Unassociated Document


    


    AMENDMENT
      NO. 3 TO

    DISTRIBUTION
      AND MANUFACTURING

    SERVICES
      AGREEMENT

    


    This
      Amendment No. 3 to Distribution and Manufacturing Services Agreement (this
      “Amendment”)
      is
      made as of September 24, 2007 (the “Effective
      Date”)
      and
      amends the Distribution and Manufacturing Services Agreement, dated as of
      January 16, 2004, by and between Lev Development Corp.(formerly known as Lev
      Pharmaceuticals, Inc.), a Delaware corporation (“LEVPHARMA”),
      and
      Sanquin Blood Supply Foundation (“SANQUIN”),
      a
      not-for-profit corporation organized under the laws of The Netherlands, as
      amended by a First and Second Amendment (collectively, the “Original
      Agreement”
and
      together with this Amendment, the “Agreement”).
      Capitalized terms used in this Amendment without definition shall have the
      meanings given them in the Original Agreement.

    


    WHEREAS,
      LEVPHARMA and SANQUIN entered into the Original Agreement in January 2004;
      

    


    WHEREAS,
      LEVPHARMA is willing to fund SANQUIN’s augmentation and expansion of its
      facilities for the purposes of enabling SANQUIN to meet LEVPHARMA’s supply
      requirements for the Product, in accordance with the terms and conditions of
      this Amendment; 

     

    WHEREAS,
      the Parties desire to convert the Original Agreement into a toll manufacturing
      agreement whereby SANQUIN is willing to provide toll manufacturing of the
      Product for LEVPHARMA using blood plasma supplied by LEVPHARMA, in accordance
      with the terms and conditions set forth in
      this
      Amendment;
      and

    


    WHEREAS,
      the Parties to the Original Agreement desire to amend the Original Agreement
      as
      more fully set forth herein to reflect developments in the relationship between
      the Parties and the status of the manufacturing of the Product.

    


    NOW
      THEREFORE, in consideration of the premises and the agreements hereinafter
      set
      forth, and for other good and valuable consideration, the receipt and
      sufficiency of which are hereby acknowledged by each of the Parties, the Parties
      hereby amend the Original Agreement as follows:

    


    1.
      Section 4.1(c) of the Original Agreement is deleted in its entirety and replaced
      with the following:

    


    c)    Commercial
      Supply.
      Commencing on LEVPHARMA’s Commercial Launch (defined as the date on which
      LEVPHARMA commences marketing the Product in any country in the Territory
      following its receipt of Regulatory Approval in the applicable country) of
      the
      Product and thereafter during the term of the Agreement (including all renewal
      terms of the Agreement), subject to the terms and conditions of this Article
      IV,
      SANQUIN shall supply LEVPHARMA with LEVPHARMA’s requirements for Product for
      commercial use pursuant to this Agreement in each country in the Territory
      where
      LEVPHARMA has Regulatory Approval (the “Commercial
      Supply”).
      Said
      Commercial Supply of Product shall at all times be ordered and supplied
      according to the procedures outlined in Sections 4.2 and 4.3.

     

    
      [*CONFIDENTIAL
        TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT. EACH
        SUCH
        PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH AN ASTERISK [***],
        HAS
        BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
        COMMISSION.]

    

    


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    i. Scale
      Up
      and LEVPHARMA Funding

     

    SANQUIN
      has performed an analysis of the feasibility of scaling up the production of
      the
      Product and provided the results of this analysis to LEVPHARMA. Commencing
      on
      the Effective Date of this Amendment, SANQUIN shall initiate a project to scale
      up the production of the Product (the “Scale
      Up”)
      at
      both the Brussels and Amsterdam Facilities in accordance with the following
      terms and conditions of the Scale Up process:

     

    
      	 	
              a.

