Exhibit
10.1


 


CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


VE LONZA 270604 GFG


 


Development and Supply
Agreement


 


between


 


The Medicines Company


8 Campus Drive


Parsippany, NJ 07054


United States of America


 


-
hereinafter called “TMC” -


 


and


 


Lonza Ltd


Muenchensteinerstrasse 38


CH-4002 Basel


Switzerland


 


-
hereinafter called “LONZA” -


 


concerning


 


the delivery of Bivalirudin to TMC


 



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Table
of Contents


 


	
  Preamble

  	
   

  
	
   

  	
   

  
	
  Clause 1 Definitions

  	
   

  
	
   

  	
   

  
	
  Clause 2 Development Work

  	
   

  
	
   

  	
   

  
	
  Clause 3 Progress Reports

  	
   

  
	
   

  	
   

  
	
  Clause 4 Testing and
  Acceptance

  	
   

  
	
   

  	
   

  
	
  Clause 5 Time
  of the Essence; Delay

  	
   

  
	
   

  	
   

  
	
  Clause 6 Change In Scope

  	
   

  
	
   

  	
   

  
	
  Clause 7
  Relationship Management

  	
   

  
	
   

  	
   

  
	
  Clause
  8 Purchase Quantities, Forecasts, Manufacturing Capacity

  	
   

  
	
   

  	
   

  
	
  Clause
  9 Prices, Invoices, Terms of Payment

  	
   

  
	
   

  	
   

  
	
  Clause
  10 Delivery, Shipment and Acceptance

  	
   

  
	
   

  	
   

  
	
  Clause
  11 Warranty, Liability, Indemnification

  	
   

  
	
   

  	
   

  
	
  Clause
  12 Modifications to Process

  	
   

  
	
   

  	
   

  
	
  Clause
  13 Compliance

  	
   

  
	
   

  	
   

  
	
  Clause
  14 Audits

  	
   

  
	
   

  	
   

  
	
  Clause
  15 Confidential Information

  	
   

  
	
   

  	
   

  
	
  Clause
  16 Intellectual Property Rights

  	
   

  
	
   

  	
   

  
	
  Clause
  17 Duration/Termination

  	
   

  
	
   

  	
   

  
	
  Clause
  18 Partial Invalidity

  	
   

  



 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406 PROMULGATED
UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2 PROMULGATED
THEREUNDER.  OMITTED INFORMATION HAS BEEN
REPLACED WITH ASTERISKS.


 


	
  Clause 19 Force Majeure

  	
   

  
	
   

  	
   

  
	
  Clause 20 Applicable Law,
  Dispute Resolution

  	
   

  
	
   

  	
   

  
	
  Clause 21 Miscellaneous

  	
   

  
	
   

  	
   

  
	
  Clause 22 Number of
  Signed Copies, Counterparts

  	
   

  



 


Annexes


 


1                                          PRODUCT


2                                          SPECIFICATIONS


3                                          WORK SCHEDULE


4                                          PRICES


5                                          PURCHASE ORDER


 


CONFIDENTIAL MATERIAL APPEARING
IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406 PROMULGATED UNDER THE
SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2 PROMULGATED THEREUNDER.  OMITTED INFORMATION HAS BEEN REPLACED WITH
ASTERISKS.


 


3



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


DEVELOPMENT
AND SUPPLY AGREEMENT


 


This
DEVELOPMENT AND SUPPLY AGREEMENT, effective the 28th day of July, 2004, between
THE MEDICINES COMPANY, a Delaware corporation, having offices located at 8
Campus Drive, Parsippany, New Jersey 07054 USA, and LONZA LTD., a Swiss
corporation, having offices located at Muenchensteinerstrasse 38, CH-4002
Basel, Switzerland.


 


Preamble


 


WHEREAS,
LONZA and its Affiliates are producers of 
peptides, have expertise in processes used to commercially manufacture
peptides, and experience in large scale production of peptides in accordance
with applicable cGMP standards, using (among other methods) the *** peptides
synthesis and the  ***  methods.


 


WHEREAS, TMC is licensed to make and have made the peptide Bivalirudin
under certain patent rights and technology of Biogen, Inc, and TMC desires to
have an additional source of supply of Bivalirudin for TMC’s production of
Angiomax®, an anticoagulant.


 


WHEREAS, LONZA wishes to develop and obtain approval for a process to
commercially manufacture Bivalirudin for TMC. 
Upon successful development of a commercially viable process, TMC wishes
to have LONZA manufacture and sell Bivalirudin to TMC, and LONZA wishes to
produce such product exclusively for TMC under the terms and conditions set
forth herein.


 


NOW, THEREFORE, in consideration of the covenants and conditions herein
contained, the par­ties hereby agree as follows


 


Clause   1  
Definitions


 


Affiliate                                                                                                                 means any entity which controls, is
controlled by or is under common con­trol with a party.


 


Commercial
Phase                                                            means the period of time during the term of
this Agreement following the approval by the FDA or other applicable regulatory
authorities of a commercial process for the manufacture of the Product by LONZA,
during which LONZA will supply to TMC commercial quantities of the Product.


 


cGMP                                                                                                                           means current Good Manufacturing Practice as
stated in Title 21, Code of  Federal
Regulations Parts 210 and 211 et seq., EU
Directive 2003/94/EEC of October 8, 2003, the EU Guide to Good manufacturing
Practices and


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


                                                                                                                                                            Annexes thereto, and other regulations
pertaining to Good Manufacturing Practices in other countries as amended or
enacted from time to time and as exemplified in the FDA’s “Guidance for
Industry: Manufacturing, Processing or Holding Active Pharmaceutical
Ingredients” dated March 1998 and in the EEC guide to Good Manufacturing
Practices for Medical Products (Vol. IV Rules Governing Medical Products in the
European Community 1992).


 


Deliverables
                                                                                       shall mean the testing, qualification, and
validation quantities of Product and other materials as identified in the Work
Schedule to be delivered by LONZA to TMC during the Development Phase.


 


Development
Phase                                                  shall mean the period of time prior to
approval by the FDA of a commercial process for the manufacture of the Product
by LONZA, during which the Work is to be performed under this Agreement.


 


FDA                                                                                                                                  means the United States Food and Drug
Administration.


 


Field
                                                                                                                               means the application of PRODUCT as an
anticoagulant.


 


Product
                                                                                                               means Bivalirudin, a 20 mer peptide
conforming to the amino acid sequence set forth in Annex 1
produced in conformity with the Specifications either through a  *** 
peptide synthesis  ***  process or a 
***  process ( ***  production of 
***  followed by  ***  to
yield  *** ).


 


Confidential
Information                         shall mean information which is disclosed to
a party (“Receiving Party”) by the other party (“Disclosing Party”) and which
is identified in writing at the time of disclosure by an appropriate legend,
marking, stamp or other positive written identification on the face thereof to
be confidential and proprietary of the Disclosing Party.  Any information to be treated as Confidential
Information that is transmitted orally shall be confirmed by a written summary
to be submitted by the Disclosing Party to the Receiving Party within thirty
days after oral transmission thereof. 
Confidential Information shall also include TMC Work Product, LONZA Work
Product and Joint Work Product as defined in Clause 16.


 


Specifications                                                                                 means the specifications for the Product set
forth in Annex 2.


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Work                                                                                                                              shall mean all tasks during the Development
Phase associated with the development by LONZA of a  *** 
peptide synthesis process and a separate 
***  process for the commercial
manufacture of the Product in accordance with the Specifications and Work
Schedule.


 


Work
Schedule                                                                          shall mean the detailed work plan for
completing the development of all components of the Work, including, without
limitation, the tasks, timetables, milestones, Deliverables, acceptance tests
and reports relating to the foregoing set forth in Annex
3.


 


Clause   2  
Development Work


 


LONZA agrees to perform the Work in accordance with Work Schedule and
the provisions, conditions, warranties and agreements set forth in this
Agreement.  TMC shall issue a Purchase
Order for each component of the Work to be performed during the Development
Phase.  LONZA shall use its best efforts
to follow the Work Schedule in reaching the required level of experience for
commercial manufacturing of the Product and in developing the associated
controls for the Product.  As more fully
set forth in the Work Schedule, the primary objective of the Work is to develop
a  *** 
synthesis process for immediate use in the manufacture of Product on a
commercial scale.  A secondary objective
is to develop for possible use at a later date a  *** 
process.  LONZA represents and
warrants that it has the requisite personnel, expertise and experience to
deliver the Work in accordance with the Work Schedule, and that all Work will
be performed in accordance with best practices in the industry.


