th
   1.
    
    Amendment
  3.1
    
    On or before December 15, 2009, the Buyer shall make a one-time, non-refundable
payment in the amount of three million five hundred thousand Euros (3,500,000) to the
Seller.3.2
    
    In addition to the payment pursuant to § 3.1., Buyer shall notify Seller in
each case in the form as attached as Annex 3.1 to the Agreement or
substantially similar stating:
 3.2.1
    
    Upon the earlier of (a) four (4) months after the completion
of all Phase I clinical programs in healthy human volunteers (Phase Ia
Studies) for CU-2010, or (b) November 30, 2010 (Notification Event), whether
the Buyer intends either (i) to proceed with clinical development in patient
populations undergoing cardiac surgery (Target Indication)(Phase Ib
Studies)for CU-2010 (the First Proceed Notice for CU-2010), or (ii) not to
proceed (the Non-Proceed Notice for CU-2010).3.2.2
    
    If Buyer issued a First Proceed Notice for CU-2010, within
four (4) months after the completion of all Phase Ib Clinical Studies for the
CU-2010, whether the Buyer intends to either (i) proceed with further clinical
development for CU-2010 (the Second Proceed Notice for CU-2010), or (ii)
not to proceed (Non-Proceed Notice for CU-2010).3.2.3
    
    In addition, in either aforementioned case pursuant to § 3.2.1
or § 3.2.2., within four (4) months after the completion of all Phase Ia
Clinical Studies




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for a Backup Compound (as defined below) whether the Buyer
intends to either (i) proceed with further clinical development for a Backup
Compound (as defined below) (the First Proceed Notice for Backup Compound),
or (ii) not to proceed (Non-Proceed Notice for Backup Compound).3.2.4
    
    If Buyer has issued a First Proceed Notice for Backup
Compound, within four (4) months after the completion of all Phase Ib Clinical
Studies for the Backup Compound, whether the Buyer intends to either (i)
proceed with further clinical development for Backup Compound (the Second
Proceed Notice for Backup Compound), or (ii) not to proceed (Non-Proceed
Notice for Backup Compound).
 3.3
    
    Depending on the selection the Buyer has made under § 3.2., in each case the
following shall apply:
 3.3.1
    
    First Proceed Notice for CU-2010If the Buyer issues the First Proceed Notice for CU-2010 in accordance with
§ 3.2.1, the Buyer shall make a one-time non-refundable payment in the
amount of [**] Euros ([**]) to the Seller. This payment shall become due
and payable by the Buyer to the Seller within thirty (30) calendar days
after the Sellers receipt of the First Proceed Notice for CU-2010.
Additionally, Buyer shall have the obligation to inform Seller in writing
per December 31 and June 30 of each year about the status of the clinical
development of CU-2010 in the Target Indication (Information Obligation on
CU-2010)until the earlier of (i) the first approval of CU-2010 in the
Target Indication, (ii) the issuance of a Non-Proceed Notice for CU-2010 in
accordance with § 3.2.2, or (iii) termination of the development of CU-2010
thereafter.3.3.2
    
    Non-Proceed Notice for CU-2010If the Buyer issues a Non-Proceed Notice for CU-2010 to Seller in accordance
with § 3.2.1, the following shall apply:
 (a)
    
    The Seller shall not be entitled to, any
earn-out payments as set forth in § 4 below or any other further
purchase price for CU-2010 except as already due;(b)
    
    The Buyer shall upon request from Seller ensure
that Seller is granted a worldwide, perpetual, irrevocable, fully-paid
up, royalty- free, exclusive license (even with respect to the Buyer itself) with
the right to grant sub-licenses under any and all patent(s) and / or
pending patent application(s) that are listed in more detail in
An-
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nex 3.1.2(b) to the Agreement for the sole purpose of
making, using, developing, selling or otherwise commercializing
CU-2010;(c)
    
    Furthermore, with respect to any intellectual
property generated by Buyer or other affiliated parties to TMC after
the Transfer Date and before the receipt of the Non-Proceed Notice for
CU-2010 in accordance with § 3.2.1, the Buyer shall upon request from
Seller ensure the transfer to Seller of (i) any and all pending patent
application(s), whose claim(s) is solely directed to CU-2010, and (ii)
any and all issued patent(s), whose claim(s) is solely directed to
CU-2010 free of charge. Regarding all other intellectual property
generated by Discovery after the Transfer Date and before the receipt
of the Non-Proceed Notice for CU-2010 in accordance with § 3.2.1, the
Buyer shall upon request from Seller ensure that Seller is granted a
worldwide, perpetual, irrevocable, fully-paid up, royalty-free,
exclusive license (even with respect to the Buyer itself) with the
right to grant sub-licenses under any and all such patent(s) and / or
pending patent application(s) for the sole purpose of making, using,
developing, selling or otherwise commercializing CU-2010;(d)
    