            	
              In
                accordance with the project plan (the “Project Plan”) to be approved by
                the Parties, LEVPHARMA shall fund, up to a maximum required total
                investment of 7.5 million euros, through a loan facility upon the
                terms
                set forth in paragraph 4.1(c)(i)(e), * * * of
                the capital investments at the Brussels Facility, and * * * 
                of
                the capital investments at the Amsterdam Facility, required to conduct
                the
                Scale Up for the purposes of LEVPHARMA’s obtaining from SANQUIN the
                Commercial Supply of its requirements for the Product pursuant to
                paragraphs 4.1(c)ii(d) and (e) of this Agreement. The remaining *
                *
                * 
                of
                funding required for the Scale Up of the Amsterdam Facility shall
                be the
                obligation of SANQUIN. Further, the Project Plan and budget shall
                be
                premised on the basis that the total cost of the capital investments
                necessary for the successful completion of the Scale Up will be such
                that
                the loan maximum of LEVPHARMA will be sufficient to fund completion
                of the
                Scale Up. LEVPHARMA and SANQUIN shall cooperate in the development
                of the
                Project Plan for the Scale Up and shall jointly agree on a final
                project
                budget for the Scale Up prior to commencement of the Scale Up project.
                Other than as expressly set forth herein, the Parties shall have
                no
                liability pursuant to this Section until they have provided their
                written
                approval of the final Project Plan and budget other than LEVPHARMA’s
                obligations to fund the engineering component of the Scale Up, which
                precedes the Project Plan, as under (c) hereunder. The Project Plan
                shall
                also provide that upon completion of the Scale Up, SANQUIN shall
                have the
                manufacturing capacity to satisfy the maximum output of Product
                contemplated by this Agreement.

            


    

     

    [*CONFIDENTIAL
      TREATMENT HAS BEEN REQUESTED AS TO
      CERTAIN PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED
      HEREIN AND REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH
      THE
      SECURITIES AND EXCHANGE COMMISSION.]

     

    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              b.

            	
              LEVPHARMA’s
                loan obligation pursuant to the above paragraph a) includes, without
                limitation, the costs of all required engineering (as jointly determined
                by LEVPHARMA and SANQUIN, but subject to the ceiling set forth in
                paragraph (a)), and is based on the Parties’ assumptions as of the
                Effective Date of this Amendment. In the event that SANQUIN shall
                at any
                time anticipate or project a need for any material increase in the
                amount
                of funds required for the Scale Up, SANQUIN will promptly notify
                LEVPHARMA
                of this fact in writing and the Parties shall confer in good faith
                to
                reach agreement as to whether, and to what extent, such increase
                will be
                funded by the respective Parties. A material increase shall mean
                an amount
                equal or greater to * * * of the initial budget agreed to by the
                Parties
                for the Scale Up. Increases that are below this threshold shall be
                funded
                by SANQUIN up to a cumulative maximum of * * * of
                the initial budget.

            


    

     

    
      	 	
              c.

            	
              The
                costs for the engineering component of the Scale Up are estimated
                to be *
                * * euros.
                This includes costs for hiring an additional engineer by SANQUIN
                as well
                as the costs for engineering services contracted out. As part of
                its
                funding obligation pursuant the above paragraphs a) and b), LEVPHARMA
                will
                reimburse SANQUIN for these engineering costs within 30 days of receiving
                SANQUIN’s invoices documenting its expenditure or payment of such costs.
                LEVPHARMA’s obligations for other costs and expenses related to the Scale
                Up, and the terms and conditions pursuant to which LEVPHARMA shall
                make
                any payments, shall be as set forth in the final Project Plan and
                budget
                approved by SANQUIN and LEVPHARMA. 

            


    

     

    
      	 	
              d.

            	
              In
                addition, SANQUIN agrees to fund any necessary non-clinical studies
                required as a result of the Scale Up, including but not limited to
                conformance lot production and testing, comparability testing between
                product from the licensed facility/process and the scaled up
                facility/process, and any other non-clinical studies required by
                the
                Regulatory Authorities to obtain approval of the Scale
                Up.

            


    

     

    
      	 	
              e.

            	
              With
                respect to the loan provided by LEVPHARMA as contemplated by paragraph
                4.1(c)(i)(a), SANQUIN hereby agrees that: (a) the loan shall be due
                and
                payable in full by the maturity date as defined in paragraph 4.1(c)(i)(f);
                (b) no interest shall accrue on the outstanding principal amount
                of the
                loan; (c) SANQUIN shall repay the outstanding principal by crediting
                LEVPHARMA a * * * discount
                on the Purchase price per Unit of Commercial Product delivered to
                LEVPHARMA upon execution of this Amendment and the amount of such
                discount
                shall be applied against the outstanding balance of the loan; and
                (d)
                SANQUIN shall continue to conduct its operations in a manner substantially
                similar to its current operations for all periods prior to the repayment
                in full of the loan. 

