“
Development ” shall refer to all activities relating
to formulation, process development, manufacturing scale-up,
quality assurance/quality control, clinical studies and regulatory
affairs in connection with a Licensed Product.
“
EMEA ” shall mean the European Medicines Evaluation
Agency or any successor entity thereof.
“
FDA ” shall mean the United States Food and Drug
Administration or any successor entity thereof.
“
Initial Period ” shall mean, on a country by country
and Licensed Product-by-Licensed Product basis, the period
beginning on the Effective Date and ending on that date that is the
latest of the following dates:
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(i)
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the expiration
of the last Patent Rights containing a Valid Claim covering the
subject Licensed Product in such country;
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(ii)
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the first
commercial sale of the first to appear generic formulation of the
subject Licensed Product in such country; or
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(iii)
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the tenth (10
th ) anniversary of the first commercial sale of the
subject Licensed Product in such country.
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“ Licensed Know-how ” shall
mean all know-how, data, information or technology arising before
or during the course of this Agreement which are proprietary to the
Licensor and/or with respect to which Licensor has the power and
right to grant the licenses provided for herein and which relate to
the development or therapeutic use of Licensed Products.
“
Licensed Methods ” shall mean the methods for the
Licensed Products arising before or during the course of this
Agreement which are proprietary to the Licensor and/or with respect
to which Licensor has the power and right to grant the licenses
provided for herein and which relate to the development or
therapeutic use of Licensed Products.
“
Licensee Proprietary Information ” shall mean any
scientific and technical information or data developed, possessed
or acquired by Licensee relating to Licensed Products, Patent
Rights or Licensed Know-how which Licensee is free to disclose
other than such information that is generally available to the
public.
“
Licensed Products ” shall mean surfactant
pharmaceutical compositions which are formulations of lipids and
solely the polypeptide sinapultide and, in no manner whatsoever in
any composition including any other pharmacological agents, that
have been developed by Licensor or that may be developed by
Licensor during the term of this Agreement limited to the
following:
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(i)
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In suspension
for pulmonary instillation or in aerosol formulation, for the
prophylaxis and/or treatment of Respiratory Distress Syndrome
(RDS), Meconium Aspiration Syndrome (MAS), Acute Lung Injury (ALI),
Acute Respiratory Distress Syndrome (ARDS), and/or Bronchopulmonary
Dysplasia (BPD), in each case in the hospital setting;
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(ii)
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In any
formulations (including, without limitation, any associated
devices/ apparatus) for use in conjunction with nasal continuous
positive airway pressure for neonatal pulmonary disorders solely
treated in the Neonatal Intensive Care Unit (NICU) (collectively,
nCPAP Licensed Product(s)); and
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(iii)
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In any
formulations which may be developed for the treatment of asthma
and/or chronic obstructive pulmonary disease (COPD) diagnosed and
treated in the hospital setting.
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“
Licensed Rights ” shall mean collectively the Patent
Rights, the Licensed Methods, the Trademarks and the Licensed
Know-how.
“
Licensed Territory ” shall mean Andorra, Greece, Italy
(including the Republic of San Marino and the Vatican City),
Portugal, and Spain.
“
Marketing Regulatory Approvals ” shall mean all
permissions and applications for such permissions from the
regulatory and/or governmental health authorities in the Licensed
Territory which are necessary for the importation of the Licensed
Products and their marketing, use, distribution and sale in the
Licensed Territory.
“ MAA ” means a Marketing
Authorisation Application submitted to the EMEA or with any
regulatory authority of any country within the Licensed
Territory.
“
NDA ” shall mean a New Drug Application or Product
License Application filed with the United States Food and Drug
Administration under 21 USC 355(b) (FDCA Section
505(b)).
“
Original License ” shall mean the Sublicense Agreement
dated as of October 28, 1996 between the Original Licensor and
Licensor.
“
Original Licensor ” shall mean Johnson & Johnson,
Inc.
