EXHIBIT 10.1


 


EXECUTION COPY


 


LICENSE, DEVELOPMENT AND
COMMERCIALIZATION AGREEMENT


 


BY AND BETWEEN


 


AMAG PHARMACEUTICALS, INC.


 


AND


 


TAKEDA PHARMACEUTICAL
COMPANY LIMITED


 


MARCH 31, 2010


 

















 


LICENSE, DEVELOPMENT AND
COMMERCIALIZATION


AGREEMENT


 


This LICENSE,
DEVELOPMENT AND COMMERCIALIZATION AGREEMENT (the “Agreement”) is entered into as of March 31, 2010 (the “Effective Date”) by and between AMAG
PHARMACEUTICALS, INC.,  a Delaware
corporation with its principal place of business at 100 Hayden Ave, Lexington,
MA 02421, USA (“AMAG”),  and
TAKEDA PHARMACEUTICAL COMPANY LIMITED,
a company incorporated under the laws of Japan, with its principal place of
business at 1-1, Doshomachi 4-chome, Chuo-ku, Osaka, 540-8645, Japan (“Takeda”).  AMAG and
Takeda are sometimes referred to herein individually as a “Party”
and collectively as the “Parties”.


 


RECITALS


 


WHEREAS, AMAG has launched in the United States and is developing its proprietary
Feraheme® (ferumoxytol) Injection product for the treatment and diagnosis of
certain human diseases and conditions in
and outside the United States;


WHEREAS, Takeda possesses resources and expertise in the
development, marketing, and commercialization of pharmaceutical products in the
Licensed Territory (as defined below); and


 


WHEREAS, Takeda
desires to collaborate with AMAG on the further development of the Product (as
defined below) in the Field (as defined below) through regulatory approval in
the Licensed Territory, and to obtain commercialization rights to the Product
in the Field in the Licensed Territory, and AMAG is willing to so collaborate
and to grant such rights on the terms and conditions hereof.


 


NOW, THEREFORE, in
consideration of the foregoing premises and the mutual promises, covenants and
conditions contained in this Agreement, the Parties agree as follows:


 


ARTICLE 1


 


DEFINITIONS


 


1.1                               “Acquiror” has the meaning set forth in Section 16.5.


 


1.2                               “Affiliate” means, with respect to a particular
Party or a Takeda sublicensee set forth in Section 2.1(c), a person,
corporation, partnership, or other entity that controls, is controlled by or is
under common control with such Party or sublicensee.  For the purposes of this definition, the word
“control” (including, with correlative meaning, the terms “controlled by” or
“under common control with”) means the actual power, either directly or
indirectly through one or more intermediaries, to direct or cause the direction
of the management and policies of such entity, whether by the ownership of
fifty percent (50%) or more of the voting 


 

















 


stock of such entity, or
by contract or otherwise. Notwithstanding the foregoing, Takeda Thailand
Ltd. shall be deemed to be an Affiliate of Takeda.


 


1.3                               [***] has the meaning set forth in Section 4.9(b)(ii).


 


1.4                               “AMAG House Marks” means the AMAG names and logo as set
forth on Exhibit D.


 


1.5                               “AMAG Indemnitees” has the meaning set forth in Section 11.2.


 


1.6                               “AMAG Know-How” means all Information that is Controlled
by AMAG or its Affiliates as of the Effective Date or during the Term and is
necessary or useful for the
Development, Manufacture or Commercialization of the Product in the Field in
accordance with the terms of this Agreement. 
For clarity, AMAG Know-How excludes Information claimed in any AMAG Patent.   For avoidance of doubt, AMAG
Know-How shall exclude the Information of any Third Party that becomes an
Acquiror of AMAG, except for any Information included within the definition of
“AMAG Know-How” that is developed
by such Acquiror after the closing of such acquisition in the course of conducting
activities on behalf of AMAG under this Agreement.


 


1.7                               “AMAG Opt-In Study” has the meaning set forth in Section 4.6.


 


1.8                               “AMAG Patent” means any Patent that (a) is Controlled by AMAG or its Affiliates
as of the Effective Date or at any time during the Term, and (b) claims the composition of matter, use or
Manufacture of the Product in the Field.  A list of AMAG Patents in existence as of the
Effective Date is attached hereto as Exhibit C-1, and AMAG shall
update such list from time to time to include additional AMAG Patents,
including patents issuing from any listed application or claiming priority
thereto or otherwise continuing therefrom. 
For the avoidance of doubt, AMAG Patents shall include Product Patents,
and shall exclude the Takeda Patents and the Patents of any Third Party that
becomes an Acquiror of AMAG, except for (i) any Patents claiming inventions
that are included within the definition of an “AMAG Patent” that are developed by such Acquiror in the course
of conducting activities on behalf of AMAG under this Agreement, or (ii) any
Patents Controlled by such Acquiror at the closing of the acquisition of AMAG
that claim the composition, use or manufacture of the Product as in existence
as of the Effective Date.


 


1.9                               “AMAG Product Marks” means all trademarks in the Licensed Territory related
to the Product that are Controlled by AMAG or its Affiliates during the Term.  The AMAG Product Marks in existence (or for which AMAG or its Affiliates has submitted an application) as of the
Effective Date are set forth on Exhibit D, and shall be updated
from time to time.


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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1.10                        “AMAG Technology” means the AMAG
Patents and AMAG Know-How.


 


1.11                        “Asia-Pacific” means the countries
shown in Part II of Exhibit B attached hereto, including any successor country and
jurisdiction of any of such
countries.


 


1.12                        “Best
Knowledge” means, as applied to a Party, that such Party shall
be deemed to have knowledge of a particular fact or other matter to the extent
that a reasonably prudent person with experience in the pharmaceutical industry
and with primary responsibility for the applicable subject matter would or should know of such fact or other matter upon
diligent inquiry.


 


1.13                        “CEE” means the countries shown in Part III
of Exhibit B attached hereto, including any successor  country  or jurisdiction of any of such countries.


 


1.14                        “CIS” means the countries shown in Part IV
of Exhibit B attached hereto, including any successor  country  or jurisdiction of any of  such countries.


 


1.15                        “Claims” has the meaning set forth in Section 11.1.


 


1.16                        “CMC” means chemistry, manufacturing and
controls as specified
by the FDA.


 


1.17                        “Commercialization,” with a correlative meaning for “Commercialize”
and “Commercializing,” means all activities
undertaken before and after obtaining Regulatory Approvals
relating specifically
to the pre-launch, launch, promotion, detailing, medical education and medical
liaison activities, marketing, pricing, reimbursement, sale, distribution, and other
commercialization related activities to be detailed in the Commercialization
Plan of the Product,
including but not limited to: (a) strategic marketing, sales force
detailing, advertising, medical education and liaison, and market and Product
support; (b) all customer support, Product distribution, invoicing and
sales activities; and (c) Phase 4 Clinical Trials and other
post-approval clinical studies other than those studies required by a
Regulatory Authority or otherwise intended to be used to support the continued
Regulatory Approval of a Product in a given indication in the Field in a
country in the Licensed Territory.


 


1.18                        “Commercialization Plan” has the meaning set forth in Section 6.2.


 


1.19                        “Commercially Reasonable Efforts” means, with respect to the efforts to be
expended, or considerations to be undertaken, by a Party and its Affiliates
with respect to any objective, activity or decision to be undertaken hereunder,
reasonable, good faith efforts to accomplish such objective, activity or
decision as such Party would normally use to accomplish a similar objective,
activity or decision under similar circumstances in connection with an active
development, manufacturing
or commercialization program, it being understood and agreed that with respect
to the Development, Manufacture or Commercialization of the Product, such efforts
shall be similar to those efforts and resources commonly used by such Party for
a similar pharmaceutical product owned by it or to which it has similar rights
(and not less than the efforts that would be applied by a similarly situated
company using normal and customary level of efforts within the pharmaceutical
industry for a comparable product), which product is at a 


 


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similar stage in its
development or product life and is of similar market potential, taking into
account efficacy, safety, approved labeling, the competitiveness of alternative
products sold by Third Parties in the marketplace, the patent and other
proprietary position of the Product, the likelihood of Regulatory Approval
given the regulatory structure involved, and the profitability of the Product
taking into consideration, among other factors, Third Party costs and expenses
including the royalties, milestone and other payments payable to licensors of
patent or other intellectual property rights, the Manufacturing cost of the
Product, and the
pricing and reimbursement relating to the Product.  Commercially Reasonable Efforts shall be determined
on a market-by-market and indication-by-indication basis for the Product, and
it is anticipated that the level of effort may change over time, reflecting
changes in the status of the Product and the market(s) involved.


 


1.20                        “Committee” has the meaning set forth in Section 3.3(a).


 


1.21                        “Confidential Information” means, with respect to a Party, all
reports and other Information of such Party that are disclosed to the other
Party under this Agreement, whether in oral, written, graphic, or electronic form.  In addition, the terms of this Agreement
shall be deemed the Confidential Information of both Parties.  All Information disclosed by either Party
pursuant to the Mutual Confidentiality Agreement between the Parties dated May 19, 2009
shall be deemed to be such Party’s Confidential Information disclosed
hereunder.


 


1.22                        “Control” means, with respect to any material,
Information, or intellectual property right, that a Party (a) owns or (b) has
a license to such material, Information, or intellectual property right and, in
each case, has the ability to grant to the other Party access, a license, or a
sublicense (as applicable) to the foregoing on the terms and conditions set
forth in this Agreement without violating the terms of any then-existing agreement
or other arrangement with any Third Party.


 


1.23                        “Designated Executive”
has the meaning set forth in Section 3.1(b).


 


1.24                        “Designated Second Source
Supplier” or “DSS” means a
Third Party manufacturer of the Product designated in the Second Source Plan or
designated by AMAG and reasonably acceptable to Takeda.


 


1.25                        “Develop” or “Development”
means all activities relating to preparing and conducting non-clinical studies,
human clinical studies (other than the studies which are included in the
definition of Commercialization), regulatory activities (e.g.,
regulatory applications) and other development-related activities to be
detailed in the Development Plan with respect to the Product, but excluding in each
case any activities relating to the Manufacture of the Product.


 


1.26                        “Development Plan” means that certain mutually agreed
written development plan of all clinical studies to be performed for the
Product for the Licensed
Territory,  titled “Feraheme
Initial Clinical Development Plan,” dated March 31, 2010 and delivered to
Takeda prior to the Effective Date, which Development Plan is incorporated
herein by this reference, as amended in accordance with Section 4.3(b).


 


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1.27                        “Dollar” means a U.S. dollar, and “$” shall be
interpreted accordingly.


 


1.28                        “EMA” means the
European Medicines Agency or any successor entity.


 


1.29                        “Europe” means the countries shown in Part I
of Exhibit B attached hereto, including any successor  country  or jurisdiction of any such countries.


 


1.30                        “EU-5” means the countries of France, Germany,
Italy, Spain, and United Kingdom.


 


1.31                        “EU-15” means the
countries of Austria,
Belgium, Denmark, Finland, Ireland, Netherlands, Portugal, Norway, Sweden and
Switzerland (i.e., Europe excluding the EU-5 and EU-30).


 


1.32                        “EU-30” means the
countries of  Bulgaria, Cyprus, Czech Republic, Estonia, Greece,
Hungary, Latvia, Lithuania, Luxembourg, Malta, Poland, Romania, Slovakia,
Slovenia, and Iceland  (i.e., Europe excluding the EU-5 and EU-15).


 


1.33                        “FD&C Act” means the U.S. Federal Food, Drug and
Cosmetic Act, as amended.


 


1.34                        “FDA” means the U.S. Food and Drug
Administration or any successor entity.


 


1.35                        “Field” means the prevention, diagnosis and
treatment of all human diseases and conditions, excluding the Imaging Field.


 


1.36                        “Finish” means to label and package vials or other
containers of the
Product suitable for distribution to final users.


 


1.37                        “First Commercial Sale” means the first sale to a Third Party of
the Product in a given regulatory jurisdiction after Regulatory Approval has
been obtained in such jurisdiction. For clarity, sales for test
marketing, sampling and promotional or clinical trial purposes or compassionate
or similar use shall not be considered to constitute a First Commercial Sale.


 


1.38                        “Fiscal Year” means the twelve (12) consecutive month
period beginning April 1 and ending March 31.


 


1.39                        “FTE” means the
equivalent of a full-time individual’s work time for a twelve (12)-month period
of scientific, technical or managerial work under the Development Plan.  The portion of an FTE year devoted by an
individual to work under the Development Plan shall equal the average over
twelve (12) consecutive months of the percent of maximum potential working time
in a given month that such individual reported that he or she devoted to the
Development Plan, which shall not be greater than one hundred percent (100%),
according to Takeda’s then-current reporting practices.


 


1.40                        “FTE Costs” means the internal costs incurred by
Takeda, at the FTE Rate, for activities conducted under the Development Plan.


 


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1.41                        “FTE Rate” means the annual rate of [***] per FTE
for Takeda’s personnel conducting activities under the Development Plan.  Upon each anniversary of the
Effective Date, the FTE Rate may be adjusted upon request of either Party in
accordance with the change in the applicable government consumer price index
for the most recent twelve-month period for which such information has been
published in a relevant country(ies).


 


1.42                        “Future Required Studies” has the meaning set forth in Section 4.4(c)(ii).


 


1.43                        “Generic Product” means, with respect to a particular
Product, on a country-by-country basis, any pharmaceutical product that (i) contains
substantially the same chemical composition, approximate chemical formula, and
apparent molecular weight as the Product and has the same pharmaceutical form
as the Product, (ii) obtains regulatory approval by reference to the
Product pursuant to Article 10 (as applicable) of Directive 2001/83/EC and
Article 3(3) of Regulation EC/726/2004 of the European Parliament and
of the Council on the Community code relating to medicinal products for human
use, as amended, or any similar approval in any country of the Licensed
Territory that is based on reference to the Regulatory Approval for such
Product in such country and a demonstration of therapeutic equivalence or
similarity to such Product, and (iii) is
sold in the same country as such Product by a Third Party that is not a
sublicensee of Takeda or its Affiliates and did not purchase such product in a
chain of distribution that included any of Takeda or its Affiliates or
sublicensees.


 


1.44                        “Good Clinical Practices” or “GCP” means the
then-current standards, practices and procedures promulgated or endorsed by the
FDA as set forth in the guidelines entitled “Guidance for Industry E6 Good
Clinical Practice: Consolidated Guidance,” including related regulatory
requirements imposed by the FDA and comparable regulatory standards, practices
and procedures promulgated by the EMA or other Regulatory Authority applicable
to the Licensed Territory, as they may be updated from time to time, including
applicable quality guidelines promulgated under the International Conference on
Harmonization (“ICH”).


 


1.45                        “Good Laboratory Practices” or “GLP” means the
then-current good laboratory practice standards promulgated or endorsed by the
FDA as defined in 21 C.F.R. Part 58, and comparable regulatory standards
promulgated by the EMA or other Regulatory Authority applicable to the Licensed
Territory, as they may be updated from time to time, including applicable
quality guidelines promulgated under the ICH.


 


1.46                        “Good Manufacturing Practices,”  “cGMP” or “GMP” means the then-current good manufacturing practices
required by the FDA, as set forth in the FD&C Act and the regulations
promulgated thereunder, for the manufacture and testing of pharmaceutical
materials, and comparable laws or regulations applicable to the manufacture and
testing of pharmaceutical materials promulgated by the EMA or other Regulatory
Authority applicable to the Licensed 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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Territory, as they may
be updated from time to time, including applicable quality guidelines
promulgated under the ICH.


 


1.47                        “Good Pharmacovigilance
Practices” or “cGPvP” means the then-current good pharmacovigilance
practices recommended by the FDA, EMA (including Volume 9A of The Rules Governing
Medicinal Products in the European Union — Guidelines on Pharmacovigilance for
Medicinal Products for Human Use), or other Regulatory Authority applicable to
the Licensed Territory, as they may be updated from time to time, including
applicable guidelines under the ICH.


 


1.48                        “Governmental
Authority” means any multi-national, federal, state, local, municipal,
provincial or other government authority of any nature (including any
governmental division, prefecture, subdivision, department, agency, bureau,
branch, office, commission, council, court or other tribunal).


 


1.49                        “Group” shall mean a group of Persons whose
beneficial ownership of AMAG securities would be aggregated for purposes of Section 13(d) of
the U.S. Securities and Exchange Act of 1934, as amended, and the rules promulgated
thereunder.


 


1.50                        “IDA Indication”
is an indication for the treatment of iron deficiency anemia generally without
limit to a specific patient population or sub-population.


 


1.51                        “Imaging Field”
means any use of the Product as an imaging agent (including use as a reagent)
detected by magnetic resonance technology, including, for clarity, the use of
such imaging agent for diagnostic purposes.


 


1.52                        “Increase in Scope” has the meaning set forth in Section 4.9(b)(i).


 


1.53                        “IND” means (a) an Investigational New
Drug application as defined in the FD&C Act and applicable regulations
promulgated thereunder by the FDA, or (b) the equivalent application to
the equivalent Governmental Authority in any other regulatory jurisdiction
outside the U.S., the filing of which is necessary to commence or conduct
clinical testing of a pharmaceutical product in humans in such jurisdiction.


 


1.54                        “Indemnified Party” has the meaning set forth in Section 11.3.


 


1.55                        “Indemnifying Party” has the meaning set forth in Section 11.3.


 


1.56                        “Indication” means any human disease or condition
which can be treated, prevented or cured or the progression of which can be
delayed and for which a Product is specifically developed in order to obtain
Regulatory Approval.


 


1.57                        “Information” means any data, results, technology,
business or financial information or information of any type whatsoever, in any
tangible or intangible form, including  know-how, trade secrets, practices, techniques,
methods, processes, inventions, developments, specifications, formulations,
formulae, materials or compositions of matter of any type or kind (patentable
or otherwise), software, algorithms, marketing reports, expertise, technology,
test 


 


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data (including pharmacological,
biological, chemical, biochemical, clinical test data and data resulting from
non-clinical studies), CMC information, stability data and other study data and
procedures.


 


1.58                        “Initial Studies” has the meaning set forth in Section 4.4(a)(i).


 


1.59                        “Insolvency Event” means, with respect to a Party, except
for the event of a solvent reorganization or amalgamation, (a) the filing
by such Party in court or agency pursuant to any applicable statute or
regulation of any state or country, a petition in bankruptcy or insolvency or
for reorganization or for an arrangement or for the appointment of a receiver
or trustee of such Party or of its assets, or (b) the filing by a Third
Party against such Party of an involuntary petition in bankruptcy or seeking
reorganization, liquidation, dissolution, winding up arrangement, composition
or readjustment of such Party’s debts or any other relief under any bankruptcy,
insolvency, reorganization or other similar act or law of any jurisdiction now
or hereafter in effect, or the issuance of a warrant of attachment, execution
or similar process against a Party, and, in each case, only if the applicable
petition, warrant of attachment, execution or similar process is not dismissed
within ninety (90) days after the filing thereof, or (c) that such Party
proposes or is a party to any dissolution or liquidation under applicable law,
or makes an assignment for the benefit of creditors, or (d) with respect
to AMAG, issuance of a going concern opinion and a reasonable good faith determination
by Takeda that the current financial condition of AMAG, as reflected in such
opinion, is likely to have a material and adverse effect on AMAG’s ability to
supply Product to Takeda in accordance with the terms of this Agreement and the
Supply Agreement.


 


1.60                        “Joint Development Committee” or “JDC” means the
committee formed by the Parties as described in Section 3.2(a).


 


1.61                        “Joint Steering Committee” or “JSC” means the
committee formed by the Parties as described in Section 3.1(a).


 


1.62                        “Laws” means all laws, statutes, rules,
regulations, guidelines, ordinances and other pronouncements having the effect
of law of any federal, national, multinational, state, provincial, county, city
or other political subdivision, domestic or foreign.


 


1.63                        “Licensed Territory” means Europe, CEE, CIS, Asia-Pacific and
the countries shown in Part V of Exhibit B attached hereto,
but excluding any country or territory in which this Agreement has been
terminated under Article 13.


 


1.64                        “Loss of Meaningful Exclusivity” means, with respect to a particular
country and Product, the end of the [***] consecutive calendar month during
which one or more Third Parties sells a number of equivalent units of a Generic Product of
such Product in such country 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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comprising, during each
such month, at least [***] of the aggregate combined number of equivalent units
of such Product and such Generic Product(s) sold in such month in such
country.  All such determinations of unit
volume shall be based upon a mutually acceptable calculation method and using
market share (calculated on unit number basis) data provided by a reputable and
mutually agreed upon provider, such as IMS Health.


 


1.65                        “Manufacture”
with a correlative meaning for “Manufacturing,”
means all activities related to the manufacturing of a pharmaceutical product,
or any ingredient thereof, including manufacturing Product in finished form for
Development, manufacturing finished Product for Commercialization, packaging,
in-process and finished Product testing, release of Product or any component or
ingredient thereof, quality assurance activities related to manufacturing and
release of Product, ongoing stability tests and regulatory activities related
to any of the foregoing.


 


1.66                        “Marketing Authorization
Application” or “MAA” means an application to the appropriate Regulatory
Authority for approval to market the Product (but excluding pricing approvals)
in any particular jurisdiction.


 


1.67                        “Net Sales” means the gross amounts invoiced by
Takeda, its Affiliates and their respective sublicensees for sales of Product
made to unaffiliated Third Parties, less the following deductions to the extent
reasonable and customary provided to unaffiliated entities and actually allowed
with respect to such sales:


 


(a)                                  reasonable cash, trade or quantity
discounts, charge-back payments, and rebates actually granted or administrative
fees actually booked to trade customers, patients (including those in the form
of a coupon or voucher), managed health care organizations, pharmaceutical
benefit managers, group purchasing organizations and national, state, or local
governments, and to the agencies, purchasers and reimbursers of managed health
organizations, pharmaceutical benefit managers, group purchasing organizations,
or federal, state or local governments; provided, however, that in each case
such amounts shall be applied in a normal and customary manner with respect to
other similarly situated products of the selling party and not applied
disproportionately to the Product.  The
selling Party shall notify the other Party of any exceptional circumstances in
order to adequately maintain the competitive position of the Product and the
Parties shall confer in good faith regarding any deviation from such normal and
customary practice;


 


(b)                                  credits or allowances actually allowed
upon prompt payment or on account of claims, damaged goods, rejections or
returns of such Product, including in connection with recalls;


 


(c)                                  freight, postage, shipping,
transportation and insurance charges, in each case actually allowed or paid for
delivery of Product, to the extent billed or recognized; and


 


(d)                                  taxes (other
than income taxes), duties, tariffs or other governmental charges levied on the
sale of such Product, including value-added and sales taxes.


 


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(e)                                  Notwithstanding
the foregoing, amounts received or invoiced by Takeda, its Affiliates, or their
sublicensees for the sale of Product among Takeda, its Affiliates or their
respective sublicensees for resale shall not be included in the computation of
Net Sales hereunder.  For purposes of
determining Net Sales, the Product shall be deemed to be sold and booked when
invoiced.  Net Sales shall be accounted
for in accordance with standard Takeda practices for operation by Takeda, its
Affiliates or sublicensees, as practiced in the relevant country in the
Licensed Territory, but in any event in accordance with respective local
generally accepted accounting principles, consistently applied in such country
in the Licensed Territory.


 


(f)                                    Takeda,
its Affiliates, and their respective sublicensees will not sell Product in
combination with or as part of a bundle with other products or offer packaged
arrangements to customers that include the Product in such a manner as to
disproportionately discount the selling price of the Product, as compared with
the weighted-average discount applied to the other products, as a percent of
the respective list prices (or if not available, a good faith estimate thereof)
of such products and the Product prior to applying the discount.


 


1.68                        “New Product Marks” has the meaning
set forth in Section 6.7(a).


 


1.69                        “Non-Field Product” has the meaning
set forth in Section 6.6(a).


 


1.70                        “Off-label Use of Non-Field Product” has
the meaning set forth in Section 6.6(a).


 


1.71                        “Opt-In Study” has the meaning
set forth in Section 4.9(c).


 


1.72                        “Other AMAG Studies” has the meaning
set forth in Section 4.5.


 


1.73                        “Out-of-Pocket Costs” means any amounts
paid by a Party to Third Parties in connection with activities or services
conducted by such Third Parties, including clinical trial materials, contract
research, laboratory services, consulting services, shipping and
distribution.  For clarity, Out-of-Pocket
Costs for any Initial Studies, New Retreatment Study or New Pediatric Studies
conducted by Takeda pursuant to Sections 4.4(a)(ii) and 4.4(b)(ii) and
(iii), respectively, shall include Takeda’s payments to AMAG or to a Designated
Second Source Supplier for Product used in such studies.


 


1.74                        “Patent Challenge” has the meaning
set forth in Section 13.4.


 


1.75                        “Patent Term Extension” means any term
extensions, supplementary protection certificates and equivalents thereof
offering patent protection beyond the initial term with respect to any issued
Patents.


 


1.76                        “Patents” means (a) pending patent
applications (and patents issuing therefrom), issued patents, utility models
and designs; and (b) reissues, substitutions, confirmations,
registrations, validations, re-examinations, additions, continuations,
continued prosecution applications, continuations-in-part, or divisions of or
to any patents, patent applications, utility models or designs, in each case
being enforceable within the applicable territory.


 


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1.77                        “Pediatric Studies” has the meaning
set forth in Section 4.4(b)(i).


 


1.78                        “Person” shall mean a natural person,
corporation, partnership, trust, joint venture, limited liability company,
Regulatory Authority or any other entity or organization.


 


1.79                        “Phase 3 Clinical Trial” means a clinical
trial of a pharmaceutical product on patients, which trial(s) are designed
to (a) establish that a drug is safe and efficacious for its intended use;
(b) establish the dosage range to be prescribed; and (c) support
approval of an application to a Regulatory Authority for the commercial
marketing of such drug.


 


1.80                        “Phase 4 Clinical Trial” means a clinical
trial on patients, possibly including pharmacokinetic studies, which trial is (a) not
required to obtain Regulatory Approval of the initial indication(s) for the
Product, (b) not required by the Regulatory Authority as mandatory to be
conducted on or after the Regulatory Approval of the initial indication(s), and
(c) conducted voluntarily by a Party to enhance marketing or scientific
knowledge of the Product (e.g.,
providing additional drug profile, safety data or marketing support
information, or supporting expansion of product labeling)  (other than  for
Regulatory Approval).  For clarity, Phase
4 Clinical Trials are the responsibility of Takeda as a Takeda Study and are
not subject to the terms of Section 4.9(b).


 


1.81                        “Product” means a pharmaceutical
composition that (a) contains AMAG’s ferumoxytol described on Exhibit A
or (b) is claimed by one of the following AMAG Patents: [***] or any
patent issuing from [***], in any dosage form, formulation and form of
administration.


 


1.82                        “Product Complaint” means any written,
verbal or electronic expression of dissatisfaction regarding the Product,
including reports of actual or suspected product tampering, contamination,
mislabeling or inclusion of improper ingredients.


 


1.83                        “Product Infringement” has the meaning
set forth in Section 9.5(b)(i).


 


1.84                        “Product Inventions” has the meaning
set forth in Section 9.1.


 


1.85                        “Product Patent” has the meaning set
forth in Section 9.1.


 


1.86                        “Regulatory Approval” means all
approvals necessary for the commercial sale of the Product for the Field, in a
given country or regulatory jurisdiction, including a price and/or
reimbursement permit, if required for commercial sale of the Product, and
including approval of the MAA.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


11

















 


1.87                        “Regulatory Authority” means, in a
particular country or jurisdiction, any applicable Governmental Authority
involved in granting Regulatory Approval in such country or jurisdiction.


 


1.88                        “Regulatory Exclusivity” means any
exclusive marketing rights or data exclusivity rights (other than a patent
right) conferred by any Governmental Authority with respect to the Product in  a
country in the Licensed Territory, including rights similar to those conferred
in the U.S. under the Hatch-Waxman Act or the FDA Modernization Act of 1997.


 


1.89                        “Regulatory Lead” has the meaning
set forth in Section 5.2(a).


 


1.90                        “Regulatory Materials” means regulatory
applications, submissions, notifications, communications, correspondence,
registrations, Regulatory Approvals and/or other filings made to, received from
or otherwise conducted with a Governmental Authority in order to Develop,
Manufacture, market, sell or otherwise Commercialize the Product in a
particular country, territory or possession. 
Regulatory Materials include INDs and MAAs.


 


1.91                        “Royalty Term” means, with
respect to a particular country in the Licensed Territory, the period of time
beginning upon the date of First Commercial Sale of the Product for the Field
in such country and continuing until the Loss of Meaningful Exclusivity for the
Product in such country.


 


1.92                        “SOPs” or “Standard Operating Procedures” has the meaning set forth in Section 7.4.


 


1.93                        “Supply Agreement” has the meaning
set forth in Section 7.2.


 


1.94                        [***]  has the meaning set
forth in Section 4.9(b)(i).


 


1.95                        “Takeda Indemnitees” has the meaning
set forth in Section 11.1.


 


1.96                        “Takeda Know-How” means all
Information that (a) is Controlled by Takeda or its Affiliates as of the
Effective Date and applied or used in connection with the Development,
Manufacture or Commercialization by Takeda of the Product, or (b) arises
from Takeda’s activities under this Agreement, but excluding any and all
Product Inventions.  For clarity, Takeda
Know-How excludes  Information claimed in any
Takeda Patent.  For the avoidance of
doubt, Takeda Know-How shall exclude the Information of any Third Party that
becomes an Acquiror of Takeda, except for any Information included within the
definition of “Takeda Know-How” that is developed by such Acquiror after the
closing of such acquisition in the course of conducting activities on behalf of
Takeda under this Agreement.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


12

















 


1.97                        “Takeda Marks” has the meaning
set forth in Section 6.7(b).


 


1.98                        “Takeda Opt-In Study” has the meaning
set forth in Section 4.5.


 


1.99                        “Takeda Patent” means any Patent
that (a) is Controlled by Takeda or its Affiliates as of the Effective
Date and applied or used in connection with the Development, Manufacture or
Commercialization by Takeda of the Product hereunder, or (b) claims any
inventions made by Takeda, other than the Product Inventions, in the course of
conducting its activities under this Agreement. 
A list of the Takeda Patents in existence as of the Effective Date, if
any, is as attached hereto as Exhibit C-2, and Takeda shall update
such list from time to time to include additional Takeda Patents, including
patents issuing from any listed application or claiming priority thereto or
otherwise continuing therefrom.  For the
avoidance of doubt, Takeda Patents shall exclude the Patents of any Third Party
that becomes an Acquiror of Takeda, except for (i) any Patents claiming
inventions that are included within the definition of a “Takeda Patent” that
are developed by such Acquiror in the course of conducting activities on behalf
of Takeda under this Agreement, or (ii) any Patents Controlled by such
Acquiror at the closing of the acquisition of Takeda that claim the
composition, use or manufacture of the Product as in existence as of the
Effective Date.


 


1.100                 “Takeda Studies” has the meaning
set forth in Section 4.6.


 


1.101                 “Takeda Technology” means the Takeda
Patents and Takeda Know-How.


 


1.102                 “Term” means the term of this
Agreement, as determined in accordance with Article 13.


 


1.103                 “Third Party” means any entity other than
AMAG or Takeda or an Affiliate of either of them.


 


1.104                 “Transfer Event” has the meaning
set forth in Schedule 7.2.


 


1.105                   [***]
has the meaning set forth in Section 4.9(a)(ii).


