ex4_88.htm


    EXHIBIT
4.88

    


    


    


    DATED:
May 25th,
2009

    


    


    
      	
              AMARIN
      CORPORATION, PLC

               

               

              ESTER
      NEUROSCIENCES LTD.

               

               

              MEDICA
      II MANAGEMENT L.P.

              (AS
      THE SELLERS’ REPRESENTATIVE)

               

               

               

               

            


    

    
      


      AMENDMENT
AND WAIVER AGREEMENT

    

    


    


    


    


    


    


    


    


    


    


    


    


    


    


    


    


    


    


    


    Certain
portions of this Exhibit have been omitted pursuant to a request for
“Confidential Treatment” under Rule 24b-2 of the Securities and Exchange
Commission.  Such portions have been redacted and bracketed in the
request and appear as [*] in the text of this Exhibit.  The omitted
confidential information has been filed with the Securities and Exchange
Commission.

    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    THIS AMENDMENT AND WAIVER AGREEMENT dated as of May
25th,
2009 (this “Agreement”)

     

    AMONG:

     

    
      	
              (1)  

            	
              AMARIN CORPORATION, PLC,
      a public limited company incorporated under the laws of England and Wales
      (the “Buyer”);

            


    

     

    
      
        	
                (2)  

              	
                ESTER NEUROSCIENCES LTD., an
      Israeli company (the “Company”);
      and

              

        

    

    
      	
              (3)  

            	
              MEDICA II MANAGEMENT
      L.P., a Cayman Islands limited partnership, in its capacity as the
      Sellers’ Representative appointed pursuant to Section 13 of that certain
      Stock Purchase Agreement dated December 5, 2007 between Buyer, the
      Security Holders (each a “Seller” and collectively
      the “Sellers”) of
      the Company, the Company, and
      the Sellers' Representative.

            


    

     

    


     

    RECITALS:

     

    
      	
              A.  

            	
              The
      Buyer, the Sellers, the Company and
      the Sellers' Representative entered into a Stock Purchase Agreement dated
      December 5, 2007, as subsequently amended by Amendment No. 1 (“Amendment No.
      1”)  to Stock Purchase Agreement dated April 7, 2008
      (together the “SPA”).

            


    

     

    
      	
              B.  

            	
              The
      Buyer is continuing various activities to conclude its auditing and
      reporting of the Phase IIa Clinical
Study.

            


    

     

    
      	
              C.  

            	
              The
      Buyer announced in September 2008 that following a change in strategic
      direction, the Buyer would seek partnerships for its CNS pipeline,
      including Monarsen in MG.  At the date of this Agreement, the
      Buyer does not intend to conduct any new development work on Monarsen but
      intends to seek to enter into an agreement with a third party partner
      whereby such third party partner would conduct any such development work
      in the future.

            


    

     

    
      	
              D.  

            	
              The
      parties hereto acknowledge that it is necessary to agree a number of
      amendments to, and waivers under, the SPA to reflect the circumstances
      described in Recitals C and E and to facilitate the Buyer’s intention to
      seek a future partnership for Monarsen in
MG.

            


    

     

    
      	
              E.  

            	
              The
      Buyer has agreed to make a settlement payment to the Sellers in the form
      of Buyer Ordinary Shares and to amend certain provisions of the SPA
      relating to the Escrow Fund in consideration of the Sellers’
      Representative and each of the Sellers agreeing to the amendments and
      waivers referred to herein and to terminate and extinguish any obligations
      of the Buyer to pay the Milestone Ia Consideration to the Sellers pursuant
      to the SPA (all of the foregoing as set forth in detail under Section
      2).

            


    

     

    
      	
              F. 
      

            	
              The
      parties hereto have also agreed certain terms which supplement the SPA and
      which are also set forth in this
Agreement.

            


    

     

    


     

    IN
CONSIDERATION OF THE MUTUAL COVENANTS CONTAINED HEREIN, AND OTHER GOOD AND
VALUABLE CONSIDERATION, THE RECEIPT AND ADEQUACY OF WHICH ARE HEREBY
ACKNOWLEDGED, IT IS HEREBY AGREED AS FOLLOWS:

     

    


     

    
      	
              1

            	
              DEFINITIONS / REPRESENTATIONS AND
      WARRANTIES

            


    

    


    
      	
              1.1

            	
              Definitions:

            


    

    


    All
capitalized terms used in this Agreement, and not otherwise defined herein,
shall have the meanings ascribed to them in the SPA.


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    “Accelerated Payment” has the
meaning set forth in Section 3.4.3.

    


    “Accelerated Payment Allocation
Schedule” means the schedule to be prepared by the Sellers’
Representative and submitted to the Buyer prior to the payment of any
Accelerated Payment setting forth the allocation of the Accelerated Payment to
the Sellers.

    


    “Actual Milestone II
Consideration” has the meaning set forth in Section 3.4.2.

    


    “Additional Milestone II
Consideration” has the meaning set forth in Section 3.3.3.

    


    “Effective Date” has the
meaning set forth in Section 2.1.1.

     

    “MG Field” means the treatment
of MG in humans.

     

    “MG Phase II Third Party Partner
Consideration” means any Third Party Partner Consideration received by
the Buyer in respect of the grant of any MG Sub-license up to the date preceding
the completion of the MG Phase II Development Program.

     

    “MG Sub-license” means a
sub-license granted to any Person (other than an Affiliate of Buyer) to any
Company Business Intellectual Property in the MG Field.

     

    “Milestone Ib Shortfall Amount”
has the meaning set forth in Section 3.3.3.

     

    “Proposed Partnership
Agreement” has the meaning set forth in Section 3.1.3.

     

    “Reduced Milestone Ib Payment”
has the meaning set forth in Section 3.3.3.

     

    “Releasor” and “Releasee” have the meanings
set forth in Section 4.

     

    “Repayable Amount” has the
meaning set forth in Section 3.4.2.

     

    “Settlement Payment” has the
meaning set forth in Section 2.1.

     

    “Shortfall Advance Payment(s)”
has the meaning set forth in Section 3.4.2.

     

    “Shortfall Advance Payment Allocation
Schedule” means the schedule to be prepared by the Sellers’
Representative and submitted to the Buyer prior to the payment of any Shortfall
Advance Payment setting forth the allocation of the Shortfall Advance Payment to
the Sellers.

     

    “SPA Future Waiver” has the
meaning set forth in Section 2.1.4.

     

    “Termination Agreement” has the
meaning set forth in Section 3.5.

     

    “Terminated Section 12
Provisions” has the meaning set forth in Section 2.2.

     

    “Third Party Partner” has the
meaning set forth in Section 3.3.

     

    “Third Party Partner
Consideration” means all milestone and license payments in cash that the
Buyer is paid by the Third Party Partner under the Proposed Partnership
Agreement and any Non-MG Sub-license Fees and any other consideration that the
Buyer is paid as aforesaid that is not in the form of cash, the value of which
shall be determined pursuant to Section 3.4.4.

     

    “211 Month Trigger Date”, “27 Month Trigger Date”, “30 Month Trigger Date” and
“Ultimate Transfer Date” have the
meanings set forth in Section 3.5.

     

    “United States Dollar” and
“US$” and “$” means the lawful currency
of the United States of America.