“
Patent Rights ” shall mean any patents and/or patent
applications which contain one or more Valid Claims covering the
Licensed Products whether owned by Licensor or to which Licensor
may have rights during the term of this Agreement, including (i)
the patents and patent applications set forth on Schedule I hereto;
(ii) any other patents or patent applications covering the
surfactant pharmaceutical compositions referenced in the patents
and patent applications in Schedule I or their use or
administration owned by Licensor or under which Licensor has the
right, at any time while this Agreement is in effect, to license to
Licensee; and (iii) with respect to the foregoing letters patent
and patent applications, all corresponding national patents and
patent applications, Patent Cooperation Treaty and European Patent
Convention filings and applications and filings and applications
under similar administrative international conventions, together
with any divisional, continuation, continuation-in-part,
substitution, reissue, extension, supplementary protection
certificate or other application based thereon. Notwithstanding the
foregoing, “Patent Rights” shall not include any
patents or patent applications, filings, or applications under any
treaty, or any divisional, continuation, continuation-in-part,
substitution, reissue, extension, supplementary protection
certificate or other application that do not relate in whole or in
part to any of the Licensed Products.
“
Person ” shall mean any natural person, corporation,
limited liability company, unincorporated association, partnership,
joint venture or other entity.
“ Phase 2 ” shall mean that
portion of clinical trials of a candidate drug in the target
patient population of a sufficient number and sufficient length of
time whereby adequate safety data is provided and there is a clear
indication of dosage effects with respect to efficacy as defined in
the study protocol for such drug candidate.
“ Phase 3 Development ” means
those clinical trials intended to generate safety and efficacy data
to support regulatory approval in the proposed therapeutic
indication.
“
Pricing Approvals ” shall mean approvals by the
regulatory and/or governmental health authorities in the Licensed
Territory granting the prices of the Licensed Products and
reimbursement conditions for the sale thereof.
“ Scripps Patent Rights ”
shall mean the Patent Rights identified in part (a) of Schedule
I.
“
Trademark ” shall mean Surfaxin ® and
such other trademarks owned by Licensor that are selected by the
Development Committee (as defined in Section 5.6) for use within
the Licensed Territory in connection with one or more Licensed
Products.
“
Valid Claim ” shall mean a claim of an unexpired
patent within the Patent Rights which has matured into an issued
patent or a claim being prosecuted in a pending application within
the Patent Rights. In each case a claim shall be presumed to be
valid unless and until it has been held to be invalid by a final,
unappealable judgment of a court of competent
jurisdiction.
ARTICLE 2
GRANT
Section
2.1. Grant of License . Licensor hereby grants to Licensee, and
Licensee hereby accepts from Licensor, upon the terms and
conditions herein specified, an exclusive license under the Patent
Rights, the Licensed Know-how and the Trademark, and the right to
practice Licensed Methods, solely in connection with the
importation, promotion, distribution, use and sale of Licensed
Products under the Trademark in the Licensed Territory. Licensor
hereby agrees that it shall not grant any other licenses to exploit
the Licensed Rights or the Licensed Products in the Licensed
Territory to any third party (including, without limitation, its
Affiliates) during the term of this Agreement. The license granted
hereunder does not include any right or license of Licensee to make
or have made Licensed Products, all such right and license being
hereby retained by Licensor. The license granted under this Article
2 shall be subject to the terms and conditions of this Agreement
and the following terms:
(a) The rights of the Original Licensor to use the
Scripps Patent Rights for educational and research
purposes;
(b) To the extent applicable, the rights of the
United States Government pursuant to 35 U.S.C. 202 et seq. and 37
C.F.R. 401.1 et seq. which may have arisen or resulted from federal
funding of research relating to the Scripps Patent Rights,
including the non-exclusive right of the United States Government
to practice the inventions covered by the Scripps Patent
Rights;
(c) The reserved right of Licensor, to use the
Licensed Rights for research and development purposes and, to the
extent permitted by Section 7.2, for publication purposes subject
to approval by Licensee, which approval shall not be unreasonable
withheld; and
(d) The Standard of Diligence (as such term is set
forth in Section 5.6).
Licensee shall
have no right to sublicense or otherwise share its rights hereunder
with any other Person other than (i) Affiliates of Licensee
(provided that Licensee shall not be relieved of any of its
obligations under this Agreement), as provided for in Section 15.9,
and (ii) third parties pursuant to a sublicense or distribution
agreement complying with Section 2.3.
Section 2.2 No Active Sales Outside Licensed
Territory . Licensee
shall neither directly nor indirectly carry out any active sales of
or actively seek customers for the Licensed Products outside the
Licensed Territory and it shall not advertise the Licensed Products
or maintain branches for the distribution of the Licensed Products
outside the Licensed Territory.
