parameters as appropriate. Further
statistical
evaluations will be applied for select safety endpoints, if
warranted. All
baseline data and safety data collected during the study will
be listed
for each subject and dose group.
|
48
*****
Confidential material redacted and filed separately with the
Commission.
Exhibit
E
(XTL
Licensor Payments)
Note
that
confidential
treatment has been requested and one (1) page of material from this Exhibit
E
has been omitted and filed separately with the Commission.
*****
49
*****
Confidential material redacted and filed separately with the
Commission.
Exhibit
E
(XTL
Licensor Payments)
Note
that
confidential
treatment has been requested and one (1) page of material from this Exhibit
E
has been omitted and filed separately with the Commission.
*****
50