Document:

ex4_83.htm

     

    Exhibit 4.83

    

    

    

    

    

    

    

    (1)           AMARIN
NEUROSCIENCE LIMITED

    

    (2)           AMARIN
PHARMACEUTICALS IRELAND LIMITED

    

    AND

    

    
      (3)          
CHARLES
RIVER LABORATORIES PRECLINICAL SERVICES EDINBURGH LIMITED

    

    

    

    

    

    

    

    

    

    

    

    

    

    
      
        
          

        

    

    

    MASTER
SERVICES AGREEMENT FOR NON-CLINICAL SERVICES

     

    
      

    

    
      
        

      

    

    

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    THIS MASTER CLINICAL SERVICES
AGREEMENT (this ‘AGREEMENT’)

    

    BETWEEN:

    

    
      	
              (1)  

            	
              AMARIN NEUROSCIENCES
      LTD, having its principal place of business at Magdelen Centre
      North, Oxford Science Park, Oxford, OX4 4GA and its Affiliates, (‘Amarin
    ’);

            

    

    

    
      	
              (2)

            	
              AMARIN PHARMACEUTICALS IRELAND
      LIMITED having its principal place of business at First Floor,
      Block 3, The Oval, Shelbourne Road, Ballsbridge, Dublin 4, Ireland (“APIL”);
      and

            

    

    

    
      	
              (3)

            	
              CHARLES RIVER LABORATORIES
      PRECLINICAL SERVICES EDINBURGH LIMITED having its principal place
      of business at Elphinstone Research Centre, Tranent, Edinburgh, EH33 2NE,
      UK and its Affiliates listed on Exhibit A, (“Charles
      River”).

            

    

     
 

    RECITALS

    

    
      	
              A.

            	
              Amarin
      is in the business of research, developing, manufacturing and/or
      distributing pharmaceutical products. Charles River is in the business of
      providing clinical trial services, research services, and other services
      for the pharmaceutical industries.

            

    

    

    
      	
              B.

            	
              Amarin
      and Charles River desire to enter into this Agreement to provide the terms
      and conditions upon which Amarin may engage Charles River from
      time-to-time to provide non-clinical services including toxicology and
      other services for individual projects by executing individual Work Orders
      (as defined below) specifying the details of the services and the related
      terms and conditions.

            

    

    

    NOW, IT IS HEREBY AGREED AS
FOLLOWS in consideration of the mutual covenants contained
herein:

    

    
      	
              1.  

            	
              DEFINITIONS

            

    

    

    
      	
              1.1.  

            	
              “Affiliate” shall mean a
      corporation or entity controlling, controlled by, or under the common
      control with Amarin or Charles River, as the case may be. For the purposes
      of this Agreement, “control” shall mean the direct or indirect ownership
      of more than 50% of the issued voting shares or other voting rights of the
      subject entity to elect directors, or if not meeting the preceding
      criteria, any entity owned or controlled by or owning or controlling at
      the maximum control or ownership right permitted in the country where such
      entity exists.

            

    

    

    
      	
              1.2.  

            	
              “Amarin Materials” shall
      mean the materials provided by Amarin to Charles River, as more
      particularly described in each Work
Order.

            

    

    

    
      	
              1.3.  

            	
              “Change Order” shall
      have the meaning given to the term in Clause
  2.3.

            

    

    

    
      	
              1.4.  

            	
              “Claims” shall mean all
      and any claims (whether successful or otherwise), loss, liability, damages
      and expenses, including reasonable attorneys’ fees and expenses and legal
      costs.

            

    

    

    
      	
              1.5.  

            	
              “Confidential
      Information” shall mean all know-how, trade secrets, inventions
      (including patent applications covering such inventions), data,
      information, and any improvements, modifications, derivations, or
      compilations thereto that is owned, licensed by or controlled by the
      disclosing party, provided however, that Confidential Information shall
      not include any information which
is:

            

    

    

    
      	
              1.5.1.  

            	
              already
      known to the receiving party at the time of disclosure, as evidenced by
      such party’s written records, provided such information was not obtained
      directly or indirectly by the receiving party from the disclosing party
      pursuant to a confidentiality
agreement;

            

    

    

    
      	
              1.5.2.  

            	
              publicly
      known prior to or after disclosure, through no default of the receiving
      party;

            

    

    

    
      	
              1.5.3.  

            	
              disclosed
      in good faith to the receiving party by a third party, lawfully and
      contractually entitled to make such disclosure;
  or

            

    

    

    
      	
              1.5.4.  

            	
              is
      independently discovered without the aid or application of the
      Confidential Information as shall be evidenced by the written records of
      the receiving party.

            

    

    

    
      	
              1.6.  

            	
              “Effective Date” shall
      mean the date of last signature of this
  Agreement.

            

    

    
      
         

      

      
        2

        
          

        

      

      
         

      

    

    

    

    
      	
              1.7.  

            	
              “Intellectual Property Rights”
      shall mean all patents, patent applications, copyrights, copyright
      applications, trademarks, trade secrets, know-how and other intellectual
      property rights.

            

    

    

    
      	
              1.8.  

            	
              “Project” shall have the
      meaning given to the term in Clause
2.2.1.

            

    

    

    
      	
              1.9.  

            	
              “Project Protocol” shall
      have the meaning given to the term in Clause
  2.2.2.

            

    

     

    
      	
               
      1.10.  

            	
              “Services” shall have
      the meaning given to the term in Clause
2.2.2.

            

    

    

    
      	
               1.11.  

            	
              “Work Orders” shall have
      the meaning given to the term in Clause
2.2.1.

            

    

    

    
      	
              2.  

            	
              SCOPE
      OF THE AGREEMENT AND WORK ORDERS

            

    

    

    
      	
              2.1.  

            	
              Scope
      of Agreement

            

    

    

    
      	
              2.1.1.  

            	
              This
      Master Agreement allows the parties to contract for multiple projects
      regarding toxicology and other non-clinical services requested by Amarin
      and agreed to by Charles River through the issuance of multiple Work
      Orders in accordance with the terms of this
  Agreement.

            

    

    

    
      	
              2.2.  

            	
              Work
      Orders/Project Protocol

            

    

    

    
      	
              2.2.1.  

            	
              The
      specific details of each project under this Agreement (each a “Project”) shall be
      separately negotiated and specified in writing in substantially the form
      attached hereto in Appendix 1 (each a “Work
      Order”).

            

    

    

    
      	
              2.2.2.  

            	
              The
      parties shall agree the terms of a protocol for each Project which will
      set out the nature, design and scope of the Project and the schedule of
      work to be performed or consulting services to be provided during the
      course of each Project (the “Services”) (the “Project
      Protocol”).

            

    

    

    
      	
              2.2.3.  

            	
              Each
      Work Order will include details of the Services as set out in the relevant
      Project Protocol, time line, budget and payment schedule for the Services
      to be provided for each Project.

            

    

    

    
      	
              2.2.4.  

            	
              For
      the avoidance of doubt, the terms of any Project Protocol are hereby
      incorporated into the relevant Work Order and any reference to any Work
      Order includes the terms of any Project Protocol set out
      therein.

            

    

    

    
      	
              2.2.5.  

            	
              Each
      Work Order upon execution shall be incorporated into this Agreement and
      shall be subject to all of the terms and conditions of this Agreement, in
      addition to the specific details set forth in the Work
    Order.

            

    

    

    
      	
              2.2.6.  

            	
              To
      the extent any terms or provisions of a Work Order conflict with the terms
      and provisions of this Agreement, the terms and provisions of this
      Agreement shall prevail, except to the extent that the applicable Work
      Order expressly and specifically states an intent to supersede the
      Agreement on a specific matter.

            

    

    

    
      	
              2.3.  

            	
              Change
      Orders

            

    

    

    
      	
              2.3.1.  

            	
              Subject
      to Clause 2.4, any material change in the details of a Work Order,
      including without limitation any change to the relevant Project protocol,
      shall require written amendment to the Work Order in substantially the
      form attached hereto in Appendix 2 (a “Change
      Order”).

            

    

    

    
      	
              2.3.2.  

            	
              For
      the avoidance of doubt, other than as provided in Clauses 2.3.1 and 2.4,
      no other changes to, or deviations from, a Work Order, including without
      limitation the relevant Project protocol, can be made without the prior
      written consent of Amarin.