 


1.106                 “U.S. Studies” has the meaning
set forth in Section 4.4(b).


 


1.107                 “Withdrawal Notice” has the meaning
set forth in Section 3.3(d).


 


ARTICLE 2


 


LICENSES AND EXCLUSIVITY


 


2.1                               Licenses to Takeda under AMAG Technology


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


13

















 


(a)                                  Licenses to Takeda.


 


(i)                                    Subject
to the terms and conditions of this Agreement, AMAG hereby grants Takeda an
exclusive (even as to AMAG except as provided in Section 2.1(b) below),
royalty-bearing license, with the right to sublicense directly or through
multiple tiers as provided in Section 2.1(c), under the AMAG Technology,
to research, Develop, Finish, use, sell, offer for sale, distribute, import,
export and otherwise Commercialize the Product in the Field in the Licensed
Territory.  In addition, for any
Development or Commercialization activities permitted under Article 4,
AMAG hereby grants Takeda a non-exclusive, royalty-bearing license, with the
right to sublicense directly or through multiple tiers as provided in Section 2.1(c),
under the AMAG Technology, to Develop, use, import and export the Product in
the Field outside the Licensed Territory to conduct any such permitted
activities solely to the extent for the Development or Commercialization of the
Product in the Licensed Territory pursuant to the license granted in the
immediately preceding sentence.  Takeda’s right to
use and access certain AMAG Know-How is subject to Takeda’s payment of certain
Development expenses, as described in Section 4.11.  For clarity, the foregoing licenses exclude
the right to Manufacture or have Manufactured the Product, except for the right
to Finish the Product, subject to the following subsection (ii).


 


(ii)                                Subject
to the terms and conditions of this Agreement and the Supply Agreement, and
effective only upon a Transfer Event and for so long thereafter as provided in
the Supply Agreement, AMAG hereby grants Takeda a co-exclusive (with AMAG and
the Designated Second Source Suppliers) license under the AMAG Technology to
have Manufactured the Product by a Designated Second Source Supplier for
Development and Commercialization of the Product by Takeda or its Affiliates or
sublicensees pursuant to the license granted in Section 2.1(a)(i).


 


(b)                                  AMAG Retained Rights.  Notwithstanding the rights granted to Takeda
in Section 2.1(a) and without limiting the generality of Section 2.5,
AMAG retains the following: (i) subject to Section 4.5, the right to
conduct or have conducted clinical trials and other studies in the Licensed
Territory for the generation of data in support of any regulatory submissions
to (x) any Regulatory Authority outside the Licensed Territory or (y) the
Regulatory Authorities within the Licensed Territory only to the extent as
provided in Article 4; and (ii) the right to Manufacture or have
Manufactured Product anywhere in the Licensed Territory, in each case together
with the right to import and export the Product in such territories for such
purposes.


 


(c)                                  Sublicense Rights.  Takeda shall have the right, directly or
through multiples tiers, to (i) grant sublicenses of the licenses granted
in Section 2.1(a)(i) to one or more of its Affiliates at any time; (ii) upon
written notice to the JSC, grant sublicenses of the license granted under Section 2.1(a)(i) to
one or more Third Parties; provided, however, that the right to sublicense the
right to Develop the Product under this Section 2.1(c)(ii) may be
granted only to a sublicensee of the right to Commercialize the Product, and
such Development shall be limited to clinical studies required to obtain or
maintain Regulatory Approval in a particular country, subject to Section 4.4(c);
and (iii) grant sublicenses under its Development rights under Section 2.1(a)(i) (A) in
the EU-5 to Third Parties upon the written consent of AMAG, at AMAG’s sole
discretion, and (B) in the Licensed Territory outside the EU-5 to Third
Parties upon the written 


 


14

















 


consent of AMAG, not to be
unreasonably withheld.  Takeda shall
provide all information reasonably requested by the JSC prior to entering into
any such Third Party arrangement and shall, within thirty (30) days after granting
a Third Party a sublicense under the licenses granted in Section 2.1(a)(i),
notify AMAG of the grant of such sublicense and provide AMAG with a true and
complete copy of the sublicense agreement (provided that Takeda may redact any
information contained therein that is not necessary to disclose to ensure
compliance with this Agreement).  Each
sublicense agreement shall be consistent with the terms and conditions of this
Agreement.  Takeda shall, in each
agreement under which it grants a sublicense under the license set forth in Section 2.1(a)(i) (each,
a “Takeda Sublicense Agreement”),
require the sublicensee (A) to provide Information to Takeda to the extent
necessary for Takeda and AMAG to comply with their obligations under Article 5,
and (B) to provide the following to AMAG, if this Agreement terminates, or
to Takeda, if only such Takeda Sublicense Agreement terminates: (x) the
assignment and transfer of ownership and possession of all Regulatory Materials
(including Regulatory Approvals) held or possessed by such sublicensee (which
assignment could also be directly to Takeda prior to any such termination), and
(y) the assignment of all intellectual property Controlled by such
sublicensee that covers a Product or its respective use, manufacture, sale, or
importation and was created by or on behalf of such sublicensee during the
exercise of its rights or fulfillment of its obligations pursuant to such
Takeda Sublicense Agreement.  In addition, Takeda will include
provisions in each Takeda Sublicense Agreement providing that if the
sublicensee or any of its Affiliates undertakes a Patent Challenge, Takeda may
terminate all sublicenses under the AMAG Patents granted to such
sublicensee.  If a sublicensee (or an Affiliate
of such sublicensee) undertakes a Patent Challenge, then Takeda, upon receipt
of notice thereof from AMAG, will terminate all sublicenses under the AMAG
Patents granted to such sublicensee in the applicable sublicense
agreement.  Takeda shall be responsible
for ensuring that its sublicensees comply with the terms of this Agreement, and
the operations of all such sublicensees with respect to Takeda’s rights or
obligations hereunder shall be deemed to be the operations of Takeda, for which
Takeda shall be responsible.


 


2.2                               License to AMAG.  Subject to the terms and conditions of this
Agreement, Takeda hereby grants to AMAG (a) a non-exclusive, royalty-free
license (with the right to sublicense as provided below) in the Field under the
Takeda Technology to Develop, use, make, and have made the Product in the
Licensed Territory pursuant to the terms of this Agreement and the Supply
Agreement, and (b) a non-exclusive, royalty-free, perpetual, irrevocable
license, with the right to grant sublicenses through multiple tiers, under the
Takeda Technology to develop, make, have made, use, sell, offer for sale and
import the Product in the Field outside the Licensed Territory; provided,
however, that upon any material breach of this Agreement by AMAG, and
notwithstanding AMAG’s timely cure of such breach, the foregoing license under
this subsection 2.2(b) shall become a royalty-bearing license, which shall
start to accrue on the date of such material breach, subject to a commercially
reasonable royalty rate to be negotiated in good faith by the Parties and, if
not agreed by the Parties within sixty (60) days after commencing negotiations,
determined by the panel of neutrals pursuant to Section 14.4.  In addition, upon AMAG’s written request,
Takeda shall, in good faith, negotiate with AMAG the terms and conditions under
which Takeda would grant to AMAG (c) a non-exclusive, royalty-bearing,
worldwide license, with the right to grant sublicenses through multiple tiers,
under the Takeda Technology to research, develop, make, have made, use, sell,
offer for sale and import 


 


15

















 


the Product outside the
Field.  AMAG’s right to use and access
certain Takeda Know-How is subject to AMAG’s payment of certain Development
expenses, as described in Section 4.11. 
If AMAG desires to sublicense the rights granted by Takeda under
subsection (b) or (c) above, AMAG shall notify Takeda in advance and
provide any information reasonably requested by Takeda with respect to such
proposed sublicensee. AMAG shall be responsible for ensuring that its
sublicensees comply with the terms of this Agreement, and the operations of all
such sublicensees with respect to AMAG’s rights or obligations hereunder shall
be deemed to be the operations of AMAG, for which AMAG shall be responsible.


 


2.3                               Negative Covenant.  Each Party covenants that it will not use or
practice any of the other Party’s intellectual property rights licensed to it
under this Article 2 except for the purposes expressly permitted in the
applicable license grant.


 


2.4                               Right of First Negotiation.  AMAG shall not commercialize the Product in
the Imaging Field in the Licensed Territory, whether by itself or through its
Affiliates or a Third Party, without first offering such commercialization
right to Takeda as set forth in this Section 2.4. [***]


 


2.5                               No Implied Licenses.  Except as explicitly set forth in this
Agreement, neither Party grants any license, express or implied, under its
intellectual property rights to the other Party.


 


2.6                               Exclusivity.


 


(a)                                  Takeda
hereby covenants that, [***] in any country or countries terminated under this
Agreement, neither it nor its Affiliates will, directly or indirectly, by
itself or with a Third Party, commercialize any pharmaceutical product in the
Licensed Territory and in the Field:  (i) containing
or comprising iron as the primary active pharmaceutical ingredient formulated
for delivery by parenteral means and (ii) indicated for the treatment of
anemia, including iron deficiency anemia (except for any Product under this
Agreement during the Term). 
Notwithstanding the foregoing, if [***], Takeda acquires a Third Party
that is commercializing a product in the Field in the Licensed Territory that
would constitute a breach of the immediately preceding sentence, Takeda shall
divest or otherwise cease to commercialize such product in the Field in the
Licensed Territory [***].


 


(b)                                  AMAG
hereby covenants that during the Term, neither it nor its Affiliates will,
directly or indirectly, by itself or with a Third Party, commercialize in the
Licensed Territory and in the Field any pharmaceutical product containing or
comprising iron as the primary active pharmaceutical ingredient formulated for
delivery by parenteral means. 
Notwithstanding the foregoing, if during the Term, AMAG acquires a Third
Party (and such acquisition does not result in a Change of Control of AMAG)
that is commercializing a product 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION  PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


16

















 


in the Field in the Licensed
Territory that would constitute a breach of the immediately preceding sentence,
AMAG shall divest or otherwise cease to commercialize such product in the Field
in the Licensed Territory [***].


 


(c)                                  Notwithstanding
Section 2.6(b), if an Acquiror of AMAG is conducting human clinical trials
for or commercializing, at the closing of the acquisition of AMAG, a product
that would constitute a breach of Section 2.6(b), the Acquiror may elect
one of the following by written notice to Takeda [***]: (1) to divest or
otherwise cease to clinically develop or commercialize such product in the
Field in the Licensed Territory [***], in which case such product will not be
deemed a breach of Section 2.6(b), or (2) to continue the clinical
development or commercialization of such product, in which case this Section 2.6
would immediately be of no further force and effect.  In addition, notwithstanding Section 2.6(b),
an Acquiror of AMAG shall have the right to conduct research and preclinical
development in the Field of a pharmaceutical product containing or comprising iron
as the primary active pharmaceutical ingredient formulated for delivery by
parenteral means, provided that such product does not use any AMAG Know-How and
is not claimed by any AMAG Patent. 
Commencing upon the Acquiror’s initiating human clinical trials for such
product, this Section 2.6 would be of no further force and effect.


 


2.7                               Cross-Territorial Restrictions.


 


(a)                                  Takeda
hereby covenants and agrees that it shall not, and will ensure that its
Affiliates and sublicensees will not, either directly or indirectly, actively
promote, market, distribute, import, sell or have sold Product into countries
outside the Licensed Territory.  As to
such countries outside the Licensed Territory: (i) Takeda shall not, and
will ensure that its Affiliates and sublicensees will not, engage in any
advertising or promotional activities relating to the Product directed
primarily to customers or other buyers or users of the Product located in such
countries; and (ii) Takeda shall not, and will ensure that its Affiliates
and sublicensees will not, solicit orders from any prospective purchaser
located in such countries.  If Takeda
receives any order from a prospective purchaser located in a country outside
the Licensed Territory from which re-imports into the Licensed Territory are
unlikely, Takeda shall immediately refer that order to AMAG.  Takeda shall not accept any such orders.  Takeda may not deliver or tender (or cause to
be delivered or tendered) any Product into a country outside of the Licensed
Territory from which re-imports into the Licensed Territory are unlikely.  Takeda shall not, and will ensure that its
Affiliates and sublicensees will not, restrict or impede in any manner AMAG’s exercise
of its retained rights outside the Licensed Territory, provided that any such
exercise of rights by AMAG shall comply with the terms of this Agreement.


 


(b)                                  Unless
otherwise permitted herein, AMAG hereby covenants and agrees that it shall not,
and will ensure that its Affiliates or its sublicensees will not, either
directly or indirectly, promote, market, distribute, import, sell or have sold
Product in the Field into any 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


17

















 


countries in the Licensed
Territory.  As to such countries in the
Licensed Territory, (i) AMAG shall not, and will ensure that its
Affiliates and sublicensees will not, engage in any advertising or promotional
activities relating to the Product in the Field directed primarily to customers
or other buyers or users of the Product located in such countries; and (ii) AMAG
shall not, and will ensure that its Affiliates and sublicensees will not,
solicit orders from any prospective purchaser located in such countries.  If AMAG receives any order from a prospective
purchaser located in a country in the Licensed Territory from which re-imports
to a country outside the Licensed Territory are unlikely, AMAG shall
immediately refer that order to Takeda. 
AMAG shall not accept any such orders. 
AMAG may not deliver or tender (or cause to be delivered or tendered)
any Product in the Field into a country in the Licensed Territory from which
re-imports into a country outside the Licensed Territory are unlikely. AMAG
shall not, and will ensure that its Affiliates and sublicensees will not,
restrict or impede in any manner Takeda’s exercise of its rights granted under
this Agreement in the Licensed Territory, provided that any such exercise of
rights by Takeda shall comply with the terms of this Agreement.


 


ARTICLE 3


 


MANAGEMENT


 


3.1                               Joint Steering Committee.


 


(a)                                  Formation and Role.  The Parties agree to establish a Joint
Steering Committee (or “JSC”) for
the overall coordination and oversight of the Parties’ activities under this
Agreement, promptly after the Effective Date. 
The JSC shall operate by the procedures set forth in Section 3.3.  Subject to Section 14.2(b), the role of
the Joint Steering Committee shall be:


 


(i)                                    to
review and discuss the overall strategy for the Development, Manufacture,  and
Commercialization of the Product for the Licensed Territory in the Field;


 


(ii)                                to
review, discuss and approve the Development Plan (and any proposed amendments
or revisions to such plan) and the overall strategy for Regulatory Approval
(including the initial approval and any supplements and expansions thereof);


 


(iii)                            to
review and discuss the Commercialization Plan (and any proposed amendments or
revisions to such plan); and


 


(iv)                               to
establish such subcommittees and to perform such other functions as appropriate
to further the purposes of this Agreement, as determined by the Parties in
writing.


 


(b)                                  JSC Decisions and Actions.  Actions to be taken by the Joint Steering
Committee shall be taken only following unanimous vote, with each Party having
one (1) vote.  If the Joint Steering
Committee fails to reach unanimous agreement on a matter before it for decision
for a period in excess of ten (10) business days, either Party may submit
the matter to a senior executive officer designated in writing by each Party
having sufficient decision making 


 


18

















 


authority over the particular
matter and not serving on any Committee (a “Designated
Executive”) for resolution in accordance with the decision-making
procedures described in Section 14.2, including the specific decision-making
rights of each Party as described in such section.


 


3.2                               Joint Development Committee


 


(a)                                  Formation and Role.  The Parties agree to establish a Joint
Development Committee (or “JDC”),
which will monitor and coordinate communication and operations regarding the
Parties’ efforts with respect to the Development and Regulatory Approval of the
Product in the Field in the Licensed Territory, including creation, amendment and
oversight of the Development Plan and operational Development activities.  Each Party shall have an equal number of
representatives on the Joint Development Committee.  The JDC shall operate by the procedures set
forth in Section 3.3.  The role of
the JDC shall be:


 


(i)                                    to
facilitate the exchange of Information between the Parties under this Agreement
with respect to their Product-related activities, including as and to the
extent necessary for each Party to perform its obligations under this
Agreement;


 


(ii)                                to
review and discuss the Development Plan and all amendments and updates thereto;
and


 


(iii)                            to
establish such working teams or subcommittees and to perform such other
functions as appropriate to further the purposes of this Agreement, as
determined by the Parties in writing.


 


(b)                                  JDC Decisions and Actions.  Actions to be taken by the JDC shall be taken
only following unanimous vote, with each Party having one (1) vote.  If the JDC fails to reach unanimous agreement
on a matter before it for decision for a period in excess of ten (10) business  days from the date first presented to the
JDC in writing, the matter shall be referred immediately to the JSC.


 


(c)                                  Protocols Review.  If (i) Takeda desires to conduct a
Takeda Study as permitted under Article 4, or any Development activity
assumed by Takeda under Section 4.4, or (ii) AMAG desires to conduct
an Other AMAG Study as permitted under Article 4, or Phase 4 Clinical
Trials in the Licensed Territory for the purpose of obtaining Regulatory
Approval for or Commercializing the Product outside the Licensed Territory,
then in each case (i) and (ii) such Party shall notify the JDC at the
first JDC meeting following such Party’s decision to conduct any such
activities.  With respect to any proposed
clinical trial, the proposing Party shall provide to the JDC, as soon as
available (if not available prior to such meeting), the protocol, primary and
secondary endpoints, inclusion and exclusion criteria, comparators, estimated
number of patients, and statistical power for such trial, and the countries in
which such trial will be conducted, as well and any other material matters
pertaining to such study.


 


(d)                                  AMAG Budgets.  For each clinical trial that AMAG conducts
under this Agreement and that Takeda has the right to assume under Section 4.4(a)(ii),
4.4(b)(ii), 4.4(b)(iii)


 


19

















 


or 4.4(c)(iii), AMAG shall
provide the JDC with a reasonably detailed budget of the Out-of-Pocket Costs
for such clinical trial at the first JDC meeting after the Effective Date, and
shall provide updates thereafter on an annual basis or upon material changes to
the budget by AMAG. AMAG shall respond to Takeda’s reasonable requests for
detailed information supporting any such budget.


 


3.3                               Committee Membership and Procedures.


 


(a)                                  Membership.  AMAG
and Takeda shall each designate an equal number of representatives (each of
whom shall be in a management position of the applicable Party) to serve on the
JSC and JDC (each a “Committee”)
by written notices to the other Party. 
Representatives selected for the JDC shall have appropriate
expertise/experience in clinical development of pharmaceutical products.  Initially, each Party shall designate three (3) representatives
for each Committee.  Each Committee may
elect to vary the number of representatives from time to time during the Term.  Either Party may designate substitutes for
its representatives if one (1) or more of such Party’s designated
representatives is unable to be present at a meeting.  From time to time each Party may replace its
representatives by written notice to the other Party specifying the prior
representative(s) and their replacement(s).  Each Committee will have a chairperson, to be
designated as described below.  The
chairperson shall be responsible for (i) calling meetings, (ii) preparing
and issuing minutes of each such meeting within ten (10) business days
thereafter, and (iii) preparing and circulating an agenda for the upcoming
meeting, but shall have no special authority over the other members of the
Committee, and shall have no additional voting rights or powers beyond those
held by the other members of the Committee.


 


(b)                                  Chairperson


 


(i)                                    The
initial chairperson of the JSC shall be appointed by Takeda.  On each anniversary of the Effective Date,
the Parties shall alternate designation of the chairperson of the JSC for the
commencing year.


 


(ii)                                The
initial chairperson of the JDC shall be appointed by AMAG.  On each anniversary of the Effective Date,
the Parties shall alternate designation of the chairperson of the JDC for the
commencing year.


 


(c)                                  Meetings.  Meetings
of a Committee shall be held at least quarterly during the first eighteen (18)
months after the Effective Date and twice per year thereafter during the Term,
unless the Parties mutually agree in writing to a different frequency for such
meetings.  No later than ten (10) business
days prior to any regularly scheduled meeting of a Committee, the chairperson
shall prepare and circulate an agenda for such meeting and, as soon as
practicable, materials for the meeting; provided, however, that either Party
may propose additional topics to be included on such agenda, prior to such
meeting.  A Committee may meet in person,
by videoconference or by teleconference, provided that at least one meeting
during each calendar year is in person. 
With the prior consent of the other Party’s representatives (such
consent not to be unreasonably withheld or delayed), each Party may invite
non-members to participate in the discussions and meetings of a Committee,
provided that such participants shall have no voting 


 


20

















 


rights or powers and shall be
subject to the confidentiality provisions set forth in Article 12.  Each Party will bear the expense of its
respective members’ participation in Committee meetings.  Meetings of a Committee shall be effective
only if at least two (2) representatives of each Party are present or
participating in such meeting.  The
chairperson of a Committee will be responsible for preparing reasonably
detailed written minutes of all Committee meetings that include material
decisions made at such meetings.  The
chairperson shall send draft meeting minutes to each member of the Committee
for review and approval within ten (10) business days after each Committee
meeting.  Such minutes will be deemed approved
unless one or more members of the Committee objects to the accuracy of such
minutes within ten (10) business days of receipt.


 


(d)                                  Discontinuation of Participation in a Committee.  At any time during the Term and for any
reason, either Party shall have the right to withdraw from participation in a
Committee upon written notice to the other Party, which notice shall be
effective immediately upon receipt (“Withdrawal
Notice”).  Following the
issuance of a Withdrawal Notice and subject to this Section 3.3(d), the
applicable Committee shall be disbanded and all decisions expressly delegated
to such Committee shall be made by a representative of the Parties subject to
the escalation procedures in Section 14.2. 
If, at any time following the issuance of a Withdrawal Notice, such
Party wishes to resume participating in the Committee, such Party shall notify
the other Party in writing, and after thirty (30) days from the date of such
notice, the Committee shall be reinstated and the terms of this Article 3
shall apply to such Committee from and after such date.  For
clarity, the withdrawal by a Party under this Section 3.2(d) shall
only limit such Party’s rights and obligations under this Article 3 with
respect to participation and decision-making in the Committee.  Notwithstanding the foregoing, a Party may
not withdraw from or rejoin a Committee more than once during any Fiscal Year.


 


(e)                                  Authority.  The JSC and JDC shall each perform its
responsibilities and make decisions under this Agreement based on the principles
of prompt and diligent Development and Commercialization of Product in the
Licensed Territory with Commercially Reasonable Efforts, consistent with good
pharmaceutical practices and commercially reasonable consideration of the
optimal balance of maximizing long-term profits derived from the sale of the
Product in the Licensed Territory in the context of the estimated costs for
Development and Commercialization of the Product in the Licensed Territory. The
JSC and the JDC shall each have only the powers assigned expressly to it in
this Article 3 and elsewhere in this Agreement, and shall not have any
power to amend, modify or waive compliance with this Agreement.  The JSC and JDC shall be responsible for
setting overall strategic direction relating to and the Development Plan and
Commercialization Plan as set forth in this Article 3, but day-to-day,
tactical or operational matters with respect to the Development and
Commercialization of the Product in the Licensed Territory will be decided, in
accordance with the terms of this Agreement, by the Party responsible hereunder
for the execution of such matters.


 


3.4                               Alliance Managers.  Promptly following the Effective Date, each
Party shall designate in writing an individual as its alliance manager to facilitate
communication and coordination of the Parties’ activities under this Agreement
relating to the Product.


 


21
















 


3.5          Collaboration
Guidelines. 
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.


 


ARTICLE 4


 


PRODUCT DEVELOPMENT


 


4.1          Overview
of Product Development.  The Parties desire and intend to collaborate
with respect to the Development of the Product in the Licensed Territory in the
Field, as and to the extent set forth in this Agreement.  In general, AMAG shall be responsible for
conducting the Development activities for the Product for the Licensed
Territory contemplated as of the Effective Date and any additional studies
required by a Regulatory Authority in the Licensed Territory for Regulatory
Approval, unless otherwise agreed by the Parties.


 


4.2          Principles
of Product Development.  Each Party’s Development of the Product in
the Field for the Licensed Territory shall be conducted in a manner consistent
with the following principles: (1) seeking Regulatory Approval that
includes the appropriate label for such Product in light of the clinical data,
and (2) obtaining Regulatory Approval for such Product consistent with the
preceding clause and in a timely manner in accordance with the terms of this
Agreement.


 


4.3          Development
Plan.


 


(a)           Initial
Development Plan.  All Development of the Product in the Field
for the Licensed Territory shall be conducted pursuant to the Development
Plan.  The Development Plan shall specify
(i) the plans and timeline for preparing the necessary Regulatory
Materials and for obtaining Regulatory Approval for the Product in the Licensed
Territory, (ii) the Development activities of each Party and (iii) clinical
supply for the Product.  Each Party shall
conduct its Development activities in accordance with the then-current Development
Plan and the terms of this Agreement.


 


(b)           Amendments.  From time to time and, on at least an annual
basis, the JDC shall update and amend, as appropriate, the then-current
Development Plan, including to address any changes to the Initial Studies that
the JSC deems necessary to ensure the commercial viability of the Product.  If either Party desires to materially change
a study then set forth in the Development Plan or to conduct a study or other
activity not then set forth in the Development Plan, such Party shall notify
the JDC, and the JDC shall discuss such proposed changes and corresponding
amendment to the Development Plan.  In
addition, if a Regulatory Authority in the Licensed Territory communicates to a
Party that additional studies or material changes to then-contemplated studies
may be required as a condition of approval of the MAA by such Regulatory
Authority, or for appropriate reimbursement for the Product, the Parties shall
immediately notify the JDC, and the JDC shall promptly meet to discuss a
response to such Regulatory Authority decision. 
Within ninety (90) days after such meeting, the Parties shall prepare an
amendment to the Development Plan to reflect the JDC’s discussion and decision,
subject to Section 4.9.  The JDC
shall submit each amendment to the JSC for review and 


 


22

















 


approval.  If the JSC fails to agree on any amendment to
the Development Plan, the matter shall be submitted to the Designated
Executives pursuant to Section 3.1(b) for resolution in accordance
with Section 14.2.  For clarity,
notwithstanding anything to the contrary in this Agreement, each Party shall
have the right to suspend, terminate or modify any Development activities
conducted by such Party as reasonably necessary to ensure the health, safety or
welfare of a subject in any clinical trial.


 


4.4          AMAG
Development Responsibilities.


 


(a)           Initial
Studies.


 


(i)            AMAG
shall be responsible for conducting, at its sole cost and expense, subject to
Sections 4.9(a)(ii), 4.9(a)(iii) and 4.9(b), the Development activities
reasonably necessary to perform the studies set forth on Schedule 4.4(a) (the
“Initial Studies”), as described
in the Development Plan.  AMAG shall have
the right to use any and all data and results generated from the Initial
Studies for any and all purposes outside the Licensed Territory.  For the avoidance of doubt, Takeda shall have
the right to use data and all other Information from the Initial Studies included
in the AMAG Technology for the purposes of obtaining and maintaining Regulatory
Approval for the Product in the Field in the Licensed Territory in accordance
with the terms of this Agreement.  AMAG
shall in all material respects timely conduct all Development activities for
the Initial Studies as set forth in the then-current Development Plan.


 


(ii)           In the
event that AMAG materially fails to perform the Initial Studies consistent with
the then-current Development Plan (such failure referred to herein as an “Initial Studies Failure”), Takeda shall
have the right to allege an Initial Studies Failure by written notice to AMAG,
such notice to set forth the basis for such alleged failure in reasonable
detail.  AMAG shall have a period of
[***] to cure such failure to Takeda’s reasonable satisfaction.  If AMAG does not so cure such failure, then
Takeda shall have the right to conduct the Initial Studies to which the
material failure pertains in accordance with the then-current Development Plan
as reasonably amended by Takeda, consistent with its obligation to use
Commercially Reasonable Efforts under Section 4.7, to mitigate the
consequences of such failure.  Takeda
shall provide such amended Development Plan to the JDC promptly after
preparation thereof.  Upon Takeda’s
exercise of such right, AMAG shall provide Takeda with its then-current budget
for the Out-of-Pockets Costs for the applicable study and any supporting
material reasonably requested by Takeda to the extent necessary or useful for
Takeda to conduct such studies.  If
Takeda conducts such studies, AMAG shall, at its expense, take all actions
reasonably required to transfer such studies to Takeda in a timely, efficient
and effective manner, including procurement of manufacture and supply of the
necessary Product for the studies and/or the management of the studies, which
AMAG shall facilitate by introducing Takeda to AMAG’s Third Party vendors,
including CROs, and, upon Takeda’s request, using reasonable efforts to 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


23

















 


assign to Takeda or amend as
appropriate any Third Party contracts to the extent related to such studies,
[***].  Upon the [***] of an Initial
Studies Failure, Takeda shall have the right to assume responsibility for and
conduct the Initial Studies to which such failure pertains as provided above in
this Section 4.4(a)(ii), notwithstanding AMAG’s timely cure of such
Initial Studies Failure.


 


(b)           U.S.
Studies and Pediatric Studies.


 


(i)            AMAG
shall use Commercially Reasonable Efforts to conduct, at its sole cost and
expense, subject to Sections 4.9(a)(ii), 4.9(a)(iii) and 4.9(b), (x) a
placebo-controlled Phase 3 Clinical Trial of the Product for iron deficiency
anemia and a long-term retreatment study, for the purpose of generating data to
submit to the FDA to support Regulatory Approval of the Product in the U.S.
(the “U.S. Studies”) and (y) four
(4) pediatric Phase 4 Clinical Trials set forth in the pediatric
investigation plan approved by the Pediatric Committee of the EMA (the “Pediatric Studies”).  A list of the U.S. Studies and Pediatric
Studies is set forth on Schedule 4.4(b). 
For the avoidance of doubt, Takeda shall have the right to use data and
all other Information from the U.S. Studies and the Pediatric Studies included
in the AMAG Technology for the purposes of obtaining and maintaining Regulatory
Approval for the Product in the Licensed Territory in accordance with the terms
of this Agreement.  AMAG shall use
Commercially Reasonable Efforts to timely conduct all Development activities
for the U.S. Studies and Pediatric Studies as set forth in the then-current
Development Plan.


 


(ii)           In the
event that (x) AMAG does not complete the long-term retreatment study for
iron deficiency anemia included in the U.S. Studies (“U.S. Retreatment Study”) as described in the Development Plan
as of the Effective Date, [***] as set forth in the Development Plan as of the
Effective Date, or (y) AMAG discontinues the U.S. Retreatment Study prior
to its planned completion date, upon the occurrence of which AMAG shall
immediately notify Takeda, then AMAG shall, at its expense, conduct an
additional study (“New Retreatment Study”)
to generate equivalent data in all material respects for Takeda to submit to
the EMA.  In such event, AMAG shall
initiate (i.e., first dosing of the first patient) the New Retreatment Study
[***], and shall use Commercially Reasonable Efforts to complete the New
Retreatment Study on a timely basis. 
Notwithstanding the foregoing, Takeda shall have the right to conduct
the New Retreatment Study upon written notice to AMAG [***], in accordance with
the then-current Development Plan as reasonably amended by the JDC and approved
by the JSC to mitigate the consequences of such failure, if AMAG has not then
initiated such study.  Upon Takeda’s exercise
of such right, AMAG shall provide Takeda with its then-current budget for the
Out-of-Pockets Costs for the applicable study and any supporting material
reasonably requested by Takeda to the extent necessary or useful for Takeda to
conduct such studies.  If Takeda conducts
such study, AMAG shall be relieved of its obligation to conduct such study and
shall, at its expense, take all actions reasonably required to transfer the
study to Takeda in a timely, 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


24

















 


efficient and effective
manner, including procurement of manufacture and supply of the necessary
Product for such study and/or the management of such study, which AMAG shall
facilitate by introducing Takeda to AMAG’s Third Party vendors, including CROs,
and, upon Takeda’s request, using reasonable efforts to assign or amend as
appropriate any Third Party contracts to the extent related to such study, and
[***].


