EXHIBIT 10.18
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
LICENSE AGREEMENT
Entered into by and between AstraZeneca AB and
The Medicines Company as of the 18th day of December, 2003
TABLE OF CONTENTS
1. DEFINITIONS...........................................................2
2. GRANT OF LICENSE.....................................................11
3. DEVELOPMENT AND COMMERCIALIZATION....................................15
4. SUPPLY MATTERS.......................................................25
5. EXCHANGE OF INFORMATION..............................................27
6. CONSIDERATION........................................................29
7. INTELLECTUAL PROPERTY - PROSECUTION AND MAINTENANCE..................39
8. CLAIMS REGARDING INFRINGEMENT AND INVALIDITY.........................42
9. TRADEMARK............................................................46
10. INDEMNITY............................................................47
11. CONFIDENTIALITY......................................................49
12. ADVERSE EVENTS.......................................................51
13. REPRESENTATIONS, WARRANTIES AND COVENANTS............................52
14. TERM AND TERMINATION.................................................55
15. CONSEQUENCES OF TERMINATION..........................................57
16. FORCE MAJEURE........................................................60
17. GENERAL PROVISIONS...................................................61
18. GOVERNING LAW AND ARBITRATION........................................65
-i-
1
LICENSE AGREEMENT
This Agreement is entered into as of the 18th day of December, 2003 (the
"Effective Date")
by and between
ASTRAZENECA AB, a company incorporated under the laws of Sweden with its
registered office at ▇▇-▇▇▇ ▇▇ ▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇ ("ASTRAZENECA") and
THE MEDICINES COMPANY, a company incorporated under the laws of Delaware with
its registered office at ▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇, ▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇
▇▇▇▇▇▇ ("TMC").
WITNESSETH
WHEREAS, ASTRAZENECA performs research, development and marketing of
pharmaceutical compounds and products inter alia in the cardiovascular therapy
area; and
WHEREAS, ASTRAZENECA has developed an intravenous pharmaceutical compound
designated AR-C69931MX for the selective inhibition of ADP-induced platelet
activation and aggregation; and
WHEREAS, TMC performs development of pharmaceutical compounds and marketing of
pharmaceutical products particularly in the cardiovascular therapy area; and
WHEREAS, ASTRAZENECA has expressed an interest to license AR-C69931MX to TMC
[**] for intravenous administration [**], and TMC has expressed an interest
to license said compound; and
WHEREAS, it is a mutual objective of the Parties to maximise the sales of the
Product.
NOW THEREFORE, the Parties hereto agree to the following.
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1. DEFINITIONS
When used in this Agreement the following expressions shall have the meanings
defined herein. The singular form of the defined expression shall include the
plural form thereof and vice versa.
1.1. "ANDA Act" shall have the meaning defined in Article 8.3.1(a).
1.2. "[**]" shall mean ASTRAZENECA's proprietary compound with the
chemical structure as shown in Schedule E.
1.3. "Adverse Event" shall mean the development of an undesirable
medical condition or the deterioration of a pre-existing medical
condition following or during exposure to a pharmaceutical
product whether or not considered causally related to such
product.
1.4. "Affiliate" with respect to a Person shall mean any other Person
that directly, or indirectly through one or more intermediaries,
controls, is controlled by or is under common control with such
Person. For the purposes of this Article 1.4 only, "control" and,
with correlative meanings, the terms "controlled by" and "under
common control with", shall mean (a) the possession, directly or
indirectly, of the power to direct the management or policies of
a Person, whether through the ownership of voting securities, by
contract or otherwise, and/or (b) the ownership, directly or
indirectly, of more than fifty percent (50%) of the voting
securities or other ownership interest of a Person.
1.5. "Agreement" shall mean this document including any and all
schedules, appendices and other addenda to it as may be changed,
added and/or amended from time to time in accordance with the
provisions of this Agreement.
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1.6. "ASTRAZENECA IP" shall mean the ASTRAZENECA Patent Rights and the
ASTRAZENECA Know-How.
1.7. "ASTRAZENECA Indemnified Party" shall have the meaning defined in
Article 10.1.1.
1.8. "ASTRAZENECA Know-How" shall mean any Know-How relating to the
Compound for intravenous administration [**] and/or the Product,
developed, acquired or licensed by ASTRAZENECA prior to the
Effective Date and in ASTRAZENECA's possession at the Effective
Date.
1.9. "ASTRAZENECA Patent Rights" shall mean the patents and patent
applications as set out in Schedule A, and any Patents Rights
derived therefrom.
1.10. "Baseline Quarter" shall mean the Quarter preceding the Quarter
in which ASTRAZENECA receives NDA Approval of an [**] Product.
The definition "NDA Approval" shall, for the purpose of this
Article 1.10 (and Articles 1.43 and 6.2.3) only, be deemed to
refer to [**] Product instead of Product.
1.11. "Combination Product" shall mean any pharmaceutical product which
has only an intravenous route of administration, and [**], in a
finished dosage form which comprises the Compound and at least
one other active pharmaceutical ingredient.
1.12. "Commercially Reasonable Efforts" shall mean with respect to the
efforts to be expended by a Party with respect to any objective,
the use of reasonable, diligent, good faith efforts to accomplish
such objective as such Party would normally use to accomplish a
similar objective under similar circumstances, it being
understood and agreed that with respect to the research,
development or commercialisation of Product, such efforts shall
be
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substantially equivalent to those efforts and resources commonly
used by a Party for a product owned by it or to which it has
rights, which product is at a similar stage in its development or
product life and is of similar market potential taking into
account efficacy, safety, regulatory authority-approved
labelling, the competitiveness of alternative products in the
marketplace, the patent and other proprietary position of the
Product, the likelihood of regulatory approval given the
regulatory structure involved, the profitability of the Product
taking into account the royalties payable to licensors of patent
or other intellectual property rights, alternative products and
other relevant commercial factors. Commercially Reasonable
Efforts shall be determined on a country-by-country basis for the
Product, and it is anticipated that the level of effort will
change over time (including, to the extent appropriate, the
reduction or cessation of active promotional efforts), reflecting
changes in the status of the Product and the market(s) involved.
1.13. "Compound" shall mean ASTRAZENECA's proprietary compound named
AR-C69931MX with the chemical structure as shown in Schedule C,
attached hereto, including all salts, esters, complexes,
chelates, hydrates, isomers, stereoisomers, crystalline and
amorphous forms and solvates thereof.
1.14. "Confidential Information" shall mean (i) in the case of TMC
being the Receiving Party, ASTRAZENECA IP, and (ii) in the case
of ASTRAZENECA being the Receiving Party TMC IP, and (iii) in the
case of either Party being the Receiving Party, data generated by
either or both Parties hereunder and trade secrets and/or
confidential information relating to technology, including but
not limited to compound(s), composition(s), formulation(s) and/or
manufacturing information, and/or relating to the business
affairs, including but not limited to commercial forecasts,
plans, programs, customers, assets, financial projections, costs
and customer lists and/or finances of the Disclosing Party,
supplied or otherwise made available to the Receiving Party or
coming into Receiving Party's possession in relation to the
performance of this Agreement.
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1.15. "Disclosing Party" shall mean the Party which discloses
Confidential Information to the other Party.
1.16. "Documents" shall mean reports, research notes, charts, graphs,
comments, computations, analyses, recordings, photographs, paper,
notebooks, books, files, ledgers, records, tapes, discs,
diskettes, CD-ROM, computer programs and documents thereof,
computer information storage means, samples of material, other
graphic or written data and any other media on which Know-How can
be permanently or temporarily stored.
1.17. "Drug Product" shall mean the Compound in such formulation and
associated primary packaging of dosage forms for intravenous
administration as has been developed by ASTRAZENECA as of the
Effective Date, used for, or intended for use in, human clinical
trials, as described in the Product Master File, the table of
contents of which is attached as Schedule B (the "PMF").
1.18. "Excluded Countries" shall mean [**].
1.19. "European Union" shall mean the countries that are, whether at
the Effective Date or at any time thereafter, members of the
European Union.
1.20. "European Economic Area" shall mean the European Union plus
Norway, Iceland and Liechtenstein.
1.21. "FDA" shall mean the United States Food and Drug Administration
or any successor agency thereto.
1.22. "FTE Day" shall mean the equivalent of one person employed by
ASTRAZENECA or TMC, as applicable, or their respective Affiliates
full time for one day.
1.23. "Filing of an NDA" shall mean the date of acceptance for review
by the competent registration body in a given country of an NDA.
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1.24. "Force Majeure" shall mean any cause preventing either Party from
performing any or all of its obligations which arises from or is
attributable to acts, events, omissions or accidents beyond the
reasonable control of the Party so prevented, act of God, war,
riot, civil commotion, malicious damage, accident, breakdown of
plant or machinery, fire, flood or storm.
1.25. "[**]" shall mean any of ASTRAZENECA's proprietary compounds
[**], including all salts, esters, complexes, chelates, hydrates,
isomers, stereoisomers, crystalline and amorphous forms,
solvates, metabolites and prodrugs of any such compound.
1.26. "[**] Product" shall mean any pharmaceutical formulation or
product which has [**] containing [**] as the sole active
ingredient in a finished dosage form suitable for administration
to patients.
1.27. "Know-How" shall mean technical and other information, which is
not subject to published patent rights and which is not in the
public domain, including, but not limited to, information
comprising or relating to concepts, discoveries, data, designs,
formulae, ideas, inventions, methods, models, assays, research
plans, procedures, designs for experiments and tests and results
of experimentation and testing, including results of research or
development, processes, including manufacturing processes,
specifications and techniques, laboratory records, chemical,
pharmacological, toxicological, clinical, analytical and quality
control data, trial data, case report forms, data analyses,
reports, manufacturing data or summaries and information
contained in submissions to and information from ethical
committees and regulatory authorities. Know-How includes
Documents containing Know-How, including but not limited to any
rights including trade secrets, copyright, database or design
rights protecting such Know-How. The fact that an item is known
to the public shall not be taken to preclude the possibility that
a compilation including the item, and/or a development relating
to the item, is not known to the public.
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1.28. "Launch" or "Launched" shall mean the first invoiced commercial
sale by TMC, its Affiliates, sub-licensees or distributors,
however not including sales made by one such entity to another
such entity, of the Product in a country following NDA Approval
in such country.
1.29. "Major Market" shall mean each of [**].
1.30. "NDA" shall mean a fully completed marketing license application
comparable to a New Drug Application filed with the FDA,
including all supporting documentation and data required for such
application to be accepted for review by the competent health
regulatory authorities for any country requesting approval for
commercialisation of the Product for a particular indication in
such country. NDA as herein defined shall for this purpose
include applications for pricing or reimbursement approval where
appropriate.
1.31. "NDA Approval" shall mean the approval by the competent
registration body for a given country of an NDA.
1.32. "Net Sales" shall mean (i) the gross sales of Product by a Party
or its Affiliates, or, regarding sales in the United States, its
sub-licensees or distributors, to Third Parties, and (ii)
royalties or other revenues, to the extent not included under
(i), received by such Party or its Affiliates from its
sub-licensees of the rights granted hereunder, or from its
distributors, for sales of the Product outside the United States,
after deduction of:
a) [**] and/or [**];
b) amounts [**] determined in good faith;
c) [**] such sales; and
d) [**] the Product.
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In the event the Product is sold as part of a Combination
Product, the Net Sales from the Combination Product, for the
purposes of determining royalty payments, shall be determined by
multiplying the Net Sales of the Combination Product (as defined
in the standard Net Sales definition), during the applicable
royalty reporting period, by the fraction, A/(A+B), where A is
the average sales price of the Product when sold separately in
finished form and B is the average sale price of the other
product(s) included in the Combination Product when sold
separately in finished form, in each case during the applicable
royalty reporting period or, if sales of both the Product and the
other product(s) did not occur in such period, then in the most
recent royalty reporting period in which sales of both occurred,
as adjusted, as necessary, for inflation from the date when both
the Product and all other product(s) last were sold and the date
of determination of Net Sales under this Article 1.32. In the
event that such average sales price cannot be determined for both
the Product and all other products(s) included in the Combination
Product, Net Sales for the purposes of determining royalty
payments shall be calculated by multiplying the Net Sales of the
Combination Product by the fraction of C/(C+D) where C is the
fair market value of the Product and D is the fair market value
of all other pharmaceutical product(s) included in the
Combination Product. In such event, the selling Party shall in
good faith make a determination of the respective fair market
values of the Product and all other pharmaceutical products
included in the Combination Product, and shall notify the other
Party of such determination and provide the other Party with data
to support such determination. The other Party shall have the
right to review such determination and supporting data, and to
notify the selling Party if it disagrees with such determination.
If the other Party does not agree with such determination and if
the Parties are unable to agree in good faith as to such
respective fair market values, then such matter shall be referred
to arbitration pursuant to Article 18.1.
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Net Sales shall exclude (i) the transfer of a commercially
reasonable quantity of free samples of Product to be given out to
customers for promotional purposes; (ii) the transfer of Product
for use in clinical trials; and (iii) the sales or transfers of
Product among a Party and its Affiliates, and, in the United
States, its sub-licensees or distributors, unless the receiver is
the consumer or user of the Product; however, the resale or
transfer of such Product to a Third Party shall be included in
Net Sales.
Product sold or otherwise transferred (x) in other than an arms
length transaction or for other property (e.g. barter); or (y)
where no separate price has been decided for the Product but a
price is decided jointly for the Product plus at least one other
product, shall be deemed invoiced at its fair market price in the
country of sale or transfer.