            

    

    

    
      	
              2.3.3.  

            	
              Each
      Change Order shall detail the requested changes to the applicable task,
      responsibility, duty, budget, time line or other
  matter.

            

    

    

    
      	
              2.3.4. 

            	
              The
      Change Order will become effective upon the execution of the Change Order
      by both parties.

            

    

    

    
      	
              2.3.5.  

            	
              Both
      parties agree to act in good faith and promptly when considering a Change
      Order requested by the other
party.

            

    

    
      
         

      

      
        3

        
          

        

      

      
         

      

    

    

    

    
      	
              2.4.  

            	
              Conduct
      of the Project

            

    

    

    
      	
              2.4.1.  

            	
              Charles
      River shall provide the Services in accordance with the relevant Project
      Protocol, industry standards of professional conduct, and the terms and
      conditions of this Agreement.

            

    

    

    
      	
              2.4.2.  

            	
              Emergency
      Deviations from Project Protocol

            

    

    

    
      	
              (a)  

            	
              Deviations
      from a Project Protocol may be made without Amarin’s approval in an
      emergency where issues of safety or welfare arise (“Emergency
      Deviations”).

            

    

    

    
      	
              (b)  

            	
              Additional
      costs may be incurred by Charles River as a result of such Emergency
      Deviations which could not have been foreseen at the time of the
      preparation of the Work Order (the “Additional
      Cost”).

            

    

    

    
      	
              (c)  

            	
              Charles
      River shall use commercially reasonable efforts to obtain Amarin’s
      approval before implementing such Emergency Deviations and incurring such
      Additional Cost. Should Charles River be unable to contact Amarin prior to
      the implementation of the Emergency Deviation, Amarin agrees that Charles
      River may proceed accordingly and be entitled to recover such Additional
      Costs from Amarin upon presentation of an explanation of such Emergency
      Deviations and the necessity thereof, together with any additional
      information required by Amarin.

            

    

    

    
      	
              3.  

            	
              MATERIALS

            

    

    

    
      	
              3.1.  

            	
              Amarin
      shall provide Charles River with the Amarin Materials specified in the
      applicable Work Order,as well as such complete and accurate data as is
      necessary to apprise Charles River of the identity, strength, purity,
      stability and composition or other appropriate characteristics of each
      batch, proper storage and safe handling requirements of the Amarin
      Materials, including a Material Safety Data Sheet (MSDS) or equivalent
      documentation.

            

    

    

    
      	
              3.2.  

            	
              All
      costs associated with the shipping of the Amarin Materials to Charles
      River shall be the responsibility of Amarin and Charles River shall not be
      responsible for any loss, damage or destruction of the Amarin Materials in
      transit.  Title to the Amarin Materials shall at all times
      remain in Amarin.

            

    

    

    
      	
              3.3.  

            	
              Charles
      River acknowledges that Amarin owns the Amarin
  Materials.

            

    

    

    
      	
              3.4.  

            	
              Charles
      River undertakes that it shall not, without the prior written consent of
      Amarin:

            

    

    

    
      	
              3.4.1.  

            	
              use
      the Amarin Materials for any purpose other than for the Services described
      in the applicable Work Order;

            

    

    

    
      	
              3.4.2.  

            	
              make
      any Amarin Materials available to a third
party;

            

    

    

    
      	
              3.4.3.  

            	
              allow
      access to the Amarin Materials by any employees or permitted consultants
      except those who are directly involved in providing the Services in the
      Applicable Work Order;

            

    

    

    
      	
              3.4.4.  

            	
              make
      any commercial use of the Amarin Materials or any composition made using
      the Amarin Materials;

            

    

    

    
      	
              3.4.5.  

            	
              analyse
      or otherwise attempt to determine the composition of the Amarin Materials
      except as agreed by the parties for the completion of the
      Projects;

            

    

    

    
      	
              3.4.6.  

            	
              use
      the Amarin Materials for testing in or treatment of human
      subjects.

            

    

    

    
      	
              3.5.  

            	
              Subject
      to Clause 4, upon termination of the applicable Work Order or of this
      Agreement, any remaining Amarin Materials shall be returned by Charles
      River to Amarin or, at Amarin’s option, destroyed, with written
      certification of such destruction.

            

    

    

    
      	
              3.6.  

            	
              Except
      as otherwise set forth herein, the Amarin Materials are provided by Amarin
      on an as-is basis and without warranty, express or implied, including any
      warranty as to merchantability, title, or fitness for a particular
      purpose.

            

    

    
      
         

      

      
        4

        
          

        

      

      
         

      

    

    

    

    
      	
              4.  

            	
              SAMPLES
      AND RECORDS RETENTION

            

    

    

    
      	
              4.1.  

            	
              Charles
      River shall archive all raw material, non-clinical supply and analytical
      samples (the “Samples”) and all
      books, records, data, reports, pictures and other documents (both in
      electronic and paper form) relating to the manufacture and supply of the
      Products (the “Records”) in accordance
      with the provisions of the relevant Project protocol and with Charles
      River’s standard archiving terms and conditions attached hereto as
      Appendix 3 (the “Retention
      Period”).  To the extent any terms or provisions of such
      terms and conditions conflict with the terms and provisions of this
      Agreement, the terms and provisions of this Agreement shall
      prevail.

            

    

    

    
      	
              4.2.  

            	
              The
      Parties agree that all Records shall constitute Confidential Information
      of Amarin and the provisions of Clause 6 shall apply to all such
      Records.

            

    

    

    
      	
              4.3.  

            	
              Upon
      expiry of the Retention Period, Charles River shall provide all original
      Records (both in electronic and paper form), and all copies thereof, to
      Amarin and shall, at the direction and written request of Amarin, either
      deliver all Samples to Amarin, or dispose of same, (unless such Samples
      are otherwise required to be stored or maintained by Charles River as a
      matter of law or regulation).

            

    

    

    
      	
              5.  

            	
              PAYMENT
      OF FEES AND EXPENSES

            

    

    

    
      	
              5.1.  

            	
              APIL
      (or APIL’s nominee) shall pay Charles River fees and reasonable and
      necessary vouched expenses incurred in the performance of the Services on
      the following basis:

            

    

    

    
      	
              5.1.1.  

            	
              the
      total cost of each Project and an estimate of the total expenses to be
      incurred in relation thereto (the “Total Project Cost”)
      shall be set out in the relevant Work Order and, subject to Clause 2.4, in
      no event shall APIL (or APIL’s nominee) be required to pay any amount
      exceeding the Total Project Cost unless otherwise agreed in writing by
      both parties by Change Order(s);

            

    

    

    
      	
              5.1.2.  

            	
              in
      the case of any individual expense item exceeding £500, APIL’s (or APIL’s
      nominee) prior written approval must be given for such
      expense.

            

    

    

    
      	
              5.2.  

            	
              Invoices
      for fees and expenses shall be issued on a monthly basis and APIL (or
      APIL’s nominee) shall pay each invoice within thirty (30) days of date of
      invoice.

            

    

    

    
      	
              5.3.  

            	
              All
      sums referred to in each Work Order shall be exclusive of Value Added Tax
      (VAT) and shall be paid by APIL (or APIL’s
  nominee).

            

    

    

    
      	
              5.4.  

            	
              If
      any portion of an invoice is disputed, then APIL (or APIL’s nominee) shall
      pay the undisputed amounts and the parties shall use good faith efforts to
      reconcile the disputed amount as soon as
  practicable.

            

    

    

    
      	
              5.5.  

            	
              All
      amounts not paid by APIL when due shall accrue interest from the
      applicable due date until paid, at the rate of one percent (1%) per month.
      Charles River may elect to cease or suspend Services or withhold required
      reports or other deliverables if APIL does not make undisputed payments
      when due and payable.

            

    

    

    
      	
              6.  

            	
              CONFIDENTIAL
      INFORMATION/ANNOUNCEMENTS

            

    

    

    
      	
              6.1.  

            	
              Upon
      execution of this Agreement, and thereafter during the term hereof, Amarin
      may disclose to Charles River in confidence Confidential Information
      necessary or useful to the activities contemplated by this
      Agreement.