 


(iii)         In the
event that (x) AMAG does not complete the Pediatric Studies as described
in the Development Plan as of the Effective Date, [***], or (y) AMAG
discontinues the Pediatric Studies prior to their planned completion date, upon
the occurrence of which AMAG shall immediately notify Takeda, then AMAG shall,
at its expense, conduct additional studies (“New
Pediatric Studies”) to generate equivalent data in all material
respects for Takeda to submit to the EMA. 
In such event, AMAG shall initiate (i.e., first dosing of the first
patient) the New Pediatric Studies [***], and shall use Commercially Reasonable
Efforts to complete the New Pediatric Studies on a timely basis.  Notwithstanding the foregoing, Takeda shall
have the right to conduct the New Pediatric Studies upon written notice to AMAG
[***], in accordance with the then-current Development Plan as reasonably
amended by the JDC and approved by the JSC to mitigate the consequences of such
failure, if AMAG has not then initiated such study.  Upon Takeda’s exercise of such right, AMAG
shall provide Takeda with its then-current budget for the Out-of-Pockets Costs
for the applicable study and any supporting material reasonably requested by
Takeda to the extent necessary or useful for Takeda to conduct such
studies.  If Takeda conducts such
studies, AMAG shall be relieved of its obligation to conduct such studies and
shall, at its expense, take all actions reasonably required to transfer such
studies to Takeda in a timely, efficient and effective manner, including
procurement of manufacture and supply of the necessary Product for such studies
and/or the management of such studies, which AMAG shall facilitate by
introducing Takeda to AMAG’s Third Party vendors, including CROs, and, upon
Takeda’s request, using reasonable efforts to assign or amend as appropriate
any Third Party contracts to the extent related to the clinical trials, and
[***].


 


(iv)          For
clarity, if AMAG conducts the U.S. Retreatment Study and Pediatric Studies in
accordance with the Development Plan, and the EMA or other Regulatory Authority
in the Licensed Territory determines that such study is insufficient for
approval of the MAA and an additional study is required, then such additional
required study shall be a Future Required Study subject to Section 4.4(c) below
and shall not be a New Retreatment Study or New Pediatric Study (as the case
may be) subject to this Section 4.4(b).


 


(c)           Future
Required Studies.


 


(i)            In addition to the Initial Studies, U.S. Studies and
Pediatric Studies, AMAG shall be responsible for using Commercially Reasonable
Efforts to conduct (1) all studies that are required after the Effective
Date by a Regulatory Authority in the Licensed Territory as a condition for
approval of the MAA for iron deficiency anemia associated with 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR
WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS
BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2
PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


25

















 


chronic kidney disease and/or for the IDA Indication
or for appropriate reimbursement of the Product, and (2) to the extent
agreed by the JDC and approved by the JSC, subject to Section 14.2, all
studies that are recommended after the Effective Date by a Regulatory Authority
in the Licensed Territory for approval of the MAA for the Product ((1) and
(2), collectively, the “Future  Required Studies”), subject to Sections
4.4(c)(ii) and (iii) and 4.9(b), unless agreed otherwise by the Parties.  For clarity, an MAA for a patient population
for which a previous MAA was not filed will be considered to be an MAA for a
distinct Indication.  AMAG shall have the
right to use any and all data and results generated from the Future Required
Studies for any and all purposes outside the Licensed Territory.  For the avoidance of doubt,  Takeda shall have the right to use data
from the Future Required Studies included in the AMAG Technology for the
purposes of obtaining and maintaining Regulatory Approval for the Product in
the Licensed Territory in accordance with the terms of this Agreement.  AMAG shall use Commercially Reasonable
Efforts to timely conduct all Development activities for the Future Required
Studies as set forth in the then-current Development Plan.


 


(ii)           If
Takeda desires to conduct any Future Required Studies in a country outside of
Europe through its sublicensee of commercial rights in such country, Takeda
shall notify AMAG, and the Parties shall meet and discuss in good faith the
qualifications of such sublicensee to conduct such activities and a budget for
such activities, as well as AMAG’s qualifications and budget for such
activities.  Takeda shall have the right
to conduct such activities through such sublicensee if such sublicensee is
reasonably qualified (based on local requirements and capabilities) and if such
budget is reasonably similar to AMAG’s budget for such activities.


 


(iii)         In the
event that AMAG materially fails to perform a Future Required Study consistent
with the then-current Development Plan (such failure referred to herein as a “Future Required Study Failure”) Takeda
shall have the right to allege a Future Required Study Failure by written
notice to AMAG, such notice to set forth the basis for such alleged failure in
reasonable detail.  AMAG shall have a
period of [***] to cure such failure to Takeda’s reasonable satisfaction.  If AMAG does not so cure such failure, then
Takeda shall have the right to conduct the Future Required Study to which the
material failure pertains in accordance with the then-current Development Plan
as reasonably amended by Takeda, consistent with its obligation to use
Commercially Reasonable Efforts under Section 4.7, to mitigate the
consequences of such failure.  Takeda
shall provide such amended Development Plan to the JDC promptly after
preparation thereof.  Upon Takeda’s
exercise of such right, AMAG shall provide Takeda with its then-current budget
for the Out-of-Pockets Costs for the applicable study and any supporting
material reasonably requested by Takeda to the extent necessary or useful for
Takeda to conduct such studies.  If
Takeda conducts such studies, AMAG shall, at its expense, take all actions
reasonably required to transfer such responsibility to Takeda in a timely,
efficient and effective manner, including the responsibility for procuring the 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


26

















 


manufacture and supply of the necessary Product for the clinical trials
and/or the management of the related clinical trials, which AMAG shall
facilitate by introducing Takeda to AMAG’s Third Party CROs and, upon Takeda’s
request, using reasonable efforts to assign to Takeda any Third Party contracts
to the extent related to the clinical trials. 
Upon the [***] of a Future Required Study Failure, Takeda shall have the
right to assume responsibility for and conduct the Future Required Study to
which such failure pertains as provided above in this Section 4.4(c)(iii),
notwithstanding AMAG’s timely cure of such Future Required Study Failure.


 


4.5          Other
AMAG Studies.  AMAG
may not conduct any studies of the Product for use outside the Licensed
Territory that would be likely to have a material adverse impact on the product
profile, safety or efficacy of the Product in the Field in the Licensed
Territory.  As provided in Section 3.2(c),
AMAG shall notify the JDC of its intent to conduct any studies of the Product
(other than the Initial Studies, Future Required Studies, U.S. Studies or
Pediatric Studies) that AMAG intends to use in obtaining or maintaining
Regulatory Approval outside the Licensed Territory in the Field and under which
AMAG may grant Takeda rights (the “Other AMAG
Studies”), at the first JDC meeting following AMAG’s decision to
conduct such studies.  Takeda shall have
the right to use data from an Other AMAG Study included in the AMAG Technology
only if Takeda bears a share of the costs and expenses for such study as
provided in Section 4.9(c).  Upon
Takeda’s request, AMAG shall provide Takeda with a reasonably detailed plan and
budget for the conduct of such Other AMAG Study.  At any time between receipt of such plan and
budget and completion (i.e., delivery of the final study report) of the Other
AMAG Study, Takeda shall have the right to elect to opt in to such Other AMAG
Study by providing written notice to AMAG. 
Upon such election, Takeda shall [***], such Other AMAG Study shall be a
“Takeda  Opt-In Study”, and such Takeda Opt-In Study shall be included
in the Development Plan.  AMAG shall use
Commercially Reasonable Efforts to conduct such Takeda Opt-In Study in
accordance with the Development Plan.


 


4.6          Takeda
Product Development.  Takeda may, in its sole discretion, conduct
studies of the Product for the purpose of obtaining or maintaining Regulatory
Approval or for Commercializing the Product in the Licensed Territory that are
not Future Required Studies, such as Phase 4 Clinical Trials in the Licensed
Territory, in which it may grant AMAG rights (the “Takeda Studies”); provided, however, that Takeda may not
conduct any such studies that would be likely to have a material adverse impact
on the product profile, safety or efficacy of the Product in the Field outside
the Licensed Territory.  AMAG shall have
the right to use data from a Takeda Study only if AMAG bears a share of the
costs and expenses for such study as provided in Section 4.9(c).  As provided in Section 3.2(c), Takeda
shall notify the JDC of its intent to conduct a Takeda Study at the first JDC
meeting following Takeda’s decision to conduct such study.  Upon AMAG’s request, Takeda shall provide
AMAG with a reasonably detailed plan and budget for the conduct of such Takeda
Study.  At any time between receipt of such
plan and budget and completion (i.e., delivery of the final study report) of
the Takeda Study, AMAG shall 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


27

















 


have the right to elect to opt
in to such Takeda Study, by providing written notice to Takeda.  Upon such election, AMAG shall [***], such
Takeda Study shall be an “AMAG  Opt-In Study”, and such AMAG Opt-In Study
shall be included in the Development Plan. 
Takeda shall use Commercially Reasonable Efforts to conduct such AMAG
Opt-In Study in accordance with the Development Plan.


 


4.7          Development
Diligence.  Takeda shall
use Commercially Reasonable Efforts to Develop (either through AMAG, a Third
Party sublicensee or by Takeda or its Affiliates with respect to a study that
Takeda conducts or assumes) and seek Regulatory Approval of the Product for use
in the Field throughout the Licensed Territory in accordance with the terms and
conditions of this Agreement.  Takeda
shall conduct all Development activities that Takeda assumes in accordance with
the then-current Development Plan.  With
respect to any country in the Licensed Territory for which Takeda has not
initiated Development activities or the Development Plan has not included
activities for such country, Takeda shall use Commercially Reasonable Efforts
to determine whether to conduct Development activities and seek Regulatory
Approval for the Product in such country.


 


4.8          Reports.  The Parties shall
discuss the status, progress and results of each Party’s Development activities
under the Development Plan at meetings of the JDC.  In addition, each Party shall update the JDC
at each meeting on all Development activities such Party is conducting for the
Product outside the scope of the Development Plan.  Upon any discontinuation of the JDC pursuant
to Section 3.3(d), each Party shall keep the other party informed as to
progress of the Development activities for the Product by providing such other
Party with written quarterly reports summarizing the work performed and the
timelines regarding such activities.


 


4.9          Development
Costs.


 


(a)           Initial
Studies, U.S. Studies, Pediatric Studies.


 


(i)            Subject
to Sections 4.9(a)(ii), 4.9(a)(iii) and 4.9(b)(i), AMAG shall be solely
responsible for all costs and expenses it incurs to conduct the Initial
Studies, U.S. Studies and Pediatric Studies. 
AMAG acknowledges that based on Regulatory Authority communications as
of the Effective Date, the Initial Studies are highly beneficial to support
Regulatory Approval and Commercialization in the Field in the Licensed
Territory.  AMAG shall keep complete and
accurate records of all Out-of-Pocket Costs it incurs to conduct the Initial
Studies.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


28

















 


(ii)           If
Takeda assumes responsibility for an Initial Study pursuant to Section 4.4(a)(ii),
[***], Within thirty (30) days after the end of each calendar quarter during
which Takeda is conducting an Initial Study, Takeda shall provide the JDC with
a reasonably detailed statement setting forth all [***].


 


(iii)         [***]


 


(b)                                  Changes to Initial Studies, U.S. Studies, Pediatric Studies;
Future Required Studies.


 


(i)              [***] All Development activities conducted by a Party
for an Increase in Scope shall be in accordance with the Development Plan, and
the other Party shall have the right to use the resulting data pursuant to the
licenses granted in this Agreement.


 


(ii)           Within thirty (30) days after the end of each calendar
quarter during which AMAG, Takeda and/or Takeda’s sublicensee is conducting
Development activities resulting from an Increase in Scope, AMAG and/or Takeda,
as applicable, shall provide the JDC with a reasonably detailed statement
setting forth [***].


 


(c)                                  Opt-In Studies. 
Within thirty (30) days after the end of each calendar quarter in which
an AMAG Opt-In Study or Takeda Opt-In Study (each, an “Opt-In Study”) is conducted, the Party
conducting such Opt-In Study shall provide the other Party with a reasonably
detailed statement setting forth all Out-of-Pocket Costs it incurred in such
calendar quarter to conduct such Opt-In Study, and an invoice for such other
Party’s share of such costs.  In
addition, if such invoice is the first invoice for such Opt-In Study following
the non-funding Party’s election to opt in to such study, the Party conducting
the Opt-In Study shall include in such invoice the other Party’s share of all Out-of-Pocket
Costs previously incurred to conduct such Opt-In Study.  The other Party shall pay each such invoice
within thirty (30) days after receipt thereof; provided, however, that
[***].


 


4.10        Delayed Opt-In. 
If Takeda fails to elect to pay a portion of the Out-of-Pocket Costs for
the conduct of any Other AMAG Study under Section 4.5, or if AMAG fails to
elect to pay a portion of the Out-of-Pocket Costs for the conduct of any Takeda
Study under Section 4.6, in each case within the applicable time period,
then within thirty (30) days after completing any such study, the Party
conducting such study shall provide the other Party with (a) a summary of
all data and results generated from such study, and (b) a reasonably
detailed statement setting forth all Out-of-Pocket Costs incurred to conduct
such study (the “Opt-In Costs”).  Within sixty (60) days after receiving such
summary and statement, the non-funding Party shall have the right to opt in to
such study, upon which such study shall become a Takeda Opt-In Study or AMAG
Opt-In Study, as applicable, by providing irrevocable written notice to the
funding Party and [***].  Upon such opt
in, the Party opting in shall have the right to use all results, data and other



 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


29

















 


Information generated under such study for all
purposes relating to Development and Commercialization of the Product in its
respective territory (i.e., the Licensed Territory in the case of Takeda under
the licenses granted herein and outside the Licensed Territory in the case of
AMAG), and such data and results shall thereafter be included within the
definition of the other Party’s Know-How for purposes of the licenses granted
in Article 2.


 


4.11        Data Exchange and Use.


 


(a)           Initial Studies, U.S. Studies,
Pediatric Studies and Future  Required Studies.  AMAG shall promptly provide Takeda with
copies of all data and reports with respect to the conduct of each Initial
Study, U.S. Study, Pediatric Study and Future Required Study as such data and
reports become available.  Takeda
acknowledges and agrees that AMAG may share any and all such Information with
AMAG’s Affiliates and Third Party collaborators and that AMAG and such
Affiliates and collaborators may use, free of charge, any such data for
developing and commercializing the Product outside the Licensed Territory or
outside the Field, including associated regulatory activities, subject to the
rights granted to Takeda under this Agreement for the Product in the Field and
in the Imaging Field (subject to Section 2.4) in the Licensed
Territory.  Takeda shall have the right
to use all results, data and other Information generated under each such study
for all purposes relating to Development and Commercialization of the Product
in the Field in the Licensed Territory, and such data and results shall be AMAG
Know-How subject to the licenses granted to Takeda in Section 2.1, subject
to [***].  For the
avoidance of doubt, if Takeda conducts any such study, AMAG shall have the
right to use all results, data and other Information generated under such study
for all purposes relating to Development, Manufacture and Commercialization of
the Product outside the Licensed Territory, and such data and results shall, to
the extent not included in the Product Inventions, be Takeda Know-How subject
to the licenses granted to AMAG in Section 2.2.


 


(b)           Takeda Studies and Other AMAG Studies. 
With respect to the Takeda Studies and the Other AMAG Studies,
notwithstanding the licenses granted in Sections 2.1 and 2.2, the non-funding
Party shall have no rights to use any data resulting from, or reference any
Regulatory Materials relating to, any such study (and it shall not be included
within the definition of the funding Party’s Know-How or Patents), except with
respect to safety or other information necessary to support such non-funding
Party’s adverse event reporting requirements with Regulatory Authorities in its
respective territory (i.e., outside the Licensed Territory for AMAG, and the
Licensed Territory for Takeda), unless and until such non-funding Party opts in
under the terms of Section 4.5, 4.6 or 4.10.  Following an opt-in, the Party opting in
shall have the right to use all results, data and other Information generated under
the applicable Opt-In Study for all purposes relating to Development and
Commercialization of the Product in its territory (i.e., the Licensed Territory
for Takeda, and outside the Licensed Territory for AMAG),


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


30
















 


and such data and results
shall thereafter be included within the definition of such Party’s Information
and Patents for purposes of the licenses granted in Article 2.


 


(c)           Ownership
of Information.  All data
and reports disclosed by one Party to the other under this Agreement shall be
deemed Confidential Information of the disclosing Party, subject to Articles 9
and 12 and the permitted uses and disclosures described in this Section 4.11
and disclosure to any Regulatory Authority in connection with a Party’s
obligations under Article 5.


 


4.12        Cooperation;
Compliance with Laws.  Each Party
shall conduct its activities under this Agreement in good scientific manner and
in compliance in all material respects with all applicable Laws, including
applicable national and international (e.g.,
ICH, GCP, GLP, GPvP, and GMP) guidelines.


 


4.13        Records,
Reports and Information.  Each
Party shall maintain complete, current and accurate records of all Development
activities conducted by it hereunder, and all data and other Information
resulting from such activities.  Such
records shall fully and properly reflect all work done and results achieved in
the performance of the Development activities in good scientific manner
appropriate for regulatory purposes. 
Each Party shall document all non-clinical Studies and clinical trials
in formal written study reports according to applicable national and
international (e.g., ICH, GCP,
GLP, GPvP, and GMP) guidelines.  Subject
to restrictions on data access under Section 4.11, each Party shall have
the right to review such records, including trial management files, maintained
by the other Party at reasonable times, upon written request, which shall not
exceed once a year.


 


ARTICLE 5


 


REGULATORY MATTERS


 


5.1          Data and
Information Transfer.


 


(a)           Initial
Data Transfer.  As soon as
practicable but not later than three (3) months after the Effective Date,
AMAG shall provide Takeda (i) copies of all filings contained within the
Regulatory Materials of AMAG generated as of the Effective Date and relating to
the Product in the Field and relevant to the Licensed Territory, and (ii) access
to the clinical databases and copies of the study reports from those clinical
trials set forth on Schedule 5.1, including any updates to such
databases and reports as such updates become available to AMAG, to the extent
that they relate to the Product in the Field.


 


(b)           CMC
Information. 
Notwithstanding anything to the contrary in this Agreement or the Supply
Agreement, AMAG shall disclose Information related to CMC for the Product and
necessary to support Regulatory Approvals (“CMC
Information”) to Takeda only to the extent that Takeda requires such
CMC Information to comply with applicable Laws, and only to those certain
individuals designated to receive CMC Information on behalf of Takeda (the “CMC Recipients”).  The CMC Recipients shall not have the right
to disclose CMC Information to any other Takeda personnel.  To the extent applicable in any regulatory


 


31

















 


jurisdiction in the Licensed
Territory, AMAG shall have the right to timely file or otherwise provide CMC
Information directly to a Regulatory Authority, and Takeda shall reasonably
cooperate with AMAG in any such filing. 
If a regulatory jurisdiction does not provide a procedure whereby AMAG
may directly submit such CMC Information, then AMAG shall provide to the CMC
Recipients the relevant CMC Information, and Takeda shall have the right to
file any such CMC Information to the extent required by applicable Laws,
subject to the terms of this Section 5.1(b).  To the extent that Takeda provides any such
CMC Information to a Regulatory Authority, Takeda shall disclose only what is
required to be disclosed, shall take reasonable measures to protect the
confidentiality of such Information to the extent permitted by a Regulatory
Authority, and shall not disclose any such Information without AMAG’s prior
written approval of the form and content of such disclosure except to the
extent required by a Regulatory Authority. 
In addition, notwithstanding Article 12, Takeda shall not have the
right to disclose such CMC Information as provided in Section 12.1, and
instead shall have the right to disclose such information only to a Regulatory
Authority under the terms of this Section 5.1(b).


 


5.2          Regulatory
Responsibilities.


 


(a)           The Party with
primary responsibility for preparing, filing and holding Regulatory Materials
for the Product in a particular country or territory in the Licensed Territory
with respect to the Product shall be referred to as the “Regulatory Lead”.  Subject to Section 14.2(b)(ii), AMAG
shall be the Regulatory Lead for the Product with respect to the EMA,
Swissmedic and Health Canada, unless and until Takeda elects to assume such
responsibility pursuant to Section 5.2(b). 
Takeda, or its sublicensee(s), pursuant to Section 2.1(c)(ii) and
(iii), shall be the Regulatory Lead for the Product in all other countries in
the Licensed Territory, unless the Parties mutually agree that AMAG shall be
the Regulatory Lead in any such country. 
Except as provided in Section 5.2(f), the Regulatory Lead with
respect to a particular territory shall be the sole owner of and shall hold in
its name all Regulatory Materials for the Product in such territory; provided,
however, that Takeda shall solely own all promotional materials for the Product
throughout the Licensed Territory.  The
Regulatory Lead shall cooperate with the other Party, through the JDC or other
committee or subcommittee formed by the Parties, in conducting its activities
under this Article 5.


 


(b)           Takeda shall
have the right, upon reasonable advance written notice to AMAG, but in no event
less than [***] written
notice, to become the Regulatory Lead for the Product with respect to the EMA,
Swissmedic and/or Health Canada; provided that Takeda shall become the
Regulatory Lead for the Product with respect to the EMA, Swissmedic and Health
Canada as soon as reasonably practicable but not later than First Commercial
Sale of the Product in Europe.  Upon
Takeda’s becoming Regulatory Lead, the Parties shall establish a timeframe for
AMAG to transfer and assign to Takeda all Regulatory Materials for the Product
with respect to the EMA, Swissmedic and/or Health Canada, including the IND for
the Product with respect to 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


32

















 


the EMA, Swissmedic and/or
Health Canada.  In accordance with such
timeframe, the Parties shall execute such documents and take such actions as
are reasonably necessary to effectuate the foregoing transfer and assignment of
such Regulatory Materials.  Takeda shall
be responsible for all reasonable Out-of-Pocket Costs incurred for such
transfer and assignment.


 


(c)           Takeda and AMAG shall, through the JDC,
establish the regulatory strategy for the Product in the Licensed Territory,
including a plan and schedule of regulatory activities to be performed by the
Parties in connection with obtaining approval for the initial MAA for the
Product in the Licensed Territory and for amendments or supplements
thereto.  In establishing such strategy,
the JDC shall discuss each Party’s interpretation of applicable regulatory
guidance, regulatory precedents, scientific advice and study data.  Each Party shall assist and cooperate with
the other Party as such other Party may reasonably request in connection with
the preparation and filing of such Regulatory Materials in a timely manner.


 


(d)           The Regulatory
Lead shall provide the other Party with copies of any proposed Regulatory
Materials to be submitted (other than routine correspondence) at least ten (10) business
days in advance of submission and shall reasonably consider any comments
thereto provided by the other Party, to the extent practicable.


 


(e)           The Regulatory
Lead shall inform each applicable Regulatory Authority in the Licensed
Territory that two (2) representatives of the other Party will attend and,
to the extent permitted by applicable Laws, participate in all major meetings
between the Regulatory Lead and such Regulatory Authority, subject to the
confidentiality provisions set forth under Article 12.  The Regulatory Lead shall timely inform the
other Party of any such scheduled meetings, as soon as practicably possible.


 


(f)            AMAG, in
consultation with Takeda, shall be primarily responsible for the preparation of
any components of Regulatory Materials to be filed by Takeda that relate to the
Manufacture of Product and for communicating with Regulatory Authorities in the
Licensed Territory regarding Manufacture of Product.  Takeda shall provide AMAG with at least [***] notice of any intended
filing date of Regulatory Materials containing components to be prepared by
AMAG.  Takeda shall cooperate with AMAG
and take such actions as AMAG may reasonably request in connection with the foregoing
activities and communications as related to the Manufacture of Product for the
Licensed Territory.


 


5.3          Regulatory
Costs and Expenses.  [***]


 


5.4          Preparation
of Regulatory Materials.  The Parties
shall use Commercially Reasonable Efforts, in compliance with applicable Laws
and other regulatory obligations related to Development and Regulatory Approval
in the Licensed Territory, to prepare and file the 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


33

















 


appropriate Regulatory Materials
for those countries for which Regulatory Approval is sought under this
Agreement.


 


5.5          Rights of
Reference to Regulatory Materials.  Each Party hereby grants to the other Party a
right of reference to all Regulatory Materials filed by such Party for the
Product subject to the scope of the licenses granted under Sections 2.1 and
2.2, including, for the avoidance of doubt, all such Regulatory Materials filed
by AMAG for Regulatory Approval of the Product in the United States and all
supplemental filings related thereto, and all “Certificate(s) of
Pharmaceutical Product” and/or “Certificate(s) of Free Sales” resulting
from Regulatory Approval of such Product, solely for the purpose of seeking,
obtaining and maintaining Regulatory Approvals for, and the Commercialization
of, the Product in the Licensed Territory and the Field, consistent with the
roles of the Parties set forth in this Agreement; provided, however, that such
right of reference shall not include any Regulatory Materials to the extent
related to an Other AMAG Study that is not a Takeda Opt-In Study.  In addition, Takeda hereby grants to AMAG a
right of reference to all Regulatory Materials filed by Takeda in the Licensed
Territory for the purpose of AMAG, its Affiliates or any Third Party partners
or licensees developing and obtaining and/or maintaining regulatory approvals
anywhere in the world for the Product in the Field outside the Licensed
Territory; provided, however, that such right of reference shall not include
any Regulatory Materials to the extent related to a Takeda Study that is not an
AMAG Opt-In Study.


 


5.6          Adverse
Event Reporting and Safety Data Exchange.  The Parties agree that each Party will be
responsible for the monitoring of all clinical experiences for any clinical
trial it conducts.  AMAG will be
responsible for maintaining the global safety database and filing all required
reports for the Product to Regulatory Authorities outside the Licensed
Territory throughout the Development of the Product.  Takeda will be responsible for filing all
required reports for the Product to the Regulatory Authorities in the Licensed
Territory throughout the Development of the Product, and if AMAG is the
Regulatory Lead, AMAG shall cooperate with Takeda as necessary for Takeda to
comply with applicable regulatory requirements. 
Each Party shall have the right to review all such information and
reports prepared or maintained by the other Party at reasonable times, upon
prior written request. The Parties shall cooperate to develop methods and/or procedures
for sharing safety information relating to such clinical experiences in
accordance with safety reporting requirements of the respective Regulatory
Authorities and as necessary for a Party to comply with applicable Laws.  In connection with such discussions, the
Parties may convene any joint working groups in the subject matter to provide
recommendations to the Parties.  Specific
details regarding the sharing and management of information of adverse events related
to the Development and the Commercialization of the Product both within and
outside the Licensed Territory will be delineated in a separate
pharmacovigilance and safety data exchange agreement (the “Pharmacovigilance Agreement”) that shall be
agreed to by the Parties by the earlier of three (3) months after the
Effective Date or one (1) month from the IND.  Until the Pharmacovigilance Agreement is
signed, AMAG shall provide Takeda with AMAG’s quarterly summary, when prepared
by AMAG, of AMAG’s monitoring of all clinical experiences for trials of the
Products, and such additional related details as reasonably requested by Takeda
to evaluate the information contained in the summary.  The Parties agree that the Pharmacovigilance
Agreement shall set forth the procedures by which each Party shall report 


 


34

















 


and maintain safety data and
prescription events monitoring, and shall contain customary terms for such an
agreement no less stringent than those required by ICH guidelines, applicable
Laws and applicable local regulatory requirements.


 


5.7          Regulatory Authority Communications Received by a Party.  Each Party
shall keep the other Party informed in a timely manner compliant with the
reporting requirements of Regulatory Authorities in the Licensed Territory, but
in any event within five (5) business days or such shorter time period set
forth in the Pharmacovigilance Agreement and/or SOPs, of notification of any
action by, or notification or other information which it receives (directly or
indirectly) from, any Regulatory Authority that: (i) raises any material
concerns regarding the safety or efficacy of the Product; (ii) indicates
or suggests a potential material liability of either Party to Third Parties in
connection with the Product; (iii) is reasonably likely to lead to a
recall or market withdrawal of the Product or a discontinuation of clinical
studies for the Product; or (iv) relates to expedited and periodic reports
of adverse events with respect to the Product, or Product Complaints, and in each
case which may have a material impact on Regulatory Approval or the continued
Commercialization of the Product anywhere in the world.  The other Party will fully cooperate with and
assist such Party in complying with regulatory obligations and communications,
including by providing to such Party, in a timely manner after a request, such
information and documentation in the other Party’s possession as may be
necessary or helpful for the Party to prepare a response to an inquiry from a
Regulatory Authority.  Each Party will
provide the other Party in a timely manner with a copy of all correspondence
received from a Regulatory Authority specifically regarding the matters
referred to above. The Pharmacovigilance Agreement shall set forth the
procedures by which each Party shall report and maintain safety data and
prescription events monitoring.  In
addition to the foregoing and subject to applicable Laws, AMAG shall promptly
provide Takeda with a copy of all material correspondence received from the FDA
and any material reply correspondence by AMAG, in each case that is reasonably
likely to have a material impact on the Development, Manufacture and/or
Commercialization of the Product in the Licensed Territory; provided that AMAG
may redact AMAG’s Confidential Information (including CMC Information) from any
such correspondence provided to Takeda, and if required by a Regulatory
Authority in the Licensed Territory, AMAG shall submit any such redacted
correspondence, without redactions, directly to such Regulatory Authority and
not to Takeda The Parties shall determine as soon as reasonably practicable
after the Effective Date what types of regulatory correspondence shall be
considered “material”.  In the event a
material correspondence relating to CMC Information occurs, the Parties shall
cooperate to adequately and appropriately address the matter and, if and only
to the extent necessary, AMAG shall disclose the subject CMC information to the
CMC Recipients, who shall not disclose it to any other Takeda personnel.


 


5.8          Regulatory
Safety Reporting.  Each Party shall be permitted, and have the
right, to perform pharmacovigilance activities and/or make such safety reports
to applicable Regulatory Authorities, to comply with applicable Laws,
international best practices for pharmacovigilance activities and/or other
activities that the Party, in its reasonable and good faith judgment, believes
necessary for the health, safety and protection of patients and/or clinical
trial subjects.  The Parties shall use
good faith efforts to agree to one opinion with respect to safety issues and to
report said opinion to safety boards of any nature, investigators, and to
applicable 


 


35

















 


Regulatory
Authorities; provided, however, nothing in this Section 5.8 shall limit
either Party’s right to report safety matters to Regulatory Authorities in its
applicable territory.


 


5.9          Audit.  If a Regulatory Authority desires to conduct
an inspection or audit of a Party’s facility or a facility under contract with
such Party with regard to the Product, then the audited Party shall notify the
other Party within [***] days, or if
not possible within such time period, then as soon as practicably possible,
after receipt of such notification of such audit or inspection and provide
copies of any materials provided to it by the applicable Regulatory Authority;
provided, that the audited Party shall not be required to notify the other
Party of audits or inspections that are of a routine nature or that do not relate
to the Product or the Field, except where such audits result in communications
or actions of such Regulatory Authority which have an impact upon the Product.
The audited Party shall cooperate, and shall use reasonable efforts to cause
the contract facility, if any, to cooperate, with such Regulatory Authority and
the other Party during such inspection or audit.  Following receipt of the inspection or audit
observations of such Regulatory Authority (a copy of which the audited Party
will immediately provide to the other Party), the audited Party will also
provide the other Party with copies of any written communications received from
Regulatory Authorities with respect to such facilities in a timely manner after
receipt, to the extent such written communications relate to the Product or the
Manufacture thereof, and will prepare the response to any such observations;
provided that AMAG may redact CMC Information from any such written
communications provided to Takeda.  The
audited Party will provide the other Party with a copy of any proposed response
to such communications and will implement such other Party’s reasonable
comments with respect to such proposed response; provided that AMAG may redact
CMC Information from any such proposed response provided to Takeda.  The audited Party agrees to conform its
activities under this Agreement to any commitments made in such a
response.  In the event a Product
Complaint relating to CMC Information occurs, the Parties shall cooperate to
adequately and appropriately resolve the Product Complaint and, if and only to
the extent necessary, AMAG shall disclose the subject CMC information to the
CMC Recipients, who shall not disclose it to any other Takeda personnel.