It is acknowledged that sub-licensees of a Party or its
Affiliates and conventional distributors whose function is to
purchase and resell Product, will be considered Third Parties
when referring to Product sold outside the United States. The
Parties agree further that for the purpose of the first paragraph
of this Article 1.32 the Net Sales of the Product outside the
United States by TMC or its Affiliates to such sub-licensees and
distributors shall be the Net Sales received by TMC or its
Affiliates from such sub-licensee or distributor for the Product
or [**] percent ([**]%) of the actual gross sales, less
deductions under subsections (a) through (d) above, of the
Product by such sublicensee or distributor, whichever amount is
the higher.
1.33. "PMF" shall have the meaning defined in Article 1.17.
1.34. "Party" or "Parties" shall mean TMC and/or ASTRAZENECA.
1.35. "Patent Rights" shall mean patent applications and patents,
utility models, utility certificates, certificates of addition
and all foreign counterparts of them in all countries, including
any divisional applications and patents, refilings, renewals,
continuations, continuations-in-part, patents of addition,
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extensions (including patent term extensions and patent term
restorations), reissues, substitutions, confirmations,
registrations, revalidations, re-examinations, pipeline and
administrative protections and additions, and any equivalents of
the foregoing in any and all countries of or to any of them, as
well as any supplementary protection certificates and equivalent
protection rights in respect of any of them.
1.36. "Person" shall mean an individual, sole proprietorship,
partnership, limited partnership, limited liability partnership,
corporation, limited liability company, business trust, joint
stock company, trust, unincorporated association, joint venture
or other similar entity or organization, including a government
or political subdivision, department or agency of a government.
1.37. "Phase III Clinical Trial" shall mean a large scale, pivotal
multicentre, human clinical trial to be conducted in a number of
patients estimated to be sufficient to establish safety or
efficacy in the particular claim and indication and at a standard
suitable to obtain NDA Approval.
1.38. "Procedure" shall have the meaning defined in Article 3.5.1.
1.39. "Product" shall mean any pharmaceutical formulation or product
which has only an intravenous route of administration, and [**],
containing the Compound as the sole active ingredient in a
finished dosage form suitable for administration to patients.
Apart from in this Article 1.39, and unless the context clearly
requires otherwise in this Agreement, when used in this
Agreement, the term "Product" shall be deemed to include
"Combination Product".
1.40. "Quarter" shall mean a calendar quarter ending March 31, June 30,
September 30 or December 31.
1.41. "Receiving Party" shall mean the Party which receives
Confidential Information from the other Party.
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1.42. "Results" shall have the meaning defined in Article 7.8.
1.43. "Subsequent Quarter" shall mean the Quarter in which ASTRAZENECA
receives NDA Approval of an [**] Product or any subsequent
Quarter.
The definition "NDA Approval" shall, for the purpose of this
Article 1.43 (and Articles 1.10 and 6.2.3) only, be deemed to
refer to [**] Product instead of Product.
1.44. "Supply Agreement" shall have the meaning described in Article
4.2.1.
1.45. "TMC IP" shall mean TMC Know-How, TMC Patent Rights and the TMC
Trademark.
1.46. "TMC Indemnified Party" shall have the meaning defined in Article
10.2.1.
1.47. "TMC Know-How" shall mean any Know-How relating directly to the
Compound and/or the Product developed, acquired or licensed by
TMC during the term of this Agreement.
1.48. "TMC Patent Rights" shall mean any Patent Rights directly
relating to the Compound and/or the Product developed, acquired
or licensed by TMC during the term of this Agreement.
1.49. "TMC Trademark" shall have the meaning defined in Article 9.1.
1.50. "Territory" shall mean every country in the world, except the
Excluded Countries.
1.51. "Third Party" shall mean any Person not including the Parties or
the Parties' respective Affiliates.
2. GRANT OF LICENSE
2.1. LICENSE GRANT.
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2.1.1. ASTRAZENECA hereby grants to TMC, subject to what is stated in
Article 2.1.2, an exclusive license in the Territory under the
ASTRAZENECA IP to perform research on, have research performed
on, develop, have developed, use, have used, make, have made,
import and have imported the Compound for intravenous
administration [**], and to perform research on, have research
performed on, develop, have developed, use, have used, make, have
made, import, have imported, market, have marketed, sell and have
sold the Product for all indications [**].
2.1.2. The license granted under Article 2.1.1 shall not apply to the
Compound or the Product in relation to any formulation or product
which contains both the Compound and one or more [**] as active
ingredients, whether or not such formulation or product contains
active ingredients in addition to the Compound and the [**], and
such rights shall, for the avoidance of doubt, be retained by
ASTRAZENECA.
2.2. GRANT TO TMC'S AFFILIATES. TMC's Affiliates shall have the
benefit and burden of the licenses and rights set out in Article
2.1 for the same purposes and under the same conditions as set
forth herein, provided that TMC shall remain fully responsible
for the compliance by such Affiliates with the terms and
conditions of this Agreement as if such Affiliates were TMC
hereunder.
2.3. RIGHT TO SUB-LICENSE. TMC shall have the right to grant
sub-licenses to the rights granted under Article 2.1, provided
that TMC shall notify ASTRAZENECA of each such sub-license
without unreasonable delay following any such grant of a
sub-license. TMC shall ensure that all of its sub-licensees will
comply with all terms and conditions of this Agreement and TMC
shall remain fully responsible for the compliance by such
sub-licensees with the terms and conditions of this Agreement as
if such sub-licensees were TMC hereunder.
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2.4. RIGHT TO APPOINT DISTRIBUTORS. TMC shall also have the right to
appoint distributors in the Territory for the sale of the
Product. TMC shall at all times ensure that its distributors act
fully in compliance with the terms and conditions of this
Agreement.
2.5. DURATION OF LICENSE GRANT. The licenses set out in Article 2.1
shall continue in accordance with what is stated therein on a
country-by-country basis until royalty payment is no longer due
in the country concerned in accordance with what is stated in
Article 6.4. The licenses set out in Article 2.1 shall thereafter
continue on a non-exclusive basis and become fully paid up and
royalty-free in the country concerned.
2.6. FIRST RIGHT OF REFUSAL OF TMC REGARDING THE EXCLUDED COUNTRIES.
Should ASTRAZENECA within its sole discretion at any time
determine that ASTRAZENECA will not Launch the Product in one or
more Excluded Countries and/or that ASTRAZENECA will not license,
transfer or otherwise dispose of its interest in the ASTRAZENECA
IP regarding one or more Excluded Countries, then ASTRAZENECA
shall offer to TMC, by providing written notice, the first right
to negotiate a license on exclusive rights to commercially
exploit the Compound and the Product under the ASTRAZENECA IP in
the Excluded Country(ies) concerned on terms similar to those
under this Agreement. Should TMC wish to exercise such right,
then TMC shall notify ASTRAZENECA hereof in writing no later than
ninety (90) days upon receipt of ASTRAZENECA's notice. In
reasonable connection with such notice the Parties shall enter
into good faith negotiations using their reasonable endeavours to
reach a mutually acceptable agreement providing for such TMC's
commercial exploitation as mentioned in this Article 2.6.
2.7. TMC GRANT OF RIGHTS TO ASTRAZENECA REGARDING THE EXCLUDED
COUNTRIES.
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2.7.1. In consideration of the rights granted by ASTRAZENECA hereunder,
TMC hereby grants to ASTRAZENECA, at no cost or remuneration, a
sub-licensable non-exclusive license under the TMC IP to perform
research on, have research performed on, develop, have developed,
use, have used, make, have made, import, have imported, market,
have marketed, sell and have sold the Compound and the Product
for all indications in the Excluded Countries.
2.7.2. TMC shall for the purpose of the license granted in Article 2.7.1
make available to ASTRAZENECA, upon ASTRAZENECA's request, any
Filings of an NDA in the Territory, any NDA Approvals obtained in
the Territory and any related documents and any TMC's
correspondence with any regulatory authorities in the Territory
regarding any such Filing of an NDA, NDA Approval or related
issues, and shall allow ASTRAZENECA to make cross-references to
any such Filing of an NDA or NDA Approval in the Territory. For
any services or assistance performed by TMC pursuant to this
Article 2.7.2, ASTRAZENECA shall reimburse TMC for TMC's
out-of-pocket costs for such activities plus USD [**] ($[**]) per
FTE Day.
2.7.3. The license under Article 2.7.1 shall include an exclusive right
and license for ASTRAZENECA to utilize the TMC Trademark in the
Excluded Countries. Should ASTRAZENECA use the TMC Trademark in
connection with the sales and marketing of Product in an Excluded
Country, then ASTRAZENECA shall pay to TMC a running royalty of
[**] percent ([**]%) on the annual Net Sales of the Product in
such Excluded Country.
In each Excluded Country where ASTRAZENECA utilises, and for as
long as ASTRAZENECA utilises, the license granted under this
Article 2.7.3, ASTRAZENECA shall reimburse TMC its reasonable
costs for maintaining the TMC Trademark in such Excluded Country.
Such reimbursement shall be made within thirty (30) days of the
expiration of each calendar year during which ASTRAZENECA has
utilised such license.
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2.8. SECTION 365(n) OF TITLE 11. All rights and licenses granted under
or pursuant to any section of this Agreement, including
amendments hereto, are, for all purposes of Section 365(n) of
Title 11 of the United States Bankruptcy Code ("Title 11"),
licenses of rights to "intellectual property" as defined in Title
11. The Parties shall retain and may fully exercise all of their
respective rights under this Agreement pursuant to Title 11.
Rejection of this Agreement pursuant to Section 365 of Title 11
constitutes a material breach of this Agreement and entitles the
aggrieved Party to terminate this Agreement for material breach
upon written notice. Upon bankruptcy of either Party, the
non-bankrupt Party shall further be entitled to a complete
duplicate of (or complete access to, as appropriate) any such
intellectual property, and such, if not already in its
possession, shall be promptly delivered to the non-bankrupt
Party, unless the bankrupt Party elects to continue, and
continues, to perform all of its obligations under this
Agreement.
3. DEVELOPMENT AND COMMERCIALIZATION
3.1. TRANSFER OF ASTRAZENECA KNOW-HOW.
3.1.1. TRANSFER OF ASTRAZENECA KNOW-HOW. Without unreasonable delay
following the Effective Date, ASTRAZENECA shall make available
and transfer to TMC the following ASTRAZENECA Know-How.
a) a description of the process used by ASTRAZENECA for the
manufacturing of the Compound intended for Phase III
Clinical Trials and a summary report of the development of
such process;
b) a description of the process, available to ASTRAZENECA at
the Effective Date, for the manufacture of all intermediates
to be used for the manufacturing of the Compound;
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c) a description of the analytical methods and validation
reports, available to ASTRAZENECA at the Effective Date, for
the starting materials and intermediates to be used in the
manufacturing of the Compound.
It is acknowledged that at the Effective Date some of those
analytical methods are not fully developed and validated,
and such development and validation will not be continued or
completed by ASTRAZENECA. ASTRAZENECA will, however, provide
a summary report of the status of these methods at the
Effective Date.
d) the description of the tentative test-methods used by
ASTRAZENECA for validating the bulk Compound manufactured,
and a brief summary of the validation done thereon by
ASTRAZENECA;
e) to the extent available to ASTRAZENECA at the Effective
Date, reference and analytical standard compounds to be used
as reference material in the conduct of comparative analyses
in relation to the manufacturing process with the Compound.
It is explicitly understood that no such compound may be
used for any other purpose than the purpose now stated;
f) a description of the formula and manufacturing process used
by ASTRAZENECA for the manufacturing of the Drug Product
intended for Phase III Clinical Trials. Where available,
ASTRAZENECA will provide TMC with summary reports of the
development of such processes;
As a prerequisite of ASTRAZENECA providing the ASTRAZENECA
Know-How contemplated under this sub-section f) TMC shall
notify ASTRAZENECA in writing of the vial strengths and
batch size that TMC initially intends to manufacture the
Drug Product in and
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ASTRAZENECA's obligations under this sub-section f) shall
apply only in relation to such strengths and size.
g) a description of the analytical methods used by ASTRAZENECA
in the testing and stability assessment of the Drug Product;
It is acknowledged that at the Effective Date some of those
analytical methods are not fully developed and validated,
and such development and validation will not be continued or
completed by ASTRAZENECA. ASTRAZENECA will, however, provide
a summary report of the status of these methods at the
Effective Date.
h) stability data and shelf-life recommendations for the Drug
Product used in previous clinical trials;
i) a description of the Drug Product formulations and processes
used in previous clinical trials. This information will be
contained within existing reports available at the Effective
Date.
j) specifications on the Compound and Drug Product used in
clinical trials conducted by ASTRAZENECA prior to the
Effective Date.
k) project-related reports and documentation, which are
designated with an asterisk in Schedule D, containing
ASTRAZENECA Know-How relating to the manufacturing of the
Compound. Additional reports contained in Schedule D will be
made available by ASTRAZENECA to TMC upon request by TMC to
ASTRAZENECA in writing.
l) the PMF and, upon request by TMC to ASTRAZENECA in writing,
other relevant reports, if available to ASTRAZENECA,
containing ASTRAZENECA Know-How relating to the
manufacturing of the Drug Product.
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18
Any documents contemplated by this Article 3.1 shall be in
English when transferred to TMC.
3.1.2. Any activities to be carried out by ASTRAZENECA under Article
3.1.1 shall be made to an extent necessary and reasonable and
ASTRAZENECA shall not be obligated to devote more than the
equivalent of [**] FTE Days thereon and under no circumstances to
carry out such activities beyond the date [**] months from the
Effective Date. It is acknowledged that ASTRAZENECA may at its
discretion carry out assistance under Article 3.1.1 for up to
[**] percent ([**]%) of such FTE Days by using Third Party
consultants.