 


Clause   3  
Progress Reports


 


Upon the completion of each milestone set forth in the Work Schedule,
or at such other times as TMC may reasonably request, LONZA shall submit to TMC
a written progress report relating to the status of the Work.  Each progress report shall include, without
limitation, discussion of progress to date, problems encountered, proposed
solutions to such problems and any other items reasonably requested by TMC.
Upon successful completion of all tasks set forth in the Work Schedule LONZA
shall submit a final written report to TMC containing such information as TMC
may reasonably require.


 


Clause   4  
Testing and Acceptance


 


4.1                     Upon the completion of each phase of
development as set forth in the Work Schedule, LONZA shall deliver to TMC the
Deliverables set forth in the Work Schedule for testing and acceptance. During
the time specified in the applicable Work Schedule, TMC or its representatives
may test the Deliverables pursuant to the applicable acceptance tests set forth
in the Work Schedule.


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


4.2                     If in the course of conducting an acceptance
test, TMC or its representatives establish that a Deliverable does not pass the
acceptance test, TMC shall notify LONZA within thirty (30) days after receipt
of the Deliverable and LONZA shall, within ninety (90) days after receipt of
such notice from TMC, at LONZA’s sole cost and expense, modify or improve the
Deliverable so that the same shall perform in accordance with the acceptance
test. Without TMC’s written notice within such period, it is deemed that the
Deliverables passed the acceptance test. Upon redelivery of the Deliverable, TMC
or its representatives may conduct, as applicable, additional acceptance tests
in accordance with the Work Schedule.


 


4.3                     Failure of any Deliverable to meet the
applicable acceptance tests after the second round of acceptance tests shall
constitute a default by LONZA giving TMC cause for termination under Clause
17.4.


 


Clause   5  
Time of the Essence; Delay


 


The parties agree that time is of the essence in the performance of
this Agreement. LONZA shall notify TMC on a continuing basis of any event or
occurrence that could cause a material delay in meeting any milestone set forth
in the Work Schedule, a delivery date in a Purchase Order, or otherwise delays
the completion of the Work. Any material delay which is caused by LONZA and is
not a result of a Force Majeure shall be deemed to be a default giving TMC
cause for termination under Clause 17.4. If, in the event of such delay, TMC,
in its sole discretion, elects not to terminate this Agreement, TMC may, by
written notice, designate a new date for the completion of the delayed Work, as
to which new date time shall be of the essence.


 


Clause   6  
Change In Scope


 


Either party may request a change to the Work pursuant to a written
change order (“Change Order”).  Each
Change Order shall identify with specificity any modifications to the
applicable Specifications and Work Schedule, including, without limitation,
modifications to tasks, timetables, Deliverables, fees and charges. Within ten
(10) days after the receipt of a Change Order, the parties shall discuss the
availability of personnel and resources to fulfil such Change Order and the
resulting adjustments to the Specifications and Work Schedule. Neither party
shall have any obligation in connection with any Change Order until such Change
Order is executed by both parties.  Each
Change Order executed by TMC and LONZA shall be incorporated into and
constitute an amendment to this Agreement. The terms of any Change Order shall
control over any inconsistent provisions set forth in this Agreement or any
Annex hereto.


 


Clause   7  
Relationship Management


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406 PROMULGATED
UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2 PROMULGATED
THEREUNDER.  OMITTED INFORMATION HAS BEEN
REPLACED WITH ASTERISKS.


 


Each party shall designate one of its employees to be its project
manager (the “Project Manager”). Each Project Manager’s responsibilities shall
include, without limitation: (i) having direct responsibility for the overall
performance of its party under this Agreement and final authority vis-à-vis the
other party on all matters that relate to such party’s performance under this
Agreement; (ii) interacting with the other party’s Project Manager; (iii)
supervising the performance of such party’s obligations under this Agreement;
and (iv) resolving issues that may arise with respect to the Work or the supply
of Products, including without limitation adapting timelines, reviewing
quantities and modifying the Specifications for the Product. TMC hereby
designates  ***  as its Project Manager; LONZA hereby
designates  ***  as its Project Manager. Project Managers of
each party shall meet as needed via teleconference or in person, but no less
often than monthly, to review progress and to resolve issues relating to this
Agreement. The parties shall have the right to change their respective Project
Managers provided that any person designated as a Project Manager has the
training and experience to carry out the responsibilities of a Project Manager
hereunder.


 


Clause  
8   Purchase Quantities,
Forecasts, Manufacturing Capacity


 


8.1                       During the
Development Phase, TMC undertakes to purchase from LONZA up to the following
quantities of Product as Deliverables under the Work Schedule, to be used by
TMC for testing, qualification and validation purposes:


 


	
  Year

  	
   

  	
  Quantity

  	
   

  
	
  2004/5

  	
   

  	
  *** 

  	
  kg

  
	
  2005/6

  	
   

  	
  *** 

  	
  kg

  



 


8.2                     Except as provided below, during the Commercial Phase TMC shall
issue Purchase Orders to LONZA for a minimum of 
***  kg of Product per calendar
year. If a minimum purchase commitment is in effect for less than 365 days in
any calendar year, the minimum purchase commitment for such year shall be
prorated for the number of days during the year in which the purchase
commitment is in effect. If in any calendar year during the Commercial Phase
TMC purchases less than the required mini­mum quantity of Product, TMC shall
purchase from LONZA in January of the year following such year of shortfall an
amount of Product equal to the difference between the minimum required quantity
and the quantity of Product actually ordered in such year. Any such shortfall
purchase shall not apply against the applicable minimum in the following year.
The price of Product in effect during the year of shortfall shall apply to the
shortfall purchase. TMC’s minimum purchase commitment shall cease upon the
approval by the FDA of a competitive generic equivalent of the Product.


 


8.3                     At least fifteen
(15) days prior to the first day of each Contract Quarter during the Commercial
Phase, TMC shall provide LONZA a written forecast of the quantity of Product it
will require


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


during each of the next ensuing  *** 
Contract Years.  Each such
forecast shall represent TMC’s good faith estimate of its requirements for the
Products during the period covered thereby, but shall be submitted for planning
purposes only. Except as set forth below or as agreed otherwise by the parties,
such forecasts shall not constitute a binding commitment to purchase any given
quantity of Products. TMC’s first forecast shall be submitted to LONZA at least
ninety (90) days prior to the date on which the parties mutually expect the FDA
to approve the commercial manufacturing process for the Product.  The quantity of Product for the first two
Contract Quarters included in the first forecast submitted by TMC shall be a
binding commitment of TMC.  As used
herein, the term “Contract Quarter” means a period of three successive calendar
months beginning on the first day of each January, April, July, and October
occurring during the Commercial Phase, and the term “Contract Year” shall mean
a period of four (4) successive Contract Quarters beginning on the first day of
the first Calendar Quarter covered by a forecast.


 


8.4                       Purchase
Orders. TMC shall order Product by placing written or electronic purchase
orders (each, a “Purchase Order”) with LONZA at least six (6) months prior to
the requested delivery date.  LONZA
agrees to supply Product to TMC in accordance with such Purchase Orders.  If LONZA anticipates that, despite its
commercially reasonable efforts, it will be unable to deliver Products on or
before the requested delivery date set forth in any Purchase Order, it shall
promptly so notify TMC, and cooperate with TMC to determine a
mutually-acceptable alternative delivery date. 
The written form of Purchase Order is set forth in Annex 5.


 


8.5                     All Product supplied hereunder shall be
manufactured at LONZA’s production facilities in Visp, Switzerland, or at such
other facility approved in writing by TMC. The maximum quantity of Product
which LONZA shall be required to produce and sell hereunder during any two
successive Contract Quarters shall be 
***  percent of the volume
projected for such period in the most recent forecast applicable thereto. LONZA
agrees to reserve appropriate manufacturing capacity in its production
facilities so as to ensure that it is able to fulfil TMC’s purchase orders for
the Product.  When requested by TMC,
LONZA shall provide to TMC a capacity plan based on TMC’s forecasts for
Product.  Such capacity plan shall
identify any capital investments LONZA proposes to make in order to satisfy its
obligations hereunder.