 


ARTICLE 6




COMMERCIALIZATION


 


6.1          Overview of
Commercialization in the Licensed Territory.  Subject to the terms and conditions of this Article 6,
as between the Parties, Takeda will be responsible for all aspects of the
Commercialization of the Product in the Field in the Licensed Territory,
including but not limited to: (a) developing and executing a commercial
launch and pre-launch plan, (b) marketing and promotion; (c) booking
sales and distribution and performance of related services; (d) handling
all aspects of order processing, invoicing and collection, inventory and
receivables; 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24B-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


36

















 


(e) providing customer
support, including handling medical queries, and performing other related
functions; and (f) conforming its practices and procedures in all material
respects to applicable Laws relating to the marketing, detailing and promotion
of the Product in the Field in the countries of the Licensed Territory.  Takeda shall bear all of the costs and
expenses incurred in connection with all such Commercialization activities.


 


6.2          Commercialization
Plan for Licensed Territory.  Takeda shall prepare and submit to the JSC
for review and comment a detailed plan for Commercialization of the Product in
the Licensed Territory (the “Commercialization
Plan”).  The Commercialization
Plan will include projections, timelines and a reasonably detailed description
of Takeda’s Commercialization activities, including Product life cycle
management,  market research, sales
training, distribution channels, customer service and sales force matters
related to the launch and sale of the Product in the Field and in the Licensed
Territory, but excluding Manufacturing. 
The initial Commercialization Plan shall be delivered to the JSC not
later than [***].  On at least an annual basis, Takeda shall
update and amend, as appropriate, the then-current Commercialization Plan.  Takeda shall submit all updates and
amendments to the Commercialization Plan to the JSC for review and comment.  AMAG, at its sole discretion, shall assist
Takeda, if reasonably requested by Takeda, in preparing and developing the
strategy for commercial Product positioning and messaging for the Product for
the Licensed Territory, under oversight by the JSC.


 


6.3          Pricing.  Takeda shall have the sole right to determine
all pricing of the Product in the Licensed Territory in the Field.  Notwithstanding anything in this Agreement
express or implied to the contrary, AMAG shall not have any right to direct,
control, or approve Takeda’s pricing of the Product for the Licensed Territory
in the Field.  The provision to AMAG of
any pricing data in connection with the Commercialization Plan, which shall
occur only if permitted by applicable Laws, is for informational purposes only.


 


6.4          Commercial
Diligence.


 


(a)           Takeda shall
use Commercially Reasonable Efforts to Commercialize the Product in the Field
in each country in the Licensed Territory in accordance with this Agreement
following Regulatory Approval of the Product in such country.


 


(b)           Without
limiting Takeda’s obligation under subsection (a), Takeda shall achieve First
Commercial Sale of the Product in each country of [***]; provided that failure
to achieve such First Commercial Sale within such time shall not be a breach of
this Agreement to the extent directly attributable to existence of the
following conditions and only for so long as such conditions remain in
effect:  (i) AMAG’s breach of its
obligations under this Agreement; (ii) a determination by Takeda in its
discretion in good faith (and after consultation with AMAG) 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


37

















 


to delay the First
Commercial Sale of the Product [***] if the Product
label is impaired or restricted, or if price reimbursement is deemed to be not
commercially viable; or (iii) force majeure events as and to the extent
set forth in Section 16.2.


 


6.5          Reports.  In addition to Takeda’s obligations under Section 6.2,
Takeda shall update the JSC at each meeting with respect to lifecycle
management of the Product and its significant Commercialization activities with
the Product in the Licensed Territory. 
Each such update shall be in a form to be agreed by the JSC and shall
summarize Takeda’s significant Commercialization activities with respect to the
Product in the Licensed Territory pursuant to this Agreement, include a
forecast for the following year’s sales of the Product in the Licensed
Territory, and describe major activities with respect to the distribution and
sales channels for the Product.


 


6.6          Tracking
Sales of Product in the Field and Outside the Field.


 


(a)           Measurement;
Payment.  The Parties recognize the
possibility that customers or other Third Parties may purchase a Product sold
by AMAG or a Third Party that has received Regulatory Approval in the Licensed
Territory for use outside the Field and is sold for use outside the Field (a “Non-Field Product”) and use such Non-Field
Product off-label in the Field in the Licensed Territory (such use being the “Off-label Use of Non-Field Product”).  If Takeda believes that Off-label Use of
Non-Field Product is occurring in any country in the Licensed Territory, Takeda
may notify the JSC, providing reasonable evidence for such belief (such as data
from a commercially available prescription claims database).  The JSC shall promptly thereafter meet to
discuss such evidence and establish a mechanism to track sales of such
Non-Field Product in the Licensed Territory [***].


 


(b)           Dispute
Resolution.  If the JSC
cannot agree on: (i) the process and methodology to be implemented by the
Parties in tracking sales of Non-Field Products in the Licensed Territory, (ii) the
extent of Off-label Use of Non-Field Product, or [***], then in each such case,
at the election of either Party, the Parties shall resolve such dispute in
accordance with the provisions of Exhibit F.


 


6.7          Product
Trademarks and House Marks.


 


(a)           Product
Trademarks.  The JSC
shall determine the Product-related trademarks to be used in connection with
Commercializing the Product in the Licensed Territory, and shall give due
consideration to the AMAG Product Marks. 
Takeda may submit to the JSC for review, comment, and approval proposed
trademarks different from or in addition to the AMAG Product Marks for use in a
country or region in the Licensed Territory. 
Subject to JSC approval, Takeda shall amend the Commercialization Plan
to include any such new trademarks. 
Takeda shall own all right, title, and interest in and to all trademarks
developed by either Party 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


38

















 


under this Agreement after
the Effective Date for use in connection with Commercializing the Product in
the Licensed Territory (the “New Product
Marks”).  Takeda shall be
solely responsible, at its expense, for filing, prosecuting, maintaining,
defending and enforcing the New Product Marks, provided, however, that Takeda
shall provide AMAG reasonable opportunity to review and comment on such
prosecution, maintenance, defense and enforcement of the New Product Marks.  AMAG shall be solely responsible, at its
expense, for filing, prosecuting, and maintaining the AMAG Product Marks,
provided, however, that AMAG shall provide Takeda reasonable opportunity to
review and comment on such prosecution, maintenance, defense and enforcement of
the AMAG Product Marks with respect to the Licensed Territory.


 


(b)           House
Marks.  To the extent allowable by
applicable Laws, Product packaging, promotional materials and Product labeling
for use in the Licensed Territory shall carry, (i) one or more of the AMAG
House Marks, subject to Takeda’s reasonable approval of the size, position, and
location thereof, and (ii) at Takeda’s sole discretion, one or more of
Takeda’s trademarks or trade names (the “Takeda
Marks”).  The Parties agree
that the Takeda Marks and the AMAG House Marks shall be displayed under a
general principle of co-prominence.  AMAG
shall own all right, title and interest in the AMAG House Marks and shall be
solely responsible, at its expense, for filing, prosecuting, and maintaining
the AMAG House Marks.  Takeda shall own
all right, title and interest in the Takeda Marks and shall be solely
responsible, at its expense, for filing, prosecuting, and maintaining the
Takeda Marks.  Subject to the terms of
this Agreement, AMAG hereby grants to Takeda a royalty-free, non-exclusive
license to use and display the AMAG House Marks solely in connection with the
Commercialization of the Product in the Field in the Licensed Territory.  If pursuant to Section 6.7(a) AMAG
Product Marks are selected by Takeda to be used in connection with
Commercializing the Product in the Licensed Territory, AMAG hereby grants to
Takeda a royalty-free, exclusive license to use and display such AMAG Product
Marks solely in connection with the Commercialization of the Product in the
Field in the Licensed Territory, subject to the terms of this Agreement. Such
licenses may be sublicensed by Takeda to an Affiliate or a Third Party
sublicensee of Takeda’s right to Commercialize the Product granted in Section 2.1(a)(i).


 


(c)           Inspection.  From time to time during the Term, upon
AMAG’s reasonable request, Takeda shall provide AMAG with samples of the final
finished Product sold by Takeda or its Affiliates or sublicensees in the
Licensed Territory.  AMAG shall use such
Product samples solely to inspect the quality of such Products and use of the
AMAG Product Marks and AMAG House Marks.


 


(d)           No
Inconsistent Acts.  Takeda
acknowledges AMAG’s exclusive ownership of the AMAG Product Marks and AMAG
House Marks and agrees not to take any action inconsistent with such
ownership.  Takeda shall not use any AMAG
Product Mark or AMAG House Mark in a way that would adversely affect its
value.  Takeda covenants that it shall
not use any trademark confusingly similar to any AMAG Product Mark or AMAG
House Mark in connection with any products (including the Product).  Takeda shall comply with reasonable policies
provided by AMAG from time to time to maintain the goodwill and value of the
AMAG Product Marks and AMAG House Marks. 
AMAG acknowledges Takeda’s exclusive ownership of the New Product Marks
and agrees not to take any action inconsistent with such 


 


39

















 


ownership and covenants that
it shall not use in the Licensed Territory any trademark confusingly similar to
any AMAG Product Mark and/or the New Product Mark used in connection with the
Commercialization of the Product in or outside the Field in the Licensed
Territory.


 


ARTICLE 7


 


MANUFACTURE AND SUPPLY


 


7.1          General
Supply Terms.  AMAG shall,
itself or through one or more Third Party contract manufacturers, Manufacture
the Product in finished form in unlabeled vials in accordance with the terms of
Section 7.2, including the performance of all manufacturing process
development and scale-up for the Product (and associated regulatory
activities), and shall supply to Takeda, and Takeda shall purchase from AMAG,
all of all of Takeda and its Affiliates’ and its/their sublicensees’
requirements of the Product for Development and Commercial activities as and to
the extent set forth in this Agreement and the Supply Agreement.  Takeda shall be responsible for labelling and
packaging all Product supplied by AMAG to Takeda under the Supply Agreement.


 


7.2          Supply
Agreement.  On or
before a date to be established by the JSC, the Parties shall enter into a
supply agreement and quality agreement governing the supply of Product to
Takeda in unlabeled finished form for clinical and commercial use, as well as
the quality control and quality assurance procedures thereon (collectively the
“Supply Agreement”) and any other
operational agreements and procedures as deemed necessary by the Parties for
such supply of the Product.  The terms of
such Supply Agreement shall be negotiated in good faith by the Parties in accordance
with the terms of Schedule 7.2.


 


7.3          Second
Source.  As of the Effective Date, the
Parties have agreed to a summary plan for sourcing Product attached hereto as Schedule
7.3 (the “Second Source Plan”)
for clinical and commercial use in the Licensed Territory from a Designated
Second Source Supplier.  AMAG shall
perform its activities under the Second Source Plan on a timely basis.  The Parties may amend the Second Source Plan
from time to time upon mutual written agreement, with such agreement not to be
unreasonably withheld.  Takeda shall have
the right under the Supply Agreement to obtain Product for use in the Licensed
Territory in accordance with Schedule 7.2.


 


7.4          Recalls and
Voluntary Withdrawals.  The
Parties shall exchange their internal standard operating procedures (“SOPs”) for conducting product recalls
reasonably in advance of the First Commercial Sale of Product in the Licensed
Territory, and shall discuss and resolve any conflicts between such SOPs and
issues relating thereto promptly after such exchange.  If either Party becomes aware of information
relating to any released Product that indicates that a unit or batch of Product
may not conform to the specifications thereof, or that potential adulteration,
misbranding, and/or other issues have arisen that relate to the safety or
efficacy of such released Product, it shall promptly so notify the other
Party.  To the extent Takeda requires
such information to comply with applicable Laws or to determine whether to
conduct a recall, AMAG shall promptly disclose to the CMC Recipients any CMC
Information related to such 


 


40

















 


nonconformance,
adulteration, misbranding or other related issue.  Takeda shall have the right, at its expense
(except as provided herein), to control any Product recall, field correction,
or withdrawal of any released Product in the applicable jurisdiction in the
Licensed Territory; provided that prior to Takeda’s becoming Regulatory Lead
with respect to EMA, Swissmedic and Health Canada, and for each country that
the Parties agree that AMAG shall be the Regulatory Lead, in each case pursuant
to Section 5.2, AMAG shall have the right to control any Product recall,
field correction, or withdrawal of any released Product in the applicable
jurisdiction and AMAG shall have the right to notify Takeda and request that
such action be taken as a result of the manufacture of the Product.  AMAG shall have the right, at its expense, to
control any Product recall, field correction, or withdrawal of any released
Product outside the Licensed Territory. 
AMAG shall be responsible for all costs incurred for any recall, field
correction, or withdrawal of any released Product for the Licensed Territory to
the extent such event of recall, field correction, or withdrawal is due to the
breach by AMAG of this Agreement or the Supply Agreement.  Takeda shall be responsible for all other
costs incurred for any recall, field correction, or withdrawal of any released
Product for the Licensed Territory. The procedures and consequences of such
recalls shall be defined in the Supply Agreement.  The Party having the right to control such
recall pursuant to this Section 7.4 may, at its sole discretion, take
appropriate courses of action, which shall be consistent with the internal SOPs
of such Party; provided, however, that such controlling Party shall promptly
notify the other Party of any recall action being considered and where
practicable, consider the views of the non-controlling Party prior to taking
any recall action.  Takeda shall maintain
complete and accurate records of any recall according to its then current SOPs
in the Licensed Territory for such periods as may be required by applicable
Laws, but in no event for less than three (3) years.


 


ARTICLE 8


 


COMPENSATION


 


8.1          Upfront Fee.  Within [***] after the Effective Date and in partial
consideration for the prior and future cost of developing the Product and
Takeda’s rights in and to the AMAG Technology licensed hereunder, Takeda shall
pay to AMAG a one-time upfront fee of sixty million Dollars ($60,000,000).  Such fee shall be nonrefundable and
non-creditable against any other payments due hereunder.


 


8.2          Development
Milestone Payments.  Takeda
shall make milestone payments to AMAG based on achievement of certain milestone
events for the Product as set forth in this Section 8.2, in partial
consideration for the prior and future cost of developing the Product.  Takeda shall pay to AMAG the amounts set
forth below within [***] following the achievement of the corresponding
milestone event.  Except with respect to
[***], each milestone payment by Takeda to AMAG hereunder shall be payable only
once, regardless of the number of times


 










[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


41




















 


achieved by the
Product.  Each such payment is
nonrefundable and non-creditable against any other payments due hereunder.


 


	
  Milestone Event

  	
   

  	
  Milestone Payment

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  



 


[***]


 


8.3          Commercialization
Milestone Payments in the Licensed Territory.  Takeda shall make the following one-time,
nonrefundable, non-creditable milestone payments to AMAG [***].  Takeda shall pay to AMAG such amount within
[***].  For clarity, the milestone
payments in this Section 8.3 shall be additive [***].


 


	
  Milestone Event

  	
   

  	
  Milestone Payment

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  



 










[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


42





















 


8.4          Royalties.


 


(a)           Royalty
Rates during Royalty Term. Subject to Sections 8.4(b) and 8.4(d) below,
and during the applicable Royalty Term, Takeda shall pay to AMAG a running
royalty at the following incremental royalty rates on aggregate Net Sales of
the Product during a Fiscal Year in the Licensed Territory.


 


	
  Net Sales in the Licensed Territory

  	
   

  	
  Tier Royalty Rate

  
	
  For
  that portion of Net Sales in a Fiscal Year less than or equal to [***] (Tier
  1)

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  For
  that portion of Net Sales in a Fiscal Year greater than [***] but less than
  or equal to [***] (Tier 2)

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  For
  that portion of Net Sales in a Fiscal Year greater than [***] but less than
  or equal to [***] (Tier 3)

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  For
  that portion of Net Sales in a Fiscal Year greater than [***] (Tier 4)

  	
   

  	
  [***]

  



 


(b)           [***]


 


(i)            [***]


 


(ii)           [***]


 


(iii)           [***]


 


(iv)          [***]


 


(v)            [***]


 


(c)           Clarification.  Takeda acknowledges that it will continue to
benefit from its license under, and the transfer to Takeda of certain elements
of, the AMAG Technology and AMAG Product Marks pursuant to this Agreement
(including the AMAG Know-How licensed to Takeda, and the regulatory data to be
provided to Takeda pursuant to this Agreement) as well as from Takeda’s own
development of Takeda Know-How derived from the practice of such license and
Takeda’s use of such AMAG Technology, even after the expiration of all AMAG
Patents claiming the Product in a particular country of the Licensed
Territory.  In addition, Takeda
acknowledges that the application of a uniform royalty structure for the
Licensed Territory throughout the Royalty Term, followed by a reduced royalty
after the expiration of the Royalty Term pursuant to Section 8.4(e), is
more convenient to the Parties, facilitates the payment of royalties, and
reduces accounting burdens on the Parties, as compared with a royalty structure
dependent on the expiration of AMAG Patents and use of AMAG Product Marks
during and after the Royalty Term. 
Accordingly, the Parties have agreed to apply the same 


 










[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


43





















 


royalty rate in the Licensed
Territory throughout the Royalty Term, subject to Sections 8.4(b) and
8.4(d), and a reduced royalty following the Royalty Term.  For the avoidance of doubt, the Net Sales of
the Product in a country after the Royalty Term expires in such country shall
not be included in the aggregate annual Net Sales for the calculation of a
royalty pursuant to Section 8.4(a) or 8.4(b) and shall be used
only to determine the royalty set forth in Section 8.4(e).


 


(d)           Reduction
of Royalty Following Entry of Generic Product.  During the applicable Royalty Term, the
royalty rates set forth in Section 8.4(a) for Net Sales in such
country for a particular Product shall be reduced by [***] at the end of the
first to occur [***] during which one or more Third Parties sells a number of
equivalent units of a Generic Product of the applicable Product in such country
of the Licensed Territory comprising, [***] of the aggregate combined number of equivalent
units of such Product and such Generic Product(s) sold in such month in
such country (“Generic Entry”).  If in any month thereafter the number of
equivalent units of Generic Product(s) sold decreases to [***] of the
aggregate combined number of equivalent units of such Product and such Generic
Product(s) sold in such month in such country, the royalty rate reduction
set forth in this Section 8.4(d) shall no longer apply (unless and
until the criteria set forth in the first sentence of this Section 8.4(d) again
applies).  All such determinations of
unit volume shall be based upon a mutually acceptable calculation method and
using market share (on unit number basis) data provided by a reputable and
mutually agreed upon provider, such as IMS Health.  By way of example, if [***], then the above
mentioned royalty reduction shall apply.


 


(e)           After
Royalty Term.  Following
the expiration of the Royalty Term in any country of the Licensed Territory,
Takeda shall pay to AMAG a royalty of [***] of Net Sales of such Product in
such country.


 


8.5          Third Party
Royalties.


 


(a)           AMAG
Obligations.  AMAG will be
responsible for all amounts owed to Third Parties after the Effective Date
pursuant to agreements with Third Parties regarding the Product entered into
prior to the Effective Date.  AMAG also
will be solely responsible for all amounts owed to Third Parties after the
Effective Date (A) pursuant to any future license or technology
acquisition agreement under which AMAG obtains rights to Third Party Patents or
Information (i) claiming the composition of matter, use or manufacture of
the Product as in existence as of the Effective Date; or (ii) covering
AMAG’s Manufacture of the Product and (B) paid in settlement or final
judgement of a claim that the composition of matter, use or manufacture of the
Product as in existence as of the Effective Date or AMAG’s Manufacture of the
Product infringes the Patent of such Third Party.


 


(b)           Takeda
Obligations.  Except as
provided in Section 8.5(a), Takeda will be solely responsible for all
amounts owed to Third Parties after the Effective Date pursuant to 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


44

















 


any future license or
technology acquisition agreement under which Takeda obtains rights to Third Party
Patents or Information related to the Development and Commercialization of the
Product by Takeda, its Affiliates and their respective sublicensees in the
Licensed Territory under this Agreement.


 


8.6          Royalty
Reports and Payment.  Within [***], Takeda shall provide AMAG
with a report containing the following information for the applicable calendar
month:  the amount of gross sales of
Product in the Licensed Territory, an itemized calculation of Net Sales in the
Licensed Territory showing deductions, to the extent practicable, provided for
in the definition of “Net Sales,” a calculation of the royalty payment due on
such sales, an accounting of the number of units and prices for Product sold,
the exchange rate for each country in which Product was sold, and [***] made in
accordance with the terms of Section 8.4(b).  Within [***], AMAG shall review and record
such information as it determines necessary under its internal financial
reporting procedures.  Within [***],
Takeda shall provide AMAG with a report containing the information described
above in respect of such calendar quarter for AMAG’s review.  In the event that either Party determines
that the calculation of Net Sales for a calendar quarter deviates from the amounts
previously reported to AMAG for any reason (such as, on account of additional
amounts collected or Product returns), Takeda shall reasonably cooperate with
AMAG to reconcile any such deviations to the extent necessary under applicable
legal or financial reporting requirements. 
Within [***], Takeda shall pay all amounts due to AMAG pursuant to Section 8.4
with respect to Net Sales by Takeda, its Affiliates and their respective
sublicensees for such calendar quarter. AMAG understands that some of the
reductions may need annual review, so at the end of the each Fiscal Year,
necessary reconciliation, if any, for true-up shall be made.


 


8.7          Foreign
Exchange.  The rate of
exchange to be used in computing the amount of currency equivalent in Dollars
owed to a Party under this Agreement shall be the quarterly average exchange
rate between each currency of origin and Dollars as reported by Bloomberg on
the last business day of the calendar quarter for which the relevant royalty
payment applies.


 


8.8          Payment
Method; Late Payments.  All
payments due to a Party hereunder shall be made in Dollars by wire transfer of
immediately available funds into an account designated by such Party.  If such Party does not receive payment of any
sum due to it on or before the due date, simple interest shall thereafter accrue
on the sum due to such Party until the date of payment at the per annum rate of
[***].


 


8.9          Records;
Audits.  Each Party will maintain
complete and accurate records in sufficient detail to permit (a) AMAG to
confirm the accuracy of the calculation of royalty payments, and (b) with
respect to any Increase in Scope, Takeda Opt-In Studies and AMAG Opt-In
Studies, Takeda and AMAG to confirm the accuracy of the calculation of
Out-of-Pocket Costs under this Agreement. 
Upon reasonable prior notice, such records shall be available during 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


45

















 


regular business hours for a
period of three (3) years from the end of the Fiscal Year to which they
pertain for examination at the expense of the auditing Party, and not more
often than once each calendar year, by an independent certified public
accountant selected by the auditing Party and reasonably acceptable to the
audited Party, for the sole purpose of verifying the accuracy of the financial
reports and/or invoices furnished by the audited Party pursuant to this
Agreement.  Any such auditor shall not
disclose the audited Party’s Confidential Information, except to the extent
such disclosure is necessary to verify the accuracy of the financial reports
furnished by such Party or the amount of payments due by or to such Party under
this Agreement.  Any amounts shown to be
owed but unpaid shall be paid within thirty (30) days from the accountant’s
report, plus interest (as set forth in Section 8.8) from the original due
date.  Any amounts shown to have been
overpaid shall be refunded within thirty (30) days from the accountant’s
report.  The auditing Party shall bear
the full cost of such audit unless such audit discloses an underpayment by the
audited Party of more than five percent (5%) of the amount due, in which case
the audited Party shall bear the full cost of such audit.


 


8.10        Taxes.


 


(a)           Cooperation
and Coordination.  The Parties
acknowledge and agree that it is their mutual objective and intent to
appropriately calculate, to the extent feasible and legal, taxes payable with
respect to their collaborative efforts under this Agreement and that they shall
use all commercially reasonable efforts to cooperate and coordinate with each
other to achieve such objective.


 


(b)           Payment of
Tax.  A Party receiving a payment
pursuant to this Article 8 shall pay any and all taxes levied on such
payment.  If applicable Laws require that
taxes be deducted and withheld from a payment made pursuant to this Article 8,
the remitting Party shall (i) deduct those taxes from the payment; (ii) pay
the taxes to the proper taxing authority; and (iii) send evidence of the
obligation together with proof of payment to the other Party within ninety (90)
days following that payment.


 


(c)           Tax
Residence Certificate.  A
Party (including any entity to which this Agreement may be assigned, as
permitted under Section 16.5) receiving a payment pursuant to this Article 8
shall provide the remitting Party appropriate certification from relevant
revenue authorities that such Party is a tax resident of that jurisdiction, if
such receiving Party wishes to claim the benefits of an income tax treaty to
which that jurisdiction is a party.  Upon
the receipt thereof, any deduction and withholding of taxes shall be made at
the appropriate treaty tax rate.


 


(d)           Assessment.  Either Party may, at its own expense, protest
any assessment, proposed assessment, or other claim by any Governmental
Authority for any additional amount of taxes, interest or penalties or seek a
refund of such amounts paid if permitted to do so by applicable Laws.  The Parties shall cooperate with each other
in any protest by providing records and such additional information as may
reasonably be necessary for a Party to pursue such protest.


 


46

















 


ARTICLE 9


 


INTELLECTUAL PROPERTY MATTERS


 


9.1          Ownership
of Inventions; Assignment.  Each Party shall own all right, title, and
interest in and to any inventions made solely by such Party’s employees,
agents, independent contractors and sublicensees in the course of conducting
its activities under this Agreement during the Term, together with all
intellectual property rights therein, including any rights to applications or
other protections for any of the foregoing. 
The Parties shall jointly own all inventions made jointly by the
employees, agents, independent contractors or sublicensees of each Party, in
accordance with joint ownership interests of co-inventors under U.S. patent
laws (that is, each Party shall have full rights to license, assign and exploit
such joint inventions (and any patents arising therefrom) anywhere in the
world, without any requirement of gaining the consent of, or accounting to, the
other Party), subject to the licenses granted herein and subject to any other
intellectual property held by such other Party; provided, however, that Takeda
shall not have the right to practice any jointly owned invention in any
activities related to a product that competes with the Product.  The Parties shall determine which Party will
file, prosecute and maintain the Patents claiming or covering such jointly
owned inventions.  Inventorship shall be
determined in accordance with U.S. patent laws. 
Notwithstanding the foregoing, Takeda agrees to assign and hereby
assigns and transfers to AMAG all of its right, title and interest in and to
any such solely owned or jointly owned inventions that relate to the
composition of matter, manufacture or use of the Product (“Product Inventions”), and agrees to take,
and to cause its employees, agents, consultants and sublicensees to take, all
further acts reasonably required to evidence such assignment and transfer to
AMAG, at AMAG’s reasonable expense. 
Takeda hereby appoints AMAG as its attorney-in-fact to sign such
documents as AMAG deems necessary for AMAG to obtain ownership and to apply
for, secure, and maintain patent or other proprietary protection of such
Product Inventions if AMAG is unable, after reasonable inquiry, to obtain
Takeda’s (or its employee’s or agent’s) signature on such a document.  Takeda hereby waives, on behalf of itself,
its parent, subsidiaries, Affiliates and partners as well as all of its
employees and independent contractors, any rights of first refusal it, he, or
she may have with respect to any contemplated technology transfer, in whole or
in part, of the Product Inventions or any related patent, patent application,
copyright or copyright application related thereto as well as any right
accorded to it, him, or her, by statute or otherwise, to use any Product
Invention or any Patent or copyright related thereto. All Patents claiming or
covering any Product Invention shall be referred to herein as “Product Patents.”


 


9.2          Disclosure
of Inventions.  Takeda
shall, and shall cause its sublicensees to, promptly disclose to AMAG any
invention disclosures, or other similar documents, submitted to it by its
employees, agents or independent contractors describing inventions that may be
Product Inventions, and all Information relating to such inventions to the
extent necessary for the preparation, filing and maintenance of any Patent with
respect to such invention.


 


9.3          Prosecution
of Patents.


 


(a)           AMAG
Patents.  AMAG shall have the sole right
to prepare, file, prosecute and maintain the AMAG Patents at AMAG’s own costs
and expenses. 
AMAG shall 


 


47

















 


provide Takeda reasonable
opportunity to review and comment on such efforts regarding such AMAG Patents
in the Licensed Territory, including by providing Takeda with a copy of
material communications from any patent authority in the Licensed Territory
regarding such AMAG Patent(s), and by providing drafts of any material filings
or responses to be made to such patent authorities in advance of submitting
such filings or responses.  AMAG shall
reasonably consider such comments by Takeda in connection with the prosecution
of the AMAG Patents in the Licensed Territory. 
If AMAG determines in its sole discretion to abandon all claims in any
AMAG Patent in the Licensed Territory, then AMAG shall provide Takeda with
written notice of such determination within a period of time reasonably
necessary to allow Takeda to determine its interest in such AMAG
Patent(s).  In the event Takeda provides
written notice expressing its interest in obtaining such AMAG Patent(s), AMAG
shall assign and transfer to Takeda the ownership of, and interest in, such
AMAG Patent(s) in the Licensed Territory, such transfer to be at Takeda’s
reasonable expense (but without payment to AMAG).  Thereafter, Takeda shall bear [***], and AMAG shall bear [***]
of the costs of preparation, filing, prosecution and maintenance of such
assigned and transferred Patents, which shall not be treated as AMAG Patents
and shall be treated as Takeda Patents, and Takeda may prosecute such Takeda
Patents at its sole discretion; provided, however, in the event that Takeda
decides to abandon or not maintain any such Patent(s), Takeda shall promptly
provide AMAG with written notice of such decision.


 


(b)           Takeda
Patents.  Takeda shall be solely
responsible to file, prosecute and maintain Takeda Patents.  With respect to Takeda Patents under which
AMAG receives a royalty-bearing license pursuant to Section 2.2 hereof,
Takeda shall provide AMAG reasonable opportunity to review and comment on such
prosecution efforts regarding such Takeda Patents, including by providing AMAG
with a copy of material communications from any patent authority in the
Licensed Territory regarding such Takeda Patent(s), and by providing drafts of
any material filings or responses to be made to such patent authorities in
advance of submitting such filings or responses.  Takeda shall reasonably consider such
comments by AMAG in connection with the prosecution of Takeda Patents.


 


9.4          Patent Term
Extensions in the Licensed Territory.  The JSC will discuss and recommend for which,
if any, of the Patents within the AMAG Patents and Takeda Patents in the
Licensed Territory the Parties should seek Patent Term Extensions in the
Licensed Territory.  AMAG, in the case of
the AMAG Patents, and Takeda in the case of the Takeda Patents, shall have the
final decision-making authority with respect to applying for any such Patent
Term Extensions in the Licensed Territory, and will act with reasonable promptness
in light of the development stage of the Product to apply for any such Patent
Term Extensions, where it so elects; provided, however, that if in a particular
country or jurisdiction in the Licensed Territory only one such Patent can
obtain a Patent Term Extension, then the Parties will consult in good faith to
determine which such Patent should be the subject of efforts to obtain a Patent
Term Extension, and in any event AMAG’s decision on such matter will control in
the case of a 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


48

















 


disagreement.  The Party that does not apply for an
extension hereunder will cooperate fully with the other Party in making such
filings or actions, for example and without limitation, by making available all
required regulatory data and information and executing any required
authorizations to apply for such Patent Term Extension.  All expenses incurred in connection with
activities of each Party with respect to the Patent(s) for which such
Party seeks Patent Term Extensions pursuant to this Section 9.4 shall be
entirely borne by such Party.