     


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


     

    
      	
              1.2  

            	
              Representations and
      Warranties of Sellers’
Representative:

            


    

    


    The
Sellers’ Representative represents and warrants to the Buyer, as of the date
hereof and as of the Effective Date, that:

    


    
      	
               
      

            	
              1.2.1

            	
              the
      Sellers’ Representative continues to hold all the authorities and powers
      granted by the Sellers to the Sellers’ Representative under Section 13 of
      the SPA;

            


    

    


    
      	
              1.2.2  

            	
              the
      Sellers’ Representative has full authority and power to enter into this
      Agreement on behalf of each Seller and has all necessary authority and
      power to bind each Seller to each of the provisions of this
      Agreement;

            


    

    


    
      	
              1.2.3  

            	
              all
      necessary corporate, shareholder and other legal action has been taken by
      the Sellers’ Representative to authorize the execution, delivery and
      performance by it of this Agreement.  The Sellers’
      Representative has duly executed and delivered this Agreement. This
      Agreement is the legal, valid and binding obligation of the Sellers’
      Representative, enforceable against it in accordance with its respective
      terms, except as enforceability of such objections may be limited by
      bankruptcy, insolvency, reorganization, moratorium and other similar laws
      now or hereafter in effect relating to or limiting creditors’ rights
      generally and general principles of equity relating to the availability of
      specific performance and injunctive and other forms of equitable
      relief;

            


    

    


    
      	
               
      

            	
              1.2.4

            	
              the
      Sellers’ Representative will execute this Agreement in its capacity as the
      Sellers’ Representative and, based on its authority as such, as agent and
      attorney-in-fact of each Seller (so appointed under Section 13 of the
      SPA); and

            


    

    


    
      	
               
      

            	
              1.2.5

            	
              the
      Sellers’ Representative acknowledges that the Buyer is entering into this
      Agreement with each of the Sellers in reliance on the provisions of
      Section 13 of the SPA (including, without limitation, Section 13(g) of the
      SPA) and the representations and warranties of the Sellers’ Representative
      set forth in this Section 1.2.

            


    

    


    
      	
              1.3

            	
              Representations
      and Warranties of Buyer:

            


    

    


    Buyer
represents and warrants to the Sellers' Representative and to each Seller, as of
the date hereof and as of the Effective Date, that:

    


    
      	
               
      

            	
              1.3.1

            	
              Organization
      and Good Standing:  The Buyer
      has been duly incorporated and is validly existing as a public limited
      company under the laws of England and Wales and has all necessary
      corporate power and authority to perform all of its obligations under this
      Agreement.

            


    

    
      	
               
      

            	 


    

    
      	
               
      

            	
              1.3.2

            	
              Power
      and Authorization:  The
      Buyer has all requisite power and authority to execute and deliver this
      Agreement, to perform its obligations hereunder and to carry out the
      transactions contemplated hereby. All necessary corporate, shareholder and
      other legal action has been taken by the Buyer to authorize the execution,
      delivery and performance by it of this Agreement.  The Buyer has
      duly executed and delivered this Agreement. This Agreement is the legal,
      valid and binding obligation of the Buyer, enforceable against it in
      accordance with its respective terms, except as enforceability of such
      objections may be limited by bankruptcy, insolvency, reorganization,
      moratorium and other similar laws now or hereafter in effect relating to
      or limiting creditors’ rights generally and general principles of equity
      relating to the availability of specific performance and injunctive and
      other forms of equitable relief.

            


    

    


    
      	
               
      

            	
              1.3.3

            	
              Buyer
      Ordinary Shares:  As of the Effective Date, subject to
      Section 2.1.1, upon issuance and delivery of the Buyer Ordinary Shares
      comprising the Settlement Payment: (a) such Buyer Ordinary Shares will
      have been duly authorized and validly issued and will be fully paid and
      non-assessable, will have been issued in compliance with all applicable
      English laws and the ADSs representing Amarin Shares will have been issued
      in compliance with all applicable U.S. securities laws, and will not have
      been issued in violation of any preemptive right, resale right, right of
      first refusal or similar right, (b) such delivery will convey to the
      Sellers good, valid and

            


    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    marketable
title to such Buyer Ordinary Shares, free and clear of any Encumbrances (other
than applicable securities laws), and subject to Section 9.6 of the SPA, the
Buyer will have complied with all applicable rules in connection with the
issuance of freely tradeable Buyer Ordinary Shares on Nasdaq.

    


    
      	
              1.4

            	
              Representations
      and Warranties of each
Seller:

            


    

    


    Each
Seller represents and warrants to the Buyer, severally, as of the date hereof
and as of the Effective Date that:

    


    
      	
               
      

            	
              1.4.1

            	
              Organization
      and Good Standing:  Such Seller
      is duly organized, validly existing and in good standing under the laws of
      its jurisdiction of incorporation, formation or organization, as
      applicable, and has (as applicable) all necessary corporate, partnership
      or limited liability company power and authority, as the case may be, to
      perform all of its obligations under this
  Agreement.

            


    

    


    
      	
               
      

            	
              1.4.2

            	
              Power
      and Authorization:  Such Seller
      has all legal right, power, authority and legal capacity to execute and
      deliver this Agreement, to perform its obligations hereunder and to carry
      out the transactions contemplated
hereby.

            


    

    


    
      	
               
      

            	
              1.4.3

            	
              Status
      of Shareholder:  Such
      Seller is not a “U.S. Person” as defined by Rule 902 of Regulation S
      promulgated under the Securities Act, was not formed (if an entity) by a
      “U.S. Person” as defined by United States jurisdiction, and was not formed
      (if an entity) for the purpose of investing in securities not registered
      under the Securities Act.  Such Seller is not acquiring the
      Buyer Ordinary Shares for the benefit of a “U.S. Person” as defined by
      Rule 902 of Regulation S.  Such Seller is outside the United
      States.  Such Seller acknowledges, agrees and covenants that it
      will not engage in hedging transactions with regard to Buyer Ordinary
      Shares prior to the expiration of the distribution compliance period
      specified in Rule 903 of Regulation S promulgated under the Securities
      Act, unless in compliance with the Securities Act.  Absent
      another exemption from registration, such Seller will not resell Buyer
      Ordinary Shares to “U.S. Persons” or within the United States, unless
      pursuant to registration of such Buyer Ordinary Shares under the
      Securities Act.

            


    

    


    
      	
               
      

            	
              1.4.4

            	
              Reliance
      Upon Seller’s Representations:  Such
      Seller understands that the issuance and sale thereto of Buyer Ordinary
      Shares will not be registered under the Securities Act on the ground that
      such issuance and sale will be exempt from registration under the
      Securities Act pursuant to Regulation S promulgated under the Securities
      Act and that Buyer’s reliance on such exemption is based on each Seller’s
      representations set forth herein.

            


    

    


    
      	
               
      

            	
              1.4.5

            	
              Receipt
      of Information:  Such
      Seller has had an opportunity to ask questions and receive answers from
      Buyer regarding the terms and conditions of the issuance and sale of the
      Buyer Securities and the business, properties, prospects and financial
      condition of Buyer and to obtain any additional information requested, and
      has received and considered all information such Seller deems relevant to
      make an informed decision to purchase Buyer Securities.  Neither
      such inquiries nor any other investigation conducted by or on behalf of
      such Seller or its representatives or counsel shall modify, amend or
      affect such Seller’s right to rely the Buyer’s representations and
      warranties contained in this
Agreement.

            


    

    


    
      	
               
      

            	
              1.4.6

            	
              Restricted
      Securities:  Such
      Seller understands that the Buyer Ordinary Shares have not been registered
      under the Securities Act and such Seller will not sell, offer to sell,
      assign, pledge, hypothecate or otherwise transfer any of the Buyer
      Ordinary Shares during the 40 days following the Effective
      Date.  Such Seller agrees that Buyer may place stop transfer
      orders with Citibank N.A. (the “Transfer
      Agent”) (or any other transfer agent) with respect to the Buyer
      Ordinary Shares in order to implement the restrictions on transfer set
      forth in this Agreement.

            


    

    


    
      	
               
      

            	
              1.4.7

            	
              Independent
      Investment:  Such
      Seller acknowledges that it is aware of its obligations as a beneficial
      owner of Buyer Ordinary Shares pursuant to Section 12(d) of the Exchange
      Act.

            


    

    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    
      	
              1.5

            	
              No
      other Representations
      and Warranties:

            


    

    


    Each of
the parties hereto acknowledges that it has not made any representation or
warranty to any other party hereto, express or implied, as to the matters set
forth in this Agreement, or any matter related thereto, except as specifically
and explicitly set forth in this Agreement.