 


Clause  
9   Prices, Invoices, Terms of
Payment


 


9.1                      The prices to be
charged for the Work and Products are set forth in Annex 4 and
are calculated in United States Dollars (USD) according to the terms set forth
herein. All prices are firm and shall not be subject to change, except as
provided herein.  LONZA’s prices shall be
deemed to include all sovereign, state and local sales, use, excise, value
added, privilege, payroll, occupational and any other applicable taxes, fees,
or duties, provided that TMC shall cooperate by providing sale and resale
certificates and such other information reasonably required to avoid such
taxes, fees or duties and which it typically provides to vendors or
suppliers.  No extra


 


9



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406 PROMULGATED
UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2 PROMULGATED
THEREUNDER.  OMITTED INFORMATION HAS BEEN
REPLACED WITH ASTERISKS.


 


charges or deductions of any kind will be
allowed unless specifically agreed to in writing by the Parties.


 


9.2                      The price may be
adjusted as follows to reflect exchange rate fluctuations between the Swiss
Franc and US Dollar.  At any time during
the first fifteen (15) days of a calendar quarter, either Party may request an
adjustment to be made if, on the date of such a request, the average exchange
rate of US Dollars into Swiss Francs, as reported in the Wall Street Journal
(Eastern Edition), for the ten (10) business day period immediately proceeding
that date as compared with the rate of exchange between those currencies
applicable upon execution of this Agreement or the date of the last purchase
price adjustment varies by five percent (5%) or more.  If the variance is more that five percent
(5%) but less than ten percent (10%), then the purchase price shall be adjusted
to reflect 50% of such change.  If the
variance is more than ten percent (10%), the parties shall meet and negotiate
in good faith a solution protecting the interests of both parties. If the
variance is less than five percent (5%), there shall be no purchase price
adjustment at that time.


 


9.3                      Except as
provided in Clause 9.2, the prices charged during the Development Phase  *** . 
During the Commercial Phase, the price for Products may be adjusted  *** . 
Any such price increase shall be subject to good faith negotiations and
mutual agreement of the parties, provided that under no circumstances shall any
price  *** , where: (i)  *** 
equals the  ***  published and in effect on the then most
recent anniversary of this Agreement; (ii) “ *** ” equals the  *** 
published and in effect on the date the price subject to adjustment was
established; and (iii) “ *** ” shall mean the 
*** .


 


9.4                      During the
Development Phase, LONZA shall issue an invoice upon achieving a milestone or
acceptance of a Deliverable. During the Commercial Phase, LONZA shall issue an
invoice upon shipment of the Product to TMC. Each invoice shall refer to the
applicable milestone or Deliverable in the Work Schedule, or to any Purchase
Order number, item number, quantity, unit of measure, unit price, total invoice
amount, and such other information as may be required by the Purchase Order or
other written instructions from TMC. If an invoice is issued and the milestone
is achieved or the shipment complies with the requirements of the Purchase
Order and this Agreement, unless agreed in writing otherwise, TMC will pay the
invoice within thirty (30) calendar days following receipt of the invoice.


 


Clause 10   Delivery, Shipment and Acceptance


 


10.1               LONZA will ship Products in the quantities
and at the times specified in a Purchase Order. 
Each shipment shall include a packing list which shall contain the
Purchase Order number, Product identification, quantity shipped, date of
shipment and such other information as TMC may require.  Each shipment shall be accompanied by a
Certificate of Analysis by LONZA confirming conformance of the Product to the
Specifications, and a Certificate of Compliance by LONZA


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


confirming compliance with cGMP. Unless otherwise expressly stated,
time is of the essence.  In the event any
shipment is not made on the date and in the quantity set forth on the Purchase
Order, TMC may: (i) return to LONZA some or all of the Products in the shipment
at LONZA’s risk and expense, including without limitation warehouse or handling
cost, (ii) direct LONZA to make an expedited shipment of additional or
replacement Products, with the difference in cost between any expedited routing
and the Purchase Order routing to be paid by LONZA, or (iii) purchase
substitute Products elsewhere and charge LONZA any resulting loss in the event
LONZA has not made such expedited shipment pursuant to the foregoing item (ii)
within ten (10) days after TMC’s direction. LONZA agrees to notify TMC
immediately if LONZA ever has reason to believe that any Product will not be
delivered as ordered, or a shipment will not be made as scheduled.


 


10.2               Delivery of Product will be made in
accordance with cGMP, in compliance with the relevant standard operating
procedures of LONZA in effect at LONZA’s Visp facility (or such other facility
as may be approved by TMC), and any particular requirement of TMC previously
approved by LONZA. Terms of delivery are FCA, LONZA’s facility Visp,
Switzerland (Incoterms 2000). Packaging is included, provided all Products will
be packaged as requested in an applicable Purchase Order. Title and risk of
loss for Products will pass to TMC when the Products are delivered to TMC’s
designated carrier.


 


10.3               LONZA shall ship Products to TMC using TMC’s
designated carrier with transportation charges billed directly to TMC by the
carrier. TMC will not pay premium transportation charges unless authorized by
TMC in writing. If LONZA ships Products by an unauthorized method or carrier,
LONZA will pay any resulting increased freight costs. LONZA will release
shipments at the lowest valuation permitted and will not declare value on
Products shipped.


 


10.4               Products are subject to TMC’s right of
inspection and rejection. TMC’s making of any payment to LONZA does not
constitute TMC’s acceptance of Products and TMC reserves its rights with
respect to defects in Products. LONZA agrees to provide and maintain inspection
and process control systems acceptable to TMC with respect to the manufacture
of Products and LONZA agree to keep and make available complete records of all
of LONZA’s inspection work and process control work for the life of the
Products as defined by TMC. TMC may inspect the Products at any place of
manufacture during production without waiving its right subsequently to reject
or revoke acceptance for undiscovered or latent defects. LONZA agrees to
furnish, at LONZA’s expense, facilities and assistance reasonably necessary to
ensure the safety and convenience of TMC’s personnel.  TMC undertakes to inform LONZA within twenty
(20) days after receipt of the delivered Product about objections concerning
the quantity of Product and within sixty (60) days after receipt of the
delivered Product about objections concerning the quality of Product. Unless
TMC given written notice of objection within such periods, it shall be deemed
that LONZA has delivered the contractually agreed quantity of Product and that,
except to the extent of any latent defects in the Product that could not have
been discovered by TMC testing, the Product meets the required Specifications.
In case TMC makes a timely objection as


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


to quantity or quality of Product, LONZA’s obligation is to replace the
missing/faulty Product or, at the sole option, to refund the purchase price
thereof.


 


Clause 11   Warranty, Liability, Indemnification


 


11.1                 LONZA represents and
warrants that the Products will: (i) be owned by LONZA free of all liens,
claims or encumbrances; (ii) conform strictly to Specifications; (iii) be
manufactured under conditions complying with cGMP; (iv) be fit and sufficient
for the purpose(s) for which they were manufactured and sold; (v) be new and
merchantable; and (vi) be free from defects in design, material and
workmanship, whether latent or otherwise. LONZA represents and warrants any
LONZA Work Product, TMC Work Product or Joint Work Product developed by LONZA
(as those terms are defined in Clause 16) will not infringe any patent, trade
secret, trademark or other property right of a third party. LONZA agrees that
these warranties: (x) as to latent defects in the Products, survive the
inspection, acceptance and use of the Products by TMC, (y) are for the benefit
of TMC and its successors, and (z) are in addition to any warranties and
remedies to which TMC may otherwise agree or which are provided by law.


 


11.2                 LONZA agrees that TMC
may change the Specifications in order to conform to applicable regulatory
requirements in one or more jurisdictions, provided that TMC informs LONZA
immediately of such requirements. Costs arising out of such changes to the
Specifications shall be borne by TMC. Any changes to the Specification for
other reasons shall be subject to the mutual agreement of the parties.


 


11.3                 LONZA’s warranty
obligations do not extend to any Product which has been mis­used, mistreated or
improperly stored. Upon learning of the breach of any warranty, TMC shall take
appropriate and reasonable measures to minimize dam­ages resulting therefrom.


 


11.4                 Any further warranty
or liability of LONZA, including but not limited to liability for conse­quential
and indirect damages, such as loss of profit, loss of production, claims by
third parties is hereby expressly excluded.