            

    

    

    
      	
                              6.2.

            	
              Except
      as specifically authorised or permitted by this Agreement, Charles
      River shall,
      for a period of 10 years after termination of the applicable Work Order
      keep confidential and not disclose to others (except its Affiliates), and
      use only as permitted hereunder, all of the Confidential Information owned
      by Amarin.

            

    

    

    
      	
                             
      6.3.

            	
              The
      parties agree that the provisions of this Clause 6 shall apply to any
      Confidential Information of Amarin provided to Charles River prior to the
      Effective Date and to any Confidential Information of Charles River
      provided to Amarin.

            

    

    
      
         

      

      
        5

        
          

        

      

      
         

      

    

    

    

    
      	
                             
      6.4.

            	
              Save
      as otherwise specifically provided herein, Charles River shall disclose
      Confidential Information of Amarin only to those employees,
      representatives and agents requiring knowledge thereof in connection with
      fulfilling Charles River obligations under this
      Agreement.  Charles River further agrees to (i) inform all such
      employees, representatives and agents of the terms and provisions of this
      Agreement relating to Confidential Information and their duties hereunder,
      and (ii) obtain their agreement hereto as a condition of receiving
      Confidential Information, provided that such agreement shall be deemed
      given in respect of such employees, representatives and agents that, at
      the time of disclosure, are under existing obligations of confidentiality
      no less onerous than those contained herein covering such
      disclosure.  Charles River shall exercise the same standard of
      care as it would itself exercise in relation to its own confidential
      information (but in no event less than a reasonable standard of care) to
      protect and preserve the proprietary and confidential nature of the
      Confidential Information disclosed to it by
  Amarin.

            

    

    

    
      	
                            
      6.5.

            	
              Notwithstanding
      the provisions of this Clause 6, Confidential Information may be disclosed
      to the extent required by applicable laws or regulations or as ordered by
      a court or other regulatory body having competent jurisdiction, provided
      that if Charles River becomes legally required to disclose any
      Confidential Information of Amarin hereunder, Charles River shall give
      Amarin prompt notice of such requirement to enable Amarin to seek a
      protective order or other appropriate remedy concerning any such
      disclosure. Charles River shall fully co-operate with Amarin in connection
      with Amarin’s efforts to obtain any such order or other
      remedy.  If any such order or other remedy does not fully
      preclude disclosure, Charles River shall make such disclosure only to the
      extent that such disclosure is legally
required.

            

    

    

    
      	
                            
      6.6.

            	
              The
      parties agree that the obligations of this Clause 6 are necessary and
      reasonable in order to protect Amarin’s business, and Charles River agrees
      that monetary damages would be inadequate to compensate Amarin for any
      breach by Charles River of its covenants and agreements set forth
      herein.

            

    

    

    
      	
                             6.7.

            	
              The
      parties agree that any such violation or threatened violation shall cause
      irreparable injury to Amarin and that, in addition to any other remedies
      that may be available, in law and equity or otherwise, Amarin shall be
      entitled to seek injunctive relief against the threatened breach of the
      provisions of this Clause 6, or a continuation of any such breach by
      Charles River, specific performance and other equitable relief to redress
      such breach together with damages and reasonable counsel fees and expenses
      to enforce its rights hereunder.

            

    

    

    
      	
                            
      6.8.

            	
              Subject
      to Clauses 6.4 and 6.5, Charles River shall not be entitled to disclose to
      third parties the existence of this Agreement or any of the terms and
      conditions hereof without the prior written consent of
    Amarin.

            

    

    

    
      	
                            
      6.9.

            	
              Amarin
      shall be entitled to provide a copy of this Agreement (and any related
      agreements or documents) to a potential third party acquirer or other
      commercialization partner provided that the relevant third
      party has entered into a confidentiality agreement on terms to be agreed
      between Amarin and such relevant third
party.

            

    

    

    
      	
              7.  

            	
              DATA
      AND INTELLECTUAL PROPERTY RIGHTS

            

    

    

    
      	
              7.1.  

            	
              Any
      inventions and/or techniques for carrying out the Services hereunder which
      relate to the conduct of Charles River’s business that are not developed
      hereunder and that are not developed using the Confidential Information of
      Amarin are and shall remain Charles River’s exclusive property, including
      but not limited to present and future documentation, scientific and
      technical data, test procedures and other information that is owned or
      licensed by Charles River.

            

    

    

    
      	
              7.2.  

            	
              Charles
      River shall have the right to use Control Data as part of its general
      historical database.  “Control Data” shall
      mean data generated solely from the control animals used in the relevant
      Project.

            

    

    

    
      	
              7.3.  

            	
              All
      Intellectual Property Rights conceived, discovered, developed, made,
      produced or created as a result of performing the Services and all rights
      therein (the “Project
      IP”), shall be owned exclusively by APIL (or APIL’s nominee) or an
      Affiliate of APIL (or APIL’s
nominee).

            

    

    

    
      	
              7.4.  

            	
              Charles
      River agrees to promptly disclose all such Project IP to APIL (or APIL’s
      nominee) and hereby assigns to APIL (or APIL’s nominee) all right title
      and interest in and to all Project
IP.

            

    

    
      
         

      

      
        6

        
          

        

      

      
         

      

    

    

    

    
      	
              7.5.  

            	
              All
      data and information generated or derived by or Charles River as the
      result of Services performed by Charles River under this Agreement,
      including the Reports, and all rights therein (the “Project Results”) shall
      be owned exclusively by APIL (or APIL’s
  nominee).

            

    

    

    
      	
              7.6.  

            	
              Charles
      River hereby assigns to APIL (or APIL’s nominee) all rights, title and
      interest in and to all Project
Results.

            

    

    

    
      	
              7.7.  

            	
              Subject
      to Clause 7.2, Charles River shall not be entitled to use the Project
      Results or Project IP after the termination or expiry of the relevant Work
      Order under which such Project Results or Project IP were created for any
      purpose whatsoever without the prior written consent of
      Amarin.

            

    

    

    
      	
              7.8.  

            	
              Charles
      River represents and warrants that each employee, agent, developer,
      consultant and contractor who has access to, contributes to, or
      participates in the creation of any Project Results or Project IP
      hereunder during the term of this Agreement is bound by confidentiality
      obligations that protect the confidentiality of such Project Results and
      Project IP and shall execute an assignment or an agreement to assign in
      favour of Charles River all such person’s right, title and interest in the
      Project Results and Project IP.

            

    

    

    
      	
              7.9.  

            	
              For
      the avoidance of doubt, APIL (or APIL’s nominee) may use the Project
      Results and Project IP without any restriction or additional
      compensation.

            

    

    

    
      	
              7.10.  

            	
              At
      APIL’s cost and expense, at the completion of Services by Charles River,
      all Project Results and Project IP and other materials owned by APIL (or
      APIL’s nominee), regardless of the method of storage or retrieval, shall
      either be delivered to APIL (or APIL’s nominee) disposed of, at the
      direction and written request of APIL (or APIL’s nominee) (unless such
      Project Results or materials are otherwise required to be stored or
      maintained by Charles River as a matter of law or
    regulation).

            

    

    

    
      	
              7.11.  

            	
              Reports

            

    

    

    
      	
              7.11.1.  

            	
              Charles
      River will provide Amarin with regular updates by telephone and/or by
      email on the progress of each Project in a timely manner and as
      needed.

            

    

    

    
      	
              7.11.2.  

            	
              On
      completion of each Project, Charles River will provide draft and final
      reports in writing on the Services conducted (each a “Report”) to Amarin in
      accordance with the relevant Project
protocol.

            

    

    

    
      	
              7.11.3.  

            	
              Charles
      River shall not disclose or publish any Report prepared for Amarin, or use
      the Reports for any purpose other than to perform its obligations
      hereunder, without the prior written consent of
  Amarin.

            

    

    

    
      	
              8.  

            	
              REGULATORY
      COMPLIANCE

            

    

    

    
      	
              8.1.  