    


    


    
      	
              2

            	
              SETTLEMENT PAYMENT / RELEASE OF
      ESCROW FUND

            


    

    


    
      	
              2.1

            	
              The
      Buyer has agreed with the Sellers’ Representative and the Sellers to make
      a settlement payment (the “Settlement Payment”) to
      the Tax Trustee for the Sellers in the form of 1,315,789 Buyer Ordinary
      Shares in consideration of the agreement of the Sellers’ Representative
      and of each Seller to the amendment, termination and waiver of certain
      provisions of the SPA (as set forth in this Agreement) and subject to the
      following additional terms:

            


    

    


    
      	
               
      

            	
              2.1.1

            	
              as
      soon as practicable following the date hereof, taking into account the
      then relevant issues arising under U.S. securities laws, but not later
      than 60 days hereafter, the Buyer shall issue to the Tax
      Trustee  (the date of such issuance, the "Effective Date")
      1,315,789 Buyer Ordinary Shares that are freely tradeable on Nasdaq
      (pursuant to an effective Buyer registration statement, Regulation S or
      other applicable exemption from registration under the Securities Act) in
      discharge of the obligation to pay the Settlement Payment under Section
      2.1;

            


    

    


    
      	
               
      

            	
              2.1.2

            	
              for
      the avoidance of doubt, and as a consequence of the amendment to the SPA
      set forth in Section 2.2, no amount of the Settlement Payment will be paid
      by the Buyer to the Escrow Agent for deposit to the Escrow
      Fund;

            


    

    


    
      	
               
      

            	
              2.1.3

            	
              all
      and any obligations of the Buyer to pay to the Sellers the Milestone Ia
      Consideration pursuant to Section 2.1(d) and Section 9.2 of the SPA shall
      be extinguished in full and, with effect from the Effective Date and at
      all times thereafter, the Buyer shall have no liability of any nature to
      any Seller under Section 2.1(d) and/or Section 9.2 of the SPA or otherwise
      in respect of the Milestone Ia Consideration;
  and

            


    

    


    
      	
               
      

            	
              2.1.4

            	
              subject
      to Section 3.4.1 and Section 3.5.5, the Sellers’ Representative on behalf
      of each Seller (pursuant to Section 14.5 of the SPA), and each Seller,
      hereby fully waives all of its rights of any nature whatsoever, on a
      perpetual basis, to require or enforce performance by the Buyer of the
      requirements of Section 2.1(h), Section 2.1(e) and/or Section 2.1(f) of
      the SPA (“SPA Future
      Waiver”) and the Buyer shall have no liability of any nature to the
      Sellers following the Effective Date for breach of, or absence of
      performance of, any of the provisions of Section 2.1(h), Section 2.1(e)
      and/or Section 2.1(f) of the SPA.

            


    

    


    
      	
              2.2

            	
              The
      Buyer and the Sellers’ Representative agree that on the  expiry
      of the Escrow Period as such term has been originally defined in the SPA,
      i.e., on June 6, 2009, the parties shall execute and deliver the Final
      Instruction to Escrow Agent, in the form of Exhibit
      2.2 hereto, informing the Escrow Agent that the parties irrevocably
      instruct the Escrow Agent to pay to the Sellers on such date all of the
      Remaining Escrow Fund in the manner set forth in the Escrow
      Agreement.

            


    

    


    Further,
the parties agree that, on the Effective Date, the following provisions of
Section 12 of the SPA, Sections 12.1(i), 12.2(i)(a), 12.2(ii), 12.3(a) (other
than with respect to Section 5.2, with respect to which Section 12.3(a) shall
continue to apply in accordance with the terms of the SPA), 12.3(c), 12.6(f),
12.6(g) and 12.11 (the “Terminated Section 12
Provisions”), shall terminate and have no further force or effect, such
that:

    


    
      	
               
      

            	
              2.2.1

            	
              any
      and all of Buyer's rights and remedies for any Damages incurred as set
      forth in the Terminated Section 12 Provisions ("Covered Liabilities")
      shall terminate, and neither Buyer nor any Buyer Indemnified Party shall
      have any other claims, rights or remedies against any of the Sellers after
      the Effective Date, whether under the SPA or under any applicable law or
      otherwise, for such Covered
Liabilities.

            


    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    
      	
               
      

            	
              2.2.2

            	
              any
      and all of Sellers’ rights and remedies for any Damages incurred as set
      forth in the Terminated Section 12 Provisions ("Covered Liabilities")
      shall terminate, and none of the Sellers nor any Seller Indemnified Party
      shall have any other claims, rights or remedies against the Buyer after
      the Effective Date, whether under the SPA or under any applicable law or
      otherwise, for such Covered
Liabilities.

            


    

    


    For the
avoidance of doubt, all the provisions of Section 12 other than the Terminated
Section 12 Provisions shall be unchanged by this Agreement and shall continue in
full force and effect in accordance with their terms, it being understood that
all the provisions of Section 12, other than the Terminated Section 12
Provisions, shall continue in full force and effect solely with respect to the
Sellers' obligations under Section 12.1(ii) of the SPA (which are subject to the
waiver and release in Section 4 hereof), the Sellers' obligations under Section
12.2(i)(b) of the SPA, and Buyer's obligations under Sections 12.3(a) (only with
respect to Section 5.2), 12.3(b) (which are subject to the waiver and release in
Section 4 hereof) and 12.3(d) of the SPA, and that all such provisions shall be
read subject to the amendments to such Section 12 as stated in this Section
2.2.

    


    


    
      	
              3

            	
              FUTURE DEVELOPMENT OF MONARSEN
      / INTENTION TO PARTNER
MONARSEN

            


    

    


    
      	
              3.1

            	
              It
      is acknowledged by the Sellers’ Representative and each Seller that the
      intentions of the Buyer as at the date hereof and the Effective Date as
      regards any future development and/or commercialization activities in
      respect of Monarsen are as follows:

            


    

    


    
      	
               
      

            	
              3.1.1

            	
              the
      Buyer is currently completing certain activities to finalise the Buyer’s
      auditing and reporting of the Phase IIa Clinical Study and, save the
      completion of such activities and the activities described in Section
      3.1.3 below, the Buyer does not intend to conduct any additional
      development and/or commercialization activities on Monarsen, (including,
      without limitation, any MG Phase II Development Program, US Phase III
      Clinical Study or Phase III Clinical
Study);

            


    

    


    
      	
               
      

            	
              3.1.2

            	
              as
      a result of the Buyer’s cessation of all development activities on
      Monarsen as described in Section 3.1.1 above, and save in the
      circumstances outlined in Section 3.5.5 below where the Buyer would
      re-commence development activities on Monarsen in MG, Milestone Ib and
      Milestone II will not be achieved by the Buyer in the future and the
      potential for future payment to the Sellers of such milestones will be as
      set forth in Section 3.3;

            


    

     

    
      	
               
      

            	
              3.1.3

            	
              as
      more fully described in Section 3.3, the Buyer intends to seek to enter
      into an agreement (the “Proposed Partnership
      Agreement”) with a third party partner whereby such third party
      partner would conduct future development and/or commercialization
      activities on Monarsen in MG PROVIDED
      HOWEVER that the parties hereto agree that the provisions of this
      first paragraph of Section 3.1.3 and the provisions of Section 3.3 are
      only expressions of the Buyer’s intentions and no such provision comprises
      or contains any legally binding obligation on the
  Buyer.

            


    

     

    The
parties hereto further agree that the foregoing proviso is without prejudice to
the provisions of Section 3.5, which, for the avoidance of doubt, constitute
legally binding obligations of the parties hereto.

     

    
      	
              3.2

            	
              Upon
      agreement with the Sellers’ Representative, the Sellers’ Representative
      will make available to  the Buyer a certain portion of the
      business time of  Prof. Eli Hazum as may be reasonably required
      by the Buyer to enable the Buyer to conclude the Buyer’s auditing and
      reporting of the Phase IIa Clinical Study and to make any reports to, or
      respond to any queries of, or in relation to any inspections or
      investigations of, any regulatory authority in Europe, the USA or any
      other jurisdiction in relation to the Phase IIa Clinical
      Study.