 


11.5                 Except to the extent
of any claim, injury or damage arising out of a breach by LONZA of a
representation, warranty or covenant under this Agreement or out of the gross
negligence or wilful misconduct of LONZA, TMC agrees to indemnify, defend and
hold harmless LONZA,  its officers,
directors, employees and agents, from and against any and all claims, suits,
causes of action, liabilities, proceedings or expenses (including reasonable attorneys
fees, court costs and settlements) which may result in any way from the use or
sale of the Product and products made therefrom. LONZA shall inform TMC in
writing promptly of any such claim or litigation and shall cooperate with TMC
in the defence thereof.


 


11.6               Except to the extent that any claim, injury
or damage is due to the gross negligence or wilful misconduct of TMC, LONZA
shall defend, indemnify and hold harmless TMC, its officers, directors,
employees and agents,  from against any
and all claims, suits, causes of action,


 


12



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


liabilities, proceedings or expenses 
(including reasonable attorneys fees, court costs and settlements) which
may result in any way from: (i) any injury to persons or to property during the
progress of Work or performance of LONZA’s obligations under this Agreement;
(ii)  any act or omission of LONZA, its
agents, employees, or subcontractors; and (iii) any breach by LONZA of any
representation, warranty or covenant under this Agreement.


 


11.7               LONZA shall maintain comprehensive general
liability (including contractual liability coverage insuring the liabilities
assumed above) and employer’s liability insurance with limits as reasonably
required by TMC. At TMC’s request, LONZA shall furnish to TMC a Certificate of
Insurance completed by its insurance officer certifying that insurance
coverages are in effect and will not be cancelled or materially changed until
ten days after prior written notice has been delivered to TMC.


 


Clause 12   Modifications to Process


 


As more fully set forth in the Work Schedule, during the Development
Phase LONZA shall develop the  ***  synthesis process in order to economically
produce the Product on a commercial scale and to sell the anticipated
quantities of the Product to TMC.  During
the Commercial Phase LONZA shall not make any modification to the approved
process, including without limitation any change or modification requiring
prior notice to or approval of the FDA or any other regulatory authority,
without prior written approval of TMC. 
LONZA will document any modification to the process, and provide to TMC
such information as it may require to enable TMC to notify the FDA or other
regulatory authority.  In addition, LONZA
shall file any required updates to its Drug Master Files.


 


Clause 13   Compliance


 


13.1               LONZA agrees to comply with the applicable
provisions of any federal, state, provincial or local law or ordinance and all
lawful orders, rules, and regulations issued thereunder, including without
limitation the applicable laws and regulations of government agencies of The
United States of America, Switzerland and the European Union.  In addition, LONZA shall comply with all
applicable cGMP, including the exercise of that degree of skill, diligence,
prudence and foresight which can reasonably be expected from a competent
manufacturer and seller who is engaged in development and manufacturing
activities under similar circumstances in a manner consistent with all
applicable requirements and with all applicable generally recognized
international standards. LONZA shall obtain and maintain all necessary permits
for the conduct of activities related to the Work and Products.


 


13.2               Unless otherwise agreed, LONZA shall prepare
and file all Drug Master Files.  All
actions with respect to the delivery of Work and production of the Product
shall be in accordance with all applicable cGMPs. At TMC’s request LONZA shall
provide Batch Production Records or any


 


13



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


other documentation requested by TMC to support regulatory approvals or
compliance. Both parties commit to the completion and signing of a quality
agreement outlining the responsibilities of each party’s respective quality
assurance organization within six months following the execution of this
Agreement.


 


Clause 14   Audits


 


To ensure compliance with applicable laws and regulations of regulatory
bodies, TMC or its designee is entitled, with reasonable notice and during
working hours, to conduct an appropriate audit or inspection of LONZA’s
facilities and the corresponding documentation. Moreover, LONZA will inform TMC
immediately of any inspection by the regulatory authorities that might take
place in relation to the conduct of the Work or the manufacture and sale of the
Product and LONZA shall provide to TMC copies of any reports of any such
inspections.  TMC shall have the right,
but not the obligation, to be present and take part in any such inspection or
regulatory action.


 


Clause 15   Confidential Information


 


15.1               Each party and their employees shall maintain
in confidence and safeguard all Confidential Information of the other. Each
party recognizes and acknowledges the confidential and proprietary nature of
any Confidential Information and acknowledges the irreparable harm that could
result to the other if it is disclosed to a third party, or used for
unauthorized purposes, without the Disclosing Party’s prior written
consent.  Each party agrees to use any
Confidential Information only for the purpose of conducting business with the
other in a manner contemplated by this Agreement.  The Receiving Party agrees to take all
reasonable steps to preserve the Disclosing Party’s Confidential Information in
confidence and prevent disclosure thereof to third parties.  The Receiving Party shall restrict
disclosures of any Confidential Information to only those its employees and
consultants who have a need to know and shall bind such employees and
consultants to obligations of confidentiality to the extent that the Receiving
Party is bound by this Agreement. Upon completion of any work to which the
Confidential Information relates, and in no event later than the expiration or
termination of this Agreement, the Receiving Party shall promptly return to the
Disclosing Party all materials incorporating any such Confidential Information
and any copies thereof, except for any Confidential Information that a party
may be required to retain for regulatory or legal compliance purposes. The
foregoing obligations under this Clause 15.1 shall survive the expiration or
termination of this Agreement.


 


15.2               Notwithstanding the provisions of Clause
15.1, the parties agree that their obligations with respect to handling,
disclosing, reproducing, and using such Confidential Information are not
applicable to any portion(s) of the Confidential Information which: (i) is in
the public domain prior to receipt by the Receiving Party or subsequent to the
date of receipt without breach of this


 


14



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Agreement by the Receiving Party; (ii) is known, as evidenced by
documentation, to the Receiving Party prior to disclosure by the Disclosing
Party; (iii) is disclosed with the prior written approval of the Disclosing
Party to a third party without restrictions on disclosure or use by the third
party; or (iv) is disclosed without restriction to the Receiving Party by a
third party having a bona fide right to disclose same to the Receiving
Party.  For the purposes of this Clause
15.2, Confidential Information shall not be deemed to be available to the
public or known to the Receiving Party merely because it may be embraced by a
more general disclosure or derived from combinations of disclosures generally
available to the public or known to the Receiving Party.


 


Clause 16   Intellectual Property Rights


 


16.1                 As between the
parties, each party will retain the ownership or its right to use the products,
processes, and know how, and all patent, trade secret, copyright or other
intellectual property rights therein, which the party owned, created or had the
right to use prior to the execution of this Agreement (“Pre-existing
Intellectual Property’). For the avoidance of doubt, the parties acknowledge
that: (i) the rights of Biogen in the Bivalirudin composition licensed to TMC
and the technology related to the 
***  process for producing the
Product is Pre-existing Intellectual Property of TMC; (ii) technology related
to certain  ***  processes and 
***  techniques used in the
production of Products is Pre-existing Intellectual Property of LONZA; and
(iii) the fundamental chemical technology for producing the Product by  *** 
synthesis is in the public domain. 
Notwithstanding each party’s use of any of its Pre-existing Intellectual
Property in connection with its activities under this Agreement, except as
expressly set forth in this Agreement, each party shall retain all right, title
and interest in such Pre-existing Intellectual Property.   A party shall not acquire any right to use
the Pre-existing Intellectual Property of the other party except as expressly
set forth in this Agreement.


 


16.2                 The entire right,
title and interest throughout the world, including without limitation all
intellectual property rights, in and to all ideas, inventions, discoveries,
improvements, technologies, techniques or other know-how conceived or developed
in the performance of Work hereunder by LONZA and/or its personnel,
consultants, assis­tants and employees with respect to the Pre-existing
Intellectual Property of LONZA  (“LONZA
Work Product”) shall be the sole and exclusive property of LONZA . TMC shall
have a non-exclusive, perpetual, royalty-free (except for the payments provided
under Clause 9 and Clause 16.8), worldwide license, with a right to sublicense,
to use the LONZA Work Product in connection with the manufacture and sale of
Product. LONZA shall use the LONZA Work Product in the Field solely and
exclusively for the purpose of producing Product for TMC.   Nothing herein shall prevent or preclude
LONZA from using the LONZA Work Product outside the Field in any manner LONZA
deems appropriate.