            	
              Charles
      River represents and warrants that all Services will be conducted in
      compliance with all applicable laws, rules and regulations, including
      without limitation Good Laboratory Practice (GLP) and Good Clinical
      Practice (GCP) regulations and guidelines as appropriate, and in
      compliance with the applicable International Committee of Harmonization
      guidelines, United Kingdom Medicines and Healthcare Products Regulatory
      Agency (MHRA) guidelines, and the United States Food and Drug
      Administration’s Code of Federal Regulations Title 21, parts 11, 50, 56,
      54, 58, and 312 and all other applicable laws, regulations and guidelines,
      including for the avoidance of doubt, all laws, regulations and guidelines
      relating to data protection.

            

    

    

    
      	
              8.2.  

            	
              If
      any governmental or regulatory authority gives any party any notice to
      take any regulatory action with respect to any Project or Services
      provided under this Agreement, the notified party shall promptly notify it
      to the other party, and both parties shall cooperate in answering such
      regulatory action.

            

    

    

    
      	
              8.3.  

            	
              Upon
      reasonable advance notice and at such times as shall be agreed with
      Charles River, such agreement not to be unreasonably withheld or delayed,
      Charles River shall make (and where relevant shall procure that any
      permitted subcontractor shall make) that portion of its facility where the
      Services are conducted available for inspection by Amarin’s duly qualified
      employee, or by a duly qualified consultant, contractor or agent of
      Amarin, or by the relevant governmental or regulatory
      authority.  The investigation shall be limited to determining
      whether there is compliance with GCP and other requirements of any
      applicable laws, regulations and
guidelines.

            

    

    
      
         

      

      
        7

        
          

        

      

      
         

      

    

    

    

    
      	
              8.4.  

            	
              Charles
      River shall provide the Amarin with a list of all of Charles River
      standard operating procedures (“SOPs”) relevant to the
      Services.  Amarin shall be entitled to review all such SOPs
      during an audit of the Charles River
facility.

            

    

    

    
      	
              8.5.  

            	
              Charles
      River shall promptly notify Amarin of any material breach of any
      applicable laws, regulations or guidelines or SOPs that could potentially
      invalidate any Project.

            

    

    

    

    
      	
              9.  

            	
              REPRESENTATIONS
      AND WARRANTIES

            

    

    

    
      	
              9.1.  

            	
              Charles
      River represents and warrants as
follows:

            

    

    

    
      	
              9.1.1.  

            	
              it
      will render the Services under this Agreement and any Work Order in
      accordance with applicable professional standards and will make
      commercially reasonable efforts to produce a consistently high level of
      accuracy and expertise, and in accordance with the terms of this
      Agreement;

            

    

    

    
      	
              9.1.2.  

            	
              personnel
      assigned to perform Services under this Agreement and any Work Order shall
      have the skills necessary to efficiently perform such Services in
      accordance with the terms of this
Agreement;

            

    

    

    
      	
              9.1.3.  

            	
              it
      shall make its commercially reasonable efforts to provide the Services in
      accordance with the time lines set out in the relevant Work
      Orders;

            

    

    

    
      	
              9.1.4.  

            	
              it
      is not a party to any agreement which would prevent it from fulfilling its
      obligations under this Agreement and that during the term of this
      Agreement, Charles River agrees that it will not enter into any agreement
      to provide services which would in any way prevent it from providing
      Services contemplated under this Agreement and any Work
    Order.

            

    

    

    
      	
              9.2.  

            	
              THE
      WARRANTIES BY CHARLES RIVER SET FORTH IN THIS SECTION ARE IN LIEU OF ANY
      AND ALL OTHER REPRESENTATIONS OR WARRANTIES, EXPRESS, IMPLIED OR STATUTORY
      INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF MERCHANTABILITY
      OR FITNESS FOR A PARTICULAR PURPOSE OR FOR NON-INFRINGEMENT OF A PATENT,
      TRADEMARK OR OTHER INTELLECTUAL PROPERTY
RIGHT.

            

    

    

    
      	
              9.3.  

            	
              Amarin
      warrants that it owns, licences or controls, or is otherwise entitled to
      use, all rights, title and interest in the Amarin Materials and the
      intellectual property related
thereto.

            

    

    

    
      	
              10.  

            	
              INDEMNIFICATION

            

    

    

    
      	
              10.1.  

            	
              Subject
      to Clause 10.3, Amarin shall indemnify and hold harmless Charles River and
      its Affiliates and their respective employees, agents, officers and
      directors from and against any Claims incurred or sustained by Charles
      River and its Affiliates and their respective employees, agents, officers
      and directors arising out of the Services performed under this Agreement
      including without limitation any Claims arising
  from:

            

    

    

    
      	
              10.1.1.  

            	
              the
      research, development, manufacture, distribution, use, sales or other
      disposition by Amarin or APIL of the Amarin Materials;
  or

            

    

    

    
      	
              10.1.2.  

            	
              any
      personal injury sustained by an Amarin employee, agent, officer, or
      consultant related to contact with animals, tissues, samples or specimens
      during visits to Charles River’s facilities or after delivery of any
      animals, tissues, samples or specimens to
  Amarin;

            

    

     

                  
except to the extent such Claims arise out of, or are connected with
any:

    

    
      	
              10.1.3.  

            	
              breach
      of any representation, covenant, warranty or obligation by Charles
      River  under this Agreement;
or

            

    

    

    
      	
              10.1.4.  

            	
              negligent
      act or omission or wilful misconduct on the part of Charles River or any
      of its agents or employees in the performance of this
      Agreement;

            

    

    
      
         

      

      
        8

        
          

        

      

      
         

      

    

    

    

    
      	
              10.2.  

            	
              Subject
      to Clause 10.3, Charles River shall indemnify and hold harmless Amarin and
      its Affiliates and their respective employees, agents, officers and
      directors from and against any Claims incurred or sustained by Amarin and
      its Affiliates and their respective employees, agents, officers and
      directors arising out of or in connection with
  any:

            

    

    

    
      	
              10.2.1.  

            	
              breach
      of any representation, covenant, warranty or obligation by Charles River
      under this Agreement; or

            

    

    

    
      	
              10.2.2.  

            	
              negligent
      act or omission or wilful
      misconduct on the part of Charles River or any of its respective
      employees, agents, officers and directors in the performance of this
      Agreement;

            

    

    

    
      	
              10.3.  

            	
              The
      party seeking an indemnity shall:

            

    

    

    
      	
              10.3.1.  

            	
              fully
      and promptly notify the other party of any claim or proceedings, or
      threatened claim or proceedings;

            

    

    

    
      	
              10.3.2.  

            	
              permit
      the indemnifying party to take full control of such claim or proceedings,
      with counsel of the indemnifying party’s choice, provided that the
      indemnifying party shall reasonably and regularly consult with the
      indemnified party in relation to the progress and status of such claim or
      proceedings;

            

    

    

    
      	
              10.3.3.  

            	
              co-operate
      in the investigation and defence of such claim or proceedings;
      and

            

    

    

    
      	
              10.3.4.  

            	
              take
      all reasonable steps to mitigate any loss or liability in respect of any
      such claim or proceedings.

            

    

    

    Save as
aforesaid, neither the indemnifying party nor the party to be indemnified shall
acknowledge the validity of, compromise or otherwise settle any Claim without
the prior written consent of the other, which shall not be unreasonably
withheld.

    

    
      	
              10.4.  

            	
              NOTWITHSTANDING
      ANYTHING TO THE CONTRARY IN THIS AGREEMENT, AMARIN AND CHARLES RIVER SHALL
      NOT BE LIABLE TO THE OTHER BY REASON OF ANY REPRESENTATION OR WARRANTY,
      CONDITION OR OTHER TERM OR ANY DUTY OF COMMON LAW, OR UNDER THE EXPRESS
      TERMS OF THIS AGREEMENT, FOR ANY CONSEQUENTIAL, SPECIAL OR INCIDENTAL OR
      PUNITIVE LOSS OR DAMAGE (WHETHER FOR LOSS OF CURRENT OR FUTURE PROFITS,
      LOSS OF ENTERPRISE VALUE OR OTHERWISE) AND WHETHER OCCASIONED BY THE
      NEGLIGENCE OF THE RESPECTIVE PARTIES, THEIR EMPLOYEES OR AGENTS OR
      OTHERWISE.

            

    

    

    
      	
              10.5.  

            	
              Charles
      River’s liability under this Agreement, regardless of the form of action,
      shall not exceed the total amount paid under the Work Order under which
      such liability arises.

