Exhibit 10.4

FIRST AMENDMENT TO GLOBAL COLLABORATION AGREEMENT
THIS FIRST AMENDMENT TO GLOBAL COLLABORATION AGREEMENT (this “Amendment”) is
made and entered into as of the 24th day of July, 2012 (the “Amendment Effective
Date”), by and between AstraZeneca LP, a Delaware limited partnership
(“AstraZeneca”), and The Medicines Company, a Delaware corporation (“MDCO”).
WHEREAS, AstraZeneca and MDCO are parties to that certain Global Collaboration
Agreement dated April 25, 2012 (the “Agreement”); and
WHEREAS, AstraZeneca and MDCO wish to amend the Agreement in accordance with the
terms of this Amendment.
NOW, THEREFORE, in consideration of the mutual covenants and promises contained
in this Amendment and other good and valuable consideration, AstraZeneca and
MDCO agree as follows:
1.
Definitions. All capitalized terms not otherwise defined in this Amendment shall
have the definitions assigned to such terms in the Agreement.

2.
Joint Development and Regulatory Committee. Section 2.2(a) of the Agreement is
hereby deleted and replaced in its entirety with the following:

2.2    Joint Development and Regulatory Committee.
(a)    The Parties hereby establish a joint development and regulatory committee
(the “JDRC”). Subject to the terms and conditions hereof, the JDRC shall be
responsible for developing strategies for the global development of the
Collaboration Products that are intended to benefit both the Ticagrelor Product
and one or more other Collaboration Products. The JDRC shall prepare and deliver
a global development plan for the Collaboration Products containing the details
set forth in Exhibit E on or before September 30, 2012.
3.
Joint Commercialization Committee. Section 2.3(a) of the Agreement is hereby
deleted and replaced in its entirety with the following:

2.3    Joint Commercialization Committee.
(a)    The Parties hereby establish a joint commercialization committee (the
“JCC”). Subject to the terms and conditions hereof, the JCC shall be responsible
for the ongoing evaluation of commercialization opportunities for the
Collaboration Products in (i) the European Union, (ii) Asia Pacific, and (iii)
Latin America (the “Collaboration Regions”). The JCC shall prepare and deliver
the terms for proposed collaborations on a Collaboration Product by
Collaboration Product and country by country basis in the Collaboration Regions

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Exhibit 10.4

on or before September 30, 2012. The JCC shall establish subcommittees, which
shall include representatives of each Party, for the evaluation of
commercialization opportunities for each of the Collaboration Products in each
of the Collaboration Regions.
4.
No Other Changes. Except as explicitly set forth in this Amendment, no amendment
or modification to the Agreement is hereby made.

5.
Counterparts; Facsimile Execution. This Amendment may be executed in any number
of counterparts, each of which shall be deemed an original and all of which
taken together shall be deemed to constitute one and the same instrument. An
executed signature page of this Amendment delivered by facsimile transmission or
by electronic mail in “portable document format” (“.pdf”) shall be as effective
as an original executed signature page.

IN WITNESS WHEREOF, each of the Parties has caused this Amendment to be executed
personally or, as appropriate, by its duly authorized officers as of the
Amendment Effective Date set forth above.
AstraZeneca LP
By: /s/ Marion McCourt    
Name: Marion McCourt
Title: Chief Operating Officer AstraZeneca US
The Medicines Company
By: /s/ Brent V. Furse    
Name: Brent V. Furse
Title: Senior Vice President – Chief Customer Officer

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