3.2. THIRD PARTY MANUFACTURERS.
3.2.1. It is acknowledged that TMC may present the ASTRAZENECA Know-How
described under Article 3.1.1 to Third Party manufacturers for
the purposes permitted under Article 11.2.4. TMC shall notify
ASTRAZENECA in writing regarding the date of submission of such
information to any such Third Party manufacturer(s). ASTRAZENECA
shall in this connection assist TMC to address questions raised
about such ASTRAZENECA Know-How by no more than three (3) of such
Third Party manufacturer(s) of the Compound and no more than
three Third Party manufacturers of the Drug Product selected by
TMC, during a period of three (3) months from the date of
presentation of such ASTRAZENECA Know-How to the Third Party
manufacturer concerned. ASTRAZENECA shall also provide TMC with
advice on the technical merits of proposals regarding
manufacturing of the Compound brought forward by such Third Party
manufacturer(s). Any assistance provided under this Article 3.2.1
may be given by telephone or e-mail or by other appropriate means
as agreed by the Parties.
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19
3.2.2. ASTRAZENECA undertakes to participate in no more than one (1)
meeting in person with one Third Party manufacturer, selected by
TMC, to outline details of the manufacturing synthesis regarding
the Compound, provided that such meeting, at ASTRAZENECA's sole
discretion, shall take place either at ASTRAZENECA's Charnwood
site at Loughborough, UK, or at the Third Party manufacturer's
site.
3.2.3. ASTRAZENECA undertakes to participate in no more than one (1)
meeting in person with one Third Party manufacturer, selected by
TMC, to outline details of the manufacture of the Drug Product.
Such meeting shall, at ASTRAZENECA's sole discretion, take place
either at ASTRAZENECA's Charnwood site at Loughborough, UK, or at
the Third Party manufacturer's site.
3.2.4. ASTRAZENECA further undertakes, upon having received written
notice from TMC, for a period of three (3) months starting sixty
(60) days upon ASTRAZENECA's receipt of such notice, to assist
TMC, by telephone, e-mail or other appropriate means as agreed by
the Parties, in TMC's discussions with Drug Product contractors
in connection with the formulation program regarding the Product.
The Parties agree, however, that TMC may not give such notice
contemplated above in this Article 3.2.4 later than eight (8)
months after the Effective Date.
3.2.5. ASTRAZENECA agrees to provide reasonable assistance to the Third
Party manufacturer selected by TMC, by telephone, e-mail or other
appropriate means as agreed by the Parties, in connection with
the start-up of manufacturing operations for the Product for a
period of twelve (12) months following commencement of process
development by such contract manufacturer or fifteen (15) months
after the Effective Date, whichever is the earliest to occur.
3.3. DURATION OF AND COMPENSATION FOR ASSISTANCE BY ASTRAZENECA.
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20
3.3.1. The Parties agree that any assistance to be provided by
ASTRAZENECA under Articles 3.2 and 3.5.1 shall be given to an
extent necessary and reasonable and shall be given only within
the first [**] years after the Effective Date and shall not in
total exceed [**] FTE Days. It is acknowledged that ASTRAZENECA
may at its discretion carry out any such assistance for up to
[**] percent ([**]%) of such [**] FTE Days by using Third Party
consultants.
3.3.2. For any services or assistance performed by ASTRAZENECA pursuant
to Articles 3.1.2 and 3.3.1, TMC shall reimburse ASTRAZENECA for
ASTRAZENECA's out-of-pocket costs for such activities plus USD
[**] ($[**]) per FTE Day. Should ASTRAZENECA use a Third Party
consultant(s) for carrying out assistance for a certain FTE Day,
or part thereof, then, for the avoidance of doubt, the FTE Day
rate now stated shall apply thereon, and the out-of-pocket costs
for consultants, if any, as indicated above in this paragraph,
shall apply only to costs for consultants which would typically
have been incurred should the assistance have been actually
carried out by an employee(s) of ASTRAZENECA or its Affiliates.
3.3.3. ASTRAZENECA shall invoice TMC for all assistance during each
relevant time period within thirty (30) days of the expiration of
each calendar half-year.
3.4. DEVELOPMENT OF PRODUCT.
3.4.1. TMC shall, subject to the obligations stated in this Article 3
and in Article 5, carry out the development work permitted
hereunder within its sole discretion and at its own cost and
expense.
3.4.2. TMC shall use Commercially Reasonable Efforts to develop Product
up until the stage of Filing of an NDA in each country of the
Territory.
3.5. REGULATORY FILINGS.
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21
3.5.1. TMC shall be responsible for the preparation, submission and
prosecution of all Filings of an NDA in each country in which
TMC, its Affiliates, sub-licensees or distributors will sell
Product. TMC, its Affiliates, sub-licensees or distributors shall
be the owner and party of record for all such filings,
applications and approvals. ASTRAZENECA agrees to provide
assistance requested by TMC as reasonably necessary for
preparation and prosecution of such filings and applications in
the European Union (it being contemplated that such filings and
applications will be done by using the then most efficient
centralised procedure for applying for and obtaining
multi-country NDAs in the European Union (the "Procedure")), and
in the United States. TMC shall reimburse ASTRAZENECA in
accordance with Article 3.3 for any costs and expenses incurred
in such assistance. TMC shall be responsible for any costs
associated with preparation, submission and prosecution of all
such Filing of an NDA and NDA Approvals required.
3.5.2. TMC shall, at its own expense, use Commercially Reasonable
Efforts in Filing of an NDA and prosecution thereof and in
obtaining NDA Approvals in its own name or in the name of its
Affiliate(s), sub-licensee(s) or distributors in each country of
the Territory.
3.5.3. Regarding any country in the European Union where TMC makes a
Filing of an NDA, TMC shall for such purpose use the Procedure,
unless TMC can clearly establish that Filing of an NDA regarding
one or more separate countries within the European Union would be
more advantageous to the Product from a regulatory or commercial
perspective.
3.5.4. TMC shall promptly inform ASTRAZENECA in writing, and by
facsimile in accordance with Article 17.4.2, of any Filing of an
NDA and of any NDA Approval, and shall in immediate connection
therewith provide ASTRAZENECA with a written summary of any such
Filing of an NDA and NDA Approval, or with a copy thereof,
whichever ASTRAZENECA may elect.
License Agreement - The Medicines Company
22
3.5.5. Following NDA Approval in a country of the Territory TMC shall
use its Commercially Reasonable Efforts to Launch the Product in
such country.
3.6. MARKETING AND SALES OF PRODUCT.
3.6.1. Regarding any country of the Territory where the Product is
Launched, TMC shall promptly inform ASTRAZENECA in writing of the
occurrence of such Launch.
3.6.2. TMC shall, in each country of the Territory where the Product has
been Launched, at its own expense, or the expense of its
Affiliates, sub-licensees or distributors, use Commercially
Reasonable Efforts to market and sell the Product.
3.6.3. For the avoidance of doubt, what is stated regarding the
obligations of TMC in this Article 3 or elsewhere in this
Agreement shall always be subject to what is stated in Articles
2.2 and 2.3, such that any of TMC's obligations may be performed
by one or more of TMC's Affiliates or sublicensees. Further, in
accordance with what is stated in Article 2.4, any of TMC's
obligations under this Article 3.6 and under Article 3.7 may be
performed by one or more of TMC's distributors.
3.7. SPECIFIC TIME LIMITS FOR PERFORMANCE. Notwithstanding what is
stated in Articles 3.4.2, 3.5.2, 3.5.5 and 3.6.2, and without
limiting the general performance criteria stated therein, the
following performance criteria stated in this Article 3.7 shall
apply to the situations herein described.
3.7.1. TIME LIMIT FOR ENTERING INTO PHASE III CLINICAL TRIALS.
TMC shall no later than [**] have made the first dosing of a
patient in a Phase III Clinical Trial regarding the Compound.
3.7.2. TIME LIMIT FOR FILING OF AN NDA.
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23
a) TMC shall no later than [**] have made a Filing of an NDA
[**].
b) TMC shall no later than [**] or [**] after having made a
Filing of an NDA in the United States, whichever is the
earlier, have made a Filing of an NDA [**].
c) TMC shall no later than [**] or [**] after having made the
last Filing of an NDA under Article 3.7.2 (b), whichever is
the earlier, have made a Filing of an NDA [**].
3.7.3. Notwithstanding what is stated in Article 3.7.2 c), TMC shall not
be obligated to make a Filing of an NDA in [**] until the
[**] patent application no. [**] is granted insofar it
relates to the Compound to the extent licensed to TMC under this
Agreement. For the avoidance of doubt, such exemption from those
obligations now stated shall not relieve TMC from its obligations
under Article 3.7.2 b).
3.7.4. TIME LIMIT FOR LAUNCH OF THE PRODUCT
TMC shall no later than [**] following NDA Approval in any Major
Market Launch the Product in the Major Market in which such NDA
Approval was obtained.
3.8. REMEDY FOR FAILURE.
3.8.1. NON-COMPLIANCE.
Should TMC at any time not comply with the applicable criteria of
performance as set forth in Articles 3.4.2, 3.5.2, 3.5.5, 3.6.2,
3.7.1, 3.7.2 or 3.7.4, then TMC shall promptly so notify
ASTRAZENECA in writing.
a) In case of non-compliance with the performance criteria set
forth in Article 3.7.1, ASTRAZENECA shall have the right, by
giving ninety (90) days written notice to TMC, to require
the license granted
License Agreement - The Medicines Company
24
hereunder to terminate regarding the Compound and the
Product, subject to Article 3.8.2.
b) In case of non-compliance with the performance criteria set
forth in Articles 3.4.2, 3.5.2, 3.5.5, 3.6.2, 3.7.2 (a) or
3.7.4, ASTRAZENECA shall have the right, by giving ninety
(90) days written notice to TMC, to require the license
granted hereunder to terminate regarding the Compound and
the Product in the Major Market or other country concerned,
subject to Article 3.8.2.
c) In case of non-compliance with the performance criteria set
forth in Article or 3.7.2 (b) or (c), ASTRAZENECA shall have
the right, by giving ninety (90) days written notice to TMC,
to require the license granted hereunder to terminate
regarding the Compound and the Product in any Major
Market(s) other than the Major Market(s) regarding which the
performance criteria concerned was fulfilled (and, in the
case of non-compliance with Article 3.7.2 (c), the Major
Market(s) regarding which such criteria had been fulfilled
under Article 3.7.2 (b) or that was exempted under Article
3.7.3), subject to Article 3.8.2.
d) If ASTRAZENECA makes a request under (a), (b) or (c) above,
and provided that TMC has not remedied the default concerned
within the ninety-day period stated, then, provided that
ASTRAZENECA notifies TMC in writing hereof within thirty
(30) days after the expiration of such ninety-day period,
the license regarding the Compound and the Product shall
terminate for the Major Market or other country contemplated
by such notice and what is stated in Article 15.1 shall
apply regarding such Major Market or other country, subject
to Article 3.8.2.
3.8.2. REASONABLE DELAY OR OTHER NON-COMPLIANCE.
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25
a) Should TMC upon receipt of notice from ASTRAZENECA according
to Article 3.8.1 (a) through (c) be able to show that the
delay or other non-compliance in the country(ies) concerned
is justifiable from a clinical, scientific or regulatory
perspective, then the Parties shall meet and consult whether
the situation so occurred could be reasonably solved. Should
the Parties, despite such consultations, not be able to find
a mutually acceptable solution within three (3) months after
having entered into such consultations, then ASTRAZENECA may
terminate the license regarding the country(ies) concerned
by giving TMC a notice of same in writing, whereupon the
license regarding such country(ies) shall immediately
terminate and what is stated in Article 15.1 shall apply
regarding such country(ies).
b) Should, following the initiation of the consultations
pursuant to the first paragraph of this Article 3.8.2,
either Party reasonably believe that a solution to the
situation arisen may be solved through such consultations,
but not within the initial three-month timeframe, then such
Party may notify the other Party thereof; and the
three-month period provided for in Article 3.8.2 a) shall be
extended with a time-period as requested by such Party in
such notice but with no more than three (3) months from the
date of the notice.
3.9. The remedies stated in Article 3.8 shall be ASTRAZENECA's sole
remedy in case of any failure by TMC to comply with what is
stated in this Article 3.
4. SUPPLY MATTERS
4.1. TRANSFER OF BULK COMPOUND TO TMC. ASTRAZENECA undertakes to
supply to TMC [**] approximately [**] kilograms of bulk Compound
no later than ninety (90) days after the Effective Date. The
transport of such entire quantity of bulk Compound shall be
entirely at TMC's risk and expense. It is explicitly understood
that this quantity of Compound was
License Agreement - The Medicines Company
26
manufactured by ASTRAZENECA at an earlier date, and was not made
for the purpose of the supply now stated, and that ASTRAZENECA
gives no guarantee whatsoever as to the characteristics of the
Compound or the Compound's fitness for any particular purpose. It
is explicitly understood and agreed by the Parties that
ASTRAZENECA shall have no obligations whatsoever to transfer or
supply, other than as explicitly provided under this Article 4.1,
any quantity of Compound or Product to TMC.
4.2. SUPPLY OF COMPOUND AND PRODUCT BY TMC.
4.2.1. TMC undertakes to supply ASTRAZENECA and/or any of its
Affiliates, at TMC's [**] ASTRAZENECA's and/or its Affiliates
entire need of Product for clinical trials, sale, promotion and
marketing in the Excluded Countries, pursuant to the Supply
Agreement between TMC and ASTRAZENECA, attached hereto, subject
to what is stated in Article 4.2.3, as Schedule F. In addition
ASTRAZENECA will reimburse TMC for costs specifically pertaining
to the development of a formulation necessary only for the
purpose of enabling ASTRAZENECA to obtain NDA Approval in one or
more of the Excluded Countries.