            


    

     

    
      	
              3.3

            	
              The
      Buyer intends to seek to negotiate with any potential third party partner
      which is an experienced company in the business of developing drugs
      (“Third Party
      Partner”) to include the following terms in the Proposed
      Partnership Agreement:

            


    

     


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


     

    
      	
               
      

            	
              3.3.1

            	
              the
      Third Party Partner would have direct obligations to the Sellers,
      including diligence obligations as regards future development activities
      relating to Monarsen in MG identical to the Diligence Obligation set forth
      in Section 2.1(h) of the SPA, and including reporting and audit
      obligations (provided, however, that if the Third Party Partner is not a
      publicly traded company, then its reporting and audit obligations shall be
      broadened as required to provide Sellers' Representative reasonable
      comfort in such circumstances);

            


    

     

    
      	
               
      

            	
              3.3.2

            	
              the
      Third Party Partner would have an obligation to pay to the Sellers a
      milestone payment of [********]2 in cash within 14
      days after the Milestone Ib Date (the "First Payment Date") and
      would assume the obligations to the Sellers as regards Milestone II set
      forth in Section 2.1(f) of the SPA (other than Section 2.1(f)(iv) of the
      SPA, which is hereby terminated);

            


    

     

    
      	
               
      

            	
              3.3.3

            	
              if
      in the negotiation of the matters described in Section 3.3.2, the Third
      Party Partner is not agreeable to pay to the Sellers a milestone payment
      of [********] in
      cash on the First Payment Date, and is only agreeable to pay a cash
      milestone that is less than [********] (“Reduced Milestone Ib
      Payment”) resulting in a shortfall amount (the “Milestone Ib Shortfall
      Amount”), without prejudice to the provisions of Section 3.4.2, the
      Buyer intends to seek to negotiate with the Third Party Partner an
      addition to the Milestone II Consideration whereby the Third Party Partner
      would assume the obligations to the Sellers as regards Milestone II set
      forth in Section 2.1(f) of the SPA (other than Section 2.1(f)(iv) of the
      SPA, which is hereby terminated) and agree to pay an additional cash
      payment to the Sellers within 14 days after the Milestone II Date, in
      addition to the Milestone II Consideration, equal to the Milestone Ib
      Shortfall Amount (“Additional Milestone II
      Consideration”); and

            


    

     

    
      	
               
      

            	
              3.3.4

            	
              the
      Third Party Partner would have direct obligations to the Buyer, separate
      and distinct from the Third Party Partner’s obligations described in
      Section 3.3.1 above, including diligence obligations and payment
      obligations.

            


    

     

    
      	
              3.4

            	
              If
      the Buyer executes a Proposed Partnership Agreement, the following
      additional provisions shall apply as between the Buyer and the
      Sellers:

            


    

    


    
      	
               
      

            	
              3.4.1

            	
              without
      prejudice to Section 2.1.4, all and any obligations of the Buyer to pay to
      the Sellers the Milestone Ib Consideration pursuant to Section 2.1(e) and
      Section 9.2 of the SPA; and/or the Milestone II Consideration pursuant to
      Section 2.1(f) of the SPA; and the provisions of Section 2.1(h), shall be
      terminated and extinguished in full and, with effect from the effective
      date of the Proposed Partnership Agreement and at all times thereafter,
      the Buyer shall have no liability of any nature to any Seller under
      Section 2.1(e) and Section 9.2 of the SPA in respect of the Milestone Ib
      Consideration, or under Section 2.1(f) of the SPA in respect of the
      Milestone II Consideration, or under any of the provisions of Section
      2.1(h);

            


    

    


    
      	
              3.4.2  

            	
              in
      the event that, under the Proposed Partnership Agreement, the Third Party
      Partner does not agree to pay to the Sellers a milestone payment of [********] in cash on
      the First Payment Date, or to assume the obligations to the Sellers as
      regards Milestone II set forth in Section 2.1(f) of the SPA (other than
      Section 2.1(f)(iv) of the SPA, which is hereby terminated), then Buyer
      agrees to make advance payments (“Shortfall Advance
      Payment(s)”) to each Seller equal to its portion (as set forth on
      the Shortfall Advance Payment Allocation
      Schedule) in cash, of the following
amounts:

            


    

    


    
      	
               
      

            	
              (1)

            	
              the
      amount that reflects the difference between [********] and the
      aggregate amount actually paid to the Sellers by the Third Party Partner
      on the First Payment Date; and

            


    

    


    
      	
               
      

            	
              (2)

            	
              the
      amount that reflects the difference between [********] (or [********], as may be
      applicable under Section 2.1(f)(ii) of the SPA) and the aggregate amount
      actually paid to the Sellers by the Third Party Partner on the Milestone
      II Date (or the other

            


    

    
 

     

      
         
_________________________

      

       

      
        	
                 

              	
                CONFIDENTIAL INFORMATION
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.
      ASTERISKS [*] DENOTE SUCH
OMISSIONS.

              


      

       

    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    
      	
               
      

            	
              applicable
      payment date), as applicable, plus the Additional Milestone II
      Consideration (“Actual
      Milestone II
Consideration”);

            


    

    


    such
Shortfall Advance Payments(s) to be paid by Buyer only from any Third Party
Partner Consideration the Buyer actually receives from the Third Party Partner
less any Accelerated Payments made to the Sellers under Section 3.4.3, and less
any Non-MG Consideration made to the Sellers under Section 2.1(g) of the SPA
PROVIDED
HOWEVER that
the Sellers’ Representative shall irrevocably instruct the Third Party Partner
to pay to Buyer the amount (“Repayable Amount”) of any such
Shortfall Advance Payments (or part thereof), out of the payment agreed to be
made by the Third Party Partner to the Sellers of the Milestone II Consideration
and any Additional Milestone II Consideration, only if and to the extent that
the Milestone II Consideration and any Additional Milestone II Consideration is
actually due to the Sellers.  The Repayable Amount shall be calculated
as follows:

    


    Reduced
Milestone Ib Payment  +
(plus) Shortfall Advance
Payment(s)  +
(plus)  Accelerated Payments   +
(plus)  Non-MG Consideration  +
(plus)  Actual Milestone II Consideration

    


    –
(less)

    


    [********]3

    


    –
(less)

    


    Milestone
II Consideration

    


    =
(equals)  Repayable Amount;

    


    
      	
               
      

            	
              3.4.3

            	
              in
      addition, the Buyer shall pay to each Seller a payment (the “Accelerated Payment”)
      equal to its portion (as set forth on the Accelerated Payment Allocation
      Schedule) in cash, of [**] of any MG Phase II
      Third Party Partner Consideration actually received from the Third Party
      Partner within 10 Business Days after such MG Phase II Third Party Partner
      Consideration has been actually received by the Buyer or its
      Affiliates;

            


    

    


    
      	
               
      

            	
              3.4.4

            	
              if
      the Buyer is paid milestone or license payments by the Third Party Partner
      under the Proposed Partnership Agreement that are not in the form of cash,
      save in the case of Non-MG Sub-license Fees (which are governed by Section
      2.1(g) of the SPA), the parties hereto will negotiate in good faith to
      agree terms as to how to value such payments under this
      Agreement.