Section
2.3. Sublicense Agreements . Subject to prior determination by the Steering
Committee (in accordance with Section 6.1) on a Licensed
Product-by-Licensed Product and country-by-country basis that any
sublicensing, co-marketing or co-promotion, as applicable, is
consistent with maximizing the value of the subject Licensed
Product, Licensee shall be entitled to (X) sublicense its rights
and obligations under the Agreement in any country of the Licensed
Territory, with the exception of the country of Spain or (Y)
co-market or co-promote in any country of the Licensed Territory,
provided that for each of (X) and (Y), above, (i) any such
sublicense or co-marketing/ promotion agreement shall be under
terms no less stringent than the ones contained in this Agreement
including, without limitation, Licensee’s performance
requirements set forth in Section 5.6; (ii) any such sublicense or
co-marketing/ promotion agreement shall not be an effective
assignment of all of Licensee’s rights and a delegation of
all of its obligations under this Agreement, (iii) Licensee shall
have obtained the approval of the Steering Committee (in accordance
with Section 6.1) for the sublicense, co-marketing or co-promotion
partner, which approval shall not be unreasonably withheld or
delayed and (iv) Licensee hereby warrants and represents that any
such sublicensee or co-promotion/ co-marketing partner of Licensee
will comply with all applicable terms of this Agreement and,
further, Licensee guarantees performance of this Agreement by any
such party.
The parties
hereto agree and acknowledge that the performance of the
obligations hereunder shall take into account the following: (A)
that solely with respect to the Licensed Product that is Surfaxin
® for RDS and/or BPD, it is the prior mutual
strategic determination of Licensor and Licensee that sublicensing
shall be allowed for Italy and Greece, without any further approval
from the Steering Committee, except as may be provided for with
respect to the selection and approval of actual sublicensees in
accordance with this Section 2.3, and (B) in the event of
co-promotion or co-marketing of Licensed Products in Spain,
Licensee shall be primarily responsible for the promotional and
marketing activities for any such Licensed Products through its own
marketing and sales forces.
Section
2.4. Consideration for Licensed Products
. Licensee shall not accept as
consideration for the sale or transfer of Licensed Products any
consideration other than cash except as consented to by Licensor
following agreement between Licensor and Licensee on the
methodology for valuing such non-cash consideration.
Section
2.5. Right of First Negotiation on New
Products . For a period
of [***] years from the Effective Date (“New Product
Negotiation Term”), subject, however, to prior termination as
hereinafter provided in Article 8, Licensor shall grant to Licensee
an exclusive right of first negotiation to a maximum of [***]
future products developed by Licensor (each a “ New
Product ”), solely to the extent to which Licensor is not
legally restricted or prevented from licensing any such rights
within the Licensed Territory, in accordance with the following
terms and conditions:
(a) Within sixty (60) days of completion of
Licensor’s written clinical study report(s) for all Phase 2
clinical trials with respect to any such product opportunity,
Licensor shall present in writing, including a copy of the relevant
Phase II clinical study final report(s), such product opportunity
to Licensee together with any additional information which, at
Licensor’s judgment, is reasonably necessary for Licensee to
evaluate its possible interest in the New Product in a manner that
is reasonably intended to provide a basis for Licensee’s
decision as to whether to exercise its option hereunder (a “
New Product Presentation ”). At Licensee’s
request, Licensor shall provide Licensee with any additional
information solely to the extent that such additional information
is reasonably necessary for Licensee to evaluate its possible
interest in the New Product.
(b) Within sixty (60) days from the date of any
such New Product Presentation, Licensee shall notify Licensor in
writing of Licensee’s intention to enter into negotiations to
license the rights to any such product. Should Licensee fail to
notify Licensor of Licensee’s intention to license such
rights or should Licensee notify Licensor of Licensee’s lack
of intent to license such rights, Licensor shall have the immediate
right to offer the New Product opportunity to any other third party
offeree(s) without any further obligation hereunder. In
the
Information marked by [***] has been omitted
pursuant to a request for confidential treatment. The omitted
portion has been separately filed with the Securities and Exchange
Commission.