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


16.3                 LONZA agrees to
transfer and assign, and hereby transfers and assigns, to TMC and its
designees, without further compensation, the entire right, title and interest
throughout the world, including without limitation all intellectual property
rights, in and to all ideas, inventions, discoveries, improvements,
technologies, techniques or other know-how first created or produced by LONZA
relating to the Pre-Existing Intellectual Property of TMC (other than LONZA
Work Product and the Joint Work Product) in the performance of the Work under
this Agreement (“TMC Work Product”).  All
TMC Work Product will be considered work(s) made by LONZA for hire for TMC and
will belong exclusively to TMC.  If by
operation of law any of such TMC Work Product is not owned in its entirety by
TMC automatically upon creation, then LONZA agrees to transfer and assign, and
hereby transfers and assigns, the same to TMC. 
LONZA agrees to promptly disclose to and assist TMC in every proper way
to obtain for TMC’s benefit, and at TMC’s expense, appropriate legal protection
for the TMC Work Product transferred and assigned, and to be transferred and
assigned, hereunder to TMC, including but not limited to testifying in any
legal proceedings, signing all lawful papers, making all rightful oaths and
executing all applications, assignments and other instruments.   LONZA shall have a non-exclusive, royalty
free, non-assignable (except to the extent this Agreement is assigned under
Clause 21.3) license (without the right to sublicense) to use the TMC Work
Product in connection with the manufacture and sale of Product to TMC under
this Agreement as well as outside the Field (including sublicense rights).


 


16.4                 The entire right,
title and interest throughout the world, including without limitation all
intellectual property rights, in and to all ideas, inventions, discoveries,
improvements, technologies, techniques or other know-how, other than the LONZA
Work Product and the TMC Work Product, conceived or developed by the parties
jointly in connection with this Agreement (“Joint Work Product”) shall be
jointly owned by the parties. The parties will negotiate on a case by case
basis the use rights with respect to the Joint Work Product, provided that in
all circumstances LONZA shall be free to use Joint Work Product outside the
Field and TMC have the exclusive right to use the Joint Work Product in the
Field.


 


16.5               TMC hereby grants to LONZA a non-exclusive, royalty
free, non-assignable (except to the extent this Agreement is assigned under
Clause 21.3) license (without the right to sublicense) to use the Pre-existing
Intellectual Property of TMC in connection with performance of the Work during
the Development Phase, and in connection with the manufacture and sale of
Product to TMC during the Commercial Phase. The foregoing license shall include
a sublicense of the intellectual property rights of Biogen, Inc. licensed to
TMC under the License Agreement between TMC and Biogen, Inc. dated March 21,
1997, provided this sublicense shall be limited to the purposes of this
Agreement.


 


16.6               LONZA shall defend, indemnify and hold
harmless TMC, its officers, directors, employees and agents, from against any
and all claims, suits, causes of action, liabilities, proceedings or expenses
(including reasonable attorneys fees, court costs and settlements) brought
against


 


16



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED INFORMATION
HAS BEEN REPLACED WITH ASTERISKS.


 


TMC or its customers based upon a claim that any Pre-existing
Intellectual Property of LONZA, any LONZA Work Product, any TMC Work Product
outside the Field as stated in clause 16.3.or any contribution of LONZA to
Joint Work Product furnished under this Agreement or any Purchase Order,
constitutes an infringement of any patent, trade secret or other intellectual
property right of a third party in the United States or in another country
where the Product is produced, provided LONZA is notified promptly in writing
and given authority, information, and assistance (at LONZA’s expense) for the
defense of same, and LONZA shall pay all damages and costs awarded
therein.  In case use of any such
Pre-existing Intellectual Property, Work Product, article or process is
enjoined, LONZA shall, at its own expense and at its option, either procure for
TMC the right to continue using the same or replace the same with a
non-infringing equivalent, or remove said infringing intellectual property,
Work Product, article or process and refund the purchase price and the
transportation and installation costs associated therewith.


 


16.7               TMC shall defend, indemnify and hold harmless
LONZA, its officers, directors, employees and agents, from against any and all
claims, suits, causes of action, liabilities, proceedings or expenses
(including reasonable attorneys fees, court costs and settlements) brought
against LONZA based upon a claim that any Pre-existing Intellectual Property of
TMC, any TMC Work Product or any contribution of TMC to Joint Work Product
furnished under this Agreement constitutes an infringement of any patent, trade
secret or other intellectual property right of a third party in the United
States or in another country where the Product is produced, provided TMC is notified
promptly in writing and given authority, information, and assistance (at TMC’s
expense) for the defense of same, and TMC shall pay all damages and costs
awarded therein.  In case use of any such
Pre-existing Intellectual Property, Work Product, article or process is
enjoined, TMC shall, at its own expense and at its option, either procure for
LONZA the right to continue using the same or replace the same with a
non-infringing equivalent, or remove said infringing intellectual property,
Work Product, article or process.


 


16.8                 In the event that the Agreement
is terminated by TMC pursuant to Clause 17 and TMC after the termination wishes
to use any Pre-existing Intellectual Property of LONZA and any LONZA Work
Product in connection with the manufacture of the Product by a third party,
LONZA shall grant to TMC a non-exclusive, worldwide license, including the
right to sublicense, to use such intellectual property for those purposes in
return for payment of a royalty equal to seven percent (7%) of the amount paid
by TMC to such third party for purchases of Product in connection with the
manufacture of which any Pre-existing Intellectual Property of LONZA and any
LONZA Work Product was used.


 


Clause 17   Duration/Termination


 


17.1                 This Agreement shall
become effective on the date of signing by both parties and shall continue in
full force and effect for a period of 
***  years.


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


17.2                This Agreement shall
thereafter be automatically renewed for additional terms of  *** 
years each unless and until terminated by either party giving to the
other party twelve (12) months’ notice.


 


17.3               TMC may terminate all or any part of a
Purchase Order at its convenience, without cause, at any time by giving LONZA
thirty (30) days written notice.  In such
event, TMC shall be liable to LONZA only for its reasonable actual costs as a
direct result of the termination which may not be recovered or mitigated (e.g.
purchased materials, labor costs, or cost of work in progress not yet submitted
for acceptance, to the extent incurred prior to receipt of notice of
termination).  LONZA will notify TMC in
writing of such costs within thirty (30) days of termination.  The foregoing shall constitute TMC’s only
liability to LONZA for termination without cause of all or part of a Purchase
Order.


 


17.4               If LONZA defaults, TMC may terminate all or
any part of this Agreement or a Purchase Order without liability to LONZA by
giving written notice to LONZA.  A
default will occur if LONZA: (i) fails to deliver a Deliverable or Product, or
otherwise perform within the time period specified in the Work Schedule or
applicable Purchase Order;  (ii) so fails
to make progress as to endanger performance of the Work Schedule or Purchase
Order, and in either case LONZA does not cure the failure within ninety (90)
days if the default occurs during the Development Phase, or within thirty (30)
days if the default occurs during the Commercial Phase (or any longer period
TMC may authorize in writing) after LONZA’s receipt of TMC’s written notice of
default.  A default will also occur if
LONZA fails to meet its financial obligations as they become due, if any
proceeding under the bankruptcy or insolvency laws is brought against LONZA, a
receiver is appointed for LONZA, or LONZA makes an assignment for the benefit
of creditors.  If a Purchase Order is
terminated due to LONZA’s default, without prejudice to any other legal or
equitable remedies available to TMC, TMC will have the right to: (a) refuse to
accept delivery of any and all Products; (b) return to LONZA unused Products
already accepted and recover from LONZA payments made for such Products (and
for TMC’s freight, storage and other expenses); (c) recover any advance
payments to LONZA for undelivered or returned Products; (d) purchase Products
elsewhere and charge LONZA with any resultant damages attributable to LONZA’s
default; and (e) take title to and possession of any previously undeliverable
part of Work performed under the Purchase Order.


 


17.5               If TMC defaults, LONZA may terminate all or
any part of this Agreement or a Purchase Order without liability to TMC by
giving written notice to TMC. A default will occur if TMC fails to  perform within the time period required under
this Agreement, provided TMC does not cure the failure within thirty (30) days
(or any longer period LONZA may authorize in writing) after TMC’s receipt of
TMC’s written notice of default.  A
default will also occur if any proceeding under the bankruptcy or insolvency
laws is brought against TMC, a receiver is appointed for TMC, or TMC makes an
assignment for the benefit of creditors. 
Notwithstanding the foregoing, if TMC’s failure to pay any invoice of
LONZA is alleged to be a default under this Agreement, such failure shall


 


18



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


not constitute grounds for termination under this Clause 17.5 so long
as the matter is in the process of being resolved under the provisions of
Clause 20.2.