            


    

     

    
      	
              3.5

            	
              Subject
      to the provisions of Sections 3.5.1 to 3.5.5, if the Buyer has not
      executed the Proposed Partnership Agreement on the date which is 21 months
      following the date hereof (the “21 Month Trigger Date”),
      within 30 days of the such date (the “Ultimate Transfer
      Date”), the Seller's Representative may, but is not bound to,
      request in writing that, in accordance with the termination agreement
      described in Sections 3.5.1 and 3.5.2, the Buyer shall transfer to the
      Sellers’ Representative (or such persons as directed by the Sellers’
      Representative) all of its right, title and interest in the entire issued
      share capital of the Company:

            


    

    


    
      	
               
      

            	
              3.5.1

            	
              prior
      to any transfer of the share capital of the Company by the Buyer to the
      Sellers’ Representative (or such persons as directed by the Sellers’
      Representative), the parties hereto shall enter into a termination
      agreement (the “Termination Agreement”)
      , whereby the shares will be transferred by the Buyer to the Sellers’
      Representative (or such persons as directed by the Sellers’
      Representative), without consideration, subject to the representations and
      warranties of the Buyer set forth in Section 3.5.2 and otherwise on an “as
      is” basis; the SPA will be terminated in full and the parties hereto will
      agree mutual, full and perpetual waivers and releases under the SPA
      (pursuant to provisions in identical form to the waivers and releases set
      forth in Section 4); and, subject to Section 3.5.2, the Sellers’
      Representative and each Seller

            


    

    
 

     

      
         
_________________________

      

       

      
        	
                 

              	
                CONFIDENTIAL INFORMATION
      OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.
      ASTERISKS [*] DENOTE SUCH
OMISSIONS.

              


      

       

    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    
      	
               
      

            	
              will
      fully indemnify the Buyer in relation to any claims taken by any third
      party against the Buyer at any time following the Ultimate Transfer Date
      relating to any activities of the Company, past, present or
      future;

            


    

    


    
      	
               
      

            	
              3.5.2

            	
              in
      addition, the Buyer shall confirm to the Sellers’ Representative and the
      Sellers in the Termination Agreement (and provide any documentation
      reasonably required by the Sellers’ Representative to support such
      confirmations) that as of the Ultimate Transfer Date, (a) the shares of
      the Company being transferred to the Sellers’ Representative or to another
      person on its behalf are free and clear of any Encumbrances; (b) the
      Company owns the patents listed in Exhibit 3.5.2 and has no other assets;
      (c) such patents are owned free and clear of any Encumbrances and (d) the
      Company owes no monies to any third party; and the Buyer shall also
      confirm to the Sellers’ Representative whether any claims or proceedings
      are pending or threatened against the Company on the Ultimate Transfer
      Date or whether the Buyer has any other liability to any third party of
      which the Buyer is actually aware;

            


    

    


    
      	
               
      

            	
              3.5.3

            	
              notwithstanding
      the aforesaid, prior to the 21 Month Trigger
      Date, the Buyer shall be entitled  to notify  the
      Sellers’ Representative (such written notice to be accompanied
      by  supporting evidence), of its desire to extend the 21 Month Trigger Date
      to the date which is 6 months thereafter (the “27 Month Trigger Date”)
      which extension shall be approved by the Sellers’ Representative (such
      approval not to be unreasonably withheld or delayed) in circumstances
      where the Buyer can demonstrate to the Sellers' Representative’s
      satisfaction that it has made substantial progress towards the execution
      of the Proposed Partnership Agreement and that execution of such Proposed
      Partnership Agreement is reasonably likely within such 6-month period; if
      such extension is approved,  the Ultimate Transfer Date shall be
      similarly extended;

            


    

    


    
      	
               
      

            	
              3.5.4

            	
              notwithstanding
      the aforesaid, prior to the 27 Month Trigger Date, the Buyer shall be
      entitled, to notify the Sellers’ Representative in writing (such written
      notice to be accompanied by supporting evidence) of its desire to extend
      the 27 Month Trigger Date to the date which is 3 months thereafter (the
      “30 Month Trigger
      Date”), which extension shall be approved by the Sellers’
      Representative (such approval not to be unreasonably withheld or delayed)
      in circumstances where the Buyer can demonstrate to the Sellers'
      Representative’s satisfaction, that the execution of the Proposed
      Partnership Agreement is reasonably likely within such 3-month period; if
      such extension is approved, the Ultimate Transfer Date shall be similarly
      extended;

            


    

    


    
      	
               
      

            	
              3.5.5

            	
              if
      prior to the 27 Month Trigger Date
      the Buyer notifies the Seller in writing that it has determined that it
      will re-commence development activities on Monarsen in MG, then, subject
      to the Sellers’ Representative consenting in writing to the Buyer
      re-commencing development activities on Monarsen in MG (such consent not
      to be unreasonably withheld or delayed), such development activities will
      re-commence and all of the provisions of this Clause 3.5, save this
      Section 3.5.5, and the SPA Future Waiver shall forthwith terminate, no
      transfer of the share capital as described above will occur thereafter,
      and with effect from the date of the afore-mentioned consent of the
      Sellers’ Representative, the Buyer shall be fully bound by, and liable for
      any breach of, the provisions of Sections 2.1(h), Section 2.1(e) and
      Section 2.1(f) of the SPA, without any change.  For the
      avoidance of doubt, the re-commencement of development activities by the
      Buyer under this Section 3.5.5 shall not in itself trigger any payment by
      the Buyer to the Sellers.

            


    

    


    
      	
              3.6

            	
              From
      the date hereof until the earlier of (i) the execution of the Proposed
      Partnership Agreement, or (ii) the execution of the Termination Agreement,
      or (iii) the notice of Buyer to the Sellers' Representative as set forth
      in Section 3.5.5, the Buyer shall report in writing to the Sellers’
      Representative, on a six monthly basis, providing an update of the
      progress of its activities in that period in relation to the negotiation
      and execution of a Proposed Partnership Agreement. Such reports shall be
      provided to the Sellers’ Representative not later than the 15th day
      following June 30, 2009 and the end of each six month period thereafter.
      Further, a full and complete copy of any Proposed Partnership Agreement,
      if executed, shall be delivered to the Sellers’ Representative, together
      with a summary of the financial terms of any agreement entered into by the
      Buyer and the Third Party Partner contemporaneously with, or within 3
      months prior to or following the date of  the Proposed
      Partnership Agreement.

            


    

     

    
 


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


     

    


    
      	
              4

            	
              WAIVER OF ACCRUED RIGHTS /
      MUTUAL RELEASES
      UNDER SPA

            


    

    


    
      	
              4.1

            	
              With
      effect from the Effective Date, each party to the SPA and each of its
      Affiliates (each a “Releasor”)
      hereby:

            


    

    


    
      	
               
      

            	
              4.1.1

            	
              waives
      any accrued rights that Releasor may have accrued against the other
      parties to the SPA and each of its Affiliates, officers, directors,
      representative, agents and employees and the assigns and successors in
      interest of any of the foregoing entities (“Releasees”), whether
      known or unknown, foreseen or unforeseen, fixed or contingent, of any
      nature whatsoever from the beginning of time to the Effective Date under
      the SPA or otherwise; and

            


    

    


    
      	
               
      

            	
              4.1.2

            	
              fully
      and finally releases and discharges the Releasees from any and all manner
      of actions, claims, promises, debts, sums of money, demands, obligations,
      in law or in equity, directly or indirectly, whether known or unknown,
      foreseen or unforeseen, fixed or contingent, of any nature whatsoever that
      Releasor may have by reason of any act, omission, matter, provision, cause
      or thing whatsoever from the beginning of time to the Effective Date under
      the SPA or otherwise.

            


    

    


    


    5           MISCELLANEOUS

    


    The
parties hereto agree that the following provisions of the SPA (Sections 9.3,
9.7, 14.3, 14.4, 14.5, 14.6, 14.7, 14.8, 14.9, 14.10, 14.1, 14.12, 14.13, 14.14)
shall apply to this Agreement in the same manner as they apply in the
SPA.

    


    All
costs, expenses and Taxes incurred in connection with this Agreement, the
Proposed Partnership Agreement and any related agreement or otherwise in
connection herewith or therewith shall be paid by the party incurring such cost,
expense or Tax.

    
      	
               
      

            	
              For
      the avoidance of doubt, all shares, monies and other consideration due to
      the Sellers hereunder shall be issued or paid by the Buyer, when due, to
      the Tax Trustee in accordance with Section 13(h) of the
    SPA.