 


9.5          Infringement
of Patents by Third Parties.


 


(a)           Notification.  Each Party shall promptly notify the other
Party in writing of any existing or threatened infringement in the Licensed
Territory of the AMAG Patents or Takeda Patents of which it becomes aware, and
shall provide all evidence in such Party’s possession demonstrating such
infringement.


 


(b)           Infringement
of AMAG Patents.


 


(i)            If a Third
Party infringes any AMAG Patent in the Licensed Territory by making, using,
importing, offering for sale or selling the Product or a competitive product in
the Field (a “Product Infringement”),
each Party shall share with the other Party all Information available to it
regarding such alleged infringement. Takeda shall have the first right, but not
the obligation, to bring an appropriate suit or other action against any person
or entity engaged in such Product Infringement in the Licensed Territory,
subject to Sections 9.5(b)(ii) through 9.5(b)(v), below.


 


(ii)           Takeda shall
have a period of ninety (90) days after the first notice under Section 9.5(a) to
elect to enforce such AMAG Patent against such Product Infringement.  In the event Takeda does not so elect, Takeda
shall so notify AMAG in writing, and AMAG shall have the right to commence a
suit or take action to enforce the applicable Patent against such Third Party
perpetrating such Product Infringement in the Licensed Territory at its own
cost and expense.  If one Party elects to
bring suit or take action against the Product Infringement, then the other
Party shall have the right, prior to commencement of the trial, suit or action,
to join any such suit or action.


 


(iii)         Each Party
shall provide to the Party enforcing any such rights under this Section 9.5(b) reasonable
assistance in such enforcement, at such enforcing Party’s request and expense,
including joining such action as a party plaintiff if required by applicable
Laws to pursue such action.  The
enforcing Party shall keep the other Party regularly informed of the status and
progress of such enforcement efforts, shall reasonably consider the other
Party’s comments on any such efforts, and shall seek consent of the other Party
in any important aspects of such enforcement, including determination of
litigation strategy and filing of important papers to the competent court,
which shall not be unreasonably withheld or delayed.


 


(iv)          Each Party
shall bear all of its own internal costs incurred in connection with its activities
under this Section 9.5(b).


 


49
















 


(v)            The Party not
bringing an action with respect to a Product Infringement in the Licensed
Territory under this Section 9.5(b) shall be entitled to separate
representation in such matter by counsel of its own choice and at its own
expense, but such Party shall at all times cooperate fully with the Party
bringing such action.


 


(c)           Infringement
of Takeda Patents.  For any and
all infringement of any Takeda Patent anywhere in the Licensed Territory,
Takeda shall have the sole and exclusive right, but not the obligation, to
bring, at Takeda’s expense and in its sole control, an appropriate suit or
other action against any person or entity engaged in such infringement of the
Takeda Patent.


 


(d)           Settlement.  Each Party shall not settle any claim, suit
or action that it brought under this Section 9.5 involving AMAG Patents
without the prior written consent of the other Party, which consent shall not
be unreasonably withheld or delayed; provided that AMAG shall have the sole
discretion to withhold consent in the event it determines that such settlement
would restrict in any material respect the scope of the AMAG Patents or its
rights or interests therein.


 


(e)           Allocation
of Proceeds.  If either
Party recovers monetary damages from any Third Party in a suit or action
brought under Section 9.5(b), 9.5(c), or 9.8(b) with respect to AMAG
Patents or Takeda Patents, including in a settlement, such recovery shall be
allocated first to the reimbursement of any expenses incurred by the Parties in
such litigation (including, for this purpose, a reasonable allocation of
expenses of internal counsel), and any remaining amounts shall be split as
follows: (i) the portion of such amounts that represents recovery for lost
sales in the Licensed Territory shall be retained by Takeda and treated as Net
Sales, on which Takeda shall make a royalty payment pursuant to Section 8.4
(without applying any reduction under Section 8.4(d) to such
portion), and (ii) any remaining amounts shall be allocated [***].


 


9.6          Infringement
of Third Party Rights in the Licensed Territory.


 


(a)           Notice.  If any Product used or sold by either Party,
its Affiliates, licensees or sublicensees becomes the subject of a Third
Party’s claim or assertion of infringement of a Patent granted by a
jurisdiction within the Licensed Territory, the Party first having notice of
the claim or assertion shall promptly notify the other Party, the Parties shall
agree on and enter into an “identity of interest agreement” wherein such
Parties agree to their shared, mutual interest in the outcome of such potential
dispute, and thereafter, the Parties shall promptly meet to consider the claim
or assertion and the appropriate course of action.


 


(b)           Defense.  Takeda shall have the first right, but not
the obligation, to defend any such Third Party threatened or asserted claim of
infringement of a Patent as described in Section 9.6(a) above, at
Takeda’s expense.  If Takeda does not
commence actions to defend 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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such claim within thirty
(30) days after it receives notice thereof (or within thirty (30) days after it
should have given notice thereof to AMAG as required by Section 9.6(a)),
then to the extent allowed by applicable Laws, AMAG shall have the right, but
not the obligation, to control the defense of such claim by counsel of its
choice, at AMAG’s expense.  The
non-defending Party shall reasonably cooperate with the Party conducting the
defense of the claim or assertion, including, if required to conduct such
defense, furnishing a power of attorney.


 


(c)           Participation.  Each Party shall have the
right to participate or otherwise be involved in any such action controlled by
the other Party, in each case at the participating Party’s sole cost and
expense.  If a Party elects to so
participate or be involved, the controlling Party shall provide the
participating Party and its counsel with an opportunity to consult with the
controlling Party and its counsel regarding the prosecution of such action
(including reviewing the contents of any correspondence, legal papers or other
documents related thereto), and the controlling Party shall take into account
reasonable requests of the participating Party regarding such enforcement or
defense.


 


(d)           Settlement;
Licenses.  Neither
Party shall enter into any settlement of any claim described in this Section 9.6
that affects the other Party’s rights or interests or the scope of any AMAG
Patent and/or Takeda Patent in any material respect without such other Party’s
written consent.  Each Party shall have
the right to decline to defend or to tender defense of any such claim to the
other Party upon reasonable notice, including if the other Party fails to agree
to a settlement that such Party proposes. 
If a Party desires to take a license under any applicable Third Party
intellectual property rights for the purpose of Developing or Commercializing
the Product in the Field, then such Party shall submit the terms of such
license to the JSC for review and approval. 
Any such license agreement will require the applicable Third Party to
grant licenses to both Takeda and AMAG for performing their respective
obligations and exercising their respective rights in the Licensed Territory
under this Agreement, will contain a release of any liabilities accrued prior
to the effective date of such license agreement, and will be subject to the
mutual agreement of the Parties.


 


9.7          Patent
Marking.  Takeda (or its Affiliate or
sublicensee) shall mark Product marketed and sold by Takeda (or its Affiliate
or sublicensee) hereunder with appropriate patent numbers or indicia; provided,
however, that Takeda shall only be required to so mark such Product to the
extent such markings or such notices (i) would affect recoveries of
damages or equitable remedies available under applicable Laws with respect to
infringements of patents in the Licensed Territory and (ii) would not
incur unreasonable cost considering the market, patent or other circumstances
of the Product in such Licensed Territory, subject to consultation with AMAG.


 


9.8          Patent
Oppositions and Other Proceedings.


 


(a)           Third-Party
Patent Rights.  If either
Party desires to bring an opposition, action for declaratory judgment, nullity
action, interference, declaration for non-infringement, reexamination or other
attack upon the validity, title or enforceability of a Patent owned or
controlled by a Third Party and having one or more claims that covers the
Product, or the use, sale, offer for sale or importation of the Product (except
insofar as such action is a counterclaim 


 


51

















 


to or defense of, or
accompanies a defense of, a Third Party’s claim or assertion of infringement
under Section 9.6, in which case the provisions of Section 9.6 shall
govern), such Party shall so notify the other Party and the Parties shall
promptly confer to determine whether to bring such action or the manner in
which to settle such action.  Takeda
shall have the exclusive right, but not the obligation, to bring at its own
expense and in its sole control any such action in the Licensed Territory.  If Takeda does not bring such an action in
the Licensed Territory, within ninety (90) days of notification thereof
pursuant to this Section 9.8(a) (or earlier, if required by the
nature of the proceeding), then AMAG shall have the right, but not the
obligation, to bring, at AMAG’s sole expense, such action.  The Party not bringing an action under this Section 9.8(a) shall
be entitled to separate representation in such proceeding by counsel of its own
choice and at its own expense, and shall cooperate fully with the Party
bringing such action.  Any awards or
amounts received in bringing any such action shall be retained by the Party
initiating such action.


 


(b)           Parties’
Patent Rights.  If any AMAG
Patent or Takeda Patent or Patent Term Extension related thereto becomes the
subject of any proceeding commenced by a Third Party within the Licensed
Territory in connection with an opposition, reexamination request, action for
declaratory judgment, nullity action, interference or other attack upon the
validity, title or enforceability thereof (except insofar as such action is a
counterclaim to or defense of, or accompanies a defense of, an action for
infringement against a Third Party under Section 9.5, in which case the
provisions of Section 9.5 shall govern), then the Party responsible for
filing, preparing, prosecuting and maintaining such Patent or Patent Term
Extension as set forth in Sections 9.3 or 9.4 hereof shall control such defense
at its own cost and expense.  The
controlling Party shall permit the non-controlling Party to participate in the
proceeding to the extent permissible under applicable Laws, and to be
represented by its own counsel in such proceeding, at the non-controlling
Party’s expense.  If either Party decides
that it does not wish to defend against such action, then the other Party shall
have the right to assume defense of such Third-Party action at its own expense.  Any awards or amounts received in defending
any such Third-Party action shall be allocated between the Parties as provided
in Section 9.5(e).


 


(c)           Compendial
Listing and Register of Exclusive License.   Upon request of Takeda, AMAG shall
cooperate with Takeda to (i) file appropriate information with the
applicable Regulatory Authority listing any AMAG Patents in the patent listing
source in such country in the Licensed Territory that is equivalent or similar
to the Orange Book in the U.S., if any, and (ii) register Takeda’s license
granted hereunder to the applicable Regulatory Authority, a patent and
trademark office or other relevant governmental agency or offices in the
Licensed Territory, if any.


 


ARTICLE 10




REPRESENTATIONS AND
WARRANTIES; COVENANTS


 


10.1        Mutual
Representations and Warranties.  Each Party hereby represents and warrants to
the other Party as follows:


 


52

















 


(a)           Corporate
Existence.  As of the
Effective Date, it is a company or corporation duly organized, validly
existing, and in good standing under the laws of the jurisdiction in which it
is incorporated.


 


(b)           Corporate
Power, Authority and Binding Agreement.  As of the Effective Date, (i) it has the
corporate power and authority and the legal right to enter into this Agreement
and perform its obligations hereunder; (ii) 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 (iii) 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.


 


10.2        Additional
Representations and Warranties of AMAG.  AMAG represents and warrants to Takeda as
follows:


 


(a)           Non-Infringement
of AMAG Technology by Third Parties.  As of the Effective Date, to AMAG’s Best
Knowledge, there are no ongoing activities by Third Parties that would
constitute infringement or misappropriation of the AMAG Technology within the
Licensed Territory;


 


(b)           Right to
Grant Licenses.  As of the
Effective Date, AMAG has the full legal right, power and authority to grant the
license rights set forth in Article 2;


 


(c)           Ownership
of AMAG Technology.  As of the
Effective Date, AMAG is the sole and exclusive owner of the AMAG Technology,
all of which is free and clear of any liens, charges and encumbrances, and, to
AMAG’s Best Knowledge, no other Person has any claim of ownership whatsoever
with respect to the AMAG Technology or the Product;


 


(d)           AMAG
Patents Not Invalid or Unenforceable.  As of the Effective Date, the AMAG Patents
listed on Exhibit C-1 exist, and the issued patents in the AMAG
Patents have not been held invalid or unenforceable, in whole or in part, by a
court or other governmental agency of competent jurisdiction;


 


(e)           Manufacturing Process Patent.   As
of the Effective Date, Product is produced materially in accordance with [***],
would infringe the intellectual property rights of any Third Party.


 


(f)            Legal
Actions.  As of the Effective Date, (i) there
are no pending, or, to AMAG’s Best Knowledge, 
threatened legal actions, nor has AMAG received any written notice
regarding any pending or threatened legal actions, with respect to the AMAG
Technology or the Product; and (ii) except as disclosed to Takeda in
writing prior to the Effective Date, AMAG has 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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not received written notice
regarding any other pending legal action which would reasonably be expected to
have a material adverse effect on the operations of AMAG as a whole.


 


(g)           Patent
Litigation. As of the Effective Date, AMAG has not received
written notice of any pending or threatened claims or litigation seeking to
invalidate any AMAG Patents or claiming that the practice of the AMAG
Technology infringes the intellectual property rights of any Third Party;


 


(h)           Third Party Agreements. As of the Effective Date, AMAG
has not breached in any material respect, any agreements with Third Parties to
which AMAG is a party existing as of the Effective Date relating to the Product;


 


(i)            Sufficiency
of Licenses. As of the Effective Date, to AMAG’s Best
Knowledge,  AMAG Technology and the
licenses granted by AMAG under Article 2 are sufficient for Takeda to Develop,
seek Regulatory Approvals, Commercialize and Finish the Product in the Field in
the Licensed Territory as contemplated by this Agreement;


 


(j)            Provision
of Information. AMAG has made available to Takeda the AMAG Patents
and, to AMAG’s Best Knowledge, all written information in AMAG’s possession or
Control as of the Effective Date requested by Takeda in writing relating to the
Development or Commercialization of the Products in the Field in the Licensed
Territory as contemplated by this Agreement;


 


(k)           Safety
Data. As of the Effective Date, AMAG has provided Takeda with the
opportunity to review (i) any and all non-clinical safety data regarding
the Product that is in AMAG’s possession or Control and (ii) any and all
human subject safety data (life-threatening
adverse drug experience, Serious Adverse Drug Experience, Unexpected Adverse
Drug Experience, Adverse Event, Serious Adverse Event, Adverse Drug Reaction,
Serious Adverse Drug Reaction, Unexpected Adverse Drug Reaction, as each is
defined in 21 CFR 312 and/or ICH Guidance (ICH-E6)) regarding the Product that
is in AMAG’s possession or Control;


 


(l)            Conduct
of Activities. As of the Effective Date, to AMAG’s Best
Knowledge, each of AMAG, its contractors and its consultants has conducted all
Development of Product and all Manufacturing of Product prior to the Effective
Date in accordance with: (i) all material provisions of applicable Laws; (ii) the
known or published standards of the FDA or other applicable Regulatory
Authorities in the Licensed Territory; (iii) the prevailing scientific
standards applicable to the conduct of such studies and activities in the
Licensed Territory; and (iv) applicable regulatory materials, where the
failure to do so would have a material adverse effect on the Development,
Manufacturing and/or Commercialization of the Products in the Field for the
Licensed Territory as contemplated by this Agreement;


 


(m)          Audit of
Contractors. Prior to the Effective Date, AMAG has conducted
audits and/or assessments of its contract manufacturer organizations and
contract research organizations, which organizations are or have been involved
in activities with respect to the Product in accordance with the prevailing
pharmaceutical industry standards and, as of the Effective Date, to AMAG’s Best
Knowledge, there are no circumstances with respect to such 


 


54

















 


organizations that could
reasonably be expected to have a material adverse effect on the Development,
Manufacturing and/or Commercialization of the Product in the Field for the
Licensed Territory as contemplated by this Agreement;


 


(n)           Regulatory
Authority Communications. As of the Effective Date, to AMAG’s Best
Knowledge, neither AMAG nor any officer, employee or agent of AMAG has
knowingly made an untrue statement of a material fact to any Regulatory
Authority in or outside the Licensed Territory with respect to the Product or
knowingly failed to disclose a material fact required to be disclosed to any
Regulatory Authority in or outside the Licensed Territory with respect to the
Product; and


 


(o)           Government Funding. As of the Effective Date, none of the United States Government, any
agency of the United States Government, any foreign government, or any agency
of a foreign government has provided funding or support for any work performed
in the conception or reduction to practice of any AMAG Patents.


 


10.3        Covenants.


 


(a)           No
Debarment.  In the
course of the Development of the Product, each Party shall not use, during the
Term, any employee or consultant who has been debarred by any Regulatory
Authority, or, to such Party’s Best Knowledge, is the subject of debarment
proceedings by a Regulatory Authority. 
Each Party shall notify the other Party promptly upon becoming aware of
any employee or consultant who has been debarred or is the subject of debarment
proceedings by any Regulatory Authority.


 


(b)           Compliance.  Each Party and its Affiliates shall, to the
extent applicable to its performance hereunder, comply in all material respects
with all applicable Laws in the Development, Manufacture and Commercialization
of the Product for the Licensed Territory and performance of its obligations
under this Agreement, including the statutes, regulations and written
directives of the FDA, the EMA and any Regulatory Authority having jurisdiction
in the Licensed Territory, the FD&C Act, the Prescription Drug Marketing
Act, the Federal Health Care Programs Anti-Kickback Law, 42 U.S.C. 1320a-7b(b),
the statutes, regulations and written directives of Medicare, Medicaid and all
other health care programs, as defined in 42 U.S.C. § 1320a-7b(f), and the
Foreign Corrupt Practices Act of 1977, each as may be amended from time to
time.


 


10.4        Disclaimer.  Takeda understands that the Product is the
subject of ongoing clinical research and development and that AMAG cannot
assure the safety or usefulness of the Product. 
In addition, AMAG makes no warranties except as set forth in this Article 10
concerning the AMAG Technology.


 


10.5        No Other
Representations or Warranties.  EXCEPT AS EXPRESSLY STATED IN THIS AGREEMENT,
NO REPRESENTATIONS OR WARRANTIES WHATSOEVER, WHETHER EXPRESS OR IMPLIED,
INCLUDING WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE,
NON-INFRINGEMENT, OR NON-MISAPPROPRIATION OF THIRD PARTY INTELLECTUAL 


 


55

















 


PROPERTY RIGHTS, ARE MADE OR
GIVEN BY OR ON BEHALF OF A PARTY, AND ALL REPRESENTATIONS AND WARRANTIES,
WHETHER ARISING BY OPERATION OF LAW OR OTHERWISE, ARE HEREBY EXPRESSLY
EXCLUDED.


 


ARTICLE 11


 


INDEMNIFICATION


 


11.1        Indemnification
by AMAG.  AMAG shall defend, indemnify,
and hold Takeda and its Affiliates and their respective officers, directors,
employees, and agents (the “Takeda
Indemnitees”) harmless from and against any and all Third Party claims,
suits, proceedings, damages, expenses (including court costs and reasonable
attorneys’ fees and expenses), and recoveries (collectively, “Claims”)
to the extent that such Claims arise out of, are based on, or result
from (a) the Development, storage, handling, Manufacture (unless and to
the extent liability for Manufacturing activities are covered by separate
indemnification pursuant to the Supply Agreement, which in such event will
control), distribution, use, promotion, sale, offer for sale, and importation
of Product by or on behalf of AMAG or its Affiliates or its or their
distributors (other than Takeda), licensees (other than Takeda), contract
research organizations, contract manufacturers or other Third Party service
providers (the “AMAG Group”), or (b) the
breach of any obligation, representation, warranty or covenant of AMAG in this
Agreement, or (c) the willful misconduct or negligent acts of AMAG, its
Affiliates, or the officers, directors, employees, or agents of AMAG or its
Affiliates.  The foregoing indemnity
obligation shall not apply to the extent that (i) the Takeda Indemnitees
fail to comply with the indemnification procedures set forth in Section 11.3
and AMAG’s defense of the relevant Claims is materially prejudiced by such
failure, or (ii) any Claim arises from, is based on, or results from any
activity for which Takeda is obligated to indemnify the AMAG Indemnitees under Section 11.2.


 


11.2        Indemnification
by Takeda.  Takeda
shall defend, indemnify, and hold AMAG and its Affiliates and their respective
officers, directors, employees, and agents (the “AMAG Indemnitees”) harmless from and against any and all
Claims to the extent that such Claims arise out of, are based on, or result
from (a) the Development, storage, handling, Manufacture (unless and to
the extent liability for Manufacturing activities are covered by separate
indemnification pursuant to the Supply Agreement or the agreed upon terms and
conditions, if any, governing Takeda’s purchase of clinical supplies of the
Product prior to the Parties’ execution of the Supply Agreement, which in such
event will control), distribution, use, promotion, sale, offer for sale, and
importation of Product by or on behalf of Takeda or its Affiliates or its or
their sublicensees, distributors, contract research organizations, contract
manufacturers or other Third Party service providers, or (b) the breach of
any obligation, representation, warranty or covenant of Takeda in this
Agreement, or (c) the willful misconduct or negligent acts of Takeda, its
Affiliates, or the officers, directors, employees, or agents of Takeda or its
Affiliates.  The foregoing indemnity
obligation shall not apply to the extent that (i) the AMAG Indemnitees
fail to comply with the indemnification procedures set forth in Section 11.3
and Takeda’s defense of the relevant Claims is materially prejudiced by such
failure, or (ii) any Claim arises from, is based on, or results from any
activity for which AMAG is obligated to indemnify the Takeda Indemnitees under Section 11.1.


 


56

















 


11.3        Indemnification
Procedures.  The Party
claiming indemnity under this Article 11 (the “Indemnified Party”) shall give written notice to the Party
from whom indemnity is being sought (the “Indemnifying
Party”) in a reasonably timely manner after learning of such
Claim.  The Indemnified Party shall
provide the Indemnifying Party with reasonable assistance, at the Indemnifying
Party’s expense, in connection with the defense of the Claim for which indemnity
is being sought.  The Indemnified Party
may participate in and monitor such defense with counsel of its own choosing at
its sole expense; provided, however, the Indemnifying Party shall have the
right to assume and conduct the defense of the Claim with counsel of its
choice.  The Indemnifying Party shall not
settle any Claim without the prior written consent of the Indemnified Party,
not to be unreasonably withheld or delayed, unless the settlement involves only
the payment of money.  The Indemnified Party
shall not settle any such Claim without the prior written consent of the
Indemnifying Party.  If the Indemnifying
Party does not assume and conduct the defense of the Claim as provided above, (a) the
Indemnified Party may defend against, and consent to the entry of any judgment
or enter into any settlement with respect to, the Claim in any manner the
Indemnified Party may deem reasonably appropriate (and the Indemnified Party
need not consult with, or obtain any consent from, the Indemnifying Party in connection
therewith), and (b) the Indemnifying Party will remain responsible to
indemnify the Indemnified Party as provided in this Article 11.


 


11.4        Limitation
of Liability.  NEITHER
PARTY SHALL BE LIABLE TO THE OTHER FOR ANY SPECIAL, CONSEQUENTIAL, INCIDENTAL,
PUNITIVE, OR INDIRECT DAMAGES ARISING FROM OR RELATING TO ANY BREACH OF THIS
AGREEMENT, REGARDLESS OF ANY NOTICE OF THE POSSIBILITY OF SUCH DAMAGES.  NOTWITHSTANDING THE FOREGOING, NOTHING IN
THIS SECTION 11.4 IS INTENDED TO OR SHALL LIMIT OR RESTRICT THE
INDEMNIFICATION RIGHTS OR OBLIGATIONS OF ANY PARTY UNDER SECTION 11.1 OR
11.2, OR DAMAGES AVAILABLE FOR A PARTY’S BREACH OF CONFIDENTIALITY OBLIGATIONS
IN ARTICLE 12.


 


11.5        Insurance.  Each Party shall procure and maintain
insurance or self-insurance, including human clinical trial liability insurance
and product liability insurance, adequate to cover its obligations hereunder
and consistent with local statutory requirements and customary business
practices of prudent companies similarly situated at all times during which any
Product is being clinically tested in human subjects or commercially
distributed or sold by such Party. Each Party shall maintain such product
liability insurance or self-insurance for a period of [***] after the Term of this Agreement.
It is understood that such insurance shall not be construed to create a limit
of either Party’s liability with respect to its indemnification obligations
under this Article 11.  Each Party
shall provide the other Party with written evidence of such insurance upon
request.  Each Party shall provide the
other Party with written notice within thirty (30) days 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24B-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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after the cancellation,
non-renewal or material change in such insurance or self-insurance which
materially adversely affects the rights of the other Party hereunder.


 


ARTICLE 12


 


CONFIDENTIALITY


 


12.1        Confidentiality.  Except to the extent expressly authorized by
this Agreement or otherwise agreed in writing by the Parties during a period
that is the longer of (i) [***], each Party
agrees that it shall keep confidential and shall not publish or otherwise
disclose and shall not use for any purpose other than as provided for in this
Agreement any Confidential Information furnished to it by the other Party
pursuant to this Agreement or the Mutual Confidentiality Agreement between the
Parties dated May 19, 2009, except for that portion of such information or
materials that the receiving Party can demonstrate by competent written proof:


 


(a)           was already
known to the receiving Party or its Affiliate, other than under an obligation
of confidentiality, at the time of disclosure by the other Party;


 


(b)           was generally
available to the public or otherwise part of the public domain at the time of
its disclosure to the receiving Party;


 


(c)           became
generally available to the public or otherwise part of the public domain after
its disclosure and other than through any act or omission of the receiving
Party in breach of this Agreement;


 


(d)           was disclosed
to the receiving Party or its Affiliate by a Third Party who has a legal right
to make such disclosure; or


 


(e)           was
independently discovered or developed by or on behalf of the receiving Party or
its Affiliate without the aid, application, or use of the disclosing Party’s
Confidential Information, as evidenced by a contemporaneous writing.


 


12.2        Authorized
Disclosure.  Each Party
may disclose Confidential Information belonging to the other Party to the
extent such disclosure is reasonably necessary in the following situations:


 


(a)           regulatory
filings and other filings with Governmental Authorities, including filings with
the Securities and Exchange Commission or other relevant exchange on which such
Party is listed;


 


(b)           prosecuting or
defending litigation;


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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(c)           complying with
applicable Laws;


 


(d)           disclosure to
its employees, agents, consultants, and any bona fide Third Party potential
(sub)-licensees (including potential Third Party partners) only on a
need-to-know basis and solely as necessary in connection with the performance
of or as otherwise contemplated by this Agreement, provided that in each case
the recipient of such Confidential Information must agree to be bound by
similar obligations of confidentiality and non-use at least equivalent in scope
to those set forth in this Article 12 prior to any such disclosure; and


 


(e)           disclosure of
the material terms of this Agreement to any bona fide potential investor,
investment banker, acquiror, merger partner, licensees, sublicensees or other
potential or actual financial or commercial partner; provided that in
connection with such disclosure, the disclosing Party shall use all reasonable
efforts to inform each recipient of the confidential nature of such
Confidential Information and cause each recipient of such Confidential
Information to treat such Confidential Information as confidential.


 


Notwithstanding
the foregoing, in the event a Party is required to make a disclosure of the
other Party’s Confidential Information pursuant to clause (a) through (c) of
this Section 12.2, it will, except where impracticable, give reasonable
advance notice to the other Party of such disclosure and use diligent efforts
to secure confidential treatment of such information.  In any event, the Parties agree to take all
reasonable action to avoid disclosure of Confidential Information
hereunder.  Each Party will be
responsible for any acts or omissions of any Third Party to which such Party
discloses Confidential Information in accordance with this Section 12.2.


 


12.3        Publicity.


 


(a)           The Parties
shall make a joint public announcement of the execution of this Agreement in
the form attached as Exhibit E, which shall be issued at a time to
be mutually agreed by the Parties.


 


(b)           After release
of such press release, if either Party desires to make a public announcement
concerning the material terms of this Agreement, such Party shall give
reasonable prior advance notice of the proposed text of such announcement to
the other Party for its prior review and approval (except as otherwise provided
herein), such approval not to be unreasonably withheld.  A Party commenting on such a proposed press
release shall use Commercially Reasonable Efforts to provide its comments, if
any, within three (3) business days after receiving the press release for
review.  In addition, where required by
law or by the regulations of the applicable securities exchange upon which a
Party may be listed, such Party shall have the right to make a press release
announcing the achievement of each milestone under this Agreement as it is
achieved, and the achievements of Regulatory Approvals in the Licensed
Territory as they occur, subject only to the review procedure set forth in the
preceding sentence.  In relation to the
other Party’s review of such an announcement, such other Party may make
specific, reasonable comments on such proposed press release within the
prescribed time for commentary, but shall not withhold its consent to
disclosure of the information that the relevant milestone has been achieved and
triggered a payment hereunder.  Neither
Party shall be required to seek the permission of the other Party to repeat any
information regarding the terms of this Agreement 


 


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that has already been
publicly disclosed by such Party, or by the other Party, in accordance with
this Section 12.3.


 


ARTICLE 13


 


TERM AND TERMINATION


 


13.1        Term.  This Agreement shall become effective on the
Effective Date and, unless earlier terminated pursuant to this Article 13,
shall remain in effect on a Product-by-Product and on a country-by-country
basis until the cessation of all commercial sales of the Product in the
Licensed Territory.


 


13.2        Unilateral
Termination by Takeda.


 


(a)           Termination
Notice.  Takeda may terminate this
Agreement in its entirety, following: (i) [***] consultation with AMAG followed by [***] prior
written notice, if such termination is effective prior to the First Commercial
Sale of the Product anywhere in the Licensed Territory, or (ii) [***]
consultation with AMAG followed by [***] prior written notice if such
termination is effective after the First Commercial Sale of the Product
anywhere in the Licensed Territory. Notwithstanding the foregoing, Takeda may
terminate this Agreement in its entirety, following [***] consultation with
AMAG followed by [***] prior written notice, if Takeda has determined in good
faith that the continued Development or Commercialization of the Product would
not be in the best interest of patient welfare. 
In addition, Takeda may terminate this Agreement on a country-by-country
basis at any time after expiration of the Royalty Term in a country by giving [***]
prior written notice.


 


(b)           Effect of
Unilateral Termination.  If
Takeda terminates this Agreement in its entirety pursuant to Section 13.2(a),
then:


 


(i)            Takeda shall
not, during such applicable notice period, take any action that could
reasonably be expected to have a material adverse impact on the further
Development and Commercialization of the Product in or outside the Licensed
Territory; provided, however, that Takeda shall have the right to take any
actions it deems reasonably necessary or appropriate to avoid any human health
or safety problems;


 


(ii)           Takeda shall be
required to perform (and bear all costs and expenses of) any outstanding
obligations of Takeda that accrued prior to the effective date of termination,
but Takeda shall be released from any other obligations after the effective
date of termination, unless otherwise specifically set forth in this Section 13.2;


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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(iii)                            Takeda shall be responsible for any
reasonable and non-cancelable costs incurred by AMAG prior to the effective
date of termination in connection with its supply of Product to Takeda under
this Agreement or the Supply Agreement, provided, however, that upon receipt of
notice from Takeda, AMAG shall use Commercially Reasonable Efforts to minimize
such non-cancelable costs; and


 


(iv)                               the JSC shall coordinate the wind-down of
Takeda’s efforts under this Agreement, and the provisions of Section 13.6
shall apply.