            

    

    

    
      	
              10.6.  

            	
              Intentionally
      omitted

            

    

    

    
      	
              10.7.  

            	
              Subject
      to Clause 10.2, in no event shall Charles River be liable for any damages
      arising from or in connection with any decision by Amarin or APIL or any
      third party to further research, develop or market the Amarin Materials or
      any derivative or product or service related thereto or the use of the
      Amarin Materials or any product or derivative or service related
      thereto.

            

    

    

    
      	
              10.8.  

            	
              Insurance

            

    

    

    
      	
              10.8.1.  

            	
              Charles
      River shall, at its own cost and expense, obtain and maintain in full
      force and effect the following insurance during the term of this
      Agreement:

            

    

    

    
      	
              (a)  

            	
              General
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to $5,000,000;

            

    

    

    
      	
              (b)  

            	
              Employers
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to $13,000,000 per
accident;

            

    

    

    
      	
              (c)  

            	
              Products
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to $5,000,000;

            

    

    
      
         

      

      
        9

        
          

        

      

      
         

      

    

    

    

    
      	
              (d)  

            	
              Professional
      Services Errors & Omissions Liability Insurance with per-occurrence
      limit of not less than an amount equivalent to
  $5,000,000.

            

    

    

    
      	
              10.8.2  

            	
              Amarin
      shall, at its own cost and expense, obtain and maintain in full force and
      effect the following insurance during the term of this
      Agreement:

            

    

    

    
      	
              (a)  

            	
              General
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to €5,000,000;

            

    

    

    
      	
              (b)  

            	
              Employers
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to €13,000,000 per
accident;

            

    

    

    
      	
              (c)  

            	
              Products
      Liability Insurance with a per-occurrence limit of not less than an amount
      equivalent to €5,500,000.

            

    

    

    
      	
              10.8.3  

            	
              Each
      party shall furnish certificates of insurance evidencing the required
      insurance policies to the other as soon as practicable after the Effective
      Date and within 30 days after renewal of such policies.  In the
      event that any of the required policies of insurance are written on a
      claims made basis, then each party shall use reasonable endeavours to
      ensure that such policies shall be maintained during the entire Term and
      for a period of not less than 3 years following the expiration or
      termination of this Agreement.  Each insurance policy that is
      required under this Agreement shall be obtained from an insurance carrier
      with an A.M. Best rating of at least A-VII.  Each party shall
      notify the other party in writing at least 30 days prior to the expiration
      or termination of such coverage.  Each party shall ensure that
      each of the required policies include a general indemnity to principal
      clause.

            

    

    

    
      	
              11.  

            	
              PUBLICATION

            

    

    

    
      	
              11.1.  

            	
              It
      is acknowledged and agreed by Charles River that publication of the
      Project Results or Project IP in whole or in part shall be within the sole
      and absolute discretion of Amarin, and that Charles River shall not
      publish or refer to any Project Results or Project IP, in whole or in
      part, without the prior expressed written consent of Amarin. Neither party
      will use the other party's name in connection with any publication or
      promotion without the other party's prior, written
  consent.

            

    

    

    
      	
              12.  

            	
              TERMINATION

            

    

    

    
      	
              12.1.  

            	
              This
      Agreement shall commence on the Effective Date and shall continue for five
      (5) years or until terminated by either party in accordance with this
      Clause 12.

            

    

    

    
      	
              12.2.  

            	
              This
      Agreement or any Work Order may be terminated without cause by Amarin at
      any time during the term of the Agreement on thirty (30) days prior
      written notice to Charles River.

            

    

    

    
      	
              12.3.  

            	
              In
      addition to the rights of termination provided for elsewhere in this
      Agreement, each party shall be entitled forthwith to terminate this
      Agreement by written notice to the others
if:

            

    

    

    
      	
              12.3.1.  

            	
              either
      party commits any material breach of any provisions of this agreement, and
      in the case of a breach capable of remedy, fails to cure the same within
      30 days after receipt of a written notice giving full particulars of the
      breach and requiring it to be cured;
or

            

    

    

    
      	
              12.3.2.  

            	
              any
      party goes into liquidation (except for the purposes of amalgamation or
      reconstruction and in such manner that the company resulting therefrom
      effectively agrees to be bound by or assume the obligations imposed on
      such party under this Agreement);
or

            

    

    

    
      	
              12.3.3.  

            	
              an
      encumbrancer takes possession or a receiver is appointed over any of the
      property or assets of the any party;
or

            

    

    

    
      	
              12.3.4.  

            	
              any
      proceedings are filed or commenced by any party under bankruptcy,
      insolvency or debtor relief laws or anything analogous to any of the
      foregoing under the laws of any jurisdiction occurs in relation to such
      party.

            

    

    
      
         

      

      
        10

        
          

        

      

      
         

      

    

    

    

    
      	
              12.3.5.  

            	
              For
      the purposes of Clause 12.3.1, a breach will be considered capable of
      being cured if the party in breach can comply with the provision in
      question in all respects other than as to time of performance (provided
      that time of performance is not of the
essence).

            

    

    

    
      	
              12.4.  

            	
              The
      written termination notice shall identify the specific Work Order or Work
      Orders that are being terminated.

            

    

    

    
      	
              12.5.  

            	
              Upon
      receipt of a termination notice from Amarin, Charles River shall cease
      performing any work not necessary for the orderly close out of the
      affected Projects or for the fulfillment of regulatory
      requirements.

            

    

    

    
      	
              12.6.  

            	
              In
      case of termination of this Agreement or any Work Order after the
      completion of a certain Work Order and before the commencement of any
      activities by Charles River for a subsequent Work Order, then Amarin shall
      not be required to make any payment to Charles River for such subsequent
      Work Order.

            

    

    

    
      	
              12.7.  

            	
              In
      the event this Agreement or a particular Work Order is terminated before
      any such Work Order is completed, Amarin shall pay Charles River for all
      Services performed in accordance with any such affected Work Order
      hereunder, and reimburse Charles River for all reasonable and necessary
      expenses to which Charles River has committed in performing those Services
      and which cannot be cancelled, as evidenced in writing by Charles River,
      together with any additional information required by
    Amarin.

            

    

    

    
      	
              12.8.  

            	
              Upon
      the termination of this Agreement or any Work Order, Charles River shall
      deliver to Amarin all data and materials provided by Amarin to Charles
      River for the conduct of Services under the terminated Work Orders, and
      Charles River shall also deliver to Amarin all Project Results and any
      other data, information and documentation produced as the result of
      Services performed by Charles River under the terminated Work Orders in
      accordance with Clause 7.10.

            

    

    

    

    
      	
              13.  

            	
              MISCELLANEOUS

            

    

    

    
      	
              13.1.  

            	
              This
      Agreement shall be governed by and construed in accordance with the laws
      of England.

            

    

    

    
      	
              13.2.  

            	
              No
      waiver of any right under this Agreement shall be deemed effective unless
      contained in a written document signed by the party charged with such
      waiver, and no waiver of any breach or failure to perform shall be deemed
      to be a waiver of any future breach or failure to perform or of any other
      right arising under this Agreement.

            

    

    

    
      	
              13.3.  

            	
              Other
      than with respect to the payment of any amounts due hereunder, neither
      party to this Agreement shall be liable for delay or failure in the
      performance of any of its obligations hereunder to the extent such delay
      or failure results from causes beyond its reasonable control, including,
      without limitation, acts of God, fires, strikes, acts of war, or
      intervention of a government authority, non-availability of raw materials,
      but any such delay or failure shall be remedied by such party as soon as
      practicable.

            

    

    

    
      	
              13.4.  

            	
              Charles
      River shall not subcontract with a third party to perform the Services
      without the prior written consent of Amarin, which consent shall not be
      unreasonably withheld. Should Charles River subcontract with any third
      party upon such written consent of Amarin, Charles River represents and
      warrants that such third-party subcontractor shall comply with all
      obligations of Charles River under this Agreement and any Work Order,
      including but not limited to, obligations of confidentiality and ownership
      rights of the Project Results and Project IP, and Charles River shall
      remain fully liable for its and such third party’s performance of the
      Services and the obligations of Charles River
  hereunder.

            

    

    

    
      	
              13.5.  