 


Clause 18   Partial Invalidity


 


18.1                 Should any one
provision to this Agreement be invalid or void in whole or in part, the parties
shall substitute the invalid provision with a valid provision which achie­ves as
much as pos­sible the purport, sense and economic pur­pose of the invalid
provision.


 


18.2                 The remaining
provisions of this Agreement shall not be affected by the nul­lity/invalidity
of individual pro­visions and shall remain in full force and effect unless such
in­valid provi­sion(s) is (are) of such essential importance to this Agreement
that the parties could not be reasonably expected to have con­cluded the
Agreement without the in­valid provi­sion(s).


 


Clause 19   Force Majeure


 


19.1                 If, in the case of
Force Majeure, a party to this Agree­ment shall be unable to fulfil its
contractual obliga­tions, this shall not be considered as a breach of con­tract.


 


19.2                 For the purposes of
this Agreement, a “Force Majeure” shall be fire, explosions, actions of the
elements, war, civil war, riots, revolution, legislation and acts of the autho­rities,
strike, interrup­tion of oper­ation, short­age of raw materials, or any similar
reasons beyond the reasonable control of the par­ties.


 


19.3                 (a)                        Any occurrence of Force Majeure shall promptly be re­ported to the
other party and competent evidence thereof shall be supplied simultane­ously.


 


(b)                       The party
affected by a case of Force Majeure shall use its best ef­forts to restore
normal conditions as soon as possible.


 


(c)                        As soon as the
Force Majeure has ceased, the party affected shall inform the other party in
writing. From this moment, the Agreement shall again be fully effec­tive.


 


19.4                 If in case of a Force
Majeure situation, the party affected sustains increased cost in or­der to
maintain perfor­mance of its obligations, such additional cost shall be reim­bursed
to it. The other party has to be informed in advance of such additi­onal cost
and may renounce the performance of obliga­tions at such higher cost.


 


19.5                 If essential
obligations of either party are affected by a case of Force Ma­jeure lasting
more than 6 (six) months, either party is entitled to cancel this Agreement
with immedi­ate effect by giving written notice to the other party.


 


19



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Clause 20   Applicable Law, Dispute Resolution


 


20.1                 This Agreement shall
be governed and interpreted in accordance with the laws of the State of New
York.  The United Nations Conven­tion on
Contracts for the Interna­tional Sale of Goods of April 11, 1980, eventual
subsequent amendments thereto and any law providing its ap­plication are hereby
expressly and mu­tually excluded.


 


20.2                 Any dispute which may
arise between the parties in relation to this Agree­ment shall be settled
amicably between the parties with escalation of the matter to senior executives
of each party as necessary.  If, contrary
to expecta­tion, no amicable settle­ment can be reached, the dispute shall be
finally settled under the Rules of Arbitration of the International Chamber of
Commerce by three arbitrators appointed in accordance with said Rules.  The place of arbitration shall be The Hague,
Netherlands, and the language of the arbitration shall be in English.


 


Clause 21   Miscellaneous


 


21.1                 This Agreement may
not be amended or modified, except by a writing executed by the parties hereto.
No extension of time for, or waiver of the performance of, any obligation of
any party hereto shall be effective unless it is made in a writing signed by
the party granting such extension or waiver. Unless it specifically states
otherwise, no waiver shall constitute or be construed as a waiver of any
subsequent breach or non-performance.


 


21.2                This Agreement,
including the Annexes hereto, sets forth the entire agreement between the
parties as to the subject matter hereof, and supersedes any and all
contemporaneous or prior discussions or agreements between the parties relating
thereto including, without limitation, that certain Letter of Intent dated June
3, 2004.


 


21.3                Neither party may
assign or delegate this Agreement or any rights or obligations under this
Agreement to a third party without the prior written consent of the other
party, provided either party may, without the prior written consent of the
other, assign and delegate this Agreement and its rights and obligations
hereunder: (i) to any of its Affiliates; (ii) in connection with a merger,
consolidation or other change in control of the party; (iii) or in connection
with the sale of all or substantially all of the assets of the business of the
party to which this Agreement relates. No such assignment and delegation shall,
without the prior written consent of the other party, relieve the assigning
party of its obligations hereunder.  For
the purposes of this Clause 21.3, “change in control” shall mean the sale,
transfer or other disposition to any third party other than a Affiliate, of
more than fifty percent (50%) of capital stock of the party or other equity interests
of the company granting the holders thereof the right to elect the directors of
the party.


 


21.4                All notices or other
communications required or permitted hereunder shall be in writing and shall be
deemed given or delivered when delivered personally or when sent by facsimile,
or by recognized courier addressed as follows:


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


If to TMC, to:


 


John Richards, D Phil


Vice President-Manufacturing
Operations


The Medicines Company


200 Fifth Avenue


Waltham, MA 02451


Telephone:
+1 781 464 1500


Facsimile:  +1 781 464 1600


 


with a copy to:


 


Paul Antinori, Esq


General Counsel


The Medicines Company


 8 Campus Drive


Parsippany, NJ 07054 USA


Telephone: +1 973 656 1616


Facsimile:   +1 973 656 9898


 


If to LONZA, to:


 


Michael Petersen DPhil


Director Sales &
Business Development


Lonza
Ltd.


Muenchensteinerstrasse
38


CH-4002
Basel, Switzerland


Telephone:
+41 61 316 8528


 


with a copy to:


 


Daniel Bourgin DPhil


Associate Director Sales
& Business Development


Lonza
Ltd.


Muenchensteinerstrasse
38


CH-4002
Basel, Switzerland


Telephone:  +41 61 316 8497


 


or to such other facsimile
number or address as such party may indicate by a notice delivered to the other
party hereto.


 


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CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


21.5               Clause headings are supplied herein for
convenience only and shall not be determinative in the interpretation of any
provision of this Agreement.


 


Clause 22   Number of Signed Copies, Counterparts


 


This Agreement may be executed in two counterparts, each of which shall
be deemed an original for all purposes, and all of which together shall
constitute one agreement. The parties shall exchange signature pages by
facsimile, and confirm those signatures by delivery to each other of hard
copies of the signature pages.


 


	
  Parsippany, NJ, USA

  	
   

  	
  Basel, Switzerland

  
	
   

  	
   

  	
   

  
	
  THE
  MEDICINES COMPANY

  	
   

  	
  For
  LONZA LTD.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  /s/

  	
  Daniel
  Bourgin

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  (Signature)

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/
  Clive A. Meanwell

  	
   

  	
   

  	
   

  
	
   

  	
  CLIVE
  A. MEANWELL

  	
   

  	
   

  	
   

  
	
   

  	
  EXECUTIVE
  CHAIRMAN

  	
   

  	
  Daniel
  Bourgin, Associate Director 

  	
   

  
	
   

  	
   

  	
   

  	
  (Name
  and Position)

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  /s/

  	
  D.R.
  Evans

  	
   

  
	
   

  	
   

  	
  (Signature)

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  D.R.
  Evans, Head Sales & Business Development

  	
   

  
	
   

  	
   

  	
  (Name
  and Position)

  
											



 


Annexes 1, 2, 3, 4 and 5


 


22



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Annex             1


 


PRODUCT


 


Bivalirudin                                 Active Pharmaceutical Ingredient (API)


Abbreviation:                      *** 
(Lonza internal)


 


Structure (Structural
formula):


 


H-(D)
Phe-Pro-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH
.. xTFA . yH2O


 


23



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Annex             2


 


SPECIFICATIONS


 


Product:                                                  Bivalirudin, Active Pharmaceutical Ingredient
(API)


 


Abbreviation:                     TM-001 (Lonza internal)


 


Note:
                                                               The specifications listed below are
indicative (Reference document:  ***  Effective date:  *** 
Hardcopy received at Lonza,  ***
).  They will be adapted to the Lonza new
production processes ( ***  route
and  *** ), and will definitively be set
by Lonza and TMC during the laboratory qualification of the  *** 
processes.


 


	
  TESTS

  	
   

  	
  NORMS

  
	
  1.

  	
  Characters

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  1.1

  	
  Appearance

  	
   

  	
  *** to ***
  powder

  
	
   

  	
   

  	
   

  	
   

  
	
  2.