            


    

    


    


    
      	
              6

            	
              NO OTHER AMENDMENTS

            


    

    


    Save as
amended by Amendment No. 1 and this Agreement, the SPA shall remain in full
force and effect without any change.

    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    
      	
              IN WITNESS WHEREOF the
      parties hereto have executed this Agreement.

            
	 
      
	 
      
	
              SIGNED

            
	 
      
	 
      
	
              By:  /s/ Thomas Lynch      

            
	
                     
      for and on behalf of

            
	
                    
      AMARIN CORPORATION, PLC

            
	 
      
	 
      
	
              SIGNED

            
	 
      
	 
      
	
              By:  /s/ Alan Cooke      

            
	
                      for
      and on behalf of

            
	
                      ESTER
      NEUROSCIENCES LTD.

            
	 
      
	 
      
	
              SIGNED

            
	 
      
	 
      
	
              By:  /s/ Ehud Geller      

            
	
                     
      for and on behalf of

            
	
                     
      MEDICA II MANAGEMENT L.P

            
	
                     
      (AS THE SELLERS’ REPRESENTATIVE)

            


    

    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    Exhibit
2.2

    


    Final
Instruction to Escrow Agent

    


    


     

    
      	
              Amarin
      Corporation plc

            	
              Medica
      II Management L.P., as Sellers’
      Representative

            


    

     

    Date:
June 6, 2009

     

    


    Brightman
Almagor Freidman Trustees

    1 Azrieli
Center, Tel Aviv 67021

    Israel

    


     

    Dear
Sirs:

     

    Reference
is hereby made to that certain Escrow Agreement made
as of December 18, 2007, by and among yourselves (the “Escrow Agent”),
Amarin Corporation plc (the “Buyer”), and Medica
II Management L.P. (the “Sellers’
Representative”) (the "Escrow Agreement"; all capitalized terms used
herein and not otherwise defined herein shall have the meanings ascribed to them
in the Escrow Agreement).

     

    This is
to advise you that on the date hereof, the “Escrow Period” has
been effectively terminated at the time this letter of instruction is issued to
you, without any Indemnity Claims of Buyer or Buyer Indemnified Parties and,
consequently, no Indemnity Claim Notice that has ever been given.

    


    Accordingly,
pursuant to Section 6.6 of the Escrow Agreement, the Buyer and the Sellers'
Representative hereby irrevocably instruct you to pay to the Sellers all of the
Remaining Escrow Fund in accordance with the Allocation Schedule that was
provided to you by the Sellers' Representative prior to the date hereof, and
hereby notify you of the termination of the Escrow Agreement and your release,
after you properly affect the above payment to the Sellers, of any further duty,
obligation or liability to the parties hereto.

    


    The
Sellers agree that pursuant to Section 7 of the Escrow Agreement, the Sellers
shall pay all of the Escrow Agency’s fees and reasonable costs and expenses from
the Remaining Escrow Fund and that the Buyer shall leave no liability whatsoever
to you to pay any such fees and expenses.

    


    We thank
you for your service.

    


     
 

    
      	
              SIGNED

            
	 
      
	 
      
	
              By:

            
	
              for
      and on behalf of

            
	
              AMARIN
      CORPORATION, PLC

            
	 
      
	 
      
	 
      
	
              SIGNED

            
	 
      
	 
      
	
              By:

            
	
              for
      and on behalf of

            
	
              MEDICA
      II MANAGEMENT L.P

            
	
              (AS
      THE SELLERS’ REPRESENTATIVE)

            


    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    Exhibit
3.5.2

    


    List of
patents

    


    


    
      	
              Family:  1961

            	
              Title:   Genetically
      Engineered Human Cholinesterases

            


    

    


    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1390

            	
              Zakut
      Haim

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              1961-00

            	
              Priority

            	
              Abandoned

            	
              Israel

            	
              21/03/1989

            	
              89703

            	
              31/10/2001

            	
              Aug-01

            	
              02/03/2002

            	
              89703

            	 
      	 
      
	
              1961-00

            	
              Priority

            	
              Abandoned

            	
              Israel

            	
              21/03/1989

            	
              89703

            	
              31/10/2001

            	
              Aug-01

            	
              02/03/2002

            	
              89703

            	 
      	 
      
	
              1961-01

            	 
      	
              Abandoned

            	
              Canada

            	
              21/03/1990

            	
              2,012,720-1

            	 
      	 
      	
              20/09/1990

            	 
      	 
      	 
      
	
              1961-02

            	 
      	
              Abandoned

            	
              US

            	
              20/03/1990

            	
              07/496,554

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              1961-03

            	 
      	
              Abandoned

            	
              Europe

            	
              20/03/1990

            	
              90105274

            	 
      	 
      	
              14/06/1995

            	
              388906

            	 
      	 
      
	
              1961-04

            	 
      	
              Abandoned

            	
              France

            	
              20/03/1990

            	
              90105274

            	 
      	 
      	
              14/06/1995

            	
              388906

            	 
      	 
      
	
              1961-05

            	 
      	
              Abandoned

            	
              Switzerland

            	
              20/03/1990

            	
              90105274

            	 
      	 
      	
              14/06/1995

            	
              388906

            	 
      	 
      
	
              1961-06

            	 
      	
              Abandoned

            	
              Great
      Britain

            	
              20/03/1990

            	
              90105274.6

            	 
      	 
      	
              14/06/1995

            	
              388906

            	 
      	 
      
	
              1961-07

            	 
      	
              Abandoned

            	
              Germany

            	
              20/03/1990

            	
              90105274.6

            	 
      	 
      	
              14/06/1995

            	
              69020019

            	 
      	 
      
	
              1961-08

            	
              CIP

            	
              Granted

            	
              US

            	
              08/02/1993

            	
              08/111,314

            	 
      	 
      	
              21/01/1997

            	
              5,595,903

            	 
      	 
      


    

    


    


    


    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    
      	
              Family:  2042

            	
              Title:

            	
              Synthetic
      Antisense Deoxyoligonucleotide and Pharmaceutical Compositions
      Containing the Same

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1513

            	
              Eckstein
      Fritz

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2042-00

            	
              Priority

            	
              Granted

            	
              Israel

            	
              15/04/1992

            	
              101600

            	
              29/02/2000

            	
              JOURNAL
      11/99

            	
              30/05/2000

            	
              101600

            	 
      	 
      
	
              2042-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              15/04/1993

            	
              PCT/EP93/00911

            	
              28/10/1993

            	
              WO
      93/21202

            	 
      	 
      	 
      	 
      
	
              2042-02

            	
              NP

            	
              Abandoned

            	
              Japan

            	
              15/04/1993

            	
              517984/93

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2042-03

            	
              NP

            	
              Granted

            	
              Europe

            	
              15/04/1993

            	
              93911467.4

            	 
      	 
      	
              05/04/1997

            	
              EP
      0636137 B1

            	 
      	 
      
	
              2042-04

            	
              NP

            	
              Abandoned

            	
              Australia

            	
              15/04/1993

            	
              40399/93

            	 
      	 
      	
              14/12/1995

            	
              665087

            	 
      	 
      
	
              2042-05

            	
              NP

            	
              Abandoned

            	
              US

            	
              12/01/1994

            	
              08/318,826

            	 
      	 
      	
              04/06/1999

            	
              5,891,725

            	 
      	 
      
	
              2042-06

            	
              NP

            	
              Granted

            	
              Canada

            	
              15/04/1993

            	
              2,118,235

            	 
      	 
      	
              15/7/2008

            	
              2118235

            	 
      	 
      
	
              2042-07

            	
              CIP

            	
              Granted

            	
              US

            	
              05/02/1998

            	
              08/850,347

            	 
      	 
      	
              29/08/2000

            	
              6,110,742

            	 
      	 
      
	
              2042-08

            	
              NP

            	
              Granted

            	
              France

            	
              15/04/1993

            	 
      	 
      	 
      	
              03/12/1997

            	
              636137

            	 
      	 
      
	