event that
Licensee has notified Licensor of its intent to license any such
rights, Licensee and Licensor hereby expressly agree that such
license or any other similar grant of rights in respect thereto
shall contain, among other customary terms and conditions, the
following:
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up-front cash
payment(s) to be paid by Licensee to Licensor in amounts that are
consistent with customary pharmaceutical industry practices and
appropriate with reference to the technology value and potential
product value of such New Product;
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Licensor,
Licensee and other sublicensees of the Licensor shall share all
future clinical development work and or expenses with respect to
any such New Product opportunity, in relation with Phase 3 clinical
trials necessary to obtain and/or maintain the Marketing Regulatory
Approvals in the Licensed Territory, on a [***] basis using the
relevant IMS annual global pharmaceutical data relative to the
aggregate pharmaceutical market size of the proposed licensed
territory for all pharmaceutical products as the basis of
determining the amount of such costs to be borne by each of the
parties at the time. Licensee and its sublicensees shall be
responsible for the work and costs associated with any and all
clinical development activities that is conducted in the Licensed
Territory for the New Product that are not necessary to obtain or
maintain Marketing Regulatory Approval for any such New
Product;
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payment to
Licensor of cash milestones in amounts that are consistent with
customary pharmaceutical industry practices and are reflective of
the value of such New Product created during the development
process and which amounts take into account Licensee’s
contribution to development of any such value;
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Licensee shall
be responsible for customary commercialization costs associated
with the New Product including, without limitation, sales,
marketing, distribution, and safety and medical affairs expenses,
in a manner similar to that set forth in this Agreement with
respect to Licensed Products; and
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Licensor shall
be responsible for the manufacture of any such New Product. The
economic terms for the New Product, which shall duly take into
account the development expenses and cash milestones paid by
Licensee for any such New Product, shall ensure a reasonable profit
for the parties in the light of the prevailing and expected market
conditions at that time.
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Information marked by [***] has been omitted
pursuant to a request for confidential treatment. The omitted
portion has been separately filed with the Securities and Exchange
Commission.
(c) In cases where Licensee has indicated its
intention to enter into negotiations to license rights to a New
Product as provided hereunder and the parties fail to enter into
definitive agreements within hundred and twenty (120) days of the
date of Licensee’s notice, delivered to Licensor in
accordance with Section 2.5(b) (hereinafter, such event being
defined as an “Unrealized New Product”), Licensor shall
have the right to offer the Unrealized New Product opportunity to
any other third party offeree(s) at terms and conditions that are
in substance no more favorable for such other third party
offeree(s) than those last offered to Licensee in writing,
provided, however, that Licensor shall not execute any agreement on
the New Product with any such third party offeree(s) without
previously offering Licensee the right to enter into an agreement
on substantially similar terms than those contained in the final
agreement with the relevant third party offeree.
(d) Should senior executive officers of Licensor
become aware of the possible interest of any third party to enter
into an agreement in relation with any New Product prior to
completion of all Phase 2 clinical trials, then Licensor shall
promptly notify Licensee of such possible interest of a third
party. In such event, and notwithstanding Section 2.5(a) herein,
Licensor and Licensee agree to initiate good faith negotiations
with respect of such New Product with a view to enter into an
agreement for the development and commercialization of such New
Product prior to the completion of the Phase 2 development for that
New Product; provided , however , that in any such
event the parties agree that any negotiations hereunder shall be
performed within timeframes similar to those as set forth in
Section 2.5 and shall encompass terms and conditions similar to
those set forth in Sections 2.5(b) and (c).
(e) Prior to the expiration of the New Product
Negotiation Term, Licensee’s rights hereunder to New Products
shall be terminated upon the occurrence of any two of the following
events, in any combination thereof: (i) a New Product license is
entered into by the parties; and (ii) An Unrealized New Product
event occurs.
ARTICLE 3
GRANT BACK
In
consideration for Licensor (i) making the Licensed Know-how
(including any improvements thereto and solely to the extent
provided for in Section 2.1) available to Licensee on a continuing
basis for the duration of this Agreement and (ii) procuring, and
making available to Licensee the benefit of, equivalent grants from
Licensor’s other licensees for the Licensed Products outside
the Licensed Territory Licensee hereby grants to Licensor and such
other licensees as Licensor may designate a royalty-free,
nonexclusive license outside the Licensed Territory, with the right
to grant sublicenses, under any and all inventions and Licensee
Proprietary Information (whether patentable or not) hereafter
during the term of this Agreement, developed, possessed or acquired
by Licensee related to the Licensed Products, Patent Rights,
Licensed Know-how or Licensed Methods; provided that Licensee is
not legally restricted or prevented from granting such rights in
connection with the relevant invention. Licensee shall provide
Licensor with a written enabling disclosure of each invention (such
as a patent application or internal docket reference) unambiguously
identifying it as an invention governed by this Article 3 prior to
filing a patent application or taking any other action disclosing
or potentially disclosing the same to third parties.