4.2.2. TMC further undertakes to supply ASTRAZENECA, subject to Article
15.1 (i), at [**] and otherwise under terms to be as consistent
as possible with those under the Supply Agreement, ASTRAZENECA's
entire need of Product for clinical trials, sale, promotion and
marketing in any country where the license granted under Article
2 has been terminated pursuant to Article 3.8; provided always
that such TMC's obligation shall not become effective unless and
until TMC has Launched the Product in at least one (1) country of
the Territory.
4.2.3. The Supply Agreement has not been entered into on the Effective
Date due to the Parties' desire to expeditiously enter into this
Agreement, not delaying such procedure by awaiting the completion
of the Supply Agreement. The parties acknowledge the substantial
need for
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27
ASTRAZENECA to rely on TMC for its supply of the Product for the
countries mentioned in Articles 4.2.1 and 4.2.2 and that entering
into the Supply Agreement is a substantial prerequisite for
ASTRAZENECA entering into this Agreement. Should regardless
hereof the Supply Agreement not have been concluded within six
(6) months of the Effective Date for other reasons than
ASTRAZENECA's lack of good faith in conducting such negotiations
or unnecessary delays caused by ASTRAZENECA, then ASTRAZENECA
shall have the right to terminate this Agreement forthwith by
giving written notice to TMC.
5. EXCHANGE OF INFORMATION
5.1. OBLIGATION OF TMC TO SHARE INFORMATION. In addition to the
obligations specifically requiring TMC to inform ASTRAZENECA
regarding particular events, TMC undertakes to keep ASTRAZENECA
informed about the progress of the development work regarding the
Compound hereunder. For this purpose:
5.1.1. the Parties will, up until the date when Filing of an NDA has
been made in the last Major Market, meet at least once a year to
review TMC's progress and efforts in the development work
contemplated herein. Such meeting will take place on a location
to be agreed by the Parties, or, should the Parties not be able
to agree, alternately with each Party at a site to be determined
by the Party hosting the meeting. In advance of such meeting, TMC
will provide ASTRAZENECA a reasonable written summary of such
development work, including, without limitation, summaries of
protocol designs of any clinical trials conducted or to be
conducted, any changes to same and any Results developed during
the period concerned;
5.1.2. TMC shall further in advance of such meeting provide ASTRAZENECA
in writing a timetable for the expected Filings of an NDA,
expected NDA Approvals and expected Launches during the one-year
period, or other shorter applicable period, to come. In
connection therewith TMC shall
License Agreement - The Medicines Company
28
provide to ASTRAZENECA in writing, for the same period of time, a
non-binding marketing plan and sales forecast for the Product in
any Major Market where the Product by that time has been Launched
or is expected to be Launched during the applicable period
immediately to come;
5.1.3. TMC shall notify ASTRAZENECA forthwith and provide particulars of
any halt or substantial delay in any development program or
clinical trial, any obstacles in the Product reaching the market
and any substantial changes anticipated in the sales potential of
the Product;
5.1.4. TMC shall notify ASTRAZENECA forthwith regarding, and provide
copies of, any correspondence with the regulatory authorities in
the Territory that could reasonably be of any significance
regarding the possibility, time frame or scope of any Filing of
an NDA or any NDA Approval.
5.2. OBLIGATION OF ASTRAZENECA TO SHARE INFORMATION. ASTRAZENECA shall
keep TMC informed about the progress of the clinical trials,
sale, promotion and marketing of Product in any country in which
ASTRAZENECA has rights to sell Product. For this purpose:
5.2.1. ASTRAZENECA shall at least once each year provide TMC in writing
a timetable for the expected Filings of an NDA, expected NDA
Approvals and expected Launches during the one-year period to
come.
5.2.2. ASTRAZENECA shall notify TMC forthwith regarding, and provide
copies of, any correspondence with the regulatory authorities in
any Major Market that could reasonably be of any significance
regarding the possibility, time frame or scope of any Filing of
an NDA or any NDA Approval by TMC in any country for which TMC
has yet to file an NDA or receive NDA Approval.
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29
6. CONSIDERATION
In consideration of the rights granted hereunder TMC shall pay to ASTRAZENECA
the remuneration stated in this Article 6.
6.1. MILESTONE PAYMENTS.
6.1.1. Within thirty (30) days after the Effective Date TMC shall pay to
ASTRAZENECA the amount of USD [**] ($[**]).
6.1.2. Within thirty (30) days of TMC's receipt of NDA Approval in the
first Major Market TMC shall pay to ASTRAZENECA the amount of USD
[**] ($[**]).
6.1.3. Within thirty (30) days of TMC's receipt of NDA Approval in the
second Major Market, TMC shall pay to ASTRAZENECA the amount of
USD [**] ($[**]).
6.2. ROYALTY RATE.
6.2.1. Following Launch of the Product, on a country-by-country basis
for the period set out in Article 6.4, TMC shall pay to
ASTRAZENECA, subject to what is stated in Articles 6.2.2 and
6.2.3, a running royalty on the annual Net Sales of the Product
in the Territory as follows:
Annual Net Sales in the Territory Royalty Rate
a) up to USD [**] [**] percent ([**]%)
($ [**])
b) above USD [**] [**] percent ([**]%)
($ [**]) and up to USD [**]
($[**])
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30
c) above USD [**] [**] percent ([**]%)
($ [**]) and up to USD [**]
($ [**])
d) above USD [**] [**] percent ([**]%)
($ [**]) and up to USD [**]
($ [**])
e) above USD [**] [**] percent ([**]%)
($ [**])
The relevant royalty rate so stated shall apply to the amount of
annual Net Sales within the applicable layer only.
For convenience of example only and without limiting the above,
the royalty rate of [**]% shall apply to the amount of annual Net
Sales under $ [**] and should the annual Net Sales exceed $ [**]
then the royalty rate of [**]% shall apply only to the amount of
annual Net Sales exceeding $ [**] (and up to $ [**]).
6.2.2. Notwithstanding the royalty rates set forth in Article 6.2.1, the
running royalty rate on the Net Sales of the Product during the
time period starting on the Effective Date and ending on the date
which is one (1) year after the date of the Launch of the Product
in the first country in which the Product is Launched, shall be
reduced to [**] percent ([**]%) of the rate otherwise stated in
Article 6.2.1.
6.2.3. In the event that in a country in the Territory ASTRAZENECA
receives NDA Approval of an [**] Product, and TMC's Net Sales in
such country for a certain Subsequent Quarter is less than TMC's
Net Sales in such country in the Baseline Quarter for such
country, the royalty payable to ASTRAZENECA by TMC under Article
6.2.1 with respect to Net Sales in such country in the Subsequent
Quarter concerned shall be reduced by (i), if such reduction in
Net Sales is [**] percent ([**]%) or less compared to the
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31
Net Sales in the Baseline Quarter for such country, a percentage
equal to such reduction in Net Sales expressed in percent, or
(ii), if such reduction in Net Sales exceeds [**] percent ([**]%)
compared to the Net Sales in the Baseline Quarter for such
country, [**] percent ([**]%). The calculation of the reduction
in Net Sales under this Article 6.2.3 shall, in case Net Sales in
such country is not denominated in USD, be conducted in local
currency. The percentage of each Net Sales reduction contemplated
in this Article 6.2.3 shall be determined by the fraction (A-B)/A
multiplied by 100 where A is TMC's Net Sales during the Baseline
Quarter and B is TMC's Net Sales during the Subsequent Quarter
concerned.
The definition "NDA Approval" shall, for the purpose of this
Article 6.2.3 (and Articles 1.10 and 1.43) only, be deemed to
refer to [**] Product instead of Product.
For convenience of example only and without limiting the above
standing, the following calculation shows the application of the
provision stated.
a) If TMC's Net Sales in country A are $[**] in the
Baseline Quarter for such country and $[**] in a
Subsequent Quarter the reduction of the royalty payable to
ASTRAZENECA would be determined as follows.
The reduction in Net Sales is [**]% (($ [**]) /
$ [**] = [**]%) and hence the royalty payable to ASTRAZENECA
with respect to Net Sales in country A in the Subsequent
Quarter concerned shall be reduced by [**]%.
b) If TMC's Net Sales in country A are $[**] in the
Baseline Quarter for such country and $[**] in a
Subsequent Quarter the reduction of the royalty payable to
ASTRAZENECA would be determined as follows.
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32
The reduction in Net Sales is [**]% (($[**]) / $ [**]=
[**]%) and hence the royalty payable to ASTRAZENECA with
respect to Net Sales in country A in the Subsequent Quarter
concerned shall be reduced by [**]%.
For the purpose of determining what royalty rate to apply with
respect to Net Sales in one specific country, the following shall
apply.
The applicable royalty rate under each of items (a) through (e)
of Article 6.2.1 shall apply to TMC's Net Sales in one specific
country exceeding the amount "C" in the following formula.
TA x NS = C
--
aNS
where "NS" is TMC's Net Sales in the specific country during the
calendar year concerned; and where "aNS" is TMC's annual Net
Sales in the Territory during such calendar year; and where "TA"
is the applicable "threshold amount" under the respective items
(a) through (e) of Article 6.2.1.
6.2.4. For the purpose of Article 6.2.1 the term "annual" shall refer to
calendar years, provided, however, that for the purpose of
determining what royalty rates to apply during the first or last
calendar year of the royalty payment period pursuant to Article
6.4, which parts may not constitute a full calendar year, the
following shall apply.
a) The applicable royalty rate under each of items (a) through
(e) of Article 6.2.1, subject to what is stated in Article
6.2.2 and 6.2.3, shall apply to the Net Sales exceeding the
amount "A" in the following formula.
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33
TA x NM = A
--
12
where "NM" is the "number of full months" of sales
attracting royalty hereunder, regardless of the number of
countries in which sales are being made, during the calendar
year concerned; and where "TA" is the applicable "threshold
amount" under the respective items (a) through (e) of
Article 6.2.1.
b) For convenience of example only and without limiting the
above standing, the following calculation shows the
application of the provision stated.
If Launch occurs in the first country three months before
the end of the calendar year, and Net Sales in such three
month period are $ [**], royalties payable would be
determined as follows:
(i) the [**]% royalty rate under 6.2.1(a) would apply to
the first $ [**]of Net Sales ($[**]); and
(ii) the [**]% royalty rate under 6.2.1(b) would apply to
Net Sales above $ [**] ($[**]).
The foregoing notwithstanding, as this example is with
respect to sales in the year of first Launch, the above
stated royalty rates would be reduced by [**] percent
([**]%) pursuant to Article 6.2.2.
6.3. MINIMUM ROYALTY. Notwithstanding what is stated in Article 6.2,
during the second through fourth full calendar years following
Launch in the first Major Market, the aggregate annual royalty
amount due by TMC to ASTRAZENECA for sales of the Product shall,
regardless of the actual Net Sales amount accrued during such
calendar year, not go below the following amounts during the
years specified:
6.3.1. Second full calendar year following Launch: USD [**]
($[**]);
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34
6.3.2. Third full calendar year following Launch: USD [**] ($[**])
6.3.3. Fourth full calendar year following Launch: USD [**] ($[**])
6.3.4. Should the Net Sales by TMC for any calendar year not generate
the relevant royalty amount indicated under this Article 6.3,
then TMC shall pay the difference between the minimum royalty
amount stated and the amount actually generated within thirty
(30) days after the date when the royalty payment for the last
full quarter of the calendar year concerned is due according to
Article 6.5.1.
6.4. DURATION OF ROYALTY PAYMENTS.
Royalties under Article 6.2 shall be payable on a country by
country basis for the longer of :
a) the life of ASTRAZENECA Patent Rights which are necessary to
continue to manufacture, use or sell the Product in such
country; or
b) a period of [**] years from Launch in that country
(provided always that, in the case of a country within the
European Economic Area, such [**] year period shall run
from the date of Launch anywhere in the European Economic
Area).
6.5. REPORTS.
6.5.1. TMC shall deliver to ASTRAZENECA within sixty (60) days after the
end of each Quarter, a written report showing its computation of
the remuneration due to ASTRAZENECA under this Agreement during
such Quarter including (i) the quantity of the Product sold by or
on behalf of TMC during such Quarter; and (ii) the total
remuneration due in respect thereof; and TMC shall at the same
time make the payment of the remuneration due. Any payment to be
made hereunder shall be made in U.S. Dollars. Each such report
mentioned in this Article 6.5.1 shall include the
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35
rates of exchange used for conversion to U.S. Dollars from the
currency in which such sales were made.
6.5.2. In the event that ASTRAZENECA, its Affiliates or sublicensees
sells Product pursuant to Article 2.7.3, then ASTRAZENECA shall
deliver to TMC within sixty (60) days after the end of each
Quarter, a written report showing its computation of the
remuneration due to TMC under this Agreement during such Quarter
including (i) the quantity of the Product sold by or on behalf of
ASTRAZENECA during such Quarter; and (ii) the total remuneration
due in respect thereof and at the same time make the payment of
the remuneration due. Any payment to be made hereunder shall be
made in U.S. Dollars. Each such report mentioned in this Article
6.5.2 shall include the rates of exchange used for conversion to
U.S. Dollars from the currency in which such sales were made.
License Agreement - The Medicines Company
36
6.6. TAXES.
6.6.1. The payments to be made hereunder by either Party shall be net
payments i.e. without deduction of any bank or transfer charges.