            	
              Amarin
      may assign this Agreement to an Affiliate or a third party without the
      consent of Charles River.  Charles River shall not be entitled
      to assign this Agreement.

            

    

    

    
      	
              13.6.  

            	
              Nothing
      contained in this Agreement is intended or is to be construed to
      constitute Charles River and Amarin as partners or members of a joint
      venture.  None of the parties hereto shall have
    any

            

    

    
      
         

      

      
        11

        
          

        

      

      
         

      

    

     

                 
express or implied right or authority to assume or create any obligations on
behalf of or in the name of the other parties or to bind the other parties to
any contract, agreement or undertaking with any third party.

    

    
      	
              13.7.  

            	
              No
      amendment, modification or addition hereto shall be effective or binding
      on any party unless set forth in writing and executed by a duly authorised
      representative of each of the
parties.

            

    

    

    
      	
              13.8.  

            	
              Any
      notice to be given under this Agreement shall be sent in writing in
      English by overnight courier, registered airmail or telecopied
      to:

            

    

    

    
      	
              If
      to Amarin OR
      APIL:

            	
              Trevor
      Wyeth

            
	 
      	
              Amarin
      Neuroscience Ltd

            
	 
      	
              1st
      Floor

            
	 
      	
              Magdalen
      Centre North

            
	 
      	
              The
      Oxford Science Park

            
	 
      	
              Oxford

            
	 
      	
              O4
      4GA

            
	 
      	 
      
	 
      	
              Tel:      +44
      (0)1865 784210

            
	 
      	
              Fax:     +44
      (0)1865 784213

            
	
              Email:tervor.wyeth@amarincorp.com

            	 
      
	 
      	 
      
	
              If
      to CHARLES
      RIVER:

            	
              to
      the address set forth on Exhibit A

            

    

    

    
      	
              13.8.1.  

            	
              or
      to such other address(es) and telecopier numbers as may from time to time
      be notified by any of the parties to the others
  hereunder.

            

    

    

    
      	
              13.8.2.  

            	
              Any
      notice sent by overnight courier, registered mail or telecopier shall be
      deemed to have been delivered upon receipt by the
    addressee.

            

    

    

    
      	
              13.9.  

            	
              If
      any provision in this Agreement is agreed by the parties to be, or is
      deemed to be, or becomes invalid, illegal, void or unenforceable under any
      law that is applicable hereto:

            

    

    

    
      	
              13.9.1.  

            	
              such
      provision will be deemed amended to conform to applicable laws so as to be
      valid and enforceable or, if it cannot be so amended without materially
      altering the intention of the parties, it will be deleted, with effect
      from the date of such agreement or such earlier date as the parties may
      agree; and

            

    

    

    
      	
              13.9.2.  

            	
              the
      validity, legality and enforceability of the remaining provisions of this
      Agreement shall not be impaired or affected in any
  way.

            

    

    

    
      	
              13.10.  

            	
              This
      Agreement sets forth all of the agreements and understandings between the
      parties with respect to the subject matter hereof, and supersedes and
      terminates all prior agreements and understandings between the parties
      with respect to the subject matter
hereof.

            

    

    
      	
               
      

            	 

    

    
      	
              13.11.  

            	
              At
      the request of any of the party, the other parties shall (and shall use
      reasonable efforts to procure that any other necessary third parties
      shall) execute and do all such documents, acts and things as may
      reasonably be required subsequent to the signing of this Agreement for
      assuring to or vesting in the requesting party the full benefit of the
      terms hereof.

            

    

    

    
      	
              13.12.  

            	
              The
      provisions of Clauses 3.3, 4, 6, 7, 8, 9, 10, 11, 13.1, 13.11, 13.13, 15
      and this Clause 13.12 shall survive the termination of this Agreement or
      any Work Order.

            

    

    

    
      	
              13.13.  

            	
              A
      person who is not a party to this Agreement has no right under the
      Contracts (Rights of Third parties) Act 1999 to enforce any term of this
      Agreement, but this does not affect any right or remedy of a third party
      which exists or is available apart from that
  Act.

            

    

     

    
      	
              14.  

            	
              Employee
      Solicitation.  Amarin agrees that, during the term of a
      Work Order and for a period of one hundred eighty (180) days thereafter,
      Amarin will not solicit for hire or hire as an employee, or engage as an
      independent contractor, any employee of Charles River who has been
      involved in rendering services on the Services, without the prior written
      consent of Charles River. In the event of such solicitation, hiring or
      engagement, in addition to any other remedy Charles River may have, Amarin
      shall pay to Charles River an amount equal to such employee’s annual
      salary.

            

    

     

    
      
         

      

      
        12

        
          

        

      

      
         

      

    

    

     

    
      	
              15.  

            	
              Dispute
      Resolution.

            

    

     

    
      	
              15.1.  

            	
              Any
      controversy, claim or dispute arising out of this Agreement shall first be
      submitted in writing by both parties to the Chief Executive Officer of
      Amarin and the Chief Executive Officer of Charles River for resolution,
      who may call on others to advise them as they see
  fit.

            

    

     

    
      	
              15.2.  

            	
              If
      they fail to resolve the dispute within twenty-eight (28) days of such
      submission, any such dispute shall be finally settled by arbitration in
      London, United Kingdom, in accordance with the rules of the International
      Chamber of Commerce (ICC) then in effect, by
      three (3) commercial arbitrators with substantial experience in the
      pharmaceutical field.

            

    

     

    
      	
              15.3.  

            	
              Each
      party shall appoint one arbitrator who at their turn shall nominate the
      chairperson, who shall be qualified in English law.  If a Party
      does not appoint its arbitrator within fifteen (15) days following the
      expiry of the twenty-eight (28) day period, then such arbitrator shall be
      selected on an expedited basis in accordance with the rules of the
      ICC.  Any arbitrator so selected shall have substantial
      experience in the pharmaceutical
industry.

            

    

     

    
      	
              15.4.  

            	
              The
      arbitrators shall have the authority to allocate between the parties the
      costs of arbitration (including service fees, arbitrator fees and all
      other fees related to the arbitration) in such equitable manner as the
      arbitrators may determine.

            

    

     

    
      	
              15.5.  

            	
              The
      scope of the authority of the arbitrators is limited to the strict
      application of law.

            

    

     

    
      	
              15.6.  

            	
              The
      parties shall make sure that, except as may be otherwise required by law,
      its witnesses or the arbitrators will not disclose the existence, content
      or results of the arbitration hereunder without the prior written consent
      of the other party.

            

    

     

    
      	
              15.7.  

            	
              The
      prevailing party in the arbitration shall be entitled to receive
      reimbursement of its reasonable expenses (including reasonable attorneys’
      fees, expert witness fees and all other expenses) incurred in connection
      therewith.

            

    

     

    
      	
              15.8.  

            	
              Judgment
      upon the award so rendered may be entered in a court having jurisdiction
      or application may be made to such court for judicial acceptance of any
      award and an order of enforcement, as the case may
  be.

            

    

     

    

     

    
      
         

      

      
        13

        
          

        

      

      
         

      

    

    

    IN WITNESS WHEREOF, the
parties hereto have executed this Agreement.

    

    

    

    SIGNED

    

    for and
on behalf of

    AMARIN
NEUROSCIENCE LIMITED

    

    DATE:

    

    

    

    

    

    

    

    SIGNED

    

    for and
on behalf of

    AMARIN
PHARMACEUTICALS IRELAND LIMITED

    

    DATE:

    

    

    

    

    

    SIGNED

    

    for and
on behalf of

    CHARLES
RIVER LABORATORIES PRECLINICAL SERVICES EDINBURGH LIMITED

    

    DATE:

    

    
      
         

      

      
        14

        
          

        

      

      
         

      

    

    APPENDIX
1

    

    WORK
ORDER

    

    This
WORK ORDER dated as of
the date of last signature below

    

    BETWEEN

    

    
      	
              (1)  

            	
              AMARIN NEUROSCIENCE LTD
      of 1st
      Floor, Magdalen Centre North, The Oxford Science Park, Oxford, OX4 4GA
      (“Amarin”)

            

    

    

    
      	
              (2)  

            	
              AMARIN PHARMACEUTICALS IRELAND
      LIMITED having its principal place of business at First Floor,
      Block 3, The Oval, Shelbourne Road, Ballsbridge, Dublin 4, Ireland (“APIL”)

            

    

    

    
      	
              (3)  

            	
              CHARLES RIVER LABORATORIES
      PRECLINICAL SERVICES EDINBURGH LIMITED having its principal place
      of business at Elphinstone Research Centre, Tranent, Edinburgh, EH33 2NE,
      UK ("Charles River
      ")

            

    

    

    WHEREAS

    

    
      	
              A

            	
              Amarin,
      APIL and Charles River are bound by the terms of the Master Services
      Agreement dated XXXX 2007 between Amarin and Charles River (the "Master Services
      Agreement").