Licensee shall
promptly disclose all Licensee Proprietary Information to Licensor
and, subject to the execution of confidentiality undertakings
comparable to those set forth in Article 7, to Licensor’s
other licensees (and or Affiliates and permitted sublicensees) of
Patent Rights outside the Licensed Territory on a continuing basis
during the term of this Agreement. Licensee hereby grants to
Licensor and such licensees a royalty-free nonexclusive license,
with the right to grant sublicenses, to use the Licensee
Proprietary Information outside the Licensed Territory. Licensee
shall not disclose any such invention and or Licensee Proprietary
Information under circumstances that would reasonably be expected
to result in the loss of the protectible status of any such
invention and or Licensee Proprietary Information without the prior
written consent of Licensor, which consent shall not be
unreasonably withheld or delayed.
ARTICLE 4
CONSIDERATION
Section
4.1. Common Stock Grant . Contemporaneously with the execution of this
Agreement, Licensor shall issue 500,000 shares of Licensor’s
common stock, par value $.001 per share to Licensee for no
additional consideration. Licensee shall be entitled to the
registration rights for such shares of common stock that are
provided for in the Common Stock Letter Agreement between Licensor
and Licensee dated as of December 3, 2004.
Section
4.2. Supply Agreement . Concurrently with the execution of this
Agreement, Licensor and Licensee shall enter into an amended and
restated supply agreement for Licensed Products (the “
Revised Supply Agreement ”).
Section
4.3 Sharing of Fees . With respect to cash amounts as provided for
herein that are received by Licensor from third parties regarding
any partnerships or alliances entered into in connection with the
Development and/or commercialization of the Licensed Products
(as such term is defined in this Revised Collaboration Agreement)
anywhere in the Licensed Territory (provided, however, that solely
for the purposes of this Section 4.3 that Licensed Territory shall
be as defined in the Collaboration Agreement dated March 6, 2002,
between the parties), Licensor and Licensee shall share in any such
cash amounts according to the following ratio: Licensor [***]%;
Licensee [***]% ( provided , however , that the
aggregate of any amounts received by Licensee pursuant to this
Section 4.3 shall not exceed $20 million (USD)).
Cash amounts
received by Licensor from third parties that shall be subject to
sharing under this Section 4.3 shall expressly be limited to
license fees, technology access fees and performance-based
milestones (i.e., such milestones solely intended to reward the
Licensor upon the occurrence of events characteristic of the
product development process and of the process of application for
and grant of regulatory approval to market the subject Licensed
Products and price approval therefor) for licenses granted by
Licensor and shall exclude, without limitation, amounts received by
Licensor: in return for supplying or royalties and other revenues
associated with the sale of Licensed Products; as funding for
product development, commercialization, manufacturing, and
regulatory activities; and with respect to any bona fide equity or
loan transactions). Licensor shall conduct negotiations with third
parties with respect to potential licenses in the greatest
commercially practicable manner so as the entering into of any such
relationship would provide for cash license fees, technology access
fees and performance-based milestones that are appropriate with
reference to the technology and potential value of the Licensed
Products and the value created during the Development
process.
For the
purposes of this Section, upon execution of any such agreement with
a third party, Licensor shall immediately notify Licensee as to the
agreed upon commercial terms with such party in order to enable
Licensee to assess the cash amounts to which it is entitled.
Licensee may verify the information provided by Licensor by means
of the audit of an external consultant, acceptable to Licensor,
which, at reasonable business hours, may inspect Licensor’s
premises by giving prior reasonable notice. Any such inspections
shall be at the sole cost of Licensee, except in the event where
the adjustment shown by such inspection is greater than 10% of the
amount incurred, then the Licensor shall bear such
costs.
Section 4.4 Cash Payments to Licensor for
Milestones . Licensee
shall pay to Licensor the following cash amounts upon the
attainment of the following:
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$ [***] upon
EMEA Marketing Regulatory Approval for RDS.
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$ [***] upon
EMEA Marketing Regulatory Approval for BPD.
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$ [***] upon
price approval in the Territory for ARDS provided, however, that
the parties have reached a mutually satisfactory Transfer Price in
accordance with the Amended and Restated Supply
Agreement.