6.6.2. ASTRAZENECA shall pay any and all taxes levied on account of, or
measured exclusively by, all payments it receives under this
Agreement. Amounts payable from TMC to ASTRAZENECA under this
Agreement shall be paid by TMC without deduction for any tax,
provided however that TMC may withhold income tax as required by
internal laws of any applicable jurisdiction. In the case of such
withholding being applicable, ASTRAZENECA may apply for the
reduction of rate of withholding tax (including under the
U.S./Sweden tax treaty) with the assistance of TMC and provided
evidence of acceptance of this claim is submitted to TMC, TMC
shall apply this rate accordingly. If applicable laws require
that taxes be withheld, TMC will deduct those taxes from the
remittable payments, make timely payment of the taxes to the
proper taxing authority and send proof of such payment to
ASTRAZENECA within sixty (60) days following that payment.
6.6.3. TMC shall pay any and all taxes levied on account of, or measured
exclusively by, all payments it receives under this Agreement.
Amounts payable from ASTRAZENECA to TMC under this Agreement
shall be paid by ASTRAZENECA without deduction for any tax,
provided however that ASTRAZENECA may withhold income tax as
required by internal laws of any applicable jurisdiction. In the
case of such withholding being applicable, TMC may apply for the
reduction of rate of withholding tax (including under the
U.S./Sweden tax treaty) with the assistance of ASTRAZENECA and
provided evidence of acceptance of this claim is submitted to
ASTRAZENECA, ASTRAZENECA shall apply this rate accordingly. If
applicable laws require that taxes be withheld, ASTRAZENECA will
deduct those taxes from the remittable payments,
License Agreement - The Medicines Company
37
make timely payment of the taxes to the proper taxing authority
and send proof of such payment to TMC within sixty (60) days
following that payment.
6.6.4. For the avoidance of doubt, TMC shall be responsible and liable
for all import duties and levies payable on bulk Compound
imported to the US and to all related import clearance
requirements. The value for customs purposes of this material
provided free of charge should be the manufacturing cost to
ASTRAZENECA.
6.6.5. The parties shall cooperate fully to ensure that where legally
possible no import duties are paid by TMC in respect of Product
supplied to ASTRAZENECA for sale in the Excluded Countries.
6.6.6. All payments under this Agreement shall be exclusive of Value
Added Tax where applicable.
6.7. EXCHANGE RATES. For the purpose hereof, the rate of exchange to
be used for conversion hereunder to U.S. Dollars shall be the
average rate of exchange for the period to which the payment
relates, as published by the Wall Street Journal.
6.8. BOOKS AND AUDIT. Each Party shall keep complete and accurate
books and records with respect to its sale of the Product and
remuneration payable hereunder. Each Party shall have the right
to have such pertinent books and records of the other Party
inspected and examined once each calendar year for the purpose of
determining the accuracy of payments made hereunder. Such
inspection and examination shall be conducted by an independent,
certified, public accountant selected by the Party requesting
such examination. Such accountant shall not disclose to such
Party any information except for information necessary to verify
the accuracy of the records and payments made pursuant to this
Agreement. The charges of the independent, certified, public
accountant shall be paid by the Party
License Agreement - The Medicines Company
38
requesting examination except if the payments pursuant to this
Agreement have been understated by more than five percent (5%) in
which case the Party who has underpaid will bear the cost and pay
the shortfall in payment pursuant to this Agreement with interest
to the other Party. Should instead the payments have been
overstated the Party who has overpaid may deduct any such amount
from the royalty payments due hereunder until such amount has
been recovered by such Party.
6.9. WIRE TRANSFER INSTRUCTIONS.
6.9.1. Unless otherwise instructed by ASTRAZENECA, all payments by TMC
hereunder shall be made from the United States by wire transfer
in the requisite amount to the following account of ASTRAZENECA.
Bank Name: AstraZeneca AB
Account No: [**]
Bank: [**]
Swift: [**]
Corr bank: [**]
6.9.2. Unless otherwise instructed by TMC, all payments by ASTRAZENECA
hereunder shall be made from Sweden by wire transfer in the
requisite amount to the following account of TMC.
Bank Name: Comerica Bank - California
Account No: [**]
Bank Code: ▇▇▇▇▇▇▇▇▇
6.10. INTEREST. If any sum payable pursuant to this Agreement shall not
have been paid to a Party by the due date then (without prejudice
to any other claim or remedy of such Party) the Party owing such
sum shall pay interest thereon to the other Party at an annual
rate of LIBOR + three percent (3%) from
License Agreement - The Medicines Company
39
time to time published in respect of the period starting on the
due date of payment and ending on the actual date of payment.
"LIBOR" shall mean the thirty (30) days U.S. Dollar BBA London
Interbank Offered Rate as published by ▇▇▇▇▇▇.
7. INTELLECTUAL PROPERTY - PROSECUTION AND MAINTENANCE
7.1. Any and all ASTRAZENECA IP vested in ASTRAZENECA and/or its
Affiliates shall as between ASTRAZENECA and TMC remain vested in
ASTRAZENECA and/or its Affiliates.
7.2. Any and all TMC IP vested in TMC shall as between TMC and
ASTRAZENECA remain vested in TMC.
7.3. ASTRAZENECA or its agent shall, during the term of this Agreement
be responsible for the filing, prosecution and maintenance of the
ASTRAZENECA Patent Rights (including, without limitation, subject
to Article 7.7, patent term extension rights).
TMC shall reimburse ASTRAZENECA or its agent for any
out-of-pocket expenses (including fees to outside counsel and
consultants) incurred by ASTRAZENECA or its agent in relation to
any action taken by ASTRAZENECA or its agent pursuant to this
Article 7.3.
7.4. TMC shall have the right to give comments and recommendations as
to the overall strategy regarding the filing, prosecution and
maintenance of the ASTRAZENECA Patent Rights; and before taking
any significant step in the filing or prosecution of the
ASTRAZENECA Patent Rights, ASTRAZENECA or its agent shall allow
TMC to comment on the action proposed to be taken and ASTRAZENECA
or its agent shall consider any such comments. For purposes of
this Article 7.4 only, significant step means the filing of a
dependent application (including but not limited to divisional
License Agreement - The Medicines Company
40
or continuation applications); filing for patent term extension;
or any step taken during an appeal, re-examination, re-issue or
opposition procedure, provided, however, that no such action now
mentioned is a response to an office action. Notwithstanding the
foregoing, ASTRAZENECA or its agent may, at its own discretion,
ask for TMC's input in relation to such office action.
7.5. In the event that ASTRAZENECA should decide to permit any pending
patent application or any patent included in the ASTRAZENECA
Patent Rights to lapse by any action, inaction or failure to take
any action or to pay any fee when due, ASTRAZENECA or its agent
shall promptly inform TMC of such decision, but no later than
thirty (30) days prior to the date by which such action, inaction
or failure to pay will result in lapse of the patent application
or the patent, provided that such period is available to
ASTRAZENECA, so that TMC might, for the avoidance of doubt at
TMC's expense, seek such patent protection or prevent any such
lapse.
7.6. ASTRAZENECA shall not be liable to TMC in contract, tort,
negligence, breach of statutory duty or otherwise for any
economic loss or other loss of turnover, profits, savings,
business or goodwill or any loss, damage, costs or expenses of
any nature whatsoever incurred or suffered by TMC because of
ASTRAZENECA's or its agent's actions pursuant to or as a
consequence of Articles 7.3 and 7.4.
7.7. Should ASTRAZENECA not be able to lawfully apply for patent term
extensions, including, but not limited to, Supplementary
Protection Certificates, relating to the ASTRAZENECA Patent
Rights in the Territory in its own name, or should ASTRAZENECA
otherwise require, TMC shall co-operate with ASTRAZENECA or its
agent in any issue regarding the gaining of such patent term
extension by assisting ASTRAZENECA or its agent with any actions
or documents needed for such purpose.
License Agreement - The Medicines Company
41
Should in any country in the Territory any decision have to be
made as to what product, claim or otherwise to apply for such
patent term extension regarding, then ASTRAZENECA or its agent
shall have the right to make such decision at its own reasonable
discretion and provided that ASTRAZENECA or its agent shall allow
TMC to comment on the action proposed to be taken and ASTRAZENECA
or its agent shall consider any such comments.
7.8. RIGHTS TO THE RESULTS. Any patents and other intellectual
property rights, information, ideas, knowledge, data or know-how
relating solely to the Compound and/or the Product and that;
(i) relate solely to an intravenous route of administration; and
(ii) do not have [**]; and
(iii)do not relate to any formulation or product which contain(s)
both the Compound and one or more [**]as active ingredients,
whether or not such formulation or product contain(s) active
ingredients in addition to the Compound and the [**]
developed during the term of this Agreement (hereinafter referred
to as "Result(s)") shall as between TMC and ASTRAZENECA be TMC IP
and the sole property of TMC. TMC shall have the sole management
of, and shall bear the cost of, any Results. ASTRAZENECA shall be
given the reasonable opportunity to comment on important aspects
of the prosecution of any patent applications, and shall use its
reasonable endeavours to assist TMC in the prosecution of any
patent applications.
Any patents and other intellectual property rights, information,
ideas, knowledge, data or know-how falling outside any or all of
(i) through (iii) above in this Article 7.8 and relating to the
Compound and/or the Product
License Agreement - The Medicines Company
42
shall, as between TMC and ASTRAZENECA, be the sole property of
ASTRAZENECA.
8. CLAIMS REGARDING INFRINGEMENT AND INVALIDITY
8.1. NOTIFICATION OF CLAIM. If a Third Party notifies ASTRAZENECA or
TMC, or their respective Affiliates or sub-licensees, that any
act by TMC, or its Affiliates or sub-licensees, utilizing the
ASTRAZENECA IP allegedly infringes in the Territory any Patent
Rights or other intellectual property rights owned by or licensed
to the Third Party, ASTRAZENECA or TMC shall promptly notify the
other in writing.
8.2. DEFENCE OF CLAIMED INFRINGEMENT.
8.2.1. ASTRAZENECA shall have no obligation to defend or settle any
claim by a Third Party that the manufacture, sale or other use of
the Product by TMC resulting from the use or exercise of the
license granted hereunder under the ASTRAZENECA IP infringes any
Patent Rights or other intellectual property rights owned by or
licensed to a Third Party, subject to the provisions of Article
10.
8.2.2. If a Third Party makes an infringement claim or files an
infringement action against ASTRAZENECA, its Affiliates or
sub-licensees, or TMC, its Affiliates or sub-licensees, arising
out of TMC's, its Affiliates' or sub-licensees' manufacture, sale
or other use of the Product in the Territory, or if a Third Party
challenges any of the ASTRAZENECA IP, then TMC shall defend or
settle the claim or action at its expense, subject to the
provisions of Article 10.
8.2.3. ASTRAZENECA may join such proceedings mentioned under sub-section
8.2.2 voluntarily, subject always to TMC's, its Affiliates' or
sub-licensees' right to decide the conduct over such litigation.
Any such joining of the proceedings shall be at ASTRAZENECA's
cost and expense.
License Agreement - The Medicines Company
43
ASTRAZENECA shall for such purpose have the right to
independently retain legal counsel and consultants, at its sole
cost and expense.
8.2.4. It is understood between the Parties that any proposed settlement
will be subject to ASTRAZENECA's prior written approval, which
approval shall not be unreasonably withheld. Such approval might
be withheld primarily on the grounds that ASTRAZENECA reasonably
determines that the settlement proposed is overly burdensome,
financially or strategically, to ASTRAZENECA or that ASTRAZENECA
intends to continue such defence itself.
Should ASTRAZENECA withhold such approval, then ASTRAZENECA shall
have the right, but not the obligation other than in the case
that ASTRAZENECA has announced to TMC its intention to continue
such defence itself, to continue the defence of the claim or
action at its own expense. In such case TMC, its Affiliates or
sub-licensees shall, at ASTRAZENECA's request and at
ASTRAZENECA's expense for TMC's, its Affiliates' or
sub-licensees' costs and expenses, assist in the prosecution of
such action, including, but not limited to, consenting to being
joined in such action as a voluntary defendant.
8.2.5. Should TMC reasonably believe that the Third Party rights
contemplated by Article 8.2.1 are valid in a certain country(ies)
and that infringement is likely to be occurring in such
country(ies), TMC may seek and enter into a licence thereto from
such Third Party on appropriate commercial terms, whereby any
remuneration and any costs and expenses (including but not
limited to reasonable external legal costs) for such license
shall be [**] between TMC and ASTRAZENECA according to the
following.
TMC may deduct an amount equivalent to [**] percent ([**]%) of
TMC's payments to such Third Party pursuant to such arrangement
as indicated in the first paragraph of this Article 8.2.5 from
the royalty payments to be made by TMC to ASTRAZENECA on the Net
Sales in the country
License Agreement - The Medicines Company
44
concerned pursuant to Article 6.2 to cover ASTRAZENECA's
obligation to carry [**] percent ([**]%) of such payments and
costs. This deduction shall be subject to the proviso that the
royalty payments due to ASTRAZENECA shall not be reduced in total
by more than [**] percent ([**]%) in any calendar year, and any
residue not offset may be carried forward by TMC until such time
as it has recovered ASTRAZENECA's [**] per cent ([**]%) share of
such costs and expenses, or until the royalty payment obligations
of TMC hereunder expire, whichever is the earlier.
8.3. THIRD PARTY INFRINGEMENT. If a Third Party shall, in the
reasonable opinion of either Party, infringe any ASTRAZENECA
Patent Rights in the Territory, then the Party having such
opinion shall promptly notify the other Party.
8.3.1. Further, each Party shall within five (5) working days or as soon
as reasonably possible thereafter advise the other Party of
receipt of any notice of:
a) any certification filed under the U.S. "Drug Price
Competition and Patent Term Restoration Act of 1984" ("ANDA
Act"), claiming that any ASTRAZENECA Patent Rights are
invalid or claiming that the ASTRAZENECA Patent Rights will
not be infringed by the manufacture, use or sale of a
product for which an application under the ANDA Act is filed
or;
b) any equivalent or similar certification or notice in any
other jurisdiction.