  	
  Identification

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2.1

  	
  Mass
  spectroscopy

  	
   

  	
  Mmonoisotopic
  = ***

  
	
   

  	
   

  	
   

  	
   

  
	
  2.2

  	
   TLC

  	
   

  	
  *** 1.00 ± 0.06

  
	
   

  	
   

  	
   

  	
   

  
	
  2.3 

  	
  Amino-acids
  relative composition 

  	
   

  	
  Asp: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Leu: *** 

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Glu: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Tyr: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Pro: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Phe: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Gly: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Arg: ***

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  Ile: *** 

  
	
   

  	
   

  	
   

  	
   

  
	
  2.4 

  	
  pH
  determination

  	
   

  	
  *** to ***

  



 


24



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
  3.

  	
   

  	
  ***

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.1

  	
   

  	
  *** content

  	
   

  	
  NMT ***%
  (m/m)

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.2

  	
   

  	
  *** content

  	
   

  	
  ***% to ***%
  (m/m)

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3

  	
   

  	
  ***

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3.a

  	
   

  	
  *** purity

  	
   

  	
  NLT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3.b

  	
   

  	
  *** analog

  	
   

  	
  NMT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3.c

  	
   

  	
  *** peak

  	
   

  	
  NMT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3.d

  	
   

  	
  *** other
  *** impurity

  	
   

  	
  NMT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3.e

  	
   

  	
  ***
  impurities

  	
   

  	
  NMT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.4

  	
   

  	
  ***

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.4.a

  	
   

  	
  *** impurity
  at ***

  	
   

  	
  NMT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.5

  	
   

  	
  Residual
  solvents:

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.5.a

  	
   

  	
  Volatile

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.5.b

  	
   

  	
  Semi-volatile

  	
   

  	
   

  	
  To be
  reported

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.5.c

  	
   

  	
  Total of all
  identified solvents

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.6

  	
   

  	
  Residual ***

  	
   

  	
   

  	
  NMT *** ppm

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.7

  	
   

  	
  Bacterial
  endotoxin test

  	
   

  	
   

  	
  NMT ***
  EU/mg

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.8

  	
   

  	
  Microbial
  contamination

  	
   

  	
   

  	
  NMT *** mg

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.

  	
   

  	
  Assay

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.1

  	
   

  	
  Peptide ***
  amino-acid analysis

  	
   

  	
   

  	
  NLT ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.2

  	
   

  	
  Assay by ***

  	
   

  	
   

  	
  ***% to ***%

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.3

  	
   

  	
  *** activity

  	
   

  	
   

  	
  ***% to ***%
  inhibition

  



 


METHODS, See Reference document.


 


25



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Annex 3


 


WORK SCHEDULE


 


***


 


Main
activities foreseen before a cGMP production of bivalirudin, (TM-001) ***  strategy
at Lonza


 


	
  1.

  	
   

  	
  Development program

  
	
   

  	
   

  	
   

  
	
  1.1

  	
  R&D work (ca.
  *** months, *** of the *** to ***

  
	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** on *** on laboratory scale (*** mmol);
  investigation of the following synthesis parameter: *** equiv. of incoming *** etc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** of the *** volume of the *** use of *** conditions, etc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Isolation of the *** optimization of the *** step.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** screening of *** (e.g.,
  by *** of experiments) *** of the product *** , etc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** of *** etc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** screening of *** and *** etc.), study of the
  *** optimization of the *** of the *** and of the *** etc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Investigation of different options for *** to be defined with TMC.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Optimization of the *** of the *** etc).

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Progress report(s)

  



 


26



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
  1.2

  	
   

  	
  *** work (ca. *** month *** of the process ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • *** synthesis on a ***), using the same *** and *** as the ones *** for the production.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  *** of the *** step.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  *** of the *** and *** investigation.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Progress report

  



 


During this phase, the  ***  will be addressed: (i) Definition of  ***  of the different  *** ; (ii) Study of  ***  on  ***  times; (iii)  ***  of the process  ***  and of the  ***  (iv)  ***  of the possible  ***  points; (v)  ***  (vi)  ***


 


	
  1.3

  	
   

  	
  ***  in the laboratory (ca.  ***  months)

  
	
  The goal of the qualification experiments is to provide  *** 
  to demonstrate the  ***  and 
  ***  of the  *** 
  and to set the  ***

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Development of *** methods allowing the *** to meet the *** it is
  required to produce *** to the *** process!

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Identification of the *** (according to ***).

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  •
  Establishment of the *** and *** of the process. Determination of
  the *** (proven *** and *** The edge of *** will be *** for the *** and *** most relevant ***

  	 

	
   

  	
   

  	
   

  	 

	
  1.4

  	
   

  	
  Preparation of the *** and *** assessments (in parallel to the
***)

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • RC1 ***

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Thermal decomposition ***

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Investigation of the *** of the process *** and of the ***

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Determination of the possible ***

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Generation of *** data.

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Preparation of the *** and *** plans.

  	 

	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
  • Preparation of a *** plan prior to the campaign.

  	 

					



 


27



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
  1.5

  	
   

  	
  *** (in parallel to the different phases)

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Development of an *** method for the *** determination.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Development of *** analyses for the ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Development of an *** analysis for the ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Investigation of the *** profile of the ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Identification of potentially *** in the ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Preparation of *** of potentially
  critical ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Investigation of *** of products in ***

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • *** and ***
  of all
  the developed *** methods.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Transfer of *** methods for the *** of the final product.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  • Development and *** methods for the ***

  



 


28



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
   

  	
  ***  Strategy

  
	
   

  	
   

  
	
   

  	
  ***  Study *** 

  



 


1.)           TMC asked Lonza to include (i) a chapter on  *** 
Route and (ii) a chapter on 
***  of the  *** 
into the TMC-LONZA Bivalirudin Supply Contract.


 


2.)            We understand that TMC asks Lonza to perform in  *** 
a  ***  process development and process  *** 
study, resulting in a  ***  and 
***  and  *** , frozen new  *** 
production process.


 


3.)           Basis for this new process is the 
***  developed by  *** 
for  ***  A short program (A.) of  *** 
months based on the  ***  and 
***  (including a productivity
comparison using Lonza’s new  ***  system) can be performed  *** 
for TMC .


 


4.)           TMC also expressed interest to include efforts  ***  if
new  *** 
and  ***  system could lead to a much  *** 
and  ***  new 
***  A longer program (B.) of  *** 
can be offered for  ***


 


5.)           We suggest to perform  ***  in parallel, followed by  *** 
and  ***


 


6.)           A  ***  program with STOP/Go decisions is suggested
for  *** activities.


 


7.)           We offer an  ***  program (C.) by  *** 
batches in  ***  production (ca.  *** 
timing  ***  followed by 
***  to  *** 
and  ***  processing to 
***  in  ***  to
Bivalirudin for  ***


 


8.)           Lonza assumes that  ***  for this 
***  will be submitted by TMC
to  *** 
and  ***  in  ***


 


29



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2 PROMULGATED
THEREUNDER.  OMITTED INFORMATION HAS BEEN
REPLACED WITH ASTERISKS.


 


	
  Phases of the project

  	
   

  	
  Team and

  Duration

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  A.) Activities for improvement of the *** process

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  1.) *** Compare productivity of the *** in parallel with a ***
  Compare reported *** productivity with that of the new *** regime. Produce
  *** activities described below *** most productive option. Target: *** per L
  ***

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2.) Test and qualify new *** in *** Replace *** in *** Solution: Use
  *** and *** to *** the primary *** product, the *** into the *** Minimize ***
  by-products.

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  3.) Test and qualify new *** step: Avoid *** after *** Solution:
  Screening for alternative less *** including implementation of a *** step for
  the *** of *** and product. Check for conditions which ***

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  4.) *** related steps such as: *** to *** by-products. Do
  re-qualification of all *** process steps such as *** dosing into the *** and
  *** of product.