            


    

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]

     

    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              f.

            	
              Given
                the volumes as outlined under 4.1(c)ii, the credit per unit of Product
                as
                under (e) above allows SANQUIN to pay back the loan before July 1,
                2014
                (maturity date). Should the Agreement be terminated before July 1,
                2014
                because of the default of Levpharma or if by July 1, 2014 the volume
                of
                Product ordered by Levpharma has been less than the volume needed
                by
                SANQUIN to pay back the loan as per clause (e) above, then LEVPHARMA
                shall
                waive the part of the loan still outstanding on July 1, 2014. Also
                in the
                event that LEVPHARMA files for bankruptcy under Chapter 7 of the
                US
                Bankruptcy Code before the loan has been fully paid back by SANQUIN,
                the
                then outstanding balance of the loan shall be forgiven.
                

            


    

     

    
      	 	
              g.

            	
              Should,
                on the other hand, the Agreement be terminated because of the default
                of
                SANQUIN before
                the loan has been fully paid back, then SANQUIN shall pay to LEVPHARMA
                the
                remaining principal amount of the loan outstanding as of the date
                of
                termination within 60 (sixty) days from such termination date. For
                purposes of clarity, the Parties expressly agree that any Change
                in
                Control event at Sanquin, as defined in Article 8.d) of this Amendment
                3,
                shall not be considered a default by
                Sanquin.

            


    

     

    
      	 	
              h.

            	
              The
                Scale Up shall be conducted in accordance with the following timelines:
                

            


    

     

    


    *
      *
      *

    *
      *
      *

    *
      *
      *

    *
      *
      *

    *
      *
      *

    *
      *
      *

    08/2009:
      Scale-Up approved by regulatory Authorities

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              ii.

            	
              Minimum
                Annual Purchase.

            


    

     

    
      	 	
              a.

            	
              In
                accordance with the Product ordering process provided for in the
                Original
                Agreement, SANQUIN agrees to make available and LEVPHARMA agrees
                to
                purchase the following estimated volumes of
                Product:

            


    

     

    Q4
      2007 *
      *
      *  Units

    Q1
      2008 *
      *
      *  Units

    Q2
      2008 *
      *
      *  Units
      

    Q3
      2008 *
      *
      *  Units

    Q4
      2008 *
      *
      *  Units

    Q1
      2009 *
      *
      *  Units

    


    
      	 	
              b.

            	
              The
                Parties agree to negotiate in good faith to modify the purchase
                commitments of LEVPHARMA set forth above in the event Commercial
                Launch
                does not occur prior to the end of LEVPHARMA’s first fiscal quarter in
                2008. 

            


    

     

    
      	 	
              c.

            	
              Commencing
                in the Calendar Year that LEVPHARMA and SANQUIN receive Regulatory
                Approval in the USA for the Scale Up, LEVPHARMA shall purchase and
                SANQUIN
                shall, subject to any revised forecast which may hereafter be provided
                by
                LEVPHARMA to SANQUIN on or before January 1, 2008, supply a minimum
                of the
                Pro Rata share of * * * Units,
                on an annualized basis, based on the actual number of days from when
                the
                Registration Application for the Scale Up is approved by the Regulatory
                Authorities in the United States until the end of such Calendar Year.
                

            


    

     

    
      	 	
              d.

            	
              Subject
                to the provisions of paragraph 4(c)(ii)(h), each Calendar Year after
                Regulatory Approval in the U.S. of the Scale Up and during the term,
                LEVPHARMA shall purchase and SANQUIN shall supply a minimum of *
                *
                * Units
                of Product

            


    

     

    
      	 	
              e.

            	
              Should
                LEVPHARMA require more than * * * Units
                of Product in any Calendar Year during the term after Regulatory
                Approval
                in the U.S. of the Scale Up, SANQUIN shall supply such additional
                amounts
                upon the terms and conditions set forth herein. However, SANQUIN
                shall
                never be obliged to supply to LEVPHARMA more than * * * Units
                of Product per Calendar Year under the terms of this Agreement unless
                the
                Parties shall hereafter otherwise expressly agree in writing, except
                where
                necessary to replace nonconforming or rejected Units of
                Product.