 


13.3                        Termination for Breach.  AMAG shall have the right to terminate this Agreement
upon written notice to Takeda for material breach by Takeda of its obligations
under this Agreement if, after receiving written notice identifying such
material breach, Takeda fails to cure such material breach within [***] from the date of such notice (or within
[***] in the event such breach is solely based upon Takeda’s failure to pay any
undisputed amounts due AMAG hereunder); provided, however, that AMAG shall not
have the right to terminate this Agreement for Takeda’s breach of its
obligations under Section 4.7 to use Commercially Reasonable Efforts to
conduct any Development activities that Takeda assumes pursuant
to Section 4.4(a)(ii), 4.4(b)(ii), 4.4(b)(iii) or 4.4(c)(iii). Takeda shall have the right to terminate
this Agreement upon written notice to AMAG for material breach by AMAG of its
obligations under this Agreement if, after receiving written notice identifying
such material breach, AMAG fails to cure such breach within [***] from the date
of such notice (or within [***] in the event such breach is solely based upon
AMAG’s failure to pay any undisputed amounts due Takeda hereunder). If a
material breach affects and relates only to one or more of [***], then such
termination right (a) shall be only with respect to the Region(s) affected
by such material breach or to which such material breach relates, [***], and (b) shall
be subject to any other express provisions of this Agreement providing for
notice and cure of a Party’s alleged breach hereunder. No payment or agreement
to pay under this Agreement (including those referred to as nonrefundable or
non-creditable) shall in any way preclude or limit the rights of either Party
to seek the full recovery of its damages or to seek equitable relief for breach
of this Agreement by the other Party.


 


13.4                        Termination for Patent
Challenge.  AMAG shall have the right to terminate this
Agreement upon written notice to Takeda, effective upon receipt, if (a) Takeda
or any of its Affiliates, directly or indirectly: (i) initiates or
requests an interference, opposition proceeding or request for ex parte or
inter parties reexamination with respect to any AMAG Patent, or (ii) makes,
files or maintains any claim, demand, lawsuit or cause of action to challenge
the validity or enforceability of any an AMAG Patent (each, a “Patent Challenge”), or (b) a
sublicensee of Takeda (or an Affiliate of such sublicensee) undertakes a Patent
Challenge and Takeda fails to terminate the applicable sublicenses in
accordance with Section 2.1(c), provided that for any such proceeding that
can be terminated by Takeda after initiation, AMAG provides Takeda with 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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a notice of termination at least [***] prior to such termination and Takeda
does not within such [***] period withdraw and terminate such Patent Challenge.
If Takeda or its Affiliates or sublicensees withdraw such Patent Challenge and
such proceeding is terminated within such [***] period, then AMAG shall have no
right to terminate under this Section 13.4.


 


13.5                        Termination for
Bankruptcy.  A Party may terminate this Agreement in its
entirety upon written notice to the other Party upon or after the time that
such other Party makes a general assignment for the benefit of creditors, files
an insolvency petition in bankruptcy, petitions for or acquiesces in the
appointment of any receiver, trustee or similar officer to liquidate or
conserve its business or any substantial part of its assets, commences under
the laws of any jurisdiction any proceeding involving its insolvency,
bankruptcy, reorganization, adjustment of debt, dissolution, liquidation or any
other similar proceeding for the release of financially distressed debtors or
becomes a party to any proceeding or action of the type described above and
such proceeding or action remains un-dismissed or un-stayed for a period of
more than [***].


 


 


13.6                        AMAG Rights upon
Termination of the Agreement.  Upon the early
termination of this Agreement by Takeda under Section 13.2(a), by either
Party under Section 13.3 due to the other Party’s material uncured breach,
or by AMAG under Section 13.4 for Patent Challenge, the following shall
apply (in addition to any other rights and obligations under Section 13.2,
13.3 or 13.4 or otherwise under this Agreement with respect to such
termination). For the avoidance of doubt, in case of termination for a
particular Region(s), the following provisions shall apply solely for such Region(s):


 


(a)                                  Regulatory Materials;
Data; Trademarks.  To the extent permitted by applicable Laws,
Takeda shall transfer and assign to AMAG all Regulatory Materials, Regulatory
Approvals, and related data relating to the Product existing as of the date of
such termination throughout the Licensed Territory as and to the extent owned
or Controlled by Takeda, and shall assign to AMAG all of its right, title and
interest in the New Product Marks.


 


(b)                                  Takeda License. 
Takeda hereby grants to AMAG, effective only in event of such
termination, an exclusive, irrevocable, transferable, royalty-free license,
with the right to grant multiple tiers of sublicenses, under the Takeda
Technology existing and actually used and applied as of the date of such
termination to Develop, make, have made, use, sell, offer for sale, have sold,
import and otherwise Commercialize the Product in the Licensed Territory, which
license shall be effective as of the date of such termination.


 


(c)                                  Transition Assistance. 
For one (1) year following the effective date of such termination,
Takeda shall provide such assistance, [***] as may be reasonably necessary or
useful for AMAG to commence or continue Developing, Manufacturing or
Commercializing Product in the Licensed Territory, to the extent Takeda is then
performing or having performed 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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such activities, including transferring or amending as
appropriate, upon request of AMAG, any agreements or arrangements with Third
Party vendors to Develop, Manufacture, distribute or sell Product in the
terminated Regions of the Licensed Territory. To the extent that any such
contract between Takeda and a Third Party is not assignable to AMAG, then
Takeda shall reasonably cooperate with AMAG to arrange to continue to provide
such services from such entity for so long as may be reasonably necessary to
transition such services, provided, however, this cooperation shall not be
construed as an obligation and/or promise of Takeda to ensure that any new
arrangement between AMAG and a Third Party vendor is established. In addition,
upon any termination of this Agreement under Section 13.2(a), Takeda shall
pay its share (if any) of costs for (i) the completion of any ongoing
clinical trial of the Product to the extent such costs are incurred for those
patients already enrolled in the trial at the time of giving the termination
notice and (ii) uncancellable obligations incurred to Third Parties as a
direct result of cancellation of such trial.


 


13.7                        Rights in Bankruptcy. 
All rights and licenses granted under or pursuant to this Agreement by
AMAG are, and shall otherwise be deemed to be, for purposes of Section 365(n) of
the U.S. Bankruptcy Code, licenses of right to “intellectual property” as
defined under Section 101 of the U.S. Bankruptcy Code. The Parties agree
that Takeda, as the licensee of such rights under this Agreement, shall retain
and may fully exercise all of its rights and elections under the U.S.
Bankruptcy Code. The Parties further agree that, in the event of the
commencement of a bankruptcy proceeding by or against AMAG under the U.S.
Bankruptcy Code, Takeda shall be entitled to a complete duplicate of (or
complete access to, as appropriate) any such intellectual property and all
embodiments of such intellectual property, which, if not already in Takeda’s
possession, shall be promptly delivered to it (a) upon any such commencement of
a bankruptcy proceeding upon Takeda’s written request therefor, unless AMAG
elects to continue to perform all of its obligations under this Agreement or (b) if
not delivered under clause (a), following the rejection of this Agreement by
AMAG upon written request therefor by Takeda.


 


13.8                        Survival. 
The following provisions shall survive any expiration or termination of
this Agreement for the period of time specified: Sections 2.2(b), 2.6, 5.1(b),
8.9, 9.1, 9.2, 10.5, 13.2(b), 13.6, 13.8, 14.3, 14.4, 14.5, 14.6 and 14.7 and
Articles 11, 12, 15 and 16. For clarity and notwithstanding anything to the contrary
in the Agreement, termination of this Agreement shall be in addition to, and
shall not prejudice, the Parties’ remedies at law or in equity, including the
Parties’ ability to receive legal damages and/or equitable relief with regard
to any breach of this Agreement, regardless of whether or not such breach was
the reason for the termination.


 


ARTICLE 14


 


DISPUTE RESOLUTION


 


14.1                        Disputes. 
The Parties recognize that disputes as to certain matters may from time
to time arise during the Term 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 


 


63

















 


this Article 14 to resolve any controversy or
claim arising out of, relating to or in connection with any provision of this
Agreement, if and when a dispute arises under this Agreement.


 


14.2                        Referred from JSC.


 


(a)                                  General. 
With respect to disputes arising from matters delegated to the JSC
pursuant to the terms of Article 3, either Party may, by written notice to
the other Party, have such dispute referred to each Party’s Designated
Executive for attempted resolution by good faith negotiations within thirty
(30) days after such notice is received. If the Designated Executives are not
able to resolve such dispute within such thirty (30) day period, then if such
dispute does not relate to a matter described in Section 14.2(b), either
Party may at any time thereafter pursue any legal or equitable remedy available
to it in accordance with this Article 14.


 


(b)                                  Specific Decision-Making
Rights.  If the Designated Executives of the Parties
are not able to resolve a dispute within the thirty (30) day period described
above, and the matter is related to one of the areas listed below as delegated
to the JSC, then AMAG or Takeda, as the case may be, shall have the unilateral
right to cast the deciding vote for the JSC as provided below. Except as
otherwise provided in subsections (i) or (ii) below, neither Party
(including its JDC and JSC members and Designated Executive) shall have the
right to change the Development Plan with respect to the Initial Studies,
including their scope and time schedules, without the other Party’s prior
written consent, not to be unreasonably withheld.


 


(i)                                    AMAG Decisions. 
The Designated Executive of AMAG shall have the right to make the final
decision with respect to the following: [***] and (4) the Commercialization of
the Product outside the Licensed Territory. Notwithstanding the foregoing, the
Designated Executive of AMAG shall not make any decision (without obtaining the
prior written consent of Takeda not to be unreasonably withheld) that [***]. In
addition, nothing in this Section 14.2(b) shall (X) be construed
to limit AMAG’s ability to carry out day-to-day decisions related to its Development
activities as set forth in the Development Plan, or (Y) limit AMAG’s
compliance with applicable Laws, reporting requirements to Regulatory
Authorities or its internal policies or decisions regarding matters affecting the health, safety or welfare of a
patient.


 


(ii)                                Takeda Decisions. 
The Designated Executive of Takeda shall have the right to make the
final decision with respect to any matters not listed in subsection (i) above,
including matters involving: [***]. Notwithstanding the foregoing, the Designated
Executive of Takeda shall not make any decision (without obtaining the prior
written consent of AMAG not to be unreasonably withheld) that [***]. In
addition, nothing in this Section 14.2(b) shall limit Takeda’s
compliance with applicable Laws, reporting requirements to Regulatory
Authorities or its internal policies or decisions regarding matters affecting the health, safety or welfare of a
patient.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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14.3                        Arising Between the
Parties.  Except as provided in Section 14.2,
with respect to all other disputes arising between the Parties and not from the
JSC, including any alleged failure to perform or breach of this Agreement, or
any issue relating to the interpretation or application of this Agreement, if
the Parties are unable to resolve such dispute within thirty (30) days after
such dispute is first identified by either Party in writing to the other, the
Parties shall refer such dispute to the Designated Executive for each Party for
attempted resolution by good faith negotiations within thirty (30) days after
such notice is received. If any such dispute is not resolved by such Designated
Executives within such period, either Party may at any time thereafter invoke
the provisions of Section 14.4.


 


14.4                        ADR.


 


(a)                                  Any
dispute, controversy or claim arising out of or relating to the validity,
construction, interpretation, enforceability, breach, performance, application
or termination of this Agreement that is not resolved pursuant to Section 14.3,
except for matters subject to Section 14.2 or a dispute, claim or
controversy under Section 14.5, shall be resolved by the Alternative
Dispute Resolution (“ADR”)
provisions set forth in Exhibit F attached hereto, the result of
which shall be binding upon the Parties. The Parties shall have the right to be
represented by counsel in such a proceeding.


 


(b)                                  Survivability. 
Any duty to engage in ADR under this Agreement shall remain in effect
and be enforceable after termination of this Agreement for any reason.


 


14.5                        Patent and Trademark Disputes.  Any dispute, controversy or claim relating to
the scope, validity, enforceability or infringement of any Patents or
trademarks covering the manufacture, use, importation, offer for sale or sale
of Products shall be submitted to a court of competent jurisdiction in the
country in which such patent or trademark rights were granted or arose.


 


14.6                        Injunctive Relief.  Nothing herein may prevent either Party from
seeking a preliminary injunction or temporary restraining order or other
equitable remedy if necessary to protect the interests of such Party or to
preserve the status quo pending the arbitration proceeding, including preservation of Confidential
Information.


 


14.7                        WAIVER OF RIGHT TO JURY TRIAL.  In connection with the Parties’ rights under
Sections 14.5 and 14.6, EACH PARTY, TO THE EXTENT PERMITTED BY LAW, KNOWINGLY,
VOLUNTARILY, AND INTENTIONALLY WAIVES ITS RIGHT TO A TRIAL BY JURY IN ANY
ACTION OR OTHER LEGAL PROCEEDING ARISING OUT OF OR RELATING TO THIS AGREEMENT
AND THE TRANSACTIONS IT CONTEMPLATES. THIS WAIVER APPLIES TO ANY ACTION OR
LEGAL PROCEEDING, WHETHER SOUNDING IN CONTRACT, TORT, OR OTHERWISE.


 


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ARTICLE 15


 


STANDSTILL


 


15.1                        Standstill Agreement.  During the [***] (the “Standstill Period”), none of Takeda, Takeda’s
Affiliates, nor any of their respective directors, officers, employees, agents
or representatives (provided such person is acting on behalf of Takeda or is in
possession of Confidential Information of AMAG) will, in any manner, directly
or indirectly, without the prior express written consent of AMAG:


 


(a)                                  acquire,
offer to acquire or agree to acquire, alone or in concert with any other
Person, by purchase, tender offer, exchange offer, agreement or business
combination or any other manner: (i) more than [***] of the beneficial
ownership of any securities of AMAG or any securities of any Affiliate of AMAG;
or (ii) any assets of AMAG or any assets of any Affiliate of AMAG other
than non-material acquisitions in the ordinary course of business;


 


(b)                                  initiate,
participate in or enter into any merger, business combination,
recapitalization, restructuring, liquidation, dissolution or other
extraordinary transaction involving AMAG or any Affiliate of AMAG, or involving
any securities or assets of AMAG or any securities or assets of any Affiliate
of AMAG;


 


(c)                                  “solicit”
“proxies” (as those terms are used in the proxy rules of the Securities
and Exchange Commission) or consents with respect to any securities of AMAG;


 


(d)                                  form,
join or participate in a Group with respect to the beneficial ownership of any
securities of AMAG;


 


(e)                                  act,
alone or in concert with others, to seek to control or influence the
management, board of directors or policies of AMAG;


 


(f)                                    take
any action that would reasonably be expected to require AMAG to make a public
announcement regarding any of the types of matters set forth in clause (a),
(b), (c) or (d) of this Section 15.1;


 


(g)                                 agree,
offer to take, propose, assist, induce or encourage any other Person to take,
publicly or otherwise, any action of the type referred to in clause (a), (b),
(c), (d), (e) or (f) of this Section 15.1;


 


(h)                                 enter
into any discussions, negotiations, arrangements or agreements with any other
Person relating to any of the foregoing; or


 


(i)                                    request
or propose that AMAG or any of AMAG’s representatives amend, waive or consider
the amendment or waiver of any of the provisions set forth in this Section 15.1.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


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15.2                        Exceptions to Standstill.


 


(a)                                  Notwithstanding
the foregoing restrictions, the provisions of Section 15.1 shall not apply
to:


 


(i)                                    the
exercise by Takeda of any of its rights under this Agreement;


 


(ii)                                the
exercise by Takeda as an AMAG stockholder, if applicable, of any voting rights
available to AMAG stockholders generally pursuant to any transaction described Section 15.1(a)(ii) or
(b) above, provided that Takeda has not then either directly, indirectly,
or as a member of a Group made, effected, initiated or caused such transaction
to occur;


 


(iii)                            any
activity by Takeda after AMAG has made any public announcement of its intent to
solicit or engage in any transaction which would result in a Change of Control
of AMAG, or after any such Change of Control of AMAG shall have occurred;


 


(iv)                               making
any communication to AMAG executive management on a confidential basis that
Takeda would be interested in engaging in discussions with AMAG that could
result in a negotiated transaction described in Section 15.1(a) or (b) so
long as Takeda does not propose any such transaction without AMAG’s prior
consent.


 


(v)                                   any investment by Takeda or an Affiliate of Takeda in
third-party mutual funds or other similar passive investment vehicles that hold
interests in securities of AMAG or any of its Affiliates (and any such
interests in securities shall not be taken into account for the purpose of Section 15.1(a)),
provided that the provisions of this clause (v) shall apply with respect
to any such fund or vehicle only for so long as such fund or vehicle satisfies
the requirements of paragraphs (i) and (ii) of Rule 13d-1(b)(1) promulgated
under the Securities Exchange Act of 1934, as amended, with respect to any AMAG
securities held by such fund or vehicle; or


 


(vi)                               Takeda’s
engagement and/or discussions with legal, accounting, or financial advisors for
the limited purposes of evaluating any of the transactions contemplated in
subparagraphs (a), (b), (c), (d), (e) or (f) of Section 15.1.


 


(b)                                  Except
as provided in Section 15.3 below, the restrictions of Section 15.1
no longer shall be applicable in the event of the occurrence of any of the
following:


 


(i)                                    AMAG
enters into a definitive written merger, sale or other business combination
agreement pursuant to which fifty percent (50%) or more of the outstanding
common stock of AMAG would be converted into cash or securities of another
Person or Group or, immediately after the consummation of such transaction,
fifty percent (50%) or more of the then outstanding common stock of AMAG would
be owned by Persons other than the holders of common stock of AMAG immediately
prior to the consummation of such transaction, or which would result in all or
substantially all of AMAG’s assets being sold to any Person or Group;


 


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(ii)                                AMAG
becomes the subject of any bankruptcy, insolvency or similar proceeding (except
for an involuntary proceeding that is dismissed within sixty (60) days);


 


(iii)                            AMAG
engages in the public solicitation of one (1) or more Third Party bids for
any transaction which would result in a Change of Control of AMAG.


 


AMAG shall inform Takeda in
writing within 48 hours after the occurrence of any of the foregoing events
listed in this Section 15.2(b).


 


15.3                        Reinstatement of Standstill. The provisions of
Section 15.1 shall again be applicable if: (a)  AMAG or such Third
Party, Person or Group, as applicable, terminates or announces its intent not
to proceed with any transaction referred to in Sections 15.2(a)(iii) and
15.2(b)(i) or (iii) above, as applicable, or, in the case of Section 15.2(b)(ii) above,
AMAG shall cease to be the subject of any such bankruptcy, insolvency or
similar proceeding, as applicable; and (b) either (1) Takeda has not
made any public announcement of its intent to acquire AMAG, or (2) in the
event such a public announcement has been made by Takeda, Takeda has terminated
or announced its intent to terminate such transaction.


 


15.4                        Most Favored Nations Treatment. If, during the
Standstill Period, AMAG enters into any development and commercialization
agreement with a Third Party that is similar in size and scope to this
Agreement (the “Third Party Agreement”),
which does not contain provisions restricting the activities of such Third
Party that, taken as a whole (the “Third
Party Standstill Provisions”), are at least as onerous to the Third
Party as the provisions of Section 15.1, then, upon the effective date of
the Third Party Agreement, the provisions of Section 15.1 shall
automatically be deemed modified without further action so as to conform to the
Third Party Standstill Provisions. For the avoidance of doubt, the Parties
agree that if the Third Party Agreement contains no standstill provision, Article 15
shall terminate in its entirety upon the effective date of the Third Party
Agreement.


 


The expiration of the
Standstill Period will not terminate or otherwise affect any other provisions
of this Agreement.


 


ARTICLE 16


 


MISCELLANEOUS


 


16.1                        Entire Agreement; Amendment. 
This Agreement, including the Exhibits and Schedules hereto, sets forth
the complete, final and exclusive agreement and all the covenants, promises,
agreements, warranties, representations, conditions and understandings between
the Parties hereto with respect to the subject matter hereof and supersedes, as
of the Effective Date, all prior and contemporaneous agreements and
understandings between the Parties with respect to the subject matter hereof;
provided, that the Mutual Confidentiality Agreement between the Parties dated May 19,
2009 (the “CDA”) shall continue in
full force and effect in accordance with its terms. There are no covenants,
promises, agreements, warranties, representations, conditions or
understandings, either oral or written, between the Parties other than as are
set forth 


 


68

















 


herein and in the CDA. No subsequent alteration,
amendment, change or addition to this Agreement shall be binding upon the
Parties unless reduced to writing and signed by an authorized officer of each
Party.


 


16.2                        Force Majeure. 
Both Parties shall be excused from the performance of their obligations
under this Agreement to the extent that such performance is prevented by force
majeure and the nonperforming Party promptly provides notice of the prevention
to the other Party. Such excuse shall be continued so long as the condition
constituting force majeure continues and the nonperforming Party takes
reasonable efforts to remove the condition. For purposes of this Agreement,
force majeure shall include conditions beyond the control of the Parties,
including an act of God, war, civil commotion, terrorist act, labor strike or
lock-out, epidemic, failure or default of public utilities or common carriers,
destruction of production facilities or materials by fire, earthquake, storm or
like catastrophe, and failure of plant or machinery (provided that such failure
could not have been prevented by the exercise of skill, diligence, and prudence
that would be reasonably and ordinarily expected from a skilled and experienced
person engaged in the same type of undertaking under the same or similar
circumstances). If a force majeure persists for more than [***], then the Parties will discuss in good
faith the modification of the Parties’ obligations under this Agreement in
order to mitigate the delays caused by such force majeure.


 


16.3                        Notices. 
Any notice required or permitted to be given under this Agreement shall
be in writing, shall specifically refer to this Agreement, and shall be
addressed to the appropriate Party at the address specified below or such other
address as may be specified by such Party in writing in accordance with this Section 16.3,
and shall be deemed to have been given for all purposes (a) when received,
if hand-delivered or sent by a reputable courier service, or (b) five (5) business
days after mailing, if mailed by first class certified or registered airmail,
postage prepaid, return receipt requested.


 


	
  If to AMAG:

  	
   

  	
  AMAG Pharmaceuticals, Inc.

  
	
   

  	
   

  	
  100 Hayden Ave.

  
	
   

  	
   

  	
  Lexington, MA 02421

  
	
   

  	
   

  	
  USA

  
	
   

  	
   

  	
  Attn: General Counsel

  



 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 


69

















 


	
  With a copy to:

  	
   

  	
  Cooley Godward Kronish LLP

  
	
   

  	
   

  	
  One Freedom Square

  
	
   

  	
   

  	
  Reston Town Center

  
	
   

  	
   

  	
  11951 Freedom Drive

  
	
   

  	
   

  	
  Reston, VA 201910-565

  
	
   

  	
   

  	
  Attn: Kenneth J.
  Krisko, Esq.

  
	
   

  	
   

  	
   

  
	
  If to Takeda:

  	
   

  	
  Takeda Pharmaceutical
  Company Limited

  
	
   

  	
   

  	
  1-1, Doshomachi 4-chome,
  Chuo-ku, Osaka, 540-8645, Japan

  
	
   

  	
   

  	
  Attn: General Manager,
  Global Licensing and Business Development Department

  
	
   

  	
   

  	
   

  
	
  With copies to:

  	
   

  	
  Takeda Pharmaceutical
  Company Limited

  
	
   

  	
   

  	
  1-1, Doshomachi 4-chome,
  Chuo-ku, Osaka, 540-8645, Japan

  
	
   

  	
   

  	
  Attn: General Manager, Legal
  Department

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Takeda Pharmaceuticals
  International Inc.

  
	
   

  	
   

  	
  One Takeda Parkway

  
	
   

  	
   

  	
  Deerfield, IL 60015

  
	
   

  	
   

  	
  Attn: Vice President, Global
  Licensing and Business Development

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Takeda Pharmaceuticals North
  America, Inc.

  
	
   

  	
   

  	
  One Takeda Parkway

  
	
   

  	
   

  	
  Deerfield, IL 60015

  
	
   

  	
   

  	
  Attention: General Counsel

  



 


16.4                        No Strict Construction;
Headings.  This Agreement has been prepared jointly by
the Parties and shall not be strictly construed against either Party. Ambiguities,
if any, in this Agreement shall not be construed against any Party,
irrespective of which Party may be deemed to have authored the ambiguous
provision. The headings of each Article and Section in this Agreement
have been inserted for convenience of reference only and are not intended to
limit or expand on the meaning of the language contained in the particular Article or
Section. Except where the context otherwise requires, the use of any gender
shall be applicable to all genders, and the word “or” is used in the inclusive
sense (and/or). The term “including” as used herein means including, without
limiting the generality of any description preceding such term.


 


16.5                        Assignment. 
Neither Party may assign or transfer this Agreement or any rights or
obligations hereunder without the prior written consent of the other, except
that a Party may make such an assignment without the other Party’s consent to
its Affiliates or to a Third Party successor to substantially all of the
business of such Party in connection with a Change of Control of such Party
(such Third Party, an “Acquiror”).
Any successor or assignee of rights and/or obligations permitted hereunder shall,
in writing to the other Party, expressly 


 


70

















 


assume performance of such rights and/or obligations. Any
permitted assignment shall be binding on the successors of the assigning Party.
Any assignment or attempted assignment by either Party in violation of the
terms of this Section 16.5 shall be null, void and of no legal effect. A “Change of Control”  of a Party shall
occur if: (i) any Third Party acquires directly or indirectly the
beneficial ownership of any voting security of such Party, or if the percentage
ownership of such person or entity in the voting securities of such Party is
increased through stock redemption, cancellation or other recapitalization, and
immediately after such acquisition or increase such Third Party is, directly or
indirectly, the beneficial owner of voting securities representing more than
fifty percent (50%) of the total voting power of all of the then-outstanding
voting securities of such Party; (ii) a merger, consolidation, recapitalization,
or reorganization of such Party is consummated, other than any such transaction
which would result in stockholders or equity holders of such Party or an
Affiliate of such Party immediately prior to such transaction owning at least
fifty percent (50%) of the outstanding securities of the surviving entity (or
its parent entity) immediately following such transaction; or (iii) the
stockholders or equity holders of such Party approve a plan of complete
liquidation of such Party, or an agreement for the sale or disposition by such
Party of all or a substantial portion of such Party’s assets, other than to an
Affiliate.


 


16.6                        Performance by
Affiliates.  Each Party may discharge any obligations and
exercise any right hereunder through any of its Affiliates. Each Party hereby
guarantees the performance by its Affiliates of such Party’s obligations under
this Agreement, and shall cause its Affiliates to comply with the provisions of
this Agreement in connection with such performance. Any breach by a Party’s
Affiliate of any of such Party’s obligations under this Agreement shall be
deemed a breach by such Party, and the other Party may proceed directly against
such Party without any obligation to first proceed against such Party’s
Affiliate.


 


16.7                        Further Actions. 
Each Party agrees to execute, acknowledge and deliver such further
instruments, and to do all such other acts, as may be necessary or appropriate
in order to carry out the purposes and intent of this Agreement.


 


16.8                        Severability. 
If any one or more of the provisions of this Agreement is held to be
invalid or unenforceable by any court of competent jurisdiction from which no
appeal can be or is taken, the provision shall be considered severed from this
Agreement and shall not serve to invalidate any remaining provisions hereof. The
Parties shall make a good faith effort to replace any invalid or unenforceable
provision with a valid and enforceable one such that the objectives
contemplated by the Parties when entering this Agreement may be realized.


 


16.9                        No Waiver. 
Any delay in enforcing a Party’s rights under this Agreement or any
waiver as to a particular default or other matter shall not constitute a waiver
of such Party’s rights to the future enforcement of its rights under this
Agreement, except with respect to an express written and signed waiver relating
to a particular matter for a particular period of time.


 


16.10                 Independent Contractors. 
Each Party shall act solely as an independent contractor, and nothing in
this Agreement shall be construed to give either Party the power or authority
to act for, bind, or commit the other Party in any way. Nothing herein shall be



 


71

















 


construed to create the relationship of partners,
principal and agent, or joint-venture partners between the Parties.


 


16.11                 English Language;
Governing Law.  This Agreement was prepared in the English
language, which language shall govern the interpretation of, and any dispute
regarding, the terms of this Agreement. This Agreement and all disputes arising
out of or related to this Agreement or any breach hereof shall be governed by
and construed under the laws of the State of New York, United States of
America, without giving effect to any choice of law principles that would require
the application of the laws of a different state.


 


16.12                 Counterparts. 
This Agreement may be executed in one (1) or more counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.


 


[Signature Page Follows]


 


72
















 


IN WITNESS WHEREOF, the Parties have
executed this Agreement in duplicate originals by their duly authorized
officers as of the Effective Date.


 


	
  TAKEDA
  PHARMACEUTICAL COMPANY LIMITED

  	
  AMAG
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  
	
   

  	
   

  
	
  By:

  	
  /s/ Yasuchika
  Hasegawa

  	
   

  	
  By:

  	
  /s/ Brian J.G.
  Pereira, M.D.

  
	
   

  	
   

  
	
  Name:

  	
  Yasuchika
  Hasegawa

  	
  Name:

  	
  Brian J.G.
  Pereira, M.D.

  
	
   

  	
   

  
	
  Title: 

  	
  President and
  Chief Executive Officer

  	
  Title: 

  	
  President and
  Chief Executive Officer

  
					



 

















 


Exhibits


 


	
  Exhibit A

  	
  Product
  Description

  
	
  Exhibit B

  	
  Licensed
  Territory

  
	
  Exhibit C-1

  	
  AMAG Patents

  
	
  Exhibit C-2

  	
  Takeda Patents

  
	
  Exhibit D

  	
  AMAG House Marks
  and AMAG Product Marks

  
	
  Exhibit E

  	
  Joint Press
  Release

  
	
  Exhibit F

  	
  Dispute
  Resolution

  
	
   

  	
   

  
	
  Schedules

  
	
   

  	
   

  
	
  Schedule 4.4(a)

  	
  Initial Studies

  
	
  Schedule 4.4(b)

  	
  U.S. Studies and
  Pediatric Studies

  
	
  Schedule 5.1

  	
  Clinical Trials
  of the Product

  
	
  Schedule 7.2

  	
  Supply Agreement Terms

  
	
  Schedule 7.3

  	
  Second Source
  Plan

  



[***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


EXHIBIT
A

PRODUCT DESCRIPTION


 


[***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


EXHIBIT
B

LICENSED TERRITORY


 


Part I (Europe)


 


Austria, Belgium, Bulgaria, Cyprus, Czech Republic,
Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy,
Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Romania,
Slovakia, Slovenia, Spain, Sweden, United Kingdom, Norway, Iceland and
Switzerland


 


Part II (Asia Pacific)


 


Australia, Brunei, Cambodia, Fiji, Indonesia,
Kiribati, North Korea, South Korea, Laos, Malaysia, Marshall Islands, Federated
States of Micronesia, Nauru, New Zealand, Palau, Papua New Guinea, Philippines,
Samoa, Singapore, Solomon Islands, Thailand, Timor-Leste, Tonga, Tuvalu,
Vanuatu, Vietnam, American Samoa, Guam and Northern Mariana Islands


 


Part III (CEE)


 


Albania, Croatia, Bosnia and Herzegovina, Serbia,
Montenegro and Macedonia


 


Part IV (CIS)


 


Georgia, Armenia, Azerbaijan, Belarus, Kazakhstan,
Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Ukraine and Uzbekistan


 


Party V


 


Canada, India and Turkey


 

















 


EXHIBIT
C-1

AMAG PATENTS


 


[***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


EXHIBIT
C-2

TAKEDA PATENTS


 


None


 

















 


EXHIBIT
D

AMAG HOUSE MARKS AND AMAG PRODUCT MARKS


 


AMAG HOUSE MARKS


 


AMAG PHARMACEUTICALS and all formulations of this
name, including any stylized representation of the letter “A”


 


AMAG PRODUCT MARKS


 


FERAHEME, PROHEMA, PROHEME, WELFEROX and ZENFEROX


 


	
  MARK

  	
   

  	
  COUNTRY

  	
   

  	
  APPLICATION/

  REGISTRATION

  NO.