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Information marked by [***] has been omitted
pursuant to a request for confidential treatment. The omitted
portion has been separately filed with the Securities and Exchange
Commission.
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$ [***] upon
EMEA Marketing Regulatory Approval for ALI prophylaxis.
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$ [***] upon
filing for EMEA Marketing Regulatory Approval of the nCPAP Licensed
Product.
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$ [***] upon
EMEA Marketing Regulatory Approval of the nCPAP Licensed
Product.
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$ [***] upon
filing for EMEA Marketing Regulatory Approval for asthma in the
hospital setting.
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$ [***] upon
EMEA Marketing Regulatory Approval for asthma in the hospital
setting.
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$ [***] upon
filing for EMEA Marketing Regulatory Approval for COPD in the
hospital setting.
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$ [***] upon
EMEA Marketing Regulatory Approval for COPD in the hospital
setting.
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Section
4.5 Manner of Payment . The amounts provided for in Section 4.3 and
Section 4.4 shall be paid in United States Dollars. Any and all
taxes that are levied on payments accruing under this Article 4 of
the Agreement in a country in which provision is made in the law or
by regulation for withholding may be deducted by the payor from
such amounts and paid to the proper taxing authority and evidence
of such payment shall be secured and sent to the payee as promptly
as possible. The parties shall do all such lawful acts and things
and sign all such lawful deeds and documents as either party may
reasonably request from the other party to enable Licensee or
Licensor, or their respective Affiliates and/or sublicensees to
take advantage of any applicable legal provision or any double
taxation treaties with the object of paying the sums due to any
payee hereunder without withholding any tax or as promptly as
practicable recovering any such withheld tax. Amounts to be paid
hereunder shall be paid: (i) with respect to amounts due to
Licensee pursuant to Section 4.3, as soon as practicable following
Licensor’s receipt of any such shareable amounts received
thereunder but in no event later than ten (10) Business Days after
such receipt; and (ii) with respect to amounts due to Licensor
pursuant to Section 4.4, as promptly as practicable upon
Licensee’s receipt of Licensor’s invoice issued upon
occurrence of any such event, but in no event later than ten (10)
Business Days after receipt of Licensor’s invoice.
ARTICLE 5
SCOPE OF THE COLLABORATION
Section
5.1. Goals of the Collaboration. Subject to Section
8.6(b) hereinbelow, the parties hereto desire to collaborate in a
strategic relationship with regard to product Development and
commercialization programs for the Licensed Products with the
following goals and in the following manner:
Information marked by [***] has been omitted
pursuant to a request for confidential treatment. The omitted
portion has been separately filed with the Securities and Exchange
Commission.
(a)
the Development and clinical
testing of Licensed Products;
(b)
Marketing Regulatory Approval of
Licensed Products in the Licensed Territory; and
(c)
the manufacturing by Licensor and
the marketing, sale, and distribution by Licensee of Licensed
Products in the Licensed Territory.
In performance
of the foregoing, Licensor and Licensee agree to collaborate
diligently in the overall strategic relationship and in the
Development and commercialization of Licensed Products in the
Licensed Territory in accordance with the terms and conditions
contained in this Agreement including, without limitation, the
respective roles and responsibilities of the parties as set forth
in this Article 5.