            


    

     

    [*CONFIDENTIAL
      TREATMENT HAS BEEN REQUESTED AS TO
      CERTAIN PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED
      HEREIN AND REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH
      THE
      SECURITIES AND EXCHANGE COMMISSION.]

    


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              f.

            	
              The
                quantities specified under clauses (a), (b), (c) and (d) above are
                applicable to the Territory as defined on the Effective Date of this
                Amendment. These quantities may be modified by mutual agreement of
                the
                Parties in the event that the Territory is extended according to
                Sections
                2.1 and/or 2.2(a).

            


    

     

    
      	 	
              g.

            	
              The
                quantities specified under clauses (a), (b), (c) and (d) above shall
                supersede and replace any minimum or maximum quantities otherwise
                contained in the Original
                Agreement.

            


    

     

    
      	 	
              h.

            	
              The
                volumes of Product specified under (a), (b), (c), and (d) above as
                well as
                the Purchase price as under article 5.1 may, after good faith discussions
                between the Parties, be modified by the mutual written agreement
                in the
                event that the forecast provided by LEVPHARMA to SANQUIN on or before
                January 1, 2008 is at least * * * less
                than * * * Units
                per Calendar Year. Subsequently, the Product volume specified in
                paragraph
                (d) above may be reduced in subsequent Calendar Years in the event
                LEVPHARMA’s forecasts for the third quarter of a Calendar Year is at least
                * * * 
                less than the then-current minimum purchase commitment.
                

            


    

     

    2.
      Section
      4.1.f of the Original Agreement is deleted in its entirety and replaced with
      the
      following:

    


    (f)
      Commercial
      Specifications and Manufacturing Standards.
      The
      Commercial Product shall be manufactured by SANQUIN at the locations and
      according to the manufacturing process as used to manufacture the Product for
      the Clinical Study (including the open label clinical trials) unless otherwise
      agreed to by the Parties according to Section 4.1(d) above. LEVPHARMA and
      SANQUIN shall cooperate in good faith and shall revise the Quality Agreement
      to
      reflect the Commercial Specifications and Manufacturing Standards for this
      Agreement. This revised Quality Agreement shall also describe the services
      concerning intake, handling, processing, storage and testing of LEVPHARMA owned
      plasma as contracted out by SANQUIN to SANQUIN’s subsidiary CAF-DCF in Brussels
      on behalf of LEVPHARMA. Further, the Quality Agreement shall also provide for
      the agreed-upon parameters for the intake, handling, processing, storage,
      testing, packaging and shipment of any residuals of the LEVPHARMA owned plasma
      after it has been processed by Sanquin, including without limitation,
      cryoprecipitate and the double depleted plasma (the “Residuals”). SANQUIN shall
      hold and/or transfer the Residuals in accordance with the Quality Agreement
      and
      any instructions received from or on behalf of LEVPHARMA. The Parties shall
      conclude such Quality Agreement before the audit which the FDA is expected
      to
      carry out as part of the process of the initial BLA-review but in any event
      prior to LEVPHARMA’s Commercial Launch. The Parties agree that the Commercial
      Specifications and Manufacturing Standards for this Agreement shall conform
      to
      any requirements from the FDA or any other Regulatory Authorities where the
      Product is either subject to Registration or under review for Registration
      and,
      to the extent practicable, to the specifications and standards applicable to
      SANQUIN's current manufacturing process for the Product. The Parties agree
      that
      SANQUIN shall be obligated for the cost for upgrading the SANQUIN facilities
      and
      procedures specifically needed for the Manufacturing Standards, up to a limit
      of
      * * * euros.
      This limitation shall only reflect any changes specifically requested by the
      FDA
      and does not include any changes made at the request of any other Regulatory
      Authority. In the event that the aggregate cost for this upgrade for
      FDA-compliance would exceed * * * euros,
      the Parties shall either agree upon an arrangement whereby LEVPHARMA bears
      the
      additional cost or the Parties shall terminate the Agreement without any Party
      bearing any liability to the other Party under the terms of this
      Agreement.