    Furthermore, with respect to any data generated
by Buyer or other affiliated parties to TMC after the Transfer Date and
before the receipt of the Non-Proceed Notice for CU-2010 in accordance
with § 3.2.1, the Buyer shall upon request from Seller ensure the
transfer to Seller of any and all data relating to CU-2010 free of
charge;(e)
    
    Furthermore, with respect to any regulatory
filings (e.g. IND) relating to CU-2010 and submitted by Buyer or other
affiliated parties to TMC to the competent authorities and / or ethics
committees after the Transfer Date and before the receipt of the
Non-Proceed Notice in accordance with § 3.2.1, the Buyer shall upon
request from Seller cooperate with Seller and use commercially
reasonable efforts to effect the transfer of any and all such
regulatory filings relating to CU-2010 to Seller free of charge.(f)
    
    Additionally, Buyer shall have the obligation
to inform Seller in writing in 6-months periods whether or not
preclinical and/or clinical development in the Target Indication is
ongoing with Backup Compound (as defined below) and if so, about the
status of such activities (Development Information Obligation on
Backup Compound)until the Buyer issues a First-Proceed Notice for
Backup Compound or a Non-Proceed Notice for Backup Compound.
 3.3.3
    
    Second Proceed Notice for CU-2010
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If the Buyer issues the Second Proceed Notice for CU-2010 in accordance with
§ 3.2.2, the Buyer shall make a one-time, non-refundable payment in the
amount of [**] Euros ([**]) to the Seller. This payment shall become due
and payable by the Buyer to the Seller within thirty (30) calendar days
after the Sellers receipt of the Second Proceed Notice. In addition, Buyer
shall have the continued Information Obligation on CU-2010 according to §
3.3.1 until the earlier of (i) the first approval of CU-2010 in the Target
Indication, or (ii) termination of the development of CU-2010 thereafter.3.3.4
    
    First Proceed Notice for Backup CompoundIf the Buyer issues the First Proceed Notice for Backup Compound in
accordance with § 3.2.3 and subject to § 3.4, the Buyer shall make a
one-time, non-refundable payment in the amount of [**] Euros ([**]) to the
Seller. This payment shall become due and payable by the Buyer to the
Seller within thirty (30) calendar days after the Sellers receipt of the
First Proceed Notice for Backup Compound. Additionally, Buyer shall have the
obligation to inform Seller in writing per December 31 and June 30 of each
year about the status of the clinical development of Backup Compound in the
Target Indication (Information Obligation on Backup Compound)until the
earlier of (i) the issuance of a Non-Proceed Notice on Backup Compound
according to § 3.3.2, (ii) the first approval of the Backup Compound in the
Target Indication or (iii) termination of the development of the Backup
Compound.As used herein, the Backup Compound shall refer to a small molecule serine
protease inhibitor which is covered by at least one valid claim of the
intellectual property rights as set forth in Annex 5.1.8(c)/1, and
which has been clinically tested by the Buyer at least in Phase Ia Studies,
and Phase Ib Studies or both pursuant to this § 3.3.3.5
    
    Non-Proceed Notice for Backup CompoundIf the Buyer issues a Non-Proceed Notice for Backup Compound to Seller in
accordance with § 3.2.4, the Seller shall not be entitled to, any earn-out
payments as set forth in § 4 of the Agreement or any other further purchase
price not already due.3.3.6
    
    Second Proceed Notice for Backup CompoundIf the Buyer issues the Second Proceed Notice for Backup Compound in
accordance with § 3.2.4 and subject to § 3.4, the following shall apply:
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(a)
    
    Buyer shall make a one-time, non-refundable
payment in the amount of [**] Euros ([**]) to the Seller. This payment
shall become due and payable by the Buyer to the Seller within thirty (30)
calendar days after the Sellers receipt of the Second Proceed Notice
for Backup Compound. Additionally, Buyer shall have the continued
Information Obligation on Backup Compound as defined in § 3.3.4 until
the earlier of (i) termination of the development of the Backup
Compound thereafter or (ii) first approval for the Backup Compound in
Target Indication.(b)
    
    Seller shall grant to Buyer a (sub-) license
according to the terms as set forth in 3.3.2 (b) to the extent such
license is necessary to commercialize the Backup Compound in the Target
Indication.(c)
    