Section
5.2. Roles and Responsibilities
. The principal mechanism by which
the parties contemplate coordinating their respective clinical
Development and sales and marketing activities will be through
consensus-based decision-making through: (i) a joint Development
Committee (established and governed pursuant to Section 6.2 of this
Agreement) and (ii) a joint Commercialization Committee
(established and governed pursuant to Section 6.3 of this
Agreement); in each case, under the oversight of a joint Steering
Committee (established and governed pursuant to Section 6.1 of this
Agreement), provided, that the parties expressly acknowledge and
agree that the following shall apply:
(a) Conduct of Clinical Investigations
. The Development Committee (as such
term is defined in Section 6.2) shall be responsible for the
Development of Licensed Products in the Licensed Territory;
provided , however , that
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(i)
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Licensor, at
its cost, shall be responsible for planning and managing the
research and development work related to Licensed Products that is
necessary to obtain EMEA approval, regardless of where conducted,
subject to Section 5.2(a)(ii), below;
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(ii)
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Subject to
Section 8.6(b) hereinbelow, Licensee shall
contribute for Phase 3 Development of Licensed Products in the
Licensed Territory by conducting, sponsoring, and funding the cost
(up to the amounts specified below for each category of Licensed
Products) of Phase 3 clinical trials that are conducted in the
Licensed Territory (it being acknowledged by the parties that any
such trials are intended to be a part of a global European
development program for the Licensed Products), as discussed and
agreed to by the Development Committee. Licensee’s
contribution under this Section 5.2(a)(ii) shall be solely limited
to those costs that may be incurred with respect to Phase 3
Development conducted with respect to clinical sites located in the
Licensed Territory and shall solely include (x) shipping costs for
investigational product and other materials supplied to clinical
sites; and (y) external costs and payments for the subject Phase 3
clinical trial including, without limitation, consultants, contract
research organizations, payments to clinical investigators and
support staff, insurance companies, clinical sites, and regulatory
fees (“Phase 3 Costs”); provided ,
however , that with regards to each of (x) and (y), above,
Licensee’s obligation for contribution shall apply whether
such costs are contracted for and/ or initially paid by Licensor or
Licensee. The Development Committee shall (A) be responsible for
developing and approving the budgets for Phase 3 Costs taking into
account the nature of the Phase 3 Costs, and (B) approve the
selection, without limitation, of clinical sites and specific
consultants, contractors and clinical investigators to be used in
the performance of Phase 3 Development. Such approval by the
Development Committee shall constitute the parties’
commitment to undertake the relevant Phase 3 Development and
Licensee’s agreement to contribute to any such Phase 3 Costs
up to a maximum of the following amounts in U.S. Dollars
(“Licensee’s Maximum Contribution”):
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For Licensed
Products for the ARDS and/ or ALI indications, up to
$[***];
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For Licensed
Products for the BPD indication, up to $[***];
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For nCPAP
Licensed Product(s), up to $[***];
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For Licensed
Products for the asthma and COPD indication in the hospital
setting, up to $[***]; and
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For Licensed
Products for the COPD indication in the hospital setting, up to
$[***], only if a separate Phase 3 pivotal trial is conducted for
this indication (i.e. independent from the Phase 3 pivotal trial
for asthma).
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Provided,
however, that the determination of whether separate Phase 3
Development has occurred for the purposes of this Section
5.2(a)(ii) shall not be based upon the existence of separate
formulations of Licensed Product.
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(iii)
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Promptly upon
the completion of the experimental phase of the subject Phase 3
clinical trial in the Licensed Territory (i.e. when the last visit
of the last patient has occurred), a reconciliation of
Licensee’s Phase 3 Cost contributions determined hereunder
(including, without limitation, those costs previously invoiced,
paid or still to be invoiced and paid) shall be made with reference
to Licensee’s Maximum Contribution for such trial. Both
parties shall keep such records as are necessary to determine
accurately the sums due under this Section 5.2(a). Such records
shall be retained by each party and, at any time during the Term of
the Agreement, at the prior written request and expense of the
other party, shall be made available for inspection, review, and
audit during normal business hours, by an internationally
recognized independent certified public accounting firm selected by
the auditing Party and reasonably acceptable to the other Party for
the sole purpose of verifying the accounting reports and
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Information marked by [***] has been omitted
pursuant to a request for confidential treatment. The omitted
portion has been separately filed with the Securities and Exchange
Commission.
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payments made
or to be made pursuant to this Section 5.2(a); provided, however,
that such audits may not be performed more than once per contract
year. The auditing Party shall pay for such inspections, except
that in the event where the adjustment shown by such inspection is
greater than 10% of the amount incurred, then the audited Party
shall pay for such inspection.
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(iv)
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Licensee shall
be the sponsor in the Licensed Territory of all Phase 3 clinical
trials to which it contributes in accordance with this Section 5.2
and, subject to the prior approval of the Development Committee,
Licensee shall be entitled to conduct monitoring and auditing of
the sites at its own cost and expense. With respect to
Licensee’s sponsorship, monitoring and auditing, as
applicable, Licensor, through the operation of the Development
Committee or directly, shall (i) have the sole authority to approve
the clinical site agreement that may be entered into by Licensee
and a clinical site prior to its signature and, to the greatest
extent possible with reference to then or future applicable law, be
named as a co-sponsor thereto; and (ii) be entitled to oversee and
audit clinical site operations including, without limitation, site
interactions, site initiation, and monitoring and auditing
conducted by Licensee, all at Licensor’s expense.