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    3.
      Section 4.4
      of the
      Original Agreement is deleted in its entirety and replaced with the
      following:

     

    


    4.4
      Delivery.
      SANQUIN
      shall ship the Product “FCA (free carrier), Amsterdam airport” and in accordance
      with LEVPHARMA's written instructions as detailed on the Purchase Order. SANQUIN
      shall be responsible for obtaining insurance for the shipment until the Product
      is on board of the carrier at Amsterdam airport. LEVPHARMA shall be responsible
      for obtaining insurance for the Product as of the point time when the Product
      has been brought on board of the carrier at Amsterdam airport. For purposes
      of
      this Agreement, delivery of Product by SANQUIN to LEVPHARMA shall be deemed
      to
      have taken place upon delivery to the LEVPHARMA-designated carrier at Amsterdam
      airport identified in the Purchase Order.

     

    4.
      A new
      Section 4.12 is added as follows:

     

    4.12 Plasma
      Supply; Toll Manufacturing.

     

    a)
      LEVPHARMA herewith acknowledges that SANQUIN has fulfilled its obligations
      under
      article 4.1(a) of the Original Agreement, i.e. delivery of maximum * *
      * units
      of
      Product for the Clinical Study. Parties agree that SANQUIN shall continue to
      supply Product for the Open Label Clinical Trials as carried out by LEVPHARMA
      until LEVPHARMA has obtained Regulatory Approval in the US under terms as
      defined under Section 5.2 as revised below. In addition, LEVPHARMA is aware
      of
      the fact that SANQUIN has been and is receiving requests from patients in the
      USA concerning personal importation of Cetor®, the C1-esterase inhibitor product
      that SANQUIN has currently registered in The Netherlands. SANQUIN is willing
      to
      supply such product to those patients, subject to those patients as well as
      their treating physicians acknowledging that they understand that Cetor® is not
      registered in the USA, to meet their needs. * * *, under terms as defined under
      Section 5.2 as revised below, until LEVPHARMA has obtained Regulatory Approval
      for the Product in the US. Parties agree that all Commercial Product to be
      supplied by SANQUIN to LEVPHARMA shall be manufactured for LEVPHARMA on a
      toll-manufacturing basis, under commercial terms as defined in Section 5.1
      of
      the Original Agreement as revised below, using blood Source Plasma (as defined
      in the U.S. Code of Federal Regulations) supplied by LEVPHARMA that shall at
      all
      times have been obtained from U.S.-licensed collection centers and which shall
      comply with the quality specifications as described in the Quality Agreement
      between the Parties.

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]

     

    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    b)
      Apart
      from the provisions under section 4.1(c)i(f) concerning SANQUIN’s ability to
      repay the loan being dependent upon LEVPHARMA ordering sufficient quantities
      of
      Product, the provisions of this Agreement in respect of the quantity of, and
      delivery dates for, SANQUIN’s supply of Product, including LEVPHARMA’s
      obligation to purchase the minimum amounts of Product, are subject to and
      conditioned upon LEVPHARMA’s supply of sufficient quantities of Source Plasma to
      SANQUIN (or its permitted designee hereunder) in accordance with the schedule
      agreed to by the Parties and revised each Calendar Quarter based on the rolling
      forecast provided to SANQUIN by LEVPHARMA. All other provisions of the Original
      Agreement pertaining to the manufacture of Product shall not be affected by
      this
      new Section 4.12.

     

    c)
      LEVPHARMA shall be responsible for supplying to SANQUIN, or its subsidiaries
      or
      permitted contractors hereunder, all Source Plasma required for: 

     

    i.  the
      manufacture and supply of the Product by or on behalf of SANQUIN to LEVPHARMA
      pursuant to this Agreement; and

     

    ii.    
      the
      manufacture and supply of such other and additional products (such as, without
      limitation, * * * 
      or * *
      *) as the Parties may hereafter agree, in writing, which may be manufactured
      and
      supplied by or on behalf of SANQUIN for LEVPHARMA pursuant to a separate
      toll-manufacturing arrangement in accordance with the terms and conditions
      of
      this Agreement.

     

    d)
      LEVPHARMA shall obtain all such Source Plasma and deliver it to SANQUIN (or
      its
      permitted designee hereunder) at
      its
      own cost.