              2042-09

            	
              NP

            	
              Granted

            	
              Great
      Britain

            	
              15/04/1993

            	
              93911467.4

            	
              02/01/1995

            	 
      	
              03/12/1997

            	
              636137

            	 
      	 
      
	
              2042-10

            	
              NP

            	
              Granted

            	
              Germany

            	
              15/10/1994

            	
              93
      911467.4

            	
              02/01/1995

            	 
      	
              03/12/1997

            	
              693
      08 833.8-08

            	 
      	 
      


    

    


    
      	
               
      

            	 


    


    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    
      	
              Family:  2098

            	
              Title:

            	
              Transgenic
      Animal Assay System for Anticholinesterases
  Substances

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1777

            	
              Shani
      Moshe

            	 
      
	
              1390

            	
              Zakut
      Haim

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2098-00

            	
              Priority

            	
              Abandoned

            	
              US

            	
              28/02/1994

            	
              08/202,755

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2098-01

            	
              CIP

            	
              Abandoned

            	
              US

            	
              09/01/1995

            	
              08/370,156

            	 
      	 
      	
              03/08/1999

            	
              5,932,780

            	 
      	 
      
	
              2098-02

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              28/02/1995

            	
              PCT/US95/02806

            	
              31/08/1995

            	
              WO
      95/23158

            	 
      	 
      	 
      	 
      
	
              2098-03

            	
              NP

            	
              Abandoned

            	
              Europe

            	
              28/02/1995

            	
              95913580.7

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2098-04

            	
              CIP

            	
              Granted

            	
              US

            	
              06/03/1997

            	
              08/814,095

            	 
      	 
      	
              15/02/2000

            	
              6,025,183

            	 
      	 
      


    

    


    


    


    
      	
              Family:  2151

            	
              Title:

            	
              A
      Method and Composition for Enabling Passage Through
  BBB

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1882

            	
              Friedman
      Alon

            	 
      
	
              1881

            	
              Kaufer
      Daniela

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2151-00

            	
              Priority

            	
              Expired

            	
              US

            	
              20/11/1996

            	
              60/031,194

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2151-01

            	
              Priority2

            	
              Expired

            	
              US

            	
              12/12/1996

            	
              60/035,266

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2151-02

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              20/11/1997

            	
              PCT/US97/21696

            	
              28/05/1998

            	
              WO
      98/22132

            	 
      	 
      	 
      	 
      
	
              2151-03

            	
              From
      Priority

            	
              Granted

            	
              US

            	
              20/11/1997

            	
              08/975,084

            	 
      	 
      	
              07/10/2001

            	
              6,258,780

            	 
      	 
      
	
              2151-04

            	
              NP

            	
              Granted

            	
              Israel

            	
              20/11/1997

            	
              129990

            	
              24/01/2005

            	
              Pat
      Journal 11/2004

            	
              25/04/2005

            	
              129990

            	 
      	 
      
	
              2151-05

            	
              NP

            	
              Abandoned

            	
              Australia

            	
              20/11/1997

            	
              53642/98

            	
              06/10/1998

            	 
      	
              04/12/2001

            	
              732043

            	 
      	 
      
	
              2151-06

            	
              NP

            	
              Abandoned

            	
              Canada

            	
              20/11/1997

            	
              2,272,280

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2151-07

            	
              NP

            	
              Abandoned

            	
              Europe

            	
              20/11/1997

            	
              97950711.8

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2151-08

            	
              NP

            	
              Filed

            	
              Japan

            	
              20/11/1997

            	
              10-523989

            	 
      	 
      	 
      	 
      	 
      	 
      


    

    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    
      	
              Family:  2304

            	
              Title:

            	
              Synthetic
      Antisense Oligodeoxynucleotides and Pharmaceutical Compositions Containing
      them

            


    

    


    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1513

            	
              Eckstein
      Fritz

            	 
      
	
              1882

            	
              Friedman
      Alon

            	 
      
	
              1881

            	
              Kaufer
      Daniela

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2304-00

            	
              Priority

            	
              Expired

            	
              US

            	
              12/12/1996

            	
              60/035,266

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2304-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              12/12/1997

            	
              PCT/US97/23598

            	
              18/06/1998

            	
              WO
      98/26062

            	 
      	 
      	 
      	 
      
	
              2304-02

            	
              CIP

            	
              Granted

            	
              US

            	
              12/12/1997

            	
              08/990,065

            	 
      	 
      	
              19/09/2000

            	
              6,121,046

            	 
      	 
      
	
              2304-03

            	
              NP

            	
              Allowed

            	
              Israel

            	
              12/12/1997

            	
              130162

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2304-04

            	
              NP

            	
              Granted

            	
              Australia

            	
              12/12/1997

            	
              53856/98

            	 
      	 
      	
              14/12/2000

            	
              727611

            	 
      	 
      
	
              2304-05

            	
              NP

            	
              Examination

            	
              Canada

            	
              12/12/1997

            	
              2,274,985

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2304-06

            	
              NP

            	
              Granted

            	
              Europe*

            	
              12/12/1997

            	
              97950993.2

            	
              15/09/1999

            	
              951536

            	
              24/1/2007

            	
              EP0951536

            	 
      	 
      
	
              2304-07

            	
              NP

            	
              Filed

            	
              Japan

            	
              12/12/1997

            	
              10-527069

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2304-08

            	
              CIP

            	
              Abandoned

            	
              US

            	 
      	
              09/572,630

            	 
      	 
      	 
      	 
      	 
      	 
      


    

    (*)
Validated in GB, FR, DE & CH

    


    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    
      	
              Family:  2325

            	
              Title:

            	
              Antisense
      and Non-Catalytic Properties

            


    

    


    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    
      	
              Licensee

            
	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2325-00

            	
              Priority

            	
              Expired

            	
              US

            	
              03/06/1997

            	
              60/040,203

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2325-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              03/06/1998

            	
              PCT/US98/04503

            	
              09/11/1998

            	
              WO
      98/39486

            	 
      	 
      	 
      	 
      
	
              2325-02

            	
              NP

            	
              Abandoned

            	
              Australia

            	
              03/06/1998

            	
              64521/98

            	 
      	 
      	 
      	
              AB

            	 
      	 
      
	
              2325-03

            	
              NP

            	
              Abandoned

            	
              Canada

            	
              03/06/1998

            	
              2,283,068

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2325-04

            	
              NP

            	
              Granted

            	
              US

            	
              03/06/1998

            	
              09/380,532

            	 
      	 
      	
              11/05/2002

            	
              6,475,998

            	 
      	 
      
	
              2325-05

            	
              NP

            	
              Abandoned

            	
              Europe

            	 
      	
              98910229.8

            	 
      	 
      	 
      	
              Abandoned

            	 
      	 
      


    

    


    


    


    
      	
              Family:  2356

            	
              Title:

            	
              Use
      of A Specific AChE Peptide (I4) As A Growth
  Factor

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1969

            	
              Deutch
      Varda

            	 
      
	
              1382

            	
              Eldor
      Amiram

            	 
      
	
              1970

            	
              Grisaru
      Dan

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            
	 
      	 
      	 
      


    

    


    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2356-00

            	
              Priority

            	
              Granted

            	
              Israel

            	
              31/05/1999

            	
              130224

            	
              19/02/2004

            	
              Pat
      Journal 12/2003

            	
              20/05/2004

            	
              130224

            	 
      	 
      
	
              2356-01

            	
              From
      Priority

            	
              Abandoned

            	
              Israel

            	
              09/02/1999

            	
              131707

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2356-02

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              31/05/2000

            	
              PCT/IL00/00311

            	
              12/07/2000

            	
              WO
      00/73427

            	 
      	 
      	 
      	 
      
	
              2356-03

            	
              CIP

            	
              Granted

            	
              US

            	
              30/11/2001

            	
              09/998,042

            	
              20/02/2003

            	
              US-2003-0036632-A1

            	
              27/06/2006

            	
              7,067,486

            	 
      	 
      
	