  	
   

  	
  HISTORY & CURRENT

  STATUS

  
	
  FERAHEME

  	
   

  	
  Canada

  	
   

  	
  Application
  No. 1422447

  	
   

  	
  Filed 12/19/08,
  Allowed 1/15/10

  
	
  FERAHEME

  	
   

  	
  European Union

  	
   

  	
  Registration
  No. 7480916

  	
   

  	
  Filed 12/19/08,
  Registered 6/9/09

  
	
  FERAHEME

  	
   

  	
  India

  	
   

  	
  Application
  No. 1766038

  	
   

  	
  Filed 12/19/08

  
	
  FERAHEME

  	
   

  	
  Switzerland

  	
   

  	
  Registration
  No. 586630

  	
   

  	
  Filed 12/19/08,
  Registered 5/15/09

  



 
















 


EXHIBIT
E

JOINT PRESS RELEASE


 


AMAG
Pharmaceuticals and Takeda Pharmaceutical Company Announce Strategic
Collaboration for Feraheme® in All Therapeutic Indications in Select Ex-US
Territories, Including Europe


 


LEXINGTON, MA and Osaka, Japan (April 1, 2010) — AMAG
Pharmaceuticals, Inc. (NASDAQ: AMAG) and Takeda Pharmaceutical Company
Limited (TSE: 4502) today jointly announced that the companies have entered
into a license, development and commercialization agreement related to
Feraheme® (ferumoxytol) Injection for intravenous (IV) use in all
therapeutic indications.


 


Agreement Highlights


 


·                  Takeda receives an exclusive license to Feraheme for all therapeutic applications
in 5 regions, including Europe, Canada, Turkey, the Commonwealth of Independent
States and Asia Pacific countries, excluding Japan, China and Taiwan.


·                  AMAG receives a $60 million upfront payment and is
eligible to receive up to $220 million in development and commercial
milestones.  Additionally, AMAG will
receive tiered, double-digit royalties based on net sales of Feraheme in the licensed territories.


·                  AMAG will execute and fund the global clinical
development of Feraheme in all
potential therapeutic indications.  AMAG
will also be initially responsible for the filing of regulatory applications
for Feraheme in Europe and
Canada, with Takeda responsible for the regulatory filings in all other regions
covered by the agreement. Takeda will eventually hold all marketing
authorizations in the licensed territories.


·                  Takeda will be responsible for commercializing Feraheme in all regions included in the
licensed territories.


 


“One of our primary goals is to expand the reach of Feraheme to patients around the world with
iron deficiency anemia,” said Brian J.G. Pereira, MD, President and Chief Executive
Officer of AMAG Pharmaceuticals, Inc. 
“Takeda’s global presence, their pipeline that includes complementary
products to Feraheme and their
strength in the marketing and commercialization of therapeutics across many
specialties where iron deficiency anemia is present makes them the ideal
partner for Feraheme.”


 


“This partnership provides an exciting opportunity to
combine AMAG’s unique development abilities with Takeda’s global
commercialization capabilities,” said Alan MacKenzie, Executive Vice President,
International Operations & CEO, Takeda Pharmaceuticals International, Inc.
“Takeda is poised to maximize Feraheme’s
entry into the selected countries following approval.”


 

















 


Currently, Feraheme
is approved in the United States for the treatment of iron deficiency anemia
(IDA) in adult patients with chronic kidney disease. AMAG plans to submit a
marketing authorization application to the European Medicines Agency (EMA) for Feraheme for the treatment of IDA in adult
patients with chronic kidney disease in Europe in mid-2010. Additionally, AMAG
plans to initiate a broad global registrational program for Feraheme for the treatment of IDA
regardless of the underlying cause in mid-2010.


 


AMAG Conference Call and Webcast
Access


 


AMAG Pharmaceuticals, Inc. will host a webcast
and conference call today at 8:00 a.m. ET to discuss this announcement.


 


To access the conference call via telephone, please
dial (877) 412-6083 from the United States or (702) 495-1202 for international
access.  A telephone replay will be
available from approximately 11:00 a.m. ET on April 1, 2010 through
midnight April 2, 2010.  To access a
replay of the conference call, dial (800) 642-1687 from the United States or
(706) 645-9291 for international access. 
The passcode for the live call and the replay is 64493010.


 


The call will be webcast with slides and accessible
through the Investors section of the Company’s website at
www.amagpharma.com.  The webcast replay
will be available from approximately 11:00 a.m. ET on April 1, 2010
through midnight April 15, 2010.


 


About AMAG Pharmaceuticals, Inc.


 


AMAG Pharmaceuticals, Inc. is a biopharmaceutical
company that utilizes its proprietary technology for the development and
commercialization of a therapeutic iron compound to treat iron deficiency
anemia and novel imaging agents to aid in the diagnosis of cancer and
cardiovascular disease.  On June 30,
2009, AMAG received approval from the U.S. Food and Drug Administration to
market Feraheme® (ferumoxytol) Injection for intravenous (IV) use for the
treatment of iron deficiency anemia in adult chronic kidney disease
patients.  For additional company and
product information, please visit www.amagpharma.com.


 


About Takeda


 


Located in Osaka, Japan, Takeda is a research-based
global company with its main focus on pharmaceuticals. As the largest
pharmaceutical company in Japan and one of the global leaders of the industry,
Takeda is committed to striving toward better health for individuals and
progress in medicine. Additional information about Takeda is available through
its corporate website, www.takeda.com.


 

















 


Forward Looking Statements Related to
AMAG


 


This press release contains forward-looking statements
within the meaning of the Private Securities Litigation Reform Act of 1995 and
other federal securities laws. Any statements contained herein which do not
describe historical facts, including but not limited to, statements regarding
our plans to submit a market authorization application for Feraheme for the
treatment of IDA in chronic kidney disease patients in the European Union and
the timing of such submission and our plans to initiate a broad global
registrational program for Feraheme for the treatment of IDA regardless of the
underlying cause and the timing of such program initiation, the fact that
Takeda will eventually hold all Marketing Authorization applications in the
licensed territories, and our obligations under the agreement with Takeda are
forward looking statements which involve risks and uncertainties that could
cause actual results to differ materially from those discussed in such forward
looking statements. Such risks and uncertainties include: (1) uncertainties
regarding our ability to successfully and timely complete our clinical
development programs and obtain regulatory approval for Feraheme and compete in
the intravenous iron replacement market outside of the U.S., (2) the fact
that we have limited experience developing and commercializing a pharmaceutical
product on our own or with a partner like Takeda, particularly outside of the
U.S., (3) uncertainties regarding our ability to ensure favorable
coverage, pricing and reimbursement for Feraheme,
(4) uncertainties regarding our ability to manufacture Feraheme, (5) uncertainties relating
to our patents and proprietary rights, (6) the fact that significant
safety or drug interaction problems could arise with respect to Feraheme, and (7) other
risks identified in our Securities and Exchange Commission filings, including
our Annual Report on Form 10-K for the year ended December 31, 2009.
We caution you not to place undue reliance on any forward-looking statements,
which speak only as of the date they are made. We disclaim any obligation to
publicly update or revise any such statements to reflect any change in
expectations or in events, conditions or circumstances on which any such
statements may be based, or that may affect the likelihood that actual results
will differ from those set forth in the forward-looking statements.


 


Important Safety Information about Feraheme


 


Feraheme is indicated for the treatment of iron
deficiency anemia in adult patients with chronic kidney disease. Feraheme is contraindicated in patients
with evidence of iron overload, known hypersensitivity to Feraheme or any of its components, and
patients with anemia not caused by iron deficiency.


 


In clinical studies, serious hypersensitivity
reactions were reported in 0.2% (3/1,726) of subjects receiving Feraheme. Other adverse reactions
potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria
or wheezing) were reported in 3.7% (63/1,726) of subjects. Patients should be
observed for signs and symptoms of hypersensitivity for at least 30 minutes
following Feraheme injection and
the drug should only be administered when personnel and therapies are


 

















 


readily available for the treatment of
hypersensitivity reactions.  1.9%
(33/1,726) of Feraheme-treated
subjects experienced hypotension. Please monitor for signs and symptoms of
hypotension following each Feraheme
injection. Excessive therapy with parenteral iron can lead to excess storage of
iron with the possibility of iatrogenic hemosiderosis. Patients should be
regularly monitored for hematologic response during parenteral iron therapy,
noting that lab assays may overestimate iron and transferrin bound iron values
in the 24 hours after administration of Feraheme.  As a superparamagnetic iron oxide, Feraheme may transiently affect magnetic
resonance diagnostic imaging studies for up to 3 months following the last
Feraheme dose.  Feraheme will not affect X-ray, (CT, PET,
SPECT, ultrasound, or nuclear imaging.


 


In clinical trials, the most commonly occurring
adverse reactions in Feraheme
treated patients versus oral iron treated patients reported in > 2%
of chronic kidney disease patients were diarrhea (4.0% vs. 8.2%), nausea (3.1%
vs. 7.5%), dizziness (2.6% vs. 1.8%), hypotension (2.5% vs. 0.4%), constipation
(2.1% vs. 5.7%) and peripheral edema (2.0% vs. 3.2%). In clinical trials,
adverse reactions leading to treatment discontinuation and occurring in 2 or
more Feraheme-treated patients
included hypotension, infusion site swelling, increased serum ferritin level,
chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic renal failure,
and urticaria.


 


Feraheme is a registered trademark of AMAG Pharmaceuticals, Inc.


 


AMAG Pharmaceuticals Contacts:


 


Amy Sullivan: 
+1-617-498-3303


 


Carol Miceli: 
+1-617-498-3361


 


Takeda Pharmaceuticals Contacts:


 


Seizo Masuda:  +81 3 3278 2037


 


Nick Francis:  +44 20 3116 8861


 


###


 

















 


EXHIBIT
F

DISPUTE RESOLUTION


 


All references to “days” in
this ADR provision are to calendar days.


 


1.                                      To
begin an ADR proceeding, a Party shall provide written notice to the other
Party of the issues to be resolved by ADR. 
Within [***] after its receipt of such notice, the other Party may, by
written notice to the Party initiating the ADR, add additional issues to be
resolved within the same ADR.


 


2.                                      Within
twenty-one (21) days following receipt of the original ADR notice, the Parties
shall select a mutually acceptable panel of three (3) neutrals to preside
in the resolution of any disputes in this ADR proceeding.  If the Parties are unable to agree on a
mutually acceptable panel of three (3) neutrals within such period, either
Party may request the President of the International Institute for Conflict
Prevention and Resolution (“CPR”), 575 Lexington Avenue, 21st floor New York, New York 10022, to select a
panel of three (3) neutrals pursuant to the following procedures:


 


(a)                                  The
CPR shall submit to the Parties a list of not less than nine (9) candidates
within [***] after receipt of the request, along with a Curriculum Vitae for
each candidate.  No candidate shall be an
employee, director, or shareholder of either Party or any of their Affiliates.


 


(b)                                  Such
list shall include a statement of disclosure by each candidate of any
circumstances likely to affect his or her impartiality.


 


(c)                                  Each
Party shall number the candidates in order of preference (with the number one (1) signifying
the greatest preference) and shall deliver the list to the CPR within [***]
following receipt of the list of candidates. 
If a Party believes a conflict of interest exists regarding any of the
candidates, that Party shall provide a written explanation of the conflict to
the CPR along with its list showing its order of preference for the
candidates.  Any Party failing to return
a list of preferences on time shall be deemed to have no order of preference.


 


(d)                                  If the
Parties collectively have identified fewer than four (4) candidates deemed
to have conflicts, the CPR immediately shall designate as the panel of three (3) neutrals
the three candidates for whom the Parties collectively have indicated the
greatest preference.  If a tie should
result between two candidates, the CPR may designate either candidate.  If the Parties collectively have identified
four (4) or more candidates deemed to have conflicts, the CPR shall review
the explanations regarding conflicts and, in its sole discretion, may either (i) immediately
designate


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


as the neutral the candidate for whom the Parties collectively have
indicated the greatest preference, or (ii) issue a new list of not less
than nine (9) candidates, in which case the procedures set forth in
subparagraphs 2(a) - 2(d) shall be repeated.


 


3.                                      No
earlier than  [***] after selection, the
panel shall hold a hearing to resolve each of the issues identified by the
Parties.  The ADR proceeding shall take
place at a location agreed upon by the Parties. 
If the Parties cannot agree, the panel shall designate a location other
than the principal place of business of either Party or any of their
Affiliates.  Commencing on the date [***]
after receipt of the initial ADR notice described in paragraph 1 above, the
Parties shall be entitled to engage in reasonable discovery under procedures of
the Federal Rules of Civil Procedure; provided, however, that a party may
not submit more than fifty (50) written interrogatories or take more than six (6) depositions.  There shall not be any, and the panel shall
not permit any, discovery [***].  The
panel shall decide any disputes between the Parties related to discovery,
including ruling on reasonable requests to expedite discovery, taking into
account the applicable period of time for discovery.


 


4.                                      At
least [***] prior to the hearing, each Party shall submit the following to the
other Party and the panel:


 


(a)                                  a copy
of all exhibits on which such Party intends to rely in any oral or written
presentation to the panel;


 


(b)                                  a list
of any witnesses such Party intends to call at the hearing, and a short summary
of the anticipated testimony of each witness;


 


(c)                                  a
proposed ruling on each issue to be resolved, together with a request for a
specific damage award or other remedy for each issue.  The proposed rulings and remedies shall not
contain any recitation of the facts or any legal arguments and shall not exceed
[***].


 


(d)                                  a
brief in support of such Party’s proposed rulings and remedies, provided that
the brief shall not exceed [***].  This page limitation
shall apply regardless of the number of issues raised in the ADR proceeding.


 


5.                                      The
hearing shall be conducted on [***] and shall be governed by the following
rules:


 


(a)                                  Each
Party shall be entitled to [***] of hearing time to present its case.  The panel shall determine whether each Party
has had [***] to which it is entitled.


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2
PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


(b)                                  Each
Party shall be entitled, but not required, to make an opening statement, to
present regular and rebuttal testimony, documents or other evidence, to
cross-examine witnesses, and to make a closing argument.  Cross-examination of witnesses shall occur
immediately after their direct testimony, and cross-examination time shall be
charged against the Party conducting the cross-examination.


 


(c)                                  The
Party initiating the ADR shall begin the hearing and, if it chooses to make an
opening statement, shall address not only issues it raised but also any issues
raised by the responding Party.  The
responding Party, if it chooses to make an opening statement, also shall
address all issues raised in the ADR. 
Thereafter, the presentation of regular and rebuttal testimony and
documents, other evidence, and closing arguments shall proceed in the same
sequence.


 


(d)                                  Except
when testifying, witnesses shall be excluded from the hearing until closing
arguments.


 


(e)                                  Settlement
negotiations, including any statements made therein, shall not be admissible
under any circumstances.  Affidavits
prepared for purposes of the ADR hearing also shall not be admissible.  As to all other matters, the panel shall have
sole discretion regarding the admissibility of any evidence.


 


6.                                      Within
[***] following completion of the hearing, each Party may submit to the other
Party and the panel a post-hearing brief in support of its proposed rulings and
remedies, provided that such brief shall not contain or discuss any new
evidence and shall not exceed [***]. 
This page limitation shall apply regardless of the number of issues
raised in the ADR proceeding.


 


7.                                      The
panel shall rule on each disputed issue in writing within [***] following
completion of the hearing.  Such ruling
shall adopt in its entirety the proposed ruling and remedy of one of the
Parties on each disputed issue but may adopt one Party’s proposed rulings and
remedies on some issues and the other Party’s proposed rulings and remedies on
other issues.  The panel shall not issue
any written opinion or otherwise explain the basis of the ruling.


 


8.                                      The
panel shall be paid a reasonable fee plus expenses.  These fees and expenses, along with the
reasonable legal fees and expenses of the prevailing Party (including all
expert witness fees and expenses), the fees and expenses of a court reporter,
and any expenses for a hearing room, shall be paid as follows:


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


(a)                                  If the
panel rules in favor of one Party on all disputed issues in the ADR, the
losing Party shall pay 100% of such fees and expenses.


 


(b)                                  If the
panel rules in favor of one Party on some issues and the other Party on
other issues, the panel shall issue with the rulings a written determination as
to how such fees and expenses shall be allocated between the Parties.  The panel shall allocate fees and expenses in
a way that bears a reasonable relationship to the outcome of the ADR, with the
Party prevailing on more issues, or on issues of greater value or gravity,
recovering a relatively larger share of its legal fees and expenses.


 


9.                                      The
rulings of a majority of the panel and the allocation of fees and expenses
shall be binding, non-reviewable, and non-appealable, and may be entered as a
final judgment in any court having jurisdiction.


 


10.                               Except
as provided in paragraph 9 or as required by law, the existence of the dispute,
any settlement negotiations, the ADR hearing, any submissions (including
exhibits, testimony, proposed rulings, and briefs), and the rulings shall be
deemed Confidential Information.  The
panel shall have the authority to impose sanctions for unauthorized disclosure
of Confidential Information.


 

















 


SCHEDULE
4.4(a)

Initial Studies


 


	
  FER-CKD-201

  	
   

  	
  Ferumoxytol Compared to Iron Sucrose Trial (FIRST):
  A Randomized, Multicenter, Trial of Ferumoxytol Compared to Iron Sucrose for
  the Treatment of Iron Deficiency Anemia in Adult Subjects with Chronic Kidney
  Disease

  
	
   

  	
   

  	
   

  
	
  [***]

  	
   

  	
  [***]

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-IDA-302

  	
   

  	
  A Phase III, Randomized, Open-label,
  Active-Controlled, Trial Comparing Ferumoxytol with Iron Sucrose for the
  Treatment of Iron Deficiency Anemia

  



 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


SCHEDULE
4.4(b)

U.S. Studies and Pediatric Studies


 


	
  AMAG-FER-CKD-251

  	
   

  	
  A Randomized, Open-Label, Active-Controlled Study of
  the Safety, Efficacy, and Pharmacokinetics of Ferumoxytol Compared with Oral
  Iron for the Treatment of Iron Deficiency Anemia in Pediatric Subjects with
  Dialysis-dependent Chronic Kidney Disease

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-CKD-252

  	
   

  	
  A Randomized, Open-Label, Active-Controlled Study of
  the Safety, Efficacy, and Pharmacokinetics of Ferumoxytol Compared with Oral
  Iron for the Treatment of Iron Deficiency Anemia in Pediatric Subjects with
  Nondialysis-dependent Chronic Kidney Disease

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-CKD-253

  	
   

  	
  An Open-Label Extension Study of the Safety and
  Efficacy of Ferumoxytol for the Episodic Treatment of Iron Deficiency Anemia
  in Pediatric Subjects with Chronic Kidney Disease

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-IDA-301

  	
   

  	
  A Phase III, Randomized, Double-Blind, Placebo-Controlled
  Trial of Ferumoxytol for the Treatment of Iron Deficiency Anemia

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-IDA-303

  	
   

  	
  A Phase III, Open-Label Extension Trial of the
  Safety and Efficacy of Ferumoxytol for the Episodic Treatment of Iron
  Deficiency Anemia

  
	
   

  	
   

  	
   

  
	
  AMAG-FER-IDA-251

  	
   

  	
  A Randomized, Open-Label, Active-Controlled Study of
  the Safety, Efficacy, and Pharmacokinetics of Ferumoxytol Compared With Oral
  Iron for the Treatment of Iron Deficiency Anemia in Pediatric Subjects

  



 
















 


SCHEDULE 5.1


 


Clinical Trials of the Product


 


	
  STUDIES IN HEALTHY VOLUNTEERS

  
	
   

  
	
  Type of Study

  	
   

  	
  Phase I, PK and safety

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  7228-01, “A Phase I clinical
  investigation of Code 7228”

  Start date:
  09-June-1999; Completion date: 04-August-1999

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.3.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the PK and safety of ferumoxytol at
  increasing dose levels and at various rates of administration

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Randomized, double-blind, placebo-controlled, single
  center, ascending dose

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol:1 mg Fe/kg, 2 mg Fe/kg, 4 mg Fe/kg; IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  N=41 (randomized): Ferumoxytol- 35; Placebo - 6

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Healthy volunteers: M: 22; F: 19

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  Single dose

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR 7228-01

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase 1, Thorough QTc and PK

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-9, “A Phase I active and
  placebo-controlled study of the electrocardiogram effects and
  pharmacokinetics of ferumoxytol in healthy men and women”

  Start date:
  22-May-2006; Completion date: 4-September-2006

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.4.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To define the effect of ferumoxytol on the QT
  interval; to assess PK and tolerability

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Active- and placebo-controlled, randomized,
  double-blind (with respect to ferumoxytol and placebo), parallel group,
  single-center

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: Two 510 mg doses of ferumoxytol
  administered on two consecutive days  Placebo (saline); IV

  Moxifloxacin (400 mg) as active control; Oral

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  174 Total (randomized): Ferumoxytol -58;
  Moxifloxacin -58; Placebo-58

  



 

















 


	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Healthy volunteers: M:102, F:72

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  2 x 510 mg doses of ferumoxytol administered on two
  consecutive days

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-9

  
	
   

  	
   

  	
   

  
	
  STUDIES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

  
	
   

  
	
  Type of Study

  	
   

  	
  Phase I, PK and safety

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-2, “A Phase I open-label,
  rate administration, pharmacokinetic study of the safety of Code 7228 as an
  iron replacement therapy in chronic hemodialysis patients who are receiving
  supplemental EPO therapy”

  Start date:
  26-Sep-2001; Completion date: 10-Apr-2002

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.3.2

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  The objective of this study was to evaluate the
  safety and PK of two doses (125 and 250 mg) of ferumoxytol in subjects with
  CKD stage 5D who were on HD and receiving supplemental EPO therapy

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Open-label, single center; Uncontrolled

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: 1 x 125 mg, 1 x
  250 mg; IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  20 Total (enrolled): Ferumoxytol 125 mg — 10;
  Ferumoxytol 250 mg - 10

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of Patients

  	
   

  	
  Patients with CKD stage 5D on hemodialysis; M: 10,
  F: 10

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  Single dose

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-2

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase II, Safety/Efficacy

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-3, “A Phase II, Open-Label
  Study of the Safety and Efficacy of Two Parenteral Dose Regimens of Code 7228
  (Compared With Oral Iron) as an Iron Replacement Therapy in Chronic
  Hemodialysis Patients Who Are Receiving Supplemental EPO Therapy”

  Start date:
  20-Jan-2003; Completion date: 19-June-2003

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and efficacy of two
  parenteral dose regimens of ferumoxytol compared with oral iron

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Multicenter, open label; Active control

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: 8 x 128 mg, 2 x
  510 mg; IV

  Oral iron: 325 mg per day

  



 

















 


	
  Number of Subjects

  	
   

  	
  36 Total (enrolled): Ferumoxytol 8 x 128 mg - 15;
  Ferumoxytol 2 x 510 mg — 11;

  Oral iron - 10

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stage 5D on hemodialysis: M: 21,
  F: 15

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  8 x 128 mg doses of ferumoxytol within 4 weeks; 2x
  510 mg of ferumoxytol within 2 weeks; daily oral iron for 8 sequential
  dialysis sessions (approx. 3 weeks)

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-3

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase II, Safety/Efficacy

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-4, “A Phase II, Open-Label
  Study of the Safety and Efficacy of Two Parenteral Dose Regimens of Code 7228
  (Ferumoxytol) as an Iron Replacement Therapy in Chronic Kidney Disease
  Patients or Patients on Peritoneal Dialysis”

  Start date:
  07-Oct-2002; Completion date: 27-Dec-2002

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.2

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and efficacy of two
  parenteral dose regimens of ferumoxytol in subjects with chronic renal
  failure (not on dialysis), or who were on PD

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Multicenter, open label; Uncontrolled

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: 4 x 255 mg, 2 x
  510 mg; IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  21 Total (enrolled): Ferumoxytol 4 x 255 mg - 10;
  Ferumoxytol 2 x 510 mg - 11

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stages 1-5 not on hemodialysis; M:
  9, F: 12

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  4 x 255 mg of ferumoxytol each separated by 2-3
  days; 2 x 510 mg doses of ferumoxytol each separated by 2-3 days

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Completed; Full report CSR-62745-4

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase III, Safety/Efficacy

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-5, “A Phase III Study of the
  Safety and Efficacy of Ferumoxytol (Compared with Oral Iron) as an Iron
  Replacement Therapy in Hemodialysis Patients who are Receiving Supplemental
  Erythropoietin Therapy”

  Start date:
  09-Aug-2004; Completion date: 24-Apr-2007

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and efficacy of ferumoxytol
  versus oral iron as an iron replacement therapy in subjects with CKD stage 5D
  on HD who were receiving supplemental ESA therapy

  



 

















 


	
  Study Design and Type of Control

  	
   

  	
  Randomized, multicenter, open label; Active control

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen; Route
  of Administration

  	
   

  	
  Ferumoxytol: Post-amendment: 2 x 510 mg;
  Pre-amendment: 4 x 255 and 2 x 510 mg; IV

  Oral iron: 200 mg per day

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  378 Total (randomized): Post-amendment: 230 Total;
  Ferumoxytol -114; Oral Iron-116

  Pre-amendment: 148 Total; Ferumoxytol 4x255 mg — 62; Ferumoxytol -2x510 mg -
  64; Oral Iron - 22

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stage 5D on hemodialysis;

  Post- amendment: M: 130, F: 100; Pre-amendment: M: 63, F: 85

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  2 x 510 mg doses ferumoxytol within 7 days; 4 x 255
  mg doses of ferumoxytol, within 14 days; or oral iron for 21 consecutive days

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR 62745-5

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase III, Safety/Efficacy

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-6, “A Phase III Study of the
  Safety and Efficacy of Ferumoxytol (Compared with Oral Iron) as an Iron
  Replacement Therapy in chronic kidney disease patients not on dialysis”

  Start date:
  10-May-2004; Completion date: 25-Sep-2006

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and efficacy of ferumoxytol
  versus oral iron for iron replacement therapy in subjects with CKD stages 1-5

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Randomized, multicenter, open label; Active control

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol; 2 x 510 mg; IV;

  Oral iron: 200 mg per day

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  304 Total (randomized): Ferumoxytol - 228; Oral Iron
  - 76

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stages 1-5: M: 118, F: 186

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  2 x 510 mg doses of ferumoxytol within 5±3 days, or
  21 consecutive days of oral iron

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-6

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase III, Safety/Efficacy

  



 

















 


	
  Study Identifier

  	
   

  	
  62,745-7, “A Phase III Study of the
  Safety and Efficacy of Ferumoxytol (Compared with Oral Iron) as an Iron
  Replacement Therapy in chronic kidney disease patients not on dialysis”

  Start date:
  02-June-2004; Completion date: 20-Dec-2006

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and efficacy of ferumoxytol
  versus oral iron for iron replacement therapy in subjects with CKD stages 1-5

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Randomized, multicenter, open label; Active control

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: 2 x 510 mg; IV

  Oral iron: 200 mg per day

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  304 Total (randomized): Ferumoxytol - 227; Oral Iron
  — 77

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stages 1-5; M: 125, F: 179

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  Two IV doses of ferumoxytol within 5±3 days, or 21
  consecutive days of oral iron

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-7

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase III, Safety

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  62,745-8, “A Double Blind, Placebo
  Controlled, Crossover Design, Multicenter Study of Intravenous Ferumoxytol
  Compared with Placebo”

  Start date:
  27-Jan-2005; Completion date: 6-Sep-2006

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.1

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To compare the safety of a single 510 mg dose of IV
  ferumoxytol versus a single dose of IV saline placebo in subjects with all
  stages of CKD

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Randomized, multicenter, double-blind, placebo
  controlled, crossover design

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol; 1 x 510 mg; IV

  Placebo (saline); IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  N=750 (randomized)

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Patients with CKD stages 1-5 and 5D: M: 347, F: 403

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  A single dose, followed by the crossover dose 7±2
  days later

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Full report CSR-62745-8

  



 

















 


	
  STUDIES IN MEDICAL IMAGING SUBJECTS (PATIENTS AND HEALTHY
  VOLUNTEERS)

  
	
   

  
	
  Type of Study

  	
   

  	
  Phase I/IIA, Safety

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  58,254-2, “A Phase I/IIa Pilot Investigation Of Code 7228 As A
  Magnetic Resonance Angiography Contrast Agent”

  Start date: 01-Nov-2001; Completion date:
  11-May-2002

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.4

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and imaging feasibility of
  ferumoxytol

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Open label, single center; Uncontrolled

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol; <4 mg Fe/kg; IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  17 Total (enrolled): Healthy volunteers — 10;
  Imaging patients - 7

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Healthy volunteers and imaging patients: M: 12, F: 5

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  Single dose

  
	
   

  	
   

  	
   

  
	
  Study Status; Type of Report

  	
   

  	
  Complete; Abbreviated report CSR-58254-2

  
	
   

  	
   

  	
   

  
	
  Type of Study

  	
   

  	
  Phase II, Safety

  
	
   

  	
   

  	
   

  
	
  Study Identifier

  	
   

  	
  58,254-5, “A Phase 2 Investigation
  of Code 7228 as a Magnetic Resonance Angiography Contrast Agent”

  Start date:
  7-Aug-2002; Completion date: 6-Sep-2005

  
	
   

  	
   

  	
   

  
	
  Location of Study Report

  	
   

  	
  Module 5.3.5.4

  
	
   

  	
   

  	
   

  
	
  Objective(s) of the Study

  	
   

  	
  To evaluate the safety and imaging feasibility of
  ferumoxytol

  
	
   

  	
   

  	
   

  
	
  Study Design and Type of Control

  	
   

  	
  Open label, single center; Uncontrolled

  
	
   

  	
   

  	
   

  
	
  Test Product(s): Dosage Regimen;
  Route of Administration

  	
   

  	
  Ferumoxytol: <4 mg Fe/kg; IV

  
	
   

  	
   

  	
   

  
	
  Number of Subjects

  	
   

  	
  49 Total (enrolled): Healthy volunteers - 15;
  Imaging patients - 34

  
	
   

  	
   

  	
   

  
	
  Healthy Subjects or Diagnosis of
  Patients

  	
   

  	
  Healthy volunteers and imaging patients; M: 29, F:
  20

  
	
   

  	
   

  	
   

  
	
  Duration of Treatment

  	
   

  	
  Single or incremental dose within the same imaging
  session

  



 

















 


	
  Study Status; Type of Report

  	
   

  	
  Complete; Abbreviated report CSR-58254-5

  



 


CKD: Chronic kidney disease; HD: Hemodialysis; PK:
Pharmacokinetics; IV: Intravenous; M: Male; F: Female; ESA: Erythropoiesis
stimulating agent; PD: Peritoneal dialysis; CSR: Clinical study report; N/A:
Not applicable.