     

    e)
      Upon
      receipt of LEVPHARMA’s Source Plasma, 

    i)  SANQUIN
      shall ensure that SANQUIN’s subsidiary CAF-DCF in Brussels, Belgium, or any
      other permitted designee hereunder takes all commercially reasonable actions
      to
      handle, store and maintain said Source Plasma, and any Residuals thereof,
      including PCR-testing for the presence of parvovirus B19 (hereinafter the
“Services”), according to the Quality Agreement.

     

    [*CONFIDENTIAL
      TREATMENT HAS BEEN REQUESTED AS TO
      CERTAIN PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED
      HEREIN AND REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH
      THE
      SECURITIES AND EXCHANGE COMMISSION.]

     

    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    ii)   
      In
      the
      event of a loss or destruction of LEVPHARMA’s Source Plasma or Residuals
      received by SANQUIN (or SANQUIN’s subsidiary CAF-DCF in Brussels, Belgium, or
      any other permitted designee hereunder), SANQUIN shall be liable for the cost
      of
      the lost/destroyed Plasma.

     

    iii)  
      SANQUIN
      shall only use LEVPHARMA’s Source Plasma (and Residuals) in accordance with the
      provisions of this Agreement and the Quality Agreement, unless otherwise
      instructed in writing by an authorized representative of LEVPHARMA.

     

    f)
      LEVPHARMA shall own all rights and interest in and to the Source Plasma and
      Residuals provided to SANQUIN pursuant to this Amendment and SANQUIN’s sole
      rights to such Source Plasma shall be to perform its obligations as set forth
      herein.

     

    g)
      SANQUIN may purchase from LEVPHARMA such components of such Source Plasma as
      are, as of the time of such purchase, in surplus to the needs of LEVPHARMA
      (solely as may be determined by LEVPHARMA) and needed by SANQUIN, at such
      reasonable prices as may hereafter be agreed to in writing by the Parties.
      Any
      remaining components not purchased by SANQUIN will be stored by SANQUIN and/or
      otherwise made available for sale to other parties as LEVPHARMA shall determine.
      The Parties agree to negotiate in good faith on any fees for these additional
      services.

     

    h)
      Concerning the yield of Product per liter of LEVPHARMA’s Source
      Plasma:

    
      	 	
              i)

            	
              Parties
                shall in good faith, based on the outcome of batches of Product
                manufactured between * * * and
                * * *, determine the minimum amount of Units of finished Product
                for each
                liter of Source Plasma actually pooled in each production run
                (“Yield”).

            


    

    
      	 	
              ii)

            	
              Once
                such Yield has been determined, and in the event of an actual yield
                identified of less than the determined Yield, SANQUIN shall be liable
                for
                the cost of the Plasma necessary to make up for the lower
                yield.

            


    

     

    5.
      Section
      5.1 of the Original Agreement is deleted in its entirety and replaced with
      the
      following:

     

    


    5.1
      Prices
      for Commercial Product and Services.
      

    


    a)
      The
      Purchase Price for Commercial Product supplied by SANQUIN
      to
LEVPHARMA
      pursuant
      to this Amendment shall be as follows:

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]

     

    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    In
      any
      Calendar Year, Units

    *
      *
      *   *
      * *
      /Unit

    *
      *
      *   *
      * *
      /Unit

    


    Concerning
      such Purchase Price, the following shall apply:

    i)    the
      number of Units shall be based on the number of Units nominally present per
      vial
      (i.e.: a vial of 500 Units by definition containing 500 Units),

    ii)    the
      Product shall be delivered by SANQUIN to LEVPHARMA without Official Batch
      Release, or similar approval, by any governmental authority or
      agency,

    iii)    the
      Product shall be supplied as filled and freeze-dried product in vials which
      are
      individually labelled (using normal labelling, not including any RFID’s or
      similar devices in the label) and packed in an individual box including a
      package insert as used in the current SANQUIN C1-inhibitor product,

    iv)    the
      individually packed vials shall be grouped together in boxes containing at
      least
      twenty (20) individual vials,

    v)    those
      20
      (or more)-vial boxes again grouped together in a bigger box made out of material
      which is sufficiently sturdy to avoid damage of the vials or exposure of the
      Product to temperatures exceeding the specified limits under normal shipment
      conditions,

    vi)   *
      * *.