              2356-04

            	
              CIP
      of CIP

            	
              Published

            	
              US

            	
              04/11/2006

            	
              11/401,670

            	
              22/03/2007

            	
              US-2007-0065882-A1

            	 
      	 
      	 
      	 
      


    

    


    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    


    
      	
              Family:  2463

            	
              Title:

            	
              Novel
      Uses of Antibodies Against Ache and Peptides
  thereof

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1882

            	
              Friedman
      Alon

            	 
      
	
              1881

            	
              Kaufer
      Daniela

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    


    


    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2463-00

            	
              Priority

            	
              Abandoned

            	
              Israel

            	
              31/05/1999

            	
              130225

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2463-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              31/05/2000

            	
              PCT/IL00/00312

            	
              12/02/2000

            	
              WO
      00/73343

            	 
      	 
      	 
      	 
      
	
              2463-02

            	
              NP

            	
              Granted

            	
              US

            	
              31/05/2000

            	
              09/980,263

            	 
      	 
      	
              20/06/2006

            	
              7,063,948

            	 
      	 
      
	
              2463-03

            	
              NP

            	
              Granted

            	
              Europe

            	
              31/05/2000

            	
              931517.7

            	
              20/03/2002

            	
              1187853

            	
              23/02/2005

            	
              1187853

            	 
      	 
      
	
              2463-04

            	
              NP

            	
              Filed

            	
              Canada

            	
              31/05/2000

            	
              2,371,675

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2463-05

            	
              NP

            	
              Allowed

            	
              Israel

            	
              31/05/2000

            	
              146850

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2463-06

            	
              DIV

            	
              Published

            	
              US

            	
              02/10/2006

            	
              11/352,073

            	
              06/08/2006

            	
              US-2006-0121536-A1

            	 
      	 
      	 
      	 
      


    

    


    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    
      	
              Family:  2584

            	
              Title:

            	
              Antisense
      Oligonucleotide Against Human Ache and Uses thereof AS3
      (EN101)

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2584-00

            	
              Priority

            	
              Filed

            	
              Israel

            	
              24/05/2001

            	
              143379

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2584-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              24/05/2002

            	
              PCT/IL02/00411

            	
              01/09/2003

            	
              WO
      03002739

            	 
      	 
      	 
      	 
      
	
              2584-02

            	
              CIP
      of NP

            	
              Granted

            	
              US

            	
              27/03/2003

            	
              10/402,016

            	
              20/11/2003

            	
              US-2003-0216344-A1

            	
              07/11/2006

            	
              7,074,915

            	 
      	 
      
	
              2584-03

            	
              NP

            	
              Examination

            	
              Europe

            	
              24/05/2002

            	
              2726406.8

            	
              25/02/2004

            	
              1390493

            	 
      	 
      	 
      	 
      
	
              2584-04

            	
              NP

            	
              Filed

            	
              Canada

            	
              24/05/2002

            	
              2,458,806

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2584-05

            	
              NP

            	
              Allowed

            	
              Australia

            	
              24/05/2002

            	
              20002256873

            	 
      	 
      	
              18/10/2007

            	
              20002256873

            	 
      	 
      
	
              2584-06

            	
              NP

            	
              Filed

            	
              Japan

            	
              24/05/2002

            	
              2003-509100

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2584-07

            	
              NP

            	
              Examination

            	
              India

            	
              24/05/2002

            	
              01497/KOLNP/2003

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2584-08

            	
              NP

            	
              Examination

            	
              New
      Zealand

            	
              24/05/2002

            	
              529549

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2584-09

            	
              DIV
      of CIP

            	
              Published

            	
              US

            	
              02/01/2006

            	
              11/346,145

            	
              08/10/2006

            	
              US-2006-0178333-A1

            	 
      	 
      	 
      	 
      


    

    


    


    


    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    
      	
              Family:  2806

            	
              Title:

            	
              Ache
      Antisense Deoxyoligonucleotide As Anti-Inflammatory
  Agent

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              3170

            	
              Yirmiya
      Raz

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2806-00

            	
              Priority

            	
              Filed

            	
              Israel

            	
              26/10/2003

            	
              158600

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2806-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              26/10/2004

            	
              PCT/IL2004/000978

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2806-02

            	
              CIP

            	
              Abandoned

            	
              US

            	
              26/10/2004

            	
              11/187,719

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              CON

            	
              Filed

            	
              US

            	
              18/4/2007

            	
              11/788,321

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2806-03

            	
              NP

            	
              Published

            	
              Europe

            	
              23/10/2004

            	
              4791840.4

            	
              26/07/2006

            	
              1682072

            	 
      	 
      	 
      	 
      
	
              2806-04

            	
              NP

            	
              Examination

            	
              Canada

            	
              26/10/2004

            	
              2,543,305

            	 
      	 
      	 
      	 
      	 
      	 
      
	
              2806-05

            	
              NP

            	
              Filed

            	
              Japan

            	
              26/10/2004

            	
              2006-537550

            	 
      	 
      	 
      	 
      	 
      	 
      


    

    


    


    
      	
              Family:  2816

            	
              Title:

            	
              ARP
      As an Inducer of Granulocytopoiesis, Uses and Methods thereof
      (Hematopoietic Stem Cells)

            


    

    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	
              1969

            	
              Deutch
      Varda

            	 
      
	
              1970

            	
              Grisaru
      Dan

            	 
      
	
              2637

            	
              Perry
      Chava

            	 
      
	
              2638

            	
              Pick
      Marjorie

            	 
      
	
              1118

            	
              Soreq
      Hermona

            	
              v

            


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	
              2816-00

            	
              Priority

            	
              Filed

            	
              Israel

            	
              02/12/2004

            	
              160376

            	 
      	 
      	 
      	 
      	
              Tel-Aviv
      Sourasky Medical Center

            	
              50

            
	
              2816-01

            	
              PCT

            	
              Exhausted

            	
              PCT

            	
              02/10/2005

            	
              PCT/IL2005/000185

            	 
      	 
      	 
      	 
      	
              Tel-Aviv
      Sourasky Medical Center

            	
              50

            
	
              2816-02

            	
              NP

            	
              Filed

            	
              US

            	
              02/10/2005

            	
              10/589,116

            	
              27/9/2007

            	
              2007/0224181A1

            	 
      	 
      	
              Tel-Aviv
      Sourasky Medical Center

            	
              50

            


    

    



    
      
         


      

      
         


        
          

        

      

      
         


      

    


    


    


    


    
      	
              Family:

            	
              Title:

            	
              ANTISENSE
      OLIGONUCLEOTIDES AGAINST ACETYLCHOLINESTERASE FOR TREATING INFLAMMATORY
      DISEASES

            


    

    


    


    
      	
              Inventors

            
	
              Inventor
      ID

            	
              Inventor
      Name

            	
              Main

            
	 
      	
              Eli
      Hazum

            	 
      


    

    


    


    
      	 
      	
              Application

            	
              Publication

            	
              Patent

            	
              Co-Applicant

            
	
              Patent
      ID

            	
              Continuity

            	
              Status

            	
              Country

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Date

            	
              Number

            	
              Name

            	
              %

            
	 
      	
              Priority

            	
              Filed

            	
              US

            	
              04/10/2006

            	
              60/790,546

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              PCT

            	
              Exhausted

            	
              PCT

            	
              29/3/2007

            	
              PCT/IL2007/000413

            	
              18/10/2007

            	
              WO2007/116395

            	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              US

            	
              10/08/2008

            	
              12/296,455

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              Australia

            	
              29/3/2007

            	
              2007237059

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              New
      Zealand

            	
              29/3/2007

            	
              571861

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              Europe

            	
              29/3/2007

            	
              PCT/IL2007/000413

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              Canada

            	
              29/3/2007

            	
              PCT/IL2007/000413

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              Israel

            	
              29/3/2007

            	
              194431

            	 
      	 
      	 
      	 
      	 
      	 
      
	 
      	
              NP

            	
              Filed

            	
              Japan

            	
              29/3/2007

            	
              PCT/IL2007/000413