 
















 


SCHEDULE 7.2


 


SUPPLY AGREEMENT TERMS


 


This Schedule 7.2 describes
the basic scope and principles to be included in the Supply Agreement, which
will govern supply of Takeda’s requirements of both clinical and commercial
quantities of the Product pursuant to the terms of Article 7 of the
License, Development and Commercialization Agreement (the “Agreement”).


 


Scope


 


1)                                     Each Party shall appoint appropriate representatives
to negotiate the Supply Agreement.


 


2)                                     This Schedule 7.2 is not intended to include all terms
and conditions anticipated to be included in the Supply Agreement.  The Supply Agreement will describe and define
the procedures, terms and conditions for forecasting, manufacture, quality
assurance, delivery, price, payment and appropriate other activities relating
to the supply of the Product in the Field and in the Licensed Territory
consistent with the terms described below and will contain such other terms and
conditions customarily contained in supply agreements in the pharmaceutical
industry, including without limitation warranties and indemnities.


 


General


 


1)                                     Takeda shall purchase exclusively from AMAG, and AMAG
shall supply, all of Takeda’s and its Affiliates’ and its/their sublicensees’
requirements of the Product, except as otherwise provided in this Schedule 7.2
and the Agreement.  AMAG shall supply
Takeda (either by itself or through its Designated Second Source Suppliers
(each, a “DSS”)) with the Product
in unlabeled finished form for use under the Agreement and in accordance with
the terms of the Supply Agreement.


 


2)                                     The term of the Supply Agreement shall be coextensive
with the Term of the Agreement.


 


3)                                     AMAG shall use Commercially Reasonable Efforts to
manage Takeda’s supply needs (e.g., volumes and unit costs) for the Licensed
Territory in a manner proportionate to AMAG’s supply needs outside the Licensed
Territory.


 


23

















 


Price/ Payment


 


1)                                     The purchase price for commercial and clinical supply
shall be [***].


 


[***]


 


2)                                     The Supply Agreement will include a mechanism for
applying annual volume-based pricing, which may include an annual true-up or
other adjustment mechanism agreed by the Parties.


 


3)                                     “Fully Burdened Manufacturing Cost” means the
consolidated fully burdened cost incurred by AMAG in the Manufacture of Product
(calculated in accordance with GAAP) of the following items: (i) direct
and indirect cost of any materials; (ii) direct labor costs (including
benefits); (iii) factory overhead (fixed and variable); (iv) operating
costs of facilities and equipment (including idle plant capacity); (v) a
charge for depreciation and repairs and maintenance costs of facilities and
equipment; (vi) quality and in-process control costs; and (vii) charges
for spoilage and scrap.  Each such cost described
in items (i) through (vii) above shall be determined in accordance
with AMAG’s accounting practices applied on a normal and customary basis by
AMAG consistent with its practices. 
Notwithstanding the foregoing, Fully Burdened Manufacturing Cost shall
not include any costs for unusable batches resulting from AMAG’s failure to
conduct its manufacturing activities in accordance with the terms of the Supply
Agreement or any profit related to inter-company transfer pricing.  To the extent that a Product, or any
component thereof, is Manufactured for AMAG by a Third Party, amounts paid by
AMAG to such Third Party directly for Manufacture will be added, without mark
up, to the aggregate amount of the foregoing items.  The Parties acknowledge and agree that [***].


 


4)                                     Payment terms are [***] from receipt of invoice
(invoice will not be issued prior to shipment).


 


5)                                     [***]


 


6)                                     AMAG shall consult with Takeda regarding any capital
equipment proposed to be acquired for use in supplying Product to Takeda and
for which Takeda would bear all or some portion of the costs.  Takeda will be responsible to AMAG for any
capital equipment expenditures made after the Effective Date to the extent
attributable to AMAG’s supply of Product to Takeda for the Licensed Territory where
Takeda agrees to such expenditures or to the extent that such capital equipment
purchase is reasonably necessary to the manufacture of the Product for 


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


the
Licensed Territory.  If any such
equipment is attributable to both the Licensed Territory and outside the
Licensed Territory, the Parties will use good faith efforts to agree on a
reasonable allocation of such expenditures to the Licensed Territory and
outside the Licensed Territory, based on the volumes supplied for each such
territory.  The Supply Agreement will
include a mechanism for resolving any disagreement between the Parties as to
the acquisition of any such equipment and/or the allocation between the Parties
of the expenditure.


 


Forecasting and Ordering


 


1)                                     Commencing twelve (12) months prior to the anticipated
First Commercial Sale of the Product in the Licensed Territory, and at the
beginning of each calendar quarter thereafter, Takeda shall provide AMAG with
twelve (12) month rolling forecasts of its requirements of the Product for the
Licensed Territory, [***] of which shall be binding.  Each such forecast shall be consistent with
Takeda’s projected commercial sales of the Product in the Licensed Territory on
a quarterly basis.  If the First
Commercial Sale of the Product is delayed, upon Takeda’s request, AMAG will use
Commercially Reasonable Efforts to utilize outside of the Licensed Territory
those quantities of Product representing the binding portion of such forecasts.


 


2)                                     If Takeda places an order exceeding its forecast for
the period to which the purchase order applies, AMAG shall supply up to [***]
of Takeda’s forecasted quantities for such period. AMAG shall use Commercially
Reasonable Efforts to supply Takeda with any quantities of Product over [***]
of the relevant forecast for such period. 
For clarity, any capital expenditure required for such increased amounts
shall be addressed through the mechanism above in Price/Payment (item 6).


 


3)                                     The Supply Agreement will contain mutually agreed
information sharing and planning procedures with respect to the forecasting,
supply and quality of the Product, including a mechanism for addressing
increases and decreases to the non-binding portion of Takeda’s forecast.


 


Delivery


 


Delivery requirements,
location and Incoterms shall be defined in the Supply Agreement.


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


Manufacture
and Quality Control


 


1)                                     Product shall be manufactured in compliance with cGMP,
as defined by Regulatory Authorities within the Licensed Territory.  The Product shall be manufactured according
to specifications for the Product set forth in the Supply Agreement
(“Specifications”), which initially shall be the specifications for Product
supplied by AMAG for the U.S. as of the Effective Date.


 


2)                                     The Supply Agreement will contain change control
procedures for the Specifications and other related matters.  Change requests will be made pursuant to a
written change request process agreed by both parties.  The change request process will also document
any changes to estimated timelines and costs. 
The parties must mutually agree to any changes to the Specifications,
including any changes that require prior approval by a Regulatory
Authority.  Takeda will bear the cost of
any approved changes to the extent requested by it or implemented in connection
with any change to comply with regulatory requirements or any Regulatory
Approval in the Licensed Territory; provided that AMAG shall use Commercially
Reasonable Efforts to implement such changes in a cost-effective manner.


 


3)                                     The Supply Agreement shall define a procedure for
notification of each party in the event of a product complaint from the field
or product recall.


 


4)                                     The Supply Agreement shall define a procedure for
resolution of any disputes regarding product quality.


 


5)                                     The Supply Agreement shall define safety and waste
handling procedures relating to the Product and its Manufacture.


 


6)                                     Some or all of items (1)-(5) may be included in
the quality agreement (as described below).


 


7)                                     Each Party will have a reciprocal audit right
allowing, during regular business hours, reasonable access by the other Party’s
quality assurance, quality control, compliance and other relevant personnel
(including the other Party’s consultants who are under the same confidentiality
and limited use obligations under this Agreement), upon reasonable notice, to
audit its facilities and/or its contract manufacturing/laboratory sites where
the Product is manufactured, packaged, labeled and/or tested, and shall allow
reasonable access to related documentation; provided that AMAG shall have the
right to redact CMC Information from any documentation provided to Takeda.  The purpose of such audit shall be to assess
compliance with the cGMP and applicable Laws in the country of manufacture.


 


Transfer of Analytical
Methods (QA)


 


The Supply Agreement will
contain mutually acceptable provisions regarding release testing of the Product
and, if applicable, the transfer of information necessary for Takeda to perform
required quality testing, as applicable.


 

















 


Quality
Agreement


 


The parties will work in
good faith to complete a quality agreement on a mutually agreed time frame
prior to First Commercial Sale of the Product, or as soon as practicable
following the Effective Date if the Parties determine a quality agreement is
necessary with respect to clinical supply of Product.


 


Second
Source / Safety Stock


 


1)                                     The Supply Agreement will contain detailed procedures
for implementing the Second Source Plan in accordance with Section 7.3 of
the Agreement and this Schedule 7.2.


 


2)                                     AMAG shall pay all costs associated with qualifying,
initiating and maintaining each DSS as set forth in the Second Source Plan as
of the Effective Date.  Costs for
additional qualification, initiation and maintenance of such DSSs or additional
designated second source suppliers will be allocated between AMAG and Takeda to
the extent attributable to outside the Licensed Territory and the Licensed
Territory, respectively.  The Parties
shall use good faith efforts to agree on a reasonable allocation, based on the
volumes supplied for each such territory.


 


3)                                     AMAG and/or its DSS shall manufacture and maintain at
a designated facility at AMAG’s expense a safety stock of Product inventory
exclusive to Takeda in an amount equal to [***] in accordance with the terms of
the Supply Agreement.  On a quarterly
basis, AMAG shall inform Takeda of the then-current inventory and other
relevant information for the safety stock. 
AMAG shall have the right to supply Takeda Product from the safety
stock.  AMAG shall use Commercially
Reasonable Efforts to restore safety stock as soon as reasonably
practicable.  The Supply Agreement will
include a mechanism to address the situation where AMAG is unable to restore
safety stock to the required level within a mutually agreed time period.


 


4)                                     AMAG shall have the right to use a DSS for the supply
of Product to Takeda for the Licensed Territory (e.g., to supplement existing
capacity, to purchase safety stock, or to obtain more favorable pricing for
AMAG and Takeda).  AMAG shall notify and
consult with Takeda regarding any such decision and keep Takeda reasonably
informed of its use of the DSS.  AMAG
will consider Takeda’s comments to such arrangement in good faith and use
Commercially Reasonable Efforts to ensure that Takeda’s current and anticipated
demand of the Product, consistent with amounts forecasted by Takeda, will be
met in accordance with the terms of the Supply Agreement, and that any
incremental cost for supply of 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


Product
from the DSS is reasonably allocated to the Licensed Territory and outside the
Licensed Territory, based on the volume demands of each such territory.  In the event AMAG sources Product to supply
to Takeda from a DSS, AMAG shall provide such Product to Takeda [***].


 


5)                                     If Takeda anticipates specific Product sourcing needs
in a Product configuration not in existence as of the Effective Date (e.g.,
package size or dosage form specific to the Licensed Territory), Takeda shall
notify AMAG, and the Parties shall meet to discuss such needs in good faith and
a reasonable means for satisfying Takeda’s request for Product.  The Parties anticipate that AMAG shall be the
supplier of such Product.  AMAG shall use
Commercially Reasonable Efforts to satisfy Takeda’s new Product supply needs
itself or through one or more DSS, subject to the Parties’ mutual written
consent, not to be unreasonably withheld. 
[***]  If any such expenses are
attributable to both the Licensed Territory and outside the Licensed Territory,
the Parties will use good faith efforts to agree on a reasonable allocation of
such expenses to the Licensed Territory and outside the Licensed Territory,
based on the volumes supplied for each such territory.


 


6)                                     As to be further detailed in the Supply Agreement,
Takeda shall have the right to obtain Product for use in the Licensed Territory
from a DSS through a contract to which AMAG is a party upon the following
events:  (A) an Insolvency Event of
AMAG, (B) a failure by AMAG, in any calendar quarter, to supply in accordance
with the terms of the Supply Agreement at least [***] (C) a failure by
AMAG, in each of two (2) consecutive calendar quarters, to supply in
accordance with the terms of the Supply Agreement [***] (each of (A) through
(C), a “Transfer Event”).  Upon the occurrence of a Transfer Event,
Takeda shall notify AMAG of its intent to source from the DSS and shall have
the right to purchase from the DSS that amount of Product that AMAG failed to
supply based upon Takeda’s binding purchase orders, plus any additional amount
that takes into consideration the current deficit (if any) in safety stock,
Takeda’s customer’s orders for the applicable calendar quarter, and minimum
batch sizes or other minimum supply requirements imposed by a DSS.  For clarity, Takeda’s rights under this item (6) 
(and the licenses granted in Section 2.1(a) of the Agreement) are
limited solely to obtaining Product from a DSS, and Takeda shall have no right
to receive (or provide to any Third Party) any AMAG Know-How related to
Manufacturing of the Product except for the CMC Information expressly provided
in the Agreement or to the extent that disclosure of AMAG Know-How is
reasonably required for Takeda to Finish the Product.  The Supply Agreement shall detail AMAG’s
obligations to make all reasonably necessary arrangements with its DSS, which 


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


may
include, but is not limited to, 
amendment of its supply agreement with a DSS, to ensure that Takeda has
the right and ability to fully exercise its rights under the Supply Agreement,
to purchase its requirements of Product (including drug substance) from a DSS
upon the occurrence of a Transfer Event.


 


7)                                     If Takeda purchases Product from a DSS following a
Transfer Event as provided above, [***]. 
So long as AMAG uses Commercially Reasonable Efforts to meet Takeda’s
forecasted purchase of Product under the Supply Agreement and uses Commercially
Reasonable Efforts to work with the DSS to supply Product to Takeda in
accordance with the Second Source Plan (including using Commercially Reasonable
Efforts to manage demand and supply of the Product, taking into consideration
the demand for Product for the Licensed Territory and outside the Licensed
Territory), such right to purchase Product from a DSS [***] shall not be applicable
if such failure to supply is caused by AMAG’s or its DSS’s (i) failure to
comply with applicable Laws relating to the Manufacture of the Product or (ii) gross
negligence or wilful misconduct.


 


8)                                     Following a Transfer Event, Takeda shall resume
purchasing all of its requirements for the Product from AMAG (and cease
purchasing from a DSS), exercising Commercially Reasonable Efforts, within a
reasonable time frame after AMAG’s: (A) reasonably demonstrating that it
is able to supply Product in accordance with the terms of the Supply Agreement
and Takeda’s forecast and (B) manufacturing and maintaining a [***] of
safety stock of drug substance for the Product exclusive to Takeda (in addition
to its safety stock of Product), taking into account any residual Product
purchase and other obligations to the DSS.


 


9)                                     If, after [***], AMAG is unable to meet Takeda’s
forecasted demand for the Product, then Takeda shall obtain, at its expense,
the Product from the DSS [***].  In such
event, AMAG shall no longer be obligated to supply Product directly to Takeda
(and Takeda shall no longer be obligated to purchase Product directly from
AMAG), and Takeda will have the right to purchase all of its requirements of
the Product directly from a DSS as Takeda’s primary source of supply of the
Product.  AMAG will reasonably cooperate
with Takeda in the transition to the DSS. 
In addition, AMAG shall undertake promptly, using Commercially
Reasonable Efforts, to identify, qualify and maintain a new Designated Second
Source Supplier reasonably acceptable to the Parties for drug substance and
Product.  The Supply Agreement will
include a mechanism for allocating costs for such activities with respect to
such new Designated Second Source Supplier between the Parties.


 






[***] 
INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 24b-2 PROMULGATED UNDER THE
SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


10)                              Notwithstanding anything in this Schedule 7.2 to the
contrary, [***], if the Acquiror is conducting human clinical studies with or
commercializing in the Licensed Territory any pharmaceutical product containing
or comprising iron as the primary active pharmaceutical ingredient formulated
for delivery by parenteral means at the closing of the acquisition of AMAG,
then:


 


(a)                                  the conditions under clauses (B) and (C) in
item (6) above shall be modified as follows: (i) [***]


 


(b)                                 AMAG’s requirement to maintain safety stock of Product
inventory shall [***].


 


Product Warranty


 


AMAG will provide standard
warranties applicable in the pharmaceutical industry, including warranties that
all Product Manufactured by or on behalf of AMAG:


 


i)                                         shall be manufactured
and tested in accordance with all applicable laws, rules, regulations or
guidelines of any relevant Regulatory Authority, and GMPs applicable to,
without limitation, the manufacturing, storage, and shipment of Product,


 


ii)                                      shall not be
adulterated or misbranded within the meaning of the United States Food, Drug
and Cosmetic Act, 21 U.S.C. Section 301c et. seq., or other applicable
laws, rules, regulations or guidelines of any relevant Regulatory Authority,


 


iii)                                   at the time of
delivery to Takeda will meet the Specifications, and


 


iv)                                  will have a
shelf life of a commercially viable period of [***].


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


SCHEDULE 7.3


 


SECOND SOURCE PLAN


 


The following
plan outlines AMAG’s current plan for the availability of primary and secondary
manufacturers of API (drug substance) and drug product for the Licensed
Territory.


 


[***]


 


Secondary
Supply Source


 


AMAG
has developed a plan to provide for alternative (secondary) sources for both
drug substance and drug product for the EU (see attachment 1).


 


[***]


 


[***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


 [***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24b-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 

















 


[***]


 






[***]  INDICATES MATERIAL THAT HAS BEEN OMITTED AND
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED. ALL SUCH OMITTED MATERIAL
HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
24B-2 PROMULGATED UNDER THE SECURITIES EXCHANGE ACT OF 1934, AS AMENDED.


 
















 


TABLE OF CONTENTS


 


	
   

  	
   

  	
  PAGE

  
	
   

  	
   

  	
   

  
	
  ARTICLE 1

  	
  DEFINITIONS

  	
  1

  
	
   

  	
   

  	
   

  
	
  ARTICLE 2

  	
  LICENSES AND EXCLUSIVITY

  	
  13

  
	
   

  	
   

  	
   

  
	
  2.1

  	
  Licenses to Takeda under AMAG Technology

  	
  13

  
	
   

  	
   

  	
   

  
	
  2.2

  	
  License to AMAG

  	
  15

  
	
   

  	
   

  	
   

  
	
  2.3

  	
  Negative Covenant

  	
  16

  
	
   

  	
   

  	
   

  
	
  2.4

  	
  Right of First Negotiation

  	
  16

  
	
   

  	
   

  	
   

  
	
  2.5

  	
  No Implied Licenses

  	
  16

  
	
   

  	
   

  	
   

  
	
  2.6

  	
  Exclusivity

  	
  16

  
	
   

  	
   

  	
   

  
	
  2.7

  	
  Cross-Territorial Restrictions

  	
  17

  
	
   

  	
   

  	
   

  
	
  ARTICLE 3

  	
  MANAGEMENT

  	
  18

  
	
   

  	
   

  	
   

  
	
  3.1

  	
  Joint Steering Committee

  	
  18

  
	
   

  	
   

  	
   

  
	
  3.2

  	
  Joint Development Committee

  	
  19

  
	
   

  	
   

  	
   

  
	
  3.3

  	
  Committee Membership and Procedures

  	
  20

  
	
   

  	
   

  	
   

  
	
  3.4

  	
  Alliance Managers

  	
  21

  
	
   

  	
   

  	
   

  
	
  3.5

  	
  Collaboration Guidelines

  	
  22

  
	
   

  	
   

  	
   

  
	
  ARTICLE 4

  	
  PRODUCT DEVELOPMENT

  	
  22

  
	
   

  	
   

  	
   

  
	
  4.1

  	
  Overview of Product Development

  	
  22

  
	
   

  	
   

  	
   

  
	
  4.2

  	
  Principles of Product Development

  	
  22

  
	
   

  	
   

  	
   

  
	
  4.3

  	
  Development Plan

  	
  22

  
	
   

  	
   

  	
   

  
	
  4.4

  	
  AMAG Development Responsibilities

  	
  23

  
	
   

  	
   

  	
   

  
	
  4.5

  	
  Other AMAG Studies

  	
  27

  
	
   

  	
   

  	
   

  
	
  4.6

  	
  Takeda Product Development

  	
  27

  
	
   

  	
   

  	
   

  
	
  4.7

  	
  Development Diligence

  	
  28

  
	
   

  	
   

  	
   

  
	
  4.8

  	
  Reports

  	
  28

  
	
   

  	
   

  	
   

  
	
  4.9

  	
  Development Costs

  	
  28

  
	
   

  	
   

  	
   

  
	
  4.10

  	
  Delayed Opt-In

  	
  29

  
	
   

  	
   

  	
   

  
	
  4.11

  	
  Data Exchange
  and Use

  	
  30

  
	
   

  	
   

  	
   

  
	
  4.12

  	
  Cooperation;
  Compliance with Laws

  	
  31

  
	
   

  	
   

  	
   

  
	
  4.13

  	
  Records, Reports
  and Information

  	
  31

  



 


i

















 


	
  TABLE OF CONTENTS

  
	
  (CONTINUED)

  



 


	
   

  	
   

  	
  PAGE

  
	
   

  	
   

  	
   

  
	
  ARTICLE 5

  	
  REGULATORY MATTERS

  	
  31

  
	
   

  	
   

  	
   

  
	
  5.1

  	
  Data and
  Information Transfer

  	
  31

  
	
   

  	
   

  	
   

  
	
  5.2

  	
  Regulatory Responsibilities

  	
  32

  
	
   

  	
   

  	
   

  
	
  5.3

  	
  Regulatory Costs
  and Expenses

  	
  33

  
	
   

  	
   

  	
   

  
	
  5.4

  	
  Preparation of
  Regulatory Materials

  	
  33

  
	
   

  	
   

  	
   

  
	
  5.5

  	
  Rights of
  Reference to Regulatory Materials

  	
  34

  
	
   

  	
   

  	
   

  
	
  5.6

  	
  Adverse Event
  Reporting and Safety Data Exchange

  	
  34

  
	
   

  	
   

  	
   

  
	
  5.7

  	
  Regulatory Authority Communications Received by a
  Party

  	
  35

  
	
   

  	
   

  	
   

  
	
  5.8

  	
  Regulatory
  Safety Reporting

  	
  35

  
	
   

  	
   

  	
   

  
	
  5.9

  	
  Audit

  	
  36

  
	
   

  	
   

  	
   

  
	
  ARTICLE 6

  	
  COMMERCIALIZATION

  	
  36

  
	
   

  	
   

  	
   

  
	
  6.1

  	
  Overview of
  Commercialization in the Licensed Territory

  	
  36

  
	
   

  	
   

  	
   

  
	
  6.2

  	
  Commercialization
  Plan for Licensed Territory

  	
  37

  
	
   

  	
   

  	
   

  
	
  6.3

  	
  Pricing

  	
  37

  
	
   

  	
   

  	
   

  
	
  6.4

  	
  Commercial
  Diligence

  	
  37

  
	
   

  	
   

  	
   

  
	
  6.5

  	
  Reports

  	
  38

  
	
  38

  	
   

  	
   

  
	
  6.6

  	
  Tracking Sales
  of Product in the Field and Outside the Field

  	
  38

  
	
   

  	
   

  	
   

  
	
  6.7

  	
  Product
  Trademarks and House Marks

  	
  38

  
	
   

  	
   

  	
   

  
	
  ARTICLE 7

  	
  MANUFACTURE AND SUPPLY

  	
  40

  
	
   

  	
   

  	
   

  
	
  7.1

  	
  General Supply
  Terms

  	
  40

  
	
   

  	
   

  	
   

  
	
  7.2

  	
  Supply Agreement

  	
  40

  
	
   

  	
   

  	
   

  
	
  7.3

  	
  Second Source

  	
  40

  
	
   

  	
   

  	
   

  
	
  7.4

  	
  Recalls and
  Voluntary Withdrawals

  	
  40

  
	
   

  	
   

  	
   

  
	
  ARTICLE 8

  	
  COMPENSATION

  	
  41

  
	
   

  	
   

  	
   

  
	
  8.1

  	
  Upfront Fee

  	
  41

  
	
   

  	
   

  	
   

  
	
  8.2

  	
  Development
  Milestone Payments

  	
  41

  
	
   

  	
   

  	
   

  
	
  8.3

  	
  Commercialization
  Milestone Payments in the Licensed Territory

  	
  42

  
	
   

  	
   

  	
   

  
	
  8.4

  	
  Royalties

  	
  43

  
	
   

  	
   

  	
   

  
	
  8.5

  	
  Third Party
  Royalties

  	
  44

  
	
   

  	
   

  	
   

  
	
  8.6

  	
  Royalty Reports
  and Payment

  	
  45

  



 


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  8.7

  	
  Foreign Exchange

  	
  45

  
	
   

  	
   

  	
   

  
	
  8.8

  	
  Payment Method;
  Late Payments

  	
  45

  
	
   

  	
   

  	
   

  
	
  8.9

  	
  Records; Audits

  	
  45

  
	
   

  	
   

  	
   

  
	
  8.10

  	
  Taxes

  	
  46

  
	
   

  	
   

  	
   

  
	
  ARTICLE 9

  	
  INTELLECTUAL PROPERTY MATTERS

  	
  47

  
	
   

  	
   

  	
   

  
	
  9.1

  	
  Ownership of
  Inventions; Assignment

  	
  47

  
	
   

  	
   

  	
   

  
	
  9.2

  	
  Disclosure of
  Inventions

  	
  47

  
	
   

  	
   

  	
   

  
	
  9.3

  	
  Prosecution of
  Patents

  	
  47

  
	
   

  	
   

  	
   

  
	
  9.4

  	
  Patent Term
  Extensions in the Licensed Territory

  	
  48

  
	
   

  	
   

  	
   

  
	
  9.5

  	
  Infringement of
  Patents by Third Parties

  	
  49

  
	
   

  	
   

  	
   

  
	
  9.6

  	
  Infringement of
  Third Party Rights in the Licensed Territory

  	
  50

  
	
   

  	
   

  	
   

  
	
  9.7

  	
  Patent Marking

  	
  51

  
	
   

  	
   

  	
   

  
	
  9.8

  	
  Patent
  Oppositions and Other Proceedings

  	
  51

  
	
   

  	
   

  	
   

  
	
  ARTICLE 10

  	
  REPRESENTATIONS AND WARRANTIES; COVENANTS

  	
  52

  
	
   

  	
   

  	
   

  
	
  10.1

  	
  Mutual
  Representations and Warranties

  	
  52

  
	
   

  	
   

  	
   

  
	
  10.2

  	
  Additional
  Representations and Warranties of AMAG

  	
  53

  
	
   

  	
   

  	
   

  
	
  10.3

  	
  Covenants

  	
  55

  
	
   

  	
   

  	
   

  
	
  10.4

  	
  Disclaimer

  	
  55

  
	
   

  	
   

  	
   

  
	
  10.5

  	
  No Other
  Representations or Warranties

  	
  55

  
	
   

  	
   

  	
   

  
	
  ARTICLE 11

  	
  INDEMNIFICATION

  	
  56

  
	
   

  	
   

  	
   

  
	
  11.1

  	
  Indemnification
  by AMAG

  	
  56

  
	
   

  	
   

  	
   

  
	
  11.2

  	
  Indemnification
  by Takeda

  	
  56

  
	
   

  	
   

  	
   

  
	
  11.3

  	
  Indemnification
  Procedures

  	
  57

  
	
   

  	
   

  	
   

  
	
  11.4

  	
  Limitation of
  Liability

  	
  57

  
	
   

  	
   

  	
   

  
	
  11.5

  	
  Insurance

  	
  57

  
	
   

  	
   

  	
   

  
	
  ARTICLE 12

  	
  CONFIDENTIALITY

  	
  58

  
	
   

  	
   

  	
   

  
	
  12.1

  	
  Confidentiality

  	
  58

  
	
   

  	
   

  	
   

  
	
  12.2

  	
  Authorized
  Disclosure

  	
  58

  
	
   

  	
   

  	
   

  
	
  12.3

  	
  Publicity

  	
  59

  



 


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  ARTICLE 13

  	
  TERM AND TERMINATION

  	
  60

  
	
   

  	
   

  	
   

  
	
  13.1

  	
  Term

  	
  60

  
	
   

  	
   

  	
   

  
	
  13.2

  	
  Unilateral
  Termination by Takeda

  	
  60

  
	
   

  	
   

  	
   

  
	
  13.3

  	
  Termination for Breach

  	
  61

  
	
   

  	
   

  	
   

  
	
  13.4

  	
  Termination for
  Patent Challenge

  	
  61

  
	
   

  	
   

  	
   

  
	
  13.5

  	
  Termination for
  Bankruptcy

  	
  62

  
	
   

  	
   

  	
   

  
	
  13.6

  	
  AMAG Rights upon
  Termination of the Agreement

  	
  62

  
	
   

  	
   

  	
   

  
	
  13.7

  	
  Rights in
  Bankruptcy

  	
  63

  
	
   

  	
   

  	
   

  
	
  13.8

  	
  Survival

  	
  63

  
	
   

  	
   

  	
   

  
	
  ARTICLE 14

  	
  DISPUTE RESOLUTION

  	
  63

  
	
   

  	
   

  	
   

  
	
  14.1

  	
  Disputes

  	
  63

  
	
   

  	
   

  	
   

  
	
  14.2

  	
  Referred from
  JSC

  	
  64

  
	
   

  	
   

  	
   

  
	
  14.3

  	
  Arising Between
  the Parties

  	
  65

  
	
   

  	
   

  	
   

  
	
  14.4

  	
  ADR

  	
  65

  
	
   

  	
   

  	
   

  
	
  14.5

  	
  Patent and Trademark Disputes

  	
  65

  
	
   

  	
   

  	
   

  
	
  14.6

  	
  Injunctive Relief

  	
  65

  
	
   

  	
   

  	
   

  
	
  14.7

  	
  WAIVER OF RIGHT TO JURY TRIAL

  	
  65

  
	
   

  	
   

  	
   

  
	
  ARTICLE 15

  	
  STANDSTILL

  	
  66

  
	
   

  	
   

  	
   

  
	
  15.1

  	
  Standstill Agreement

  	
  66

  
	
   

  	
   

  	
   

  
	
  15.2

  	
  Exceptions to Standstill

  	
  67

  
	
   

  	
   

  	
   

  
	
  15.3

  	
  Reinstatement of Standstill

  	
  68

  
	
   

  	
   

  	
   

  
	
  15.4

  	
  Most Favored Nations Treatment

  	
  68

  
	
   

  	
   

  	
   

  
	
  ARTICLE 16

  	
  MISCELLANEOUS

  	
  68

  
	
   

  	
   

  	
   

  
	
  16.1

  	
  Entire
  Agreement; Amendment

  	
  68

  
	
   

  	
   

  	
   

  
	
  16.2

  	
  Force Majeure

  	
  69

  
	
   

  	
   

  	
   

  
	
  16.3

  	
  Notices

  	
  69

  
	
   

  	
   

  	
   

  
	
  16.4

  	
  No Strict
  Construction; Headings

  	
  70

  
	
   

  	
   

  	
   

  
	
  16.5

  	
  Assignment

  	
  70

  
	
   

  	
   

  	
   

  
	
  16.6

  	
  Performance by
  Affiliates

  	
  71

  
	
   

  	
   

  	
   

  
	
  16.7

  	
  Further Actions

  	
  71

  



 


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  16.8

  	
  Severability

  	
  71

  
	
   

  	
   

  	
   

  
	
  16.9

  	
  No Waiver

  	
  71

  
	
   

  	
   

  	
   

  
	
  16.10

  	
  Independent
  Contractors

  	
  71

  
	
   

  	
   

  	
   

  
	
  16.11

  	
  English
  Language; Governing Law

  	
  72

  
	
   

  	
   

  	
   

  
	
  16.12

  	
  Counterparts

  	
  72

  



 


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