8.3.2. TMC, its Affiliates or sub-licensees shall have the initial sole
right to commence an action for infringement in the Territory
against the Third Party, in its own name, together with the right
to enforce and collect any judgement thereon. ASTRAZENECA may
join such proceedings voluntarily, subject always to TMC's, its
Affiliates' or sub-licensees' right to decide the conduct of such
litigation. Any such joining of the proceedings
License Agreement - The Medicines Company
45
shall be at ASTRAZENECA's cost and expense. ASTRAZENECA shall for
such purpose have the right to independently retain legal counsel
and consultants, at its sole cost and expense.
8.3.3. Any monetary recovery (whether by settlement or judgement) in
connection with an infringement action commenced by TMC, its
Affiliates or sub-licensees shall be applied first to reimburse
TMC, its Affiliates or sub-licensees for their out-of-pocket
expenses (including reasonable attorneys fees) incurred in
prosecuting such action and the expenses of ASTRAZENECA borne by
TMC hereunder. Any balance remaining shall be allocated among
ASTRAZENECA and TMC in a manner reasonably calculated to
correspond to the distribution of profits, in accordance with
what would normally be provided for under this Agreement, on the
sales of Product to which such recovery pertains.
8.3.4. Should neither TMC, nor its Affiliates or sub-licensees, take
appropriate and diligent action with respect to any such
infringement or challenge as contemplated in this Article 8.3
within forty-five (45) days, or, in the case of a certification
filed under the ANDA Act or similar certification or notice as
contemplated under Article 8.3.1, within twenty (20) days, after
receiving notice of any infringement or possible infringement or
challenge, then ASTRAZENECA shall have the right, but not the
obligation, to take such action, at its own expense, in its own
name, and the right to enforce and collect any judgement thereon.
a) Should ASTRAZENECA elect to take such action, then TMC, its
Affiliates or sub-licensees, shall, at ASTRAZENECA's request
and at ASTRAZENECA's expense for TMC's, its Affiliates' or
sub-licensees', costs and expenses, assist in the
prosecution of such action, including, but not limited to,
consenting to being joined in such action as a voluntary
plaintiff.
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46
b) If the recovery of such action as contemplated in this
Article 8.3.4 exceeds ASTRAZENECA's out-of-pocket expenses
(including reasonable attorneys fees) for prosecuting the
action, then such excess recovery shall be shared by the
Parties on a [**].
8.3.5. ASTRAZENECA, its Affiliates or sub-licensees shall have the sole
right to commence an action for infringement of the ASTRAZENECA
IP in the Excluded Countries or in any other country in which the
license granted to TMC hereunder has reverted to ASTRAZENECA
pursuant to Article 3.8 against the Third Party, in its own name,
together with the right to enforce and collect any judgement
thereon. TMC may join such proceedings voluntarily, subject
always to ASTRAZENECA's, its Affiliates' or sub-licensees' right
to decide the conduct of such litigation. Any such joining of the
proceedings shall be at TMC's cost and expense. TMC shall for
such purpose have the right to independently retain legal counsel
and consultants, at its sole cost and expense. Any monetary
recovery (whether by settlement or judgement) in connection with
an infringement action commenced by ASTRAZENECA under this
Article 8.3.5 shall be retained by ASTRAZENECA.
9. TRADEMARK
9.1. TMC shall select a trademark to use in connection with the sales,
marketing and distribution of the Product and shall be the owner
and party of record of such trademark (the "TMC Trademark"). TMC
shall have sole responsibility for clearance and registration of
said TMC Trademark. TMC shall be responsible for all decisions
and costs relating to selection, clearance, registration, defence
and maintenance of the TMC Trademark.
9.2. TMC undertakes, should ASTRAZENECA so require in writing, to
mention on all packages, package inserts and promotional and
advertising materials for the Product "Licensed from AstraZeneca
AB" or the equivalent wording in the major language(s) of the
country in which the Product is sold, or,
License Agreement - The Medicines Company
47
should legal, regulatory or similar reasons prevent the use of
that wording, such other wording as close as possible to the
wording herein stated.
10. INDEMNITY
10.1. INDEMNITY BY TMC.
10.1.1. TMC shall be responsible for and shall indemnify ASTRAZENECA, its
Affiliates and its and its Affiliates' directors, officers, other
employees, agents and consultants (collectively the "ASTRAZENECA
Indemnified Party") against any and all liability, loss, damage,
cost and expense (including legal costs) incurred or suffered by
the ASTRAZENECA Indemnified Party as a result of any claim
brought against an ASTRAZENECA Indemnified Party by a Third Party
(i) arising out of the testing, manufacture, sale, use or
promotion by TMC, its Affiliates or sub-licensees of any Compound
or Product hereunder; (ii) arising out of any theory of product
liability (including, but not limited to, actions in the form of
tort, warranty or strict liability) based on Compounds or
Products developed by TMC hereunder; or (iii) arising out of any
other activities to be carried out by TMC, its Affiliates or
sub-licensees pursuant to this Agreement to the extent not
included in (i) and (ii) above, except where such liability,
loss, damage, cost and expense has been incurred or suffered as a
result of a material breach of ASTRAZENECA's representations,
warranties or obligations under this Agreement or by gross
negligence or misconduct on the part of ASTRAZENECA.
10.1.2. An ASTRAZENECA Indemnified Party that intends to claim
indemnification under Article 10.1.1 shall notify TMC promptly of
any such liability, loss, damage, cost or expense and permit TMC
to control the defence and disposition thereof and further agrees
to reasonably cooperate at TMC's expense with TMC in the handling
thereof. The ASTRAZENECA Indemnified Party shall not compromise
or settle such claim. TMC agrees to keep ASTRAZENECA informed of
the progress in the defence and
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48
disputation of such claims and to consult with ASTRAZENECA with
regard to any settlement thereof which TMC proposes to enter into
and will provide ASTRAZENECA with suitable information regarding
the same.
10.1.3. TMC will maintain appropriate liability insurance against such
product and other liability as contemplated under Article 10.1.1
at levels appropriate for products and activities of the relevant
type.
10.2. INDEMNITY BY ASTRAZENECA.
10.2.1. ASTRAZENECA shall be responsible for and shall indemnify TMC, its
Affiliates and its and its Affiliates' directors, officers, other
employees, agents and consultants (collectively the "TMC
Indemnified Party") against any and all liability, loss, damage,
cost and expense (including legal costs) incurred or suffered by
the TMC Indemnified Party as a result of any claim brought
against the TMC Indemnified Party by a Third Party (i) arising
out of the testing, manufacture, sale, use or promotion by
ASTRAZENECA, its Affiliates or sub-licensees, of any Compound or
Product hereunder; (ii) arising out of any theory of product
liability (including, but not limited to, actions in the form of
tort, warranty or strict liability) based on Compounds or
Products sold by ASTRAZENECA hereunder; or (iii) which arises as
a result of a material breach of ASTRAZENECA's representations,
warranties or obligations under this Agreement, except where such
liability, loss, damage, cost and expense has been incurred or
suffered as a result of a material breach of TMC's
representations, warranties or obligations under this Agreement
or by gross negligence or misconduct on the part of TMC.
10.2.2. A TMC Indemnified Party that intends to claim indemnification
under Article 10.2.1 shall notify ASTRAZENECA promptly of any
such liability, loss, damage, cost and expense and permit
ASTRAZENECA to control the defence and disposition thereof and
further agrees to reasonably cooperate at ASTRAZENECA's expense
with ASTRAZENECA in the handling thereof. The TMC Indemnified
Party shall not compromise or settle such
License Agreement - The Medicines Company
49
claim. ASTRAZENECA agrees to keep TMC informed of the progress in
the defence and disputation of such claims and to consult with
TMC with regard to any settlement thereof which ASTRAZENECA
proposes to enter into and will provide TMC with suitable
information regarding the same.
10.2.3. ASTRAZENECA will either maintain appropriate liability insurance
or be self insured against such liability as contemplated under
Article 10.2.1.
11. CONFIDENTIALITY
11.1. CONFIDENTIAL INFORMATION. At all times during the term of this
Agreement and for a period of five (5) years following
termination or expiration hereof, each Party shall, and shall
cause its officers, directors, employees and agents to, keep
confidential and not publish or otherwise disclose and not use,
directly or indirectly, for any purpose, any Confidential
Information provided to it by the other Party, PROVIDED, THAT,
each Party may disclose and use the Confidential Information of
the other Party to the extent such disclosure or use is expressly
permitted by the terms of this Agreement, including without
limitation those purposes set forth in Article 11.2, or is
otherwise reasonably necessary for the performance of this
Agreement.
11.2. PERMITTED USE AND DISCLOSURE. The Receiving Party may use and/or
disclose Confidential Information to the extent that such
disclosure is:
11.2.1. made in response to a valid order of a court of competent
jurisdiction or other competent authority provided however that
the Receiving Party shall first have given notice to the
Disclosing Party and given the Disclosing Party a reasonable
opportunity to obtain a protective order requiring that the
Confidential Information and documents that are the subject of
such order be held in confidence by such court or authority or,
if disclosed, be used only for the purpose for which the order
was issued; and provided further that if a protective order is
not obtained, the Confidential Information disclosed in response
to such court or governmental order shall be limited to
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50
that information which is legally required to be disclosed in
response to such court or governmental order;
11.2.2. made by the Receiving Party to a regulatory authority as required
in connection with any Filing of an NDA; provided, however, that
reasonable measures will be taken to assure confidential
treatment of such information;
11.2.3. made by the Receiving Party to a patent authority as required in
connection with any filing or application for Patent Rights; or
11.2.4. made by the Receiving Party to Third Parties as may be necessary
or useful in connection with the development, manufacturing,
marketing, use and sale of the Compound, Drug Product or the
Product as contemplated by this Agreement, including
subcontracting, sublicensing and distribution transactions in
connection therewith, provided that any such Third Party has
undertaken confidentiality and non-use obligations in all
material respects equal to those undertaken by the Receiving
Party hereunder with respect to the Confidential Information
disclosed by the Receiving Party to it and the results of any
such activities.
11.3. RELEASE FROM RESTRICTIONS. Notwithstanding the foregoing,
Confidential Information shall not include any information that,
as determined by competent written proof:
11.3.1. is or hereafter becomes part of the public domain by public use,
publication, general knowledge or the like through no wrongful
act, fault or negligence on the part of the Receiving Party;
11.3.2. can be demonstrated by documentation or other competent proof to
have been in the Receiving Party's possession prior to disclosure
by the Disclosing Party;
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51
11.3.3. is subsequently received by the Receiving Party from a Third
Party who is not bound by any obligation of confidentiality with
respect to the said information;
11.3.4. is generally made available to Third Parties by the Disclosing
Party without restriction on disclosure; or
11.3.5. is independently developed by or for the Receiving Party without
reference to the Disclosing Party's Confidential Information.
12. ADVERSE EVENTS
12.1. REPORTING OF ADVERSE EVENTS.
12.1.1. TMC shall be fully responsible for reporting to the relevant
regulatory or other competent authorities in the Territory any
Adverse Event(s) which are or might be attributed to the use or
application of the Compound or the Product. At ASTRAZENECA's
request in writing TMC shall inform ASTRAZENECA of any such
Adverse Event in the country(ies) contemplated, and during the
time period contemplated, by such notice.
12.1.2. ASTRAZENECA shall be fully responsible for reporting to the
relevant regulatory or other competent authorities in any country
outside the Territory or for which the license to TMC hereunder
has been terminated any Adverse Event(s) which are or might be
attributed to the use or application of the Compound or the
Product. At TMC's request in writing ASTRAZENECA shall inform TMC
of any Adverse Event in the country(ies) contemplated, and during
the time period contemplated, by such notice. For the avoidance
of doubt ASTRAZENECA may appoint any Affiliate(s) or
sub-licensee(s) carrying out the marketing of the Product in the
country concerned to fulfil any such obligation as stated
hereunder.
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52
12.2. Without limiting what is stated in Article 12.1, the Parties
shall at an appropriate point of time during development of the
Product jointly establish any such Adverse Event reporting
procedures, including, but not limited to, any agreement
regarding safety data exchange, as may be required or useful.