    


    Such
      Purchase Price shall be amended as follows:

    a)
      Yearly, starting January 1st
      2008,
      with a percentage equal to the increase or decrease in the Dutch consumer price
      index.

    b)
      As
      agreed to by both Parties through good faith negotiations in the event of a
      significant change in Processing as a result of Product improvement or
      regulatory requirements.

    c)
      As
      agreed to by both Parties to cover SANQUIN’s
      actual
      cost for liability- insurance for any country where SANQUIN
      is
      supplying Product to LEVPHARMA
      under
      this Agreement that is not already covered under its current liability-insurance
      policy.

    d)
      As
      agreed to by both Parties to repay the loan for the scale up as described
      in paragraph
      4.1(c)(i)(e).  

    


    b)
      In
      addition to the Purchase Price as under a) above, LEVPHARMA shall pay to SANQUIN
      for each liter of LEVPHARMA’s Source Plasma shipped by LEVPHARMA to the premises
      of SANQUIN’s subsidiary CAF-DCF in Belgium, independent of whether or not such
      liter of plasma is used for toll manufacturing of Product by SANQUIN, a fee
      for
      the Services as under 4.12(e)i above. 

    Such
      Services Fee shall be:

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              ·

            	
              *
                *
                * euro
                per liter of LEVPHARMA’s Source Plasma taken in at the CAF-DCF
                premises

            


    

    


    Concerning
      such Services Fee, the following shall apply:

    i)     in
      case
      the initial pool of 576 samples tests negative for parvovirus B19 in the
      PCR-test, there are no further Services Fee costs related to B19 testing for
      LEVPHARMA,

    ii)    
in
      case
      the initial pool of 576 samples tests positive in the PCR-test for parvovirus
      B19, there will be another fee of euro * * * 
      for
      identifying the individual donation(s) that tested positive within this
      pool,

    iii)    the
      Services Fee includes storage of LEVPHARMA’s Source Plasma and/or derivatives
      for up to six months at the premises of SANQUIN’s subsidiary
      CAF-DCF,

    iv)   the
      Services fee handling of any LEVPHARMA’s Source Plasma and/or derivatives in
      preparation for shipment in standard packaging to any third party customer
      of
      LEVPHARMA at conditions “ex works” the CAF-DCF premises,

    v)    in
      case
      special packaging is required by LEVPHARMA on behalf of any third party
      customer, Parties will negotiate in good faith a fee for such extended
      services.

    


    In
      addition, such Services Fee shall be amended as follows:

    a)
      Yearly, starting January 1st
      2008,
      with a percentage equal to the increase or decrease in the Dutch consumer price
      index.

    b)
      As
      agreed to by both Parties through good faith negotiations in the event of a
      significant change in handling of testing requirements as a result of Product
      improvement or regulatory requirements.

      

    


    6.
      Section 5.2(a) of the Original Agreement is deleted in its entirety and replaced
      by the following:

    


    5.2
      Invoices.
      

    a)
      Product
      supplied for the Clinical Study.
      

    i)
      SANQUIN has invoiced LEVPHARMA for the Purchase Price for the * * * 
      Units of
      Product supplied for the Clinical Study. SANQUIN has provided a loan to
      LEVPHARMA in the amount of the Purchase Price for each invoice for Product
      supplied for the Clinical Study, and LEVPHARMA has provided a purchase money
      security interest to SANQUIN in the Product supplied for the Clinical Study
      for
      each shipment of such Product. A loan statement authorized by both Parties
      is
      attached to this Amendment 3. Upon Regulatory Approval in the US, SANQUIN shall
      credit LEVPHARMA’s account for the entire cost of the Clinical Product, and
      shall provide a release of any and all security interests granted by LEVPHARMA.
      

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    ii)
      For
      any Product supplied by SANQUIN to LEVPHARMA for the LEVPHARMA Open Label
      Clinical Trials (be it manufactured from USA plasma owned by SAQUIN or from
      LEVPHARMA’s Source Plasma) and/or * * * as
      supplied by SANQUIN to * * *, SANQUIN shall invoice to LEVPHARMA, and LEVPHARMA
      shall pay to SANQUIN within thirty (30) calendar days after receiving such
      invoice, an amount of * * * /Unit.

    


    


    7.
      Section 9.4(c) of the Original Agreement is deleted in its entirety and replaced
      by the following:

    


    (c)Third
      Party Liability to Consumers of the Products.
      