            

    

    

    
      B             
The terms and conditions of the Master Services Agreement govern this Project
Work Order in respect to the following project, [ insert description of
project] (the “Project”), with the following
additional provisions applying:

    

    

    

    Schedule
1   Project Protocol

    Schedule
2   Timelines

    Schedule
3   Budget and Payment Schedule

    Schedule
4:  Budget Breakdown

    

    

    This Work
Order has an Effective Date as of the last date of signature and will remain
valid until completion of Services described herein and when Amarin has paid the
final invoice in accordance with the terms of the Master Services
Agreement.

    

    AGREED AND ACCEPTED by the
parties:

    

    

    For and
on behalf of Amarin
Neuroscience Ltd

    

    
      	
              Signed:
      ...................................................

            	
              Date:
      ..............................................

            
	 
      	 
      
	
              Name:  ....................................................

            	
              Position:
      .........................................

            

    

    

    

    

    For and
on behalf of Amarin
Pharmaceuticals Ireland Limited

    

    

    
      	
              Signed:
      ...................................................

            	
              Date:
      ..............................................

            
	 
      	 
      
	
              Name:  ....................................................

            	
              Position:
      .........................................

            

    

    

    

    

    for and
on behalf of Charles River Laboratories
Preclinical Services Edinburgh Limited.

    

    
      	
              Signed:
      ....................................................

            	
              Date:
      ................................................

            
	 
      	 
      
	
              Name:
      .....................................................

            	
              Position:
      ..........................................

            

    

    
      
         

      

      
        15

        
          

        

      

      
         

      

    

     

    

     

     

    SCHEDULE 1-: PROJECT
PROTOCOL

     

    

    

    
      
         

      

      
        16

        
          

        

      

      
         

      

    

     

    SCHEDULE 2-:
TIMELINES

     

    

    [Insert
details]

    

    
      	
              Critical
      Milestones

            	
              Estimated
      Date

            
	 
      	 
      
	 
      	 
      
	 
      	 
      
	 
      	 
      
	 
      	 
      
	 
      	 
      

    

    

     

    

     

    
      
         

      

      
        17

        
          

        

      

      
         

      

    

     SCHEDULE 3: BUDGET AND
PAYMENT SCHEDULE

    

    
      	
              ·  

            	
              All
      invoices will be issued in Pound Sterling and are to be paid in Pound
      Sterling.

            

    

    

    
      	
              ·  

            	
              The
      total cost for the Services detailed in this Work Order is
      [    ] and the total estimated related expenses have
      been detailed in Schedule 4.

            

    

    

    
      	
              ·  

            	
              The
      authorised Amarin contact shall be Trevor Wyeth. The authorised Charles
      River contact for this work shall be
      [          ].

            

    

    

    
      	
              ·  

            	
              All
      invoices will state the Amarin protocol number, activity performed,
      purchase order number (if available), contact name and will be submitted
      to the following address:

            

    

    

    Amarin
Neurosciences Ltd

    1st
Floor

    Magdalen
Centre North

    The
Oxford Science Park

    Oxford

    OX4
4GA

    

    With a
copy sent to:

    

    Amarin
Pharmaceuticals Ireland Limited

    1st
Floor, Block 3

    The
Oval

    Shelbourne
Road

    Ballsbridge

    Dublin
4

    Ireland

    

    

    

    Payment
Schedule

    

    To be
agreed, inserted

    

    

    
      
         

      

      
        18

        
          

        

      

      
         

      

    

     

    SCHEDULE
4:  BUDGET BREAKDOWN

    

    The
budget breakdown is detailed below:

    

    
      	
              Description

            	
              Unit
      
Description

            	
              Total
      
Units

            	
               Unit
      
Cost

            	
              Budget

              Total

              (£)

            
	 
      	 
      	 
      	 
      	 
      
	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	 
      	 
      	 
      	 
      	 
      
	
              Grand
      Total

            	 
      	 
      	 
      	 
      

    

    

     

    

     

    Expenses –
Estimates

    

    [to
be inserted]

    

    
      
         

      

      
        19

        
          

        

      

      
         

      

    

     

    APPENDIX
2

     

    

     

    CHANGE
ORDER

     

    

    
      	
              Amarin

            	 
      
	
              Amarin
      Contact

            	 
      

    

    

    
      	
              Charles
      River

            	 
      
	
              Charles
      River Contact

            	 
      

    

    

    
      	
              Amarin
      Project Reference:

            	 
      
	 
      	 
      

    

    

    
      	
              MSA
      Date:

            	
              DD
      MMM YYYY

            
	
              Work
      Order Date:

            	
              DD
      MMM YYYY

            

    

    

    
      	
              Date
      Change Requested:

            	
              DD
      MMM YYYY

            
	
              Date
      to Implement Change:

            	
              DD
      MMM YYYY

            

    

    

    
      	
              Original
      Contract
      Value                                                                                                                                                                                  £

            
	
              Change
      History

            	
              Change
      Value

            
	 
      	
              [insert
      details of changes to Project Protocol, budget, timelines, payment
      schedule]

               

            

    

    

    Amarin
authorizes Charles River to begin work
immediately following execution of this Change Order.

    

    Except as
expressly set forth in this Change Order, all other terms and conditions of the
Master Services Agreement remain the same.

    

    
      	
              For
      and on behalf of

              Amarin
      Neuroscience Ltd

               

               

              Signature:

              Name:

              Title:

              Date:

            	
              For
      and on behalf of

              Charles
      River Laboratories Preclinical Services Edinburgh Limited

               

               

              Signature:

              Name:

              Title:

              Date:

            
	
              For
      and on behalf of

              Amarin
      Pharmaceuticals Ireland Limited

               

               

              Signature:

              Name:

              Title:

              Date:

            	 
      

    

    

    
      
         

      

      
        20

        
          

        

      

      
         

      

    

    APPENDIX
3

    

     

    Charles
River Archive Terms and Conditions

     

    

    
      	
              1.  

            	
              All
      raw data, study documentation, protocols, interim and final reports,
      specimens generated as a result of a preclinical Study or case histories
      generated as a result of a clinical Study  that the Sponsor
      requests be held in Company’s archive facility or that Applicable Law
      requires  be held in Company’s archive facility shall
      hereinafter be referred to as “Materials”.  Company agrees to
      comply with industry standards in connection with the storage of the
      Materials and adhere to all Applicable Law with respect to the storage of
      the Materials.

            

    

     

    
      	
              2.  

            	
              Company
      shall store the Materials at its current storage rates, which may be
      increased on an annual basis.  If the Materials require
      additional and/or special storage requirements, additional charges for
      storage shall be assessed and invoiced to Sponsor.  Invoices
      shall be due and payable ten (10) days from the date of the invoice and
      Sponsor agrees to pay all invoices
submitted.

            

    

     

    
      	
              3.  

            	
              Company’s
      liability for archival services under this Agreement, regardless of the
      form of action, shall not exceed the fee paid for one year’s storage of
      the Materials.  In no event shall Company be liable for
      penalties or liquidated damages or for special, indirect, consequential
      punitive, exemplary or incidental damages of any type or kind (including,
      without limitation, lost profits) in connection with the storage of the
      Materials.  Company shall have no liability for loss of
      specimens or information beyond its reasonable control, including losses
      caused by loss of refrigeration.

            

    

     

    
      	
              4.  