13. REPRESENTATIONS, WARRANTIES AND COVENANTS
13.1. REPRESENTATIONS, WARRANTIES AND COVENANTS OF ASTRAZENECA.
ASTRAZENECA represents and warrants to, and covenants with, TMC
as follows:
a) as of the Effective Date ASTRAZENECA and/or its Affiliates
is the sole and exclusive owner of the ASTRAZENECA Patent
Rights; which to the extent covered by the license granted
hereunder is free and clear of any liens, charges and
encumbrances; and
b) as of the Effective Date ASTRAZENECA and/or its Affiliates
has not assigned, transferred, licensed, conveyed or
otherwise encumbered its right, title and interest in the
ASTRAZENECA Patent Rights to the extent covered by the
license granted hereunder, to a Third Party; and
c) as of the Effective Date ASTRAZENECA has the authority from
its Affiliates to grant to TMC the license specified in
Article 2.1 of this Agreement; and
d) as of the Effective Date and to the best of ASTRAZENECA's
knowledge, no Person other than ASTRAZENECA or any of its
Affiliates, has or shall have any claim of ownership with
respect to ASTRAZENECA Patent Rights; and
e) as of the Effective Date and to the best of ASTRAZENECA's
knowledge, the manufacture, use and sale of the Compound
does not
License Agreement - The Medicines Company
53
infringe upon any intellectual property rights of any Third
Party, although it is expressly acknowledged by TMC that
ASTRAZENECA has made no particular searches or
investigations to determinate whether such infringement
occurs; and
f) as of the Effective Date there are no claims, judgements or
settlements against or owed by ASTRAZENECA or pending or
threatened claims or litigation relating to the ASTRAZENECA
Patent Rights; and
g) except as insofar relating to any kind of formulation, or
work or development related thereto, of the Product, there
are no other Patent Rights or Know-How owned or licensed by
ASTRAZENECA required to develop and/or commercialise the
Product, and ASTRAZENECA shall not assert against TMC any
Patent Rights or other intellectual property owned or
licensed by ASTRAZENECA as of the Effective Date or at any
time thereafter which are or may be infringed by TMC when
utilizing its rights under this Agreement; and
h) as of the Effective Date ASTRAZENECA has disclosed to TMC
any known interference with the ASTRAZENECA Patent Rights or
re-examination or reissue proceeding concerning such
ASTRAZENECA Patent Rights; and
i) as of the Effective Date ASTRAZENECA has no knowledge from
which it can reasonably be inferred that the granted
ASTRAZENECA Patent Rights are invalid or unenforceable or
that the applications for ASTRAZENECA Patent Rights will not
proceed to grant; and
j) the agreements in force on the Effective Date between
ASTRAZENECA or its Affiliates and Third Parties regarding
investigational use of the Compound in laboratory research
animals or for testing in vitro will, if possible to
ASTRAZENECA, be assigned to TMC by ASTRAZENECA. Regarding
those agreements that are not possible for ASTRAZENECA to
assign to TMC, ASTRAZENECA
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54
shall keep TMC informed about the results and publications
generated by the Third Part(ies) under the agreements
concerned. None of the Third Parties to the agreements
referred to in this Article 13.1 j) has any license or
ownership rights under such agreement(s) in the results of
their investigations, or in the Compound, the Product or the
ASTRAZENECA IP that will have any material impact on the
license granted to TMC under this Agreement.
13.2. ACKNOWLEDGEMENT OF TMC.
TMC is aware;
a) that the ASTRAZENECA Patent Rights or the ASTRAZENECA
Know-How may not sufficiently enable TMC to manufacture or
conduct any other operational or manufacturing-related
activities with respect to the formulation of the Product,
and it is explicitly understood by TMC that TMC will have to
independently conduct any analysis, evaluation and
investigation regarding what intellectual property,
techniques, routes, equipment or other help or assistance
that will be required for such purpose and it will be
entirely at TMC's risk to find such intellectual property,
techniques, routes, equipment or other help or assistance in
order to conduct such activities; and
b) that certain Third Parties have access to the Compound under
the agreements referred to in Article 13.1 j) in order to
conduct investigations regarding the Compound.
13.3. REPRESENTATIONS AND WARRANTIES OF THE PARTIES. Each Party
represents and warrants to the other Party that it is a duly
organized and validly existing corporation under the laws of its
jurisdiction of incorporation, and has taken all required
corporate action to authorize the execution, delivery and
performance of this Agreement; it has the full right, power and
authority to enter into this Agreement and perform all of its
obligations hereunder; the execution and delivery of this
Agreement and the transactions contemplated
License Agreement - The Medicines Company
55
herein do not violate, conflict with, or constitute a default
under its Articles of Association or similar organization
document, its by-laws or the terms or provisions of any material
agreement or other instrument to which it is a party or by which
it is bound, or any order, award, judgement or decree to which it
is a party or by which it is bound; and upon execution and
delivery, this Agreement will constitute the legal, valid and
binding obligation of it.
13.4. LIMITATIONS. EXCEPT AS OTHERWISE SET FORTH IN THIS AGREEMENT
ASTRAZENECA EXPRESSLY DISCLAIMS ANY AND ALL IMPLIED OR EXPRESS
WARRANTIES AND MAKES NO EXPRESS OR IMPLIED WARRANTY, STATUTORY OR
OTHERWISE, OF ANY KIND, INCLUDING ANY WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR ANY PARTICULAR PURPOSE REGARDING
THE COMPOUND, ASTRAZENECA'S CONFIDENTIAL INFORMATION, DOCUMENTS,
ASTRAZENECA KNOW-HOW, ASTRAZENECA PATENT RIGHTS OR PRODUCTS.
14. TERM AND TERMINATION
14.1. TERM. This Agreement shall become effective on the Effective Date
and shall expire when TMC ceases to sell the Product in the last
country of the Territory or otherwise terminates this Agreement
as set forth in Article 14.2.
14.2. TERMINATION BY TMC. Should TMC determine that it does no longer
consider it viable to continue to exercise the rights under this
Agreement, then TMC may give written notice to ASTRAZENECA,
whereupon this Agreement shall terminate thirty (30) days after
such notice, unless ASTRAZENECA, within twenty (20) days of
having received such notice, requests TMC in writing to enter
into good faith discussions to see whether TMC's concerns could
be reasonably overcome. However, upon TMC having given such
notice TMC shall not be liable for any payments under Articles
6.1.2 and 6.1.3 or for any payments under Article 6.3 unless
License Agreement - The Medicines Company
56
corresponding to the royalty amounts actually due, which become
due after the expiration of the 30-day period mentioned above in
this Article 14.2.
Should the Parties not within three (3) months of the date of
commencement of such good faith discussions mentioned above in
this Article 14.2 have managed to reach a mutually acceptable
solution to TMC's concerns, then TMC may terminate this Agreement
by giving ninety (90) days written notice.
14.3. TERMINATION FOR BREACH. In the event that either Party (the
"Breaching Party") shall be in significant default in the
performance of any of its material obligations under this
Agreement, in addition to any other right and remedy the other
Party (the "Complaining Party") may have, the Complaining Party
may terminate this Agreement by sixty (60) days prior written
notice (the "Notice Period") to the Breaching Party, specifying
the breach and its claim of right to terminate, provided always
that the termination shall not become effective at the end of the
Notice Period if the Breaching Party cures the breach complained
about during the Notice Period.
14.4. SURVIVAL OF OBLIGATIONS. Termination or expiration of this
Agreement shall not relieve either Party from any obligation
incurred hereunder prior thereto.
14.5. SURVIVAL OF PROVISIONS UPON TERMINATION AND/OR EXPIRATION.
Subject to what is stated in Article 15, the provisions of
Articles 1, 7.1, 7.2, 10, 12, 13, 14.5, 15, 17 and 18 shall
survive termination or expiration of this Agreement. The
provisions of Article 2.5 shall survive only upon expiration of
this Agreement. The provisions of Article 11 shall survive
termination or expiration of this Agreement and shall continue to
be in force for a period of five (5) years after termination or
expiration of this Agreement.
License Agreement - The Medicines Company
57
15. CONSEQUENCES OF TERMINATION
15.1. TERMINATION AND HANDBACK OF LICENSE
In addition to any remedy either Party may have in law, tort or
in contract, subject to what is stated in Article 3.9, upon
termination of the Agreement or the license in a certain country,
the following shall apply.
Upon termination of this Agreement by TMC pursuant to Article
14.2 or by ASTRAZENECA pursuant to Article 14.3, or by
ASTRAZENECA in a certain country pursuant to Article 3.8, the
license granted under Article 2.1 regarding the country(ies)
contemplated by the termination concerned shall cease, and TMC
shall, regarding the Territory or the country concerned,
whichever is applicable:
a) at the option of ASTRAZENECA, grant to ASTRAZENECA a
non-exclusive, world-wide or for the country concerned,
whichever is applicable, sub-licensable licence under the
TMC IP to develop, have developed, make, have made, use,
have used, import, have imported, market, have marketed,
sell and have sold the Compound and the Product for any
indications. The term of such non-exclusive licence shall
continue on a country by country basis for the longer of the
life of the TMC Patent Rights, or for ten (10) years from
first commercial sale of any resultant product in such
country by ASTRAZENECA, its Affiliates, sub-licensees or
nominees, whichever is the longer. TMC shall do all such
acts and things as may reasonably be necessary to fulfil
this obligation. The licence set out in this Article 15.1
(a) shall be [**].
b) return to ASTRAZENECA any ASTRAZENECA Know-How and deliver
to ASTRAZENECA a copy of any TMC Know-How;
c) deliver to ASTRAZENECA any and all quantities of Product in
its possession, power, custody or control subject always to
TMC's right to
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58
dispose of Product which is the subject of pre-termination
date orders pursuant to Article 15.1 (h). For the avoidance
of doubt, should this Article 15.1 (c) become applicable
because of termination regarding a certain country or
countries pursuant to Article 3.8, then the quantities of
Product referred to herein shall mean only those quantities
clearly designated, by marking, labelling or similar, for
the country or countries concerned and which could only be
used for the country or countries concerned;
d) ensure that its patent attorneys transfer to ASTRAZENECA a
copy of the patent files relating to the TMC Patent Rights
which TMC has been prosecuting and maintaining and
ASTRAZENECA shall be entitled to prosecute and shall
maintain such TMC Patent Rights at its own cost and expense
on terms similar to those set out in Article 7.3 and to deal
with infringers on terms similar to those set out in
Articles 8.2 and 8.3. TMC further undertakes to take any
action and produce any documents so as to enable ASTRAZENECA
to apply for patent term extensions, including, but not
limited to, Supplementary Protection Certificates, relating
to the TMC Patent Rights in ASTRAZENECA's name.
e) Should this Article 15.1 become applicable because of the
termination of the license regarding a certain country or
countries pursuant to Article 3.8, then TMC shall,
notwithstanding the license granted under Article 15.1 (a),
on the request by ASTRAZENECA continue to prosecute,
maintain and defend the TMC Patent Rights.
f) commensurate with legislative and regulatory requirements,
transfer to ASTRAZENECA or its nominee all NDA Approvals,
and regulatory filings for the Compound or Product
(including, without limitation, all information and
documentation used in the Filings of an NDA and NDA
approvals referred to in Article 3.5.2 and 3.5.4) for the
Territory or the country concerned, to the extent
applicable. In the event that in
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59
any country such a transfer is not possible, TMC shall use
reasonable endeavours to ensure that ASTRAZENECA has the
benefit of the relevant NDA Approvals, NDA's and other
related regulatory filings and approvals and, to this end,
consents to any regulatory authority cross-referencing to
the data and information on file with any regulatory
authority as may be necessary to facilitate the granting of
second NDA Approvals to and permit Filings of an NDA by
ASTRAZENECA, and TMC agrees to complete whatever other
procedures that are reasonably necessary in relation to the
same to enable ASTRAZENECA (either itself or in conjunction
with a Third Party) freely to develop and sell the Product
in substitution for TMC;
g) if applicable, assign the TMC Trademark or grant a
royalty-free exclusive licence to ASTRAZENECA to use the TMC
Trademark for the marketing, sales and distribution of the
Product;
h) not after the date of termination itself take any further
action for the Territory or the country concerned, to the
extent applicable, to develop, manufacture, have
manufactured, use, market, distribute or sell the Compound
or Product during the life of the TMC Patent Rights or the
ASTRAZENECA Patent Rights, whichever is the longer, except
that TMC has the right to dispose of that part of its
inventory of Product on hand as of the effective date of
termination which is the subject of orders for Product
accepted prior to the date of notice of termination for a
period of three (3) months after the effective date of
termination, and, within thirty (30) days after disposition
of such inventory pursuant to the fulfilment of such orders,
TMC will forward to ASTRAZENECA a final report and pay all
royalties due on the Net Sales of Product during such
period; and
License Agreement - The Medicines Company
60
i) provide ASTRAZENECA, should ASTRAZENECA so require, with
reasonable assistance in relation to ASTRAZENECA's
appointment of a Third Party manufacturer of Product.
Upon such termination as stated in this Article 15.1, ASTRAZENECA
shall have the right to disclose Confidential Information to
Third Parties for the purpose of, and to the extent necessary
for, enabling such Third Party to evaluate the financial and
scientific status of the Compound or Product for the purpose of
making a financial offer to ASTRAZENECA on the licensing or
acquisition of the rights returned to ASTRAZENECA and the rights
licensed to ASTRAZENECA under this Article 15.1, and, if such
licensing or acquisition occurs, as necessary to exploit or
enforce such rights.
15.2. TERMINATION FOLLOWED BY CONTINUED LICENSE
Upon the termination of this Agreement by TMC pursuant to Article
14.3, ASTRAZENECA's licences granted to TMC under Article 2 shall
continue, provided that TMC continues to make payments pursuant
to Article 6 as if the Agreement was still in effect.
16. FORCE MAJEURE
16.1. If either Party is prevented or delayed in the performance of any
of its obligations under this Agreement by Force Majeure, that
Party shall forthwith serve notice in writing on the other Party
specifying the nature and extent of the circumstances giving rise
to Force Majeure, and shall subject to service of such notice and
to Article 16.3 have no liability in respect of the performance
of such of its obligations as are prevented by the Force Majeure
event during the continuation of such events, and for such time
after they cease as is necessary for that Party, using all
reasonable endeavours, to recommence its affected operations in
order for it to perform its obligations.
16.2. If either Party is prevented from performance of its obligations,
due to Force Majeure, for a continuous period in excess of six
(6) months, the other Party
License Agreement - The Medicines Company
61
may terminate this Agreement forthwith on service of written
notice upon the Party so prevented. In the event of termination
under this Article 16.2 the provisions of Article 15 shall not
apply immediately and the Parties shall meet to discuss the
ASTRAZENECA IP and TMC IP and agree on a process for arrangements
upon termination.
16.3. The Party claiming to be prevented or delayed in the performance
of any of its obligations under this Agreement by reason of Force
Majeure shall use its reasonable endeavours to bring the Force
Majeure event to a close or to find a solution by which the
Agreement may be performed despite the continuation of the Force
Majeure event.