    In
      the
      event a third party consumer asserts a Claim against LEVPHARMA for damages
      caused by a defective Product, in the event that the defect in the Product
      is
      solely due to a hidden or non-hidden defect (latent or otherwise) in the Source
      Plasma supplied by or through LEVPHARMA to SANQUIN, which defect was present
      at
      the time such Source Plasma was delivered to SANQUIN, LEVPHARMA will assume
      full
      and sole liability for all direct and indirect damages resulting
      therefrom.

    


    In
      the
      event a third party consumer asserts a Claim against LEVPHARMA for damages
      caused by a defective Product (whether or not such defect is latent), in the
      event that the defect in the Product is due to (i) the negligence or misconduct
      of SANQUIN, or (ii) errors or defects (latent or otherwise) in the manufacturing
      process at SANQUIN, or (iii) a defect (latent or otherwise) in the Product
      (except to the extent the defect is solely due to the condition of the Source
      Plasma at the time it was delivered to SANQUIN), then, except to the extent
      that
      such Claim is based on the failure of LEVPHARMA to comply with the Handling
      Specifications, SANQUIN will assume full and sole liability for all direct
      and
      indirect damages resulting therefrom.

     

    8.
      Technology Transfer.
      SANQUIN
      agrees to transfer all necessary rights and interests to its Technology for
      manufacturing and distributing the Product to LEVPHARMA and/or one or more
      third
      parties under the following circumstances:

     

    
      	 	
              a)

            	
              Upon
                the effective date of this Amendment, SANQUIN and LEVPHARMA shall
                collaborate to identify and transfer on a non-exclusive basis all
                necessary rights to the Technology to a mutually acceptable third
                party
                manufacturer, to enable such third party to serve as a second supplier
                of
                the Product to LEVPHARMA and/or of intermediates needed to manufacture
                the
                Product to SANQUIN. Nothing herein is intended to limit the minimum
                annual
                volumes of * * * units
                of Product to be supplied to LEVPHARMA by SANQUIN in accordance with
                the
                Agreement. Except as provided for herein, SANQUIN shall maintain
                ownership
                of the Technology under this transfer and receive such license fee
                (including but not limited to milestone payments and royalties) from
                the
                third party manufacturer as is mutually agreeable among SANQUIN,
                LEVPHARMA
                and such third party manufacturer. In addition, SANQUIN shall be
                reimbursed for all reasonable legal and professional costs associated
                with
                the transfer of Technology.

            


    

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              b)

            	
              In
                the event of a Change in Control event at SANQUIN as defined in d)
                hereunder, SANQUIN shall contemporaneously assign to LEVPHARMA joint
                ownership rights to the Technology. As used herein “joint ownership
                rights” means that both SANQUIN and LEVPHARMA shall be co-equal owners of
                the Technology, each with the full and unfettered right to exploit
                the
                Technology. To the extent SANQUIN does not have the right to assign
                joint
                ownership to LEVPHARMA to any aspect of the Technology, it shall
                be deemed
                to have granted LEVPHARMA an irrevocable, transferable, worldwide,
                royalty
                free (subject to the payment obligations described in paragraph (c)
                below)
                license to use and exploit such Technology for all purposes. Any
                derivative products or extensions of the Technology and/or the
                intellectual property rights therein, created by or for SANQUIN or
                LEVPHARMA shall be the sole property of the party creating such derivative
                and such party shall have no obligation to the other party with respect
                thereto (other than SANQUIN’s obligation to license certain rights to
                LEVPHARMA as provided for in the Original Agreement). The assignment
                of
                rights to LEVPHARMA pursuant to this paragraph shall not modify or
                terminate SANQUIN’s obligation to provide Product to LEVPHARMA pursuant to
                the terms and conditions set forth in the Agreement.
                

            


    

    


    
      	 	
              c)

            	
              Notwithstanding
                the foregoing, in the event of a Change in Control, LEVPHARMA shall
                have
                the option, in its sole discretion to exercise the right at any time,
                but
                not within 3 months following the Change in Control event, to transfer
                (by
                license or otherwise) all necessary rights in and to the Technology
                to a
                third party for the purpose of manufacturing and delivering Product
                and
                simultaneously reducing or terminating