    Furthermore, upon issuance of the Second
Proceed Notice for the Backup Compound by the Buyer in accordance with
§ 3.2.4, the definition of Product for the purpose of § 4 of the
Agreement shall be deleted and restated as follows:Product shall mean any pharmaceutical product that contains the
Backup Compound as an active ingredient; either alone or in
combination with another active ingredient (such Product containing
Backup Compound in combination with another active ingredient, a
Combination Product).For avoidance of doubt: Seller shall also be entitled to any earn-out
payments for the Backup Compound as set forth in § 4 of the Agreement
as originally stipulated for CU-2010 in the event that any such
earn-out payments as set forth in § 4 have not been made for CU-2010.
 3.4
    
    For avoidance of doubt, only one payment in the amount of [**] Euros ([**])
can be made under either § 3.3.1 or § 3.3.4, but not both. Only one payment in the
amount of [**] Euros ([**]) can be made under either § 3.3.3 or § 3.3.6, but not both.3.5
    
    Furthermore, the Buyer is under no obligation to develop the Backup Compound,
and any clinical development of the Backup Compound shall be at the Buyers sole
discretion.3.6
    
    If the Seller has not received the respective notification according to § 3.2
when due, the Seller may request to receive the respective notification according to §
3.2 by written reminder, also by fax. Buyer shall issue the respective notification
within a grace period of twenty (20) business days after receipt of such Sellers
reminder (the Grace Period). If the Seller receives the respective notification
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from Buyer within the Grace Period, the respective consequences according to § 3.2. shall
apply mutatis mutandis; in any other case, the consequences of a Non-Proceed Notice for
CU-2010 shall apply mutatis mutandis.3.7
    
    If the Buyer fails to make any payments or parts thereof under this § 3 when
due, the outstanding principal amount(s) shall bear interest in the amount of 12
percentage points above the base interest rate (Basiszinssatz im Sinne von § 247 BGB)
as of the due date until receipt of the payment. The additional payments plus
interest, if any, shall be paid in Euros from the Buyer to Seller when due in
immediately available funds free of any charges, taxes or other deductions by wire
transfer into the Sellers Account (or any other account designated by Seller in
writing in advance). The Seller shall immediately confirm receipt of payments to Buyer
by telefax letter.3.8
    
    In the event of Buyers failure to pay any additional payments in accordance
with this § 3, Seller shall only be entitled to late payment interest as set forth in §
3.7. No other remedy shall be available for the Seller; particularly, the Parties
explicitly agree that Seller shall under no circumstances be entitled to rescind this
Agreement (Rücktritt vom Vertrag).
 2.
    
    Miscellaneous.
 A.
    
    All terms and conditions set forth in the Agreement that are not amended by the
Amendment shall remain in full force and effect.B.
    
    § 15 and § 16 of the Agreement shall apply accordingly.C.
    
    The Amendment shall be governed by and construed in accordance with the
material laws of Germany excluding the laws of conflict and CISG.D.
    
    This Amendment may be executed in counterparts, each of which shall be deemed
an original, but all of which shall constitute one and the same instrument.E.
    
    Any term of this Amendment may be amended with the written consent of both
parties only (including this clause).F.
    
    This Amendment is the product of both of the parties hereto, and together with
the Agreement constitutes the entire agreement between such parties pertaining to the
subject matter hereof, and merges all prior agreement between such parties pertaining
to the subject matter hereof, merges all prior negotiations and drafts of the parties
with regard to the transactions contemplated herein.G.
    
    From the date hereof, any reference to the Agreement shall be deemed to refer
to the Agreement as amended by this Amendment.
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Curacyte AG
    
    
    
    The Medicines CompanyBy:
    
    /s/ Ulrich Delvos
    
    
    
    By:
    
    /s/ Glenn SblendorioName: Dr. Ulrich Delvos
    
    
    
    
    
    Name: Glenn SblendorioTitle: Chief Executive Officer
    
    
    
    
    
    Title: Executive Vice President & CFODate: December 11, 2009
    
    
    
    
    
    Date: December 2009The Medicines Company (Leipzig) GmbHBy:
    
    /s/ Dimitrios Goundis
    
    
    
    By:
    
    /s/ Marius BoderkeName: Dimitrios Goundis
    
    
    
    
    
    Name: Marius BoderkeTitle: Managing Director
    
    
    
    
    
    Title: ProkuristDate: December 15, 2009
    
    
    
    
    
    Date: December 15, 2009
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