17. GENERAL PROVISIONS
17.1. ASSIGNMENT.
17.1.1. Subject to Articles 17.1.2 and 17.1.3, neither Party shall
without the prior written consent of the other Party assign,
transfer, charge or deal in any other manner with this Agreement
or any of its rights under it.
17.1.2. Each Party shall be entitled to assign its rights under this
Agreement to an acquiror of all or substantially all of its
capital stock or assets related to the pharmaceutical business
described in this Agreement, whether through purchase, merger,
consolidation or otherwise.
17.1.3. Each Party shall be entitled to assign its rights under this
Agreement to an Affiliate provided that such Party shall require
that any such Affiliate to whom it assigns any of its rights
under this Agreement shall assign such rights back to the
assigning Party immediately prior to it ceasing to be an
Affiliate of the assigning Party.
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62
17.2. SEVERANCE.
17.2.1. If any provision of this Agreement shall be found by any court or
administrative body of competent jurisdiction to be invalid or
unenforceable, such invalidity or unenforceability shall not,
provided that the general content of the Agreement remains
substantially the same as prior to such invalidity or
unenforceability, affect the other provisions of this Agreement
which shall remain in full force and effect.
17.2.2. The Parties agree, in the circumstances referred to in Article
17.2.1, to attempt to substitute for any invalid or unenforceable
provision a valid or enforceable provision which achieves to the
greatest extent possible the same effect as would have been
achieved by the invalid or unenforceable provision.
17.3. NOTICES.
17.3.1. All notices and other communications given or made in relation to
this Agreement;
17.3.2. shall be in English and in writing;
17.3.3. shall be delivered by hand or sent by first class registered post
or facsimile;
17.3.4. shall be delivered or sent to the Party concerned at the relevant
address or facsimile number, shown in Article 17.4.1 subject to
such amendments as may be notified from time to time in
accordance with this Article by the relevant Party to the other
Party by no less than three business days notice; and
17.3.5. shall be deemed to have been duly given or made if addressed in
the aforesaid manner;
a) if delivered by hand, upon delivery;
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63
b) if posted by first class registered post, four (4) business
days after posting;
c) if sent by facsimile, when a complete and legible copy of
the communication has been received at the appropriate
address.
17.4. CONTACT INFORMATION.
17.4.1. Initial details for the purposes of Article 17.3 are:
For ASTRAZENECA
F Address: AstraZeneca AB, ▇▇-▇▇▇ ▇▇ ▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇▇
Facsimile: ▇▇▇-▇ ▇▇▇ ▇▇▇ ▇▇
For the attention of: President & CEO
For TMC
Address: The Medicines Company, ▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇,
▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇▇
Facsimile: ▇▇-▇▇▇-▇▇▇-▇▇▇▇
For the attention of: ▇▇▇▇▇ ▇▇▇▇▇▇▇▇, Executive Chairman
17.4.2. Any notice pursuant to Article 3.5.4 shall, in addition to being
delivered in accordance with Articles 17.3 and 17.4.1, be
delivered to the following address by facsimile.
AstraZeneca AB,
Global Intellectual Property,
Sweden.
Facsimile: ▇▇▇ ▇ ▇▇▇ ▇▇▇ ▇▇
For the attention of: ▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇
What is stated in Articles 17.3.1, 17.3.2, 17.3.4 and 17.3.5 c)
shall apply to such notice as well.
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64
17.5. AGENCY, PARTNERSHIP OR JOINT VENTURE EXCLUDED.
17.5.1. Nothing in this Agreement shall be construed so as to constitute
either Party to be the agent of the other.
17.5.2. Nothing in this Agreement and no action taken by the Parties
pursuant to this Agreement shall constitute a partnership or
joint venture of any kind between the Parties.
17.6. ENTIRE AGREEMENT. Each of the Parties acknowledges and agrees
that in entering into this Agreement, and the documents referred
to in it, it does not rely on, and shall have no remedy in
respect of, any statement, representation, warranty or
understanding (whether negligently or innocently made) of any
Person (whether party to this Agreement or not) other than as
expressly set out in this Agreement as a warranty. Nothing in
this Article shall either operate to limit or exclude any
liability for fraud.
17.7. AGREEMENT TO SUPERSEDE EARLIER AGREEMENTS. The Confidential
Disclosure Agreement entered into by and between the Parties on
27 February 2003 ceases to have effect from the Effective Date,
except such termination does not affect a Party's accrued rights
and obligations thereunder at the date of termination.
17.8. AMENDMENTS. No amendment to or variation of this Agreement shall
be valid unless it is in writing and signed by or on behalf of
each of the Parties.
17.9. PUBLICITY AND ANNOUNCEMENTS.
17.9.1. Subject to Article 17.9.2 no press release, announcement or any
other communication to any Third Party concerning the transaction
contemplated by this Agreement, the financial terms of this
Agreement, the subject matter of this Agreement or any ancillary
matters shall be made or permitted or authorized to be made by
either Party without the prior written approval of the other,
such approval not to be unreasonably withheld or delayed and
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65
such approval to be given by an authorized representative of the
Party in question.
17.9.2. Either Party may make an announcement concerning the transaction
contemplated by this Agreement or any ancillary matter if
required by law, existing contractual obligations or any
securities exchange or regulatory authority or governmental body
to which either Party is subject or submits, wherever situated,
provided that the Party required to make such announcement
notifies the other Party of the details of the announcement prior
to making such announcement and in sufficient time for the other
Party to consider and comment on the announcement, and takes
advantage of all provisions to keep confidential as many terms of
the Agreement as possible.
17.10. WAIVER. Failure or delay by either Party to exercise any right or
remedy under this Agreement shall not be deemed to be a waiver of
that right or remedy, or prevent it from exercising that or any
other right or remedy on that occasion or on any other occasion.
17.11. NO BENEFIT TO THIRD PARTIES. No Third Party shall be deemed a
third party beneficiary under this Agreement for any purpose.
Without limiting the foregoing, the Contracts (Rights of Third
Parties) ▇▇▇ ▇▇▇▇ and any legislation amending or replacing such
Act shall not apply in relation to this Agreement or any
agreement, arrangement, understanding, liability or obligation
arising under or in connection with this Agreement.
18. GOVERNING LAW AND ARBITRATION
18.1. ARBITRATION. The Parties shall use their reasonable efforts to
settle amicably any dispute arising out of or in connection with
this Agreement. In case the Parties are not able to settle such
dispute between themselves, such dispute shall be finally
resolved by arbitration in accordance with the Rules of the
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66
International Chamber of Commerce. The arbitration proceedings
shall be held in London. Any proceedings shall be held in the
English language.
18.2. GOVERNING LAW. The validity, construction and interpretation of
this Agreement and any determination of the performance which it
requires shall be governed by the laws of
England.
IN WITNESS WHEREOF this Agreement has entered into force on the Effective Date.
ASTRAZENECA AB (PUBL) THE MEDICINES COMPANY
Signature:/s/▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ Signature: /s/ ▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇
Name: ▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇ Name: ▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇
Title: EVP, Global Drug Development Title: Executive Chairman
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Schedule A
ASTRAZENECA Patent Rights
CASE COUNTRY APPLICATION NO. APP. DATE PATENT NO. EXPIRY DATE
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License Agreement - The Medicines Company
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CASE COUNTRY APPLICATION NO. APP. DATE PATENT NO. EXPIRY DATE
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License Agreement - The Medicines Company
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COUNTRY CODE COUNTRY
--------------------------------------
AR Argentina
AT Austria
AU Australia
BD Bangladesh
BE Belgium
BR Brazil
BY Belarus
CA Canada
CH Switzerland
CO Colombia
CY Cyprus
CZ Czech Republic
DE Germany
DK Denmark
EE Estonia
EG Egypt
EP European Patent Office
ES Spain
FI Finland
FR France
GB United Kingdom
GR Greece
HU Hungary
ID Indonesia
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IE Ireland
IL Israel
IN India
IS Iceland
IT Italy
▇▇ ▇▇▇▇▇▇▇▇▇
▇▇ ▇▇▇▇▇▇▇▇▇▇
▇▇ ▇▇▇▇▇▇
MC ▇▇▇▇▇▇
▇▇ Macedonia
MX Mexico
MY Malaysia
NL Netherlands
NO Norway
NZ New Zealand
PH Philippines
PK Pakistan
PL Poland
PT Portugal
RO Romania
RU Russia
SA Saudi Arabia
SE Sweden
SG Singapore
SI Slovenia
SK Slovak Republic
TR Turkey
UA Ukraine
US USA
VE Venezuela
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WO Patent Co-operation Treaty
ZA South Africa
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Schedule B
[**]
PRODUCT MASTER FILE
Product Monograph
This section represents the current status of the project
CONTENTS:
Clinical Supplies Strategies / Vial Strengths
Health and Safety - Assessment of health risks involved during manufacture
Composition
- Description and intended use of product
- Presentations and product numbers
- Qualitative formulation
- Quantitative formulation and formulation numbers
Manufacture
- Manufacturer(s)
- Manufacturing formula
- Manufacturing process and filling
- Equipment and manufacturing facilities
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- Process flow diagram
- Standard process instructions
- In-process controls
- Control of intermediates
- Justification of specification for intermediates
- Test methods for intermediates
Control Tests on Inactive Ingredients
- Name and address of supplier
- Specifications and test methods for inactive ingredients
- Justification of specification for inactive ingredients
- Test methods for inactive ingredients
Control Tests on Drug Substance
- Name and address of suppliers and corresponding batch details
- Statement of current route of synthesis
- Drug substance specification
- Product specific parameters
Control Tests on Product
- Product specification
- Product release specification
- Justification for product specification
- Test methods for product
- Sampling plan
Packaging (Container / Closure / Device)
- Description of packaging material and PCKs
- Manufacturers of packaging materials
- Specifications of packaging materials
- Justification of specifications of packaging materials
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- Test methods for packaging materials
Stability of Drug Substance
- Shelf-life recommendations
Stability of Product
- Shelf-life recommendation
- Compatibility
- Test methodology used for stability of product
- Stability reports
Special Notes
Product Development Master Record
This section contains archived / superseded information (eg previous versions of
specifications) and is therefore the development history.
CONTENTS:
Health and Safety - Assessment of health risks involved during manufacture
Composition
- Description and intended use of product
- Presentations and product numbers
- Qualitative formulation
- Quantitative formulation and formulation numbers
Manufacture
- Manufacturer(s)
- Manufacturing formula
- Standard process instructions
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Control Tests on Inactive Ingredients
- Name and address of supplier
- Specifications and test methods for inactive ingredients
- Justification of specification for inactive ingredients
- Test methods for inactive ingredients
Control Tests on Drug Substance
- Drug substance specification
Control Tests on Product
- Product specification
- Product release specification
- Justification for product specification
- Test methods for product
- Sampling plan
Packaging (Container / Closure / Device)
- Description of packaging material and PCKs
- Manufacturers of packaging materials
- Specifications of packaging materials
- Justification of specifications of packaging materials
- Test methods for packaging materials
Stability of Drug Substance
- Shelf-life recommendations
Stability of Product
- Shelf-life recommendation
- Test methodology used for stability of product
- Stability reports
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Special Notes
Summary Reports
- [**]
- [**]
Placebo Monograph
Composition
- Presentations and product numbers
- Qualitative formulation
- Quantitative formulation and formulation numbers
Manufacture
- Manufacturer(s)
- Manufacturing formula
- Manufacturing process and filling
- Equipment and manufacturing facilities
- Process flow diagram
- Standard process instructions
- In-process controls
- Control of intermediates
- Justification of specification for intermediates
- Test methods for intermediates
Control Tests on Inactive Ingredients
- Name and address of supplier
- Specifications and test methods for inactive ingredients
- Justification of specification for inactive ingredients
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- Test methods for inactive ingredients
Control Tests on Drug Substance
- Not applicable
- Name and address of suppliers and corresponding batch details
- Statement of current route of synthesis
- Drug substance specification
- Product specific parameters
Control Tests on Product
- Product specification
- Product release specification
- Justification for product specification
- Test methods for product
- Sampling plan
Packaging (Container / Closure / Device)
- Description of packaging material and PCKs
- Manufacturers of packaging materials
- Specifications of packaging materials
- Justification of specifications of packaging materials
- Test methods for packaging materials
Stability of Drug Substance - Not applicable
- Shelf-life recommendations
Stability of Product
- Shelf-life recommendation
- Compatibility
- Test methodology used for stability of product
- Stability reports
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Placebo Development Master Record
Contains archived / superseded information
PMF Appendices
Essentially this is the "working area" of the PMF containing:
- Stability Protocols for Drug Substance
- Stability Reports (front cover only
- this references report number with all reports filed in archive)
- Stability Protocols for Drug Product and Placebo Product
- Stability Reports (main reports in full, others front cover only
- this references report number with all reports filed in archive)
- Protocols and Development Reports (all Investigational Protocols and
Development Reports referenced)
- Compatibility with Infusion Fluids and Giving Sets (all Reports / Studies
referenced)
- Product Design Report (all Reports referenced)
- Regulatory Documents (CMC submissions referenced)
- Cleaning Verification (Reports referenced)
- Manufacturing Protocols (for clinical trial supplies manufacture at
Sodertalje (Astra Liquid Production Facility)
- Primary and Secondary Reference Standards
[**]
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Schedule C
CHEMICAL STRUCTURE [**]
[Diagram of proprietary compound deleted]
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Schedule D
REPORT AUTHOR REF DUE OUT/DATED CURRENT STATUS FORMAT CONTACT SPINE
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Schedule E
[Diagram of proprietary
compound deleted]
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Schedule F
Supply Agreement
[To be provided upon completion -- See Section 4.2.3]
License Agreement - The Medicines Company