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Sum *** inclusive
  reporting :

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  



 


30



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
  Phases of the project

  	
   

  	
  Team and

  Duration

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  B.) Activities to establish a *** process based on ***

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  1.) Design and *** of two *** Transfer of the *** into Lonza’s ***
  system for *** with the new *** Comparable activities for *** flask
  activities for first *** assessment. Stop / Go decision

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2.) Test productivity in *** Develop appropriate *** (target *** Optimize
  and qualify the *** regime with the most *** Stop / Go decision

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  3.) Develop and qualify *** for *** Test if *** and *** can be
  omitted; target: *** compared to existing process. Stop / Go decision

  	
   

  	
  *** weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Sum activities B.)  *** inclusive reporting:

  	
   

  	
  ca.  *** weeks

  	
   

  



 


31



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


	
  Phases of the project

  	
   

  	
  Team and

  Duration

  	
   

  
	
  C.)  ***  activities and  ***  program

   ***  batches)

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  1.               1.) Transfer the  *** 
  scale process to  ***

  	
   

  	
  ***  weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  3.               2.) Prepare 
  ***  in  *** 
  for the above  ***  and run 
  ***  batches (product to be used
  for  ***  studies) (each  *** 
  containing  ***  kg 
  ***  Bivalirudin ***  in 
  ***

  	
   

  	
  ***  weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  3.)  *** 
  and  ***  to 
  ***  Bivalirudin  ***

  	
   

  	
  ***  weeks

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  Sum activities  ***  inclusive reporting:

  	
   

  	
   ***  weeks

  	
   

  



 


32



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Main
 ***  foreseen before a  ***  production of bivalirudin (TM-001) via the  ***  at Lonza


 


1.          Development program for the  ***  strategy (ca.  ***  months)


 


Most of the activities planned for the
development work of the  ***  and  ***  part of the  ***  strategy are very similar to the ones listed
for the  *** .  In
particular, the development of the  ***  of the  ***  product and the optimization of the  ***  of the  ***  although route specific, shall be
comparable.  The special issues to study
and optimize for the development of a production process for  ***  are listed below ***  activities and laboratory
qualification will also be very similar to those done for the  ***  route.


 


	
  *** purchase of the *** partner.

  
	
   

  
	
  • Development of *** for the *** steps.

  
	
   

  
	
  • Detailed study and optimization of the *** of different *** groups and *** of their impact on
  the *** of the *** etc. (e.g., by *** experiments), etc.

  
	
   

  
	
  • Use test of different *** in order to set *** for the *** product.

  
	
   

  
	
  • Optimization of the *** step: *** of *** (e.g., by ***
  experiments), *** of the *** product.

  
	
   

  
	
  • Progress report(s)

  



 


33



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Annex             4


 


PRICES


 


1.) During the Development Phase ( ***  Strategy)


 


	
  Milestones

  	
   

  	
  Deliverables

  	
   

  	
  Products to be

  delivered

  	
   

  	
  Prices

  (in US-Dollars)

  	
   

  
	
  R
  & D work

  	
   

  	
  Progress
  report

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  Scale-up
  work

  	
   

  	
  Progress
  report

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  Process
  qualification, and in parallel preparation of production campaign and
  analytics.

  	
   

  	
  Progress
  report and technical meeting

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  Production
  of qualification batches.

  	
   

  	
  Campaign
  report and technical meeting

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Stability
  testing

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  TOTAL

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  ***

  	
   

  



 


2.) During the Development Phase ( ***  Strategy)


 


	
  Milestones

  	
   

  	
  Deliverables

  	
   

  	
  Products to be

  delivered

  	
   

  	
  Prices

  (in US-Dollars)

  	
   

  
	
  Activity
  A *** for *** of *** process

  	
   

  	
  Progress
  report

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  Activity
  B Activities to *** based on ***

  	
   

  	
  Various
  reports and technical meeting

  	
   

  	
   

  	
   

  	
  ***

  	
   

  
	
  Activity
  C *** activities in *** batches *** Bivalirudin

  	
   

  	
  Campaign
  report and technical meeting

  	
   

  	
  ***
  batches

  	
   

  	
  ***

  	
   

  
	
  TOTAL

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  ***

  	
   

  



 


34



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


3.) During the pre-Commercial Phase and Commercial Phase ( ***  Strategy), the parties acknowledging that
the Commercial Phase does not commence until after regulatory approval of a
commercial process for manufacture of the Product


 


	
  Milestones

  	
   

  	
  Deliverables

  	
   

  	
  Products to be

  delivered

  	
   

  	
  Prices

  (in US-Dollars)

  	
   

  
	
  Production
  of validation batches ***

  	
   

  	
   

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Production
  “commercial scale” in ***

  	
   

  	
   

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Production
  “commercial scale” in ***

  	
   

  	
   

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Production
  “commercial scale” in ***

  	
   

  	
   

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  
	
  Production
  “commercial scale” in ***

  	
   

  	
   

  	
   

  	
  ***

  	
   

  	
  ***

  	
   

  



 


4.) During the pre-Commercial Phase and Commercial Phase ( ***  Strategy), the parties acknowledging that
the Commercial Phase does not commence until after regulatory approval of a
commercial process for manufacture of the Product


 


	
  Milestones

  	
   

  	
  Deliverables

  	
   

  	
  Products to be

  delivered

  	
   

  	
  Prices

  (in US-Dollars)

  	
   

  
	
  Production
  of *** batche *** kg *** each) 

  	
   

  	
  Campaign
  report(s) and 

  	
   

  	
  Ca.
  *** kg at *** /g

  	
   

  	
   

  	
   

  
	
  and
  *** to *** in *** with *** production

  	
   

  	
  technical
  meeting(s)

  	
   

  	
  ***
  kg at *** / g

  	
   

  	
   

  	
   

  
	
  Commercial
  production with 2 combined campaigns

  	
   

  	
   

  	
   

  	
  ***
  kg at *** / g

  	
   

  	
   

  	
   

  
	
  Commercial
  production

  	
   

  	
   

  	
   

  	
  ***
  kg at *** / g

  	
   

  	
   

  	
   

  
	
  Commercial
  production

  	
   

  	
   

  	
   

  	
  ***
  kg at *** / g

  	
   

  	
   

  	
   

  



 


35



















CONFIDENTIAL
MATERIAL APPEARING IN THIS DOCUMENT HAS BEEN OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION IN ACCORDANCE WITH RULE 406
PROMULGATED UNDER THE SECURITIES ACT OF 1934, AS AMENDED, AND RULE 24B-2
PROMULGATED THEREUNDER.  OMITTED
INFORMATION HAS BEEN REPLACED WITH ASTERISKS.


 


Annex             5


 


 


PURCHASE ORDER


 





 


THE
MEDICINES COMPANY


8
Campus Drive - Parsippany, NJ 07054


Phone:800-388-1183


 


	
  Purchase
  Order

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Supplier

  
	
  P.O.
  No. 

  	
   

  	
  Date
  

  	
   

  	
  Budget
  Code 

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Bill
  To

  	
   

  	
  Account
  #

  	
   

  	
   

  	
   

  	
   

  
	
  Accounts
  Payable

  	
   

  	
   

  	
   

  	
  Ship
  To

  	
   

  	
   

  
	
  The
  Medicines Company

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8
  Campus Drive

  	
   

  	
   

  	
   

  	
  The
  Medicines Company

  	
   

  	
   

  
	
  Parsippany
  NJ 07054

  	
   

  	
   

  	
   

  	
  8
  Campus Drive

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Parsippany
  NJ 07054

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Terms

  	
  F.O.B.

  	
   

  	
  Requested
  By

  	
   

  	
  Ship
  Date

  	
  Ship
  Via

  	
   

  	
   

  	
   

  
	
  Net
  30

  	
   

  	
   

  	
   

  	
   

  	
  Ground

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Product ID

  	
   

  	
  Description

  	
   

  	
  Quantity

  	
   

  	
  Price

  	
   

  	
  Extended
 Amount

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  Subtotal:

  	
   

  	
   

  
	
  1.

  	
  Please
  send two copies of your invoice. 

  	
   

  	
   

  	
   

  	
  Discount:

  	
   

  	
   

  
	
  2.

  	
  Enter
  this order in accordance with the prices, terms, delivery method,

  and specifications listed above. 

  	
                   Tax:

  Weight:

  	
   

  	
   

  
	
  3.

  	
  Please
  notify us immediately if you are unable to ship as specified. 

  	
  Shipping:

  	
   

  	
   

  
	
  4.

  	
  Send
  all correspondence to: 

  	
  Total:

  	
   

  	
   

  
	
   

  	
  THE
  MEDICINES

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  8
  Campus Drive

  	
   

  	
   

  	
   

  	
   

  	
  Authorized
  Signature

  
	
   

  	
  Parsippany,
  NJ  07054

  	
   

  	
   

  	
   

  	
   

  	
   

  
																



 


36