            	
              The
      Materials shall be archived for the period set forth in the Supporting
      Documents (the “Retention Period”).  Upon the expiration of the
      Retention Period, Company shall contact Sponsor to determine disposition
      of the Materials as follows: (a) extended storage of the Materials; (b)
      return of the Materials to Sponsor at Sponsor’s expense to be archived in
      accordance with Applicable Law or (c) disposal of Materials at Sponsor’s
      expense.  If Sponsor requests Company to continue to store the
      Materials and Company agrees, the cost for storage of the Materials shall
      continue to be invoiced to Sponsor at Company’s then current
      rates.  If Sponsor fails to give such instructions, Company
      shall so notify Sponsor, and if such instructions are still not
      forthcoming within thirty (30) days of said notification, then Company
      shall have the option of (i) continuing storage of the Materials, which
      will be deemed to have been authorized for an additional period of not
      less than one (1) year, or (b) Company may return the Materials to Sponsor
      at Sponsor’s expense or (c) dispose of the Materials at Company’s expense
      provided regulatory retention periods have expired.  Sponsor
      shall be liable for storage charges until the Materials are returned to
      Sponsor.  At any time while the Materials are in transit to
      Sponsor, all risk of loss or exposure to the Materials shall be borne by
      Sponsor.

            

    

    

    
      	
              5.  

            	
              Company
      will not release the Materials to any third party, without Sponsor's
      written permission unless such disclosure is compelled by valid subpoena
      or Applicable Law.  If such disclosure is requested, Company
      shall use its commercially reasonable efforts to provide Sponsor with
      written notice prior to such release.  Prior to release or
      inspection of any Materials by Sponsor or its agents, Sponsor shall
      provide all reasonable documentation requested by
  Company.

            

    

     

    

     

     

     

    21ex4_84.htm

    Exhibit
4.84

     

    AMR101:  14
Day Dose Range Finding Toxicity Study in Dogs by Oral Gavage Administration
515147

     

    “Companies”

     

    APPENDIX
1

     

    WORK
ORDER

     

    This
WORK ORDER dated as of
the date of last signature below

     

    BETWEEN

     

    
      	
              (1)

            	
              AMARIN NEUROSCIENCE LTD
      of 1st Floor, Magdalen Centre North, The Oxford Science Park Oxford,
      OX44GA(“Amarin”)

            

    

     

    
      	
              (2)

            	
              AMARIN PHARMACEUTICALS IRELAND
      LIMITED having its principal place of business at First Floor,
      Block 3, The Oval, Shelbourne Road, Ballsbridge, Dublin 4, Ireland (“APIL”)

            

    

     

    
      	
              (3)

            	
              CHARLES RIVER LABORATORIES
      PRECLINICAL SERVICES EDINBURGH LIMITED having its principal place
      of business at Elphinstone Research Centre, Tranent, Edinburgh, EH33 2NE,
      UK (“Charles
      River”)

            

    

     

    WHEREAS

     

    
      	
              A

            	
              Amarin,
      APIL and Charles River are bound by the terms of the Master Services
      Agreement dated 25 August 2008 between Amarin and Charles River (the
      “Master Services
      Agreement”)

            

    

     

    
      	
              B

            	
              The
      terms and conditions of the Master Services Agreement govern this Project Work
      Order in respect to the following project:  [AMR101:  14 Day Dose
      Range Finding Toxicity Study in Dogs by Oral Gavage Administration]
      (the “Project”),
      with the following additional provisions
  applying:

            

    

    
 

    
      
        	
                Schedule
      1

              	
                Project
      Protocol

              
	
                Schedule
      2

              	
                Timelines

              
	
                Schedule
      3

              	
                Budget
      and Payment Schedule

              
	
                Schedule
      4

              	
                Budget
      Breakdown

              

      

This Work
Order has an Effective Date as of the last date of signature and will remain
valid until completion of Services described herein and when Amarin has paid the
final invoice in accordance with the terms of the Master Services
Agreement.

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    AGREED AND ACCEPTED by the
parties

     

    

      For and
on behalf of Amarin
Neuroscience Ltd

       

      
        	
                Signed
      ________________________________

              	
                Date
      ___________________________

              
	 
      	 
      
	
                Name   ________________________________

              	
                Position 
      ________________________

              

      

      

      For and
on behalf of Amarin
Pharmaceuticals Ireland Limited

      
         

        
          	
                  Signed
      ________________________________

                	
                  Date
      ___________________________

                
	 
      	 
      
	
                  Name   ________________________________

                	
                  Position 
      ________________________

                

        

        
For and
on behalf of Charles River
Laboratories Preclinical Services Edinburgh Limited

      

      
         

        
          	
                  Signed
      ________________________________

                	
                  Date
      ___________________________

                
	 
      	 
      
	
                  Name   ________________________________

                	
                  Position 
      ________________________

                

        

        

      

       

    
      
         

      

      
        -2-

        
          

        

      

      
         

      

    

    SCHEDULE
1:  PROJECT PROTOCOL

     

    AMR101:  14
Day Dose Range Finding

    Toxicity
Study In Dogs by Oral Gavage Administration

    Charles
River Study Number 515147

    
      
         

      

      
        -3-

        
          

        

      

      
         

      

    

    SCHEDULE
2.:  TIMELINES

     

    
      	
              Animal
      Arrival (Stock):

            	
              10
      April 2008

            
	 	 
	
              First
      day of dosing (Day 1):

            	
              16
      September 2008

            
	 	 
	
              Last
      day of dosing (Day 14):

            	
              29
      September 2008

            
	 	 
	
              Terminal
      necropsies (Day 15):

            	
              30
      September 2008

            
	 	 
	
              Completion
      of Experimental Work:

            	
              30
      September 2008

            
	 	 
	
              Non-QA
      Draft Report:

            	
              21
      November

            

    

    

    
      
         

      

      
        -4-

        
          

        

      

      
         

      

    

    SCHEDULE
3:  BUDGET AND PAYMENT SCHEDULE

     

    
      	
              ·  

            	
              All
      invoices will be issued in Pound Sterling and are to be paid in Pound
      Sterling.

            

    

     

    
      	
              ·  

            	
              The
      total cost far the Services detailed In this Work Order is £26,000 and the
      total estimated related expanses have been detailed in Schedule
      4.

            

    

     

    
      	
              ·  

            	
              The
      authorised Amarin contact shall be Trevor
Wyeth.

            

    

     

    
      	
              ·  

            	
              The
      authorised Charles River contact for this work shall be Catherine
      Nichols.

            

    

     

    
      	
              ·  

            	
              All
      invoices will state the Amarin protocol number, activity performed,
      purchase order number (if available), contact name and will be submitted
      to the following address:

            

    

     

    

      
        	
                Amarin
      Neurosciences Ltd

                 

                1st
      Floor

                Magdalen
      Centre North

                The
      Oxford Science Park

                Oxford

                OX4
      4GA

                 

                With
      a copy sent to:

                 

                Amarain
      Pharmaceuticals Ireland Limited

                1st
      Floor, Block 3

                The
      Oval

                Shelbourne
      Road

                Ballsbridge

                Dublin
      4

                Ireland

              

      

    Payment
Schedule

     

    
      	
              Signature
      of Contract:

            	
              30%
      of Budget - £7,800

            
	
              Start
      of Experimental Work:

            	
              40%
      of Budget - £10,400

            
	
              Completion
      of Experimental Work:

            	
              20%
      of Budget - £5,200

            
	
              Unaudited
      Drafted Report:

            	
              10%
      of Budget - £2,600

            

    

    

    
      
         

      

      
        -5-

        
          

        

      

      
         

      

    

    SCHEDULE
4:  BUDGET BREAKDOWN

     

    The
budget breakdown is detailed below:

     

    
      	
              Purchase
      and Pretrial housing of Animals

            	
              3,000

            
	 	 
	
              Study
      Management & Reporting

            	
              12,300

            
	 	 
	
              Formulation,
      including test item receipt

            	
              1,000

            
	 	 
	
              Housing,
      Dosing and animal room data collection

            	
              4,000

            
	 	 
	
              Necropsy

            	
              1,700

            
	 	 
	
              Clinical
      Pathology

            	
              4,000

            
	 	 
	
              Grand
      Total

            	
              26,000

            

    

    

     

    Expenses –
Estimates

     

    (to
be inserted)

    

     

     

     

    -6-

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00164-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00164-of-00352.parquet"}]]