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(v)
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Licensor and
Licensee shall keep each other fully informed on the progress of
all clinical trials of Licensed Products and shall promptly provide
the other with copies of all submissions to regulatory authorities
in connection therewith, all significant communications received
from such regulatory authorities and reasonably detailed
descriptions (in English) of all meetings with and verbal
communications with such regulatory authorities which are of
significance.
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(vi)
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Each of
Licensor and Licensee shall use its best commercial efforts to
complete all clinical trials for which it is responsible within the
parameters established by (and as such parameters may be modified
by) the Development Committee.
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(b) Commercialization Activities
. Through the governance mechanism
of the Commercialization Committee (as such term is defined in
Section 6.3), Licensor and Licensee shall actively participate in
the strategic marketing activities for Licensed Products in the
Licensed Territory. Without prejudice to Section 2.1 and 2.3,
Licensee shall be responsible for activities and associated costs
and expenses involved in the pre-launch, launch and post-launch
marketing, sales, and distribution of Licensed Products in the
Licensed Territory including, without limitation, (i) providing
country-specific marketing resources including, but not limited to,
personnel, marketing materials and other customary marketing tools
and methods; (ii) furnishing sufficient sales personnel to
adequately detail Licensed Products in the Licensed Territory and
achieve insertion of Licensed Products into hospital formularies;
(iii) managing and conducting order taking, storage and
distribution of Licensed Product in the Licensed Territory; (iv)
performing country-specific regulatory affairs activities and price
and reimbursement negotiations during the Regulatory Marketing
Approval process; (v) managing local medical affairs and reporting
of drug safety issues to Licensor and appropriate regulatory
authorities; and (vi) periodically report to the Commercialization
Committee and Steering Committee on Licensee’s marketing and
sales activities related to pre-launch, launch and post-launch
periods for all Licensed Products.
(c) Licensee, shall develop a sales and marketing
plan, which shall be subject to the periodic review and approval
(no less frequently than every 12 months) of the Steering Committee
as provided hereunder, comprised of individual sales and marketing
(pre-launch, launch and post-launch) plans for each Licensed
Product on a country-by-country basis in the Licensed Territory in
a form and content consistent with general pharmaceutical industry
practices (the “ Marketing Plan ”).
Section
5.3 Regulatory Approvals . (a) Subject to the completion of requisite
clinical investigations by the Licensor, Licensor shall prepare and
submit to the EMEA a MAA within 6 months of the date of acceptance
of filing of the applicable NDA by the FDA and shall use its
diligent efforts to obtain and maintain all EMEA Marketing
Regulatory Approvals for the term of this Agreement, all at the
cost and expense of Licensor, except as may otherwise be provided
for in Section 5.2. When filing for MAA, Licensor shall designate,
as appropriate, Licensee or such Licensee’s Affiliates or
permitted sublicensees and/or partners designated by Licensee as
its distributors or local representatives for the Licensed Products
in the Licensed Territory. Licensor shall, upon the granting of
each Marketing Regulatory Approval obtained by Licensor, promptly
supply Licensee with a copy of such approval.
(b) Subject to receipt of MAA Marketing Regulatory
Approval by Licensor, Licensee, where appropriate, shall prepare
and submit to the regulatory authorities in the Licensed Territory
country-specific and Licensed Product specific applications for
Pricing Approvals as soon as practicable and shall use its diligent
efforts to obtain and maintain all Pricing Approvals that are
obtained by Licensee for the term of this Agreement, all at the
cost and expense of Licensee. Licensee shall, upon the granting of
each Pricing Approval obtained by Licensee, promptly supply
Licensor with a copy of such approvals. The parties contemplate
that country-specific applications for Marketing Regulatory
Approvals shall not be necessary for any of the Licensed Products
in the Licensed Territory, however, should any such
country-specific applications be required, Licensee shall be
responsible for all associated costs for filing and maintaining
such Marketing Regulatory Approvals.
(c) Each party shall, in connection with any
Marketing Regulatory Approvals and Pricing Approvals obtained by
such party in the Licensed Territory, grant to the other party an
irrevocable right of access and reference thereto and shall effect
such notifications to regulatory authorities as shall be reasonably
necessary to accomplish the foregoing. Each party shall assist the
other party in maintaining any such Marketing Regulatory Approvals
and Pricing Approvals including supplying to the other party any
information in connection therewith.
(d) In the event of termination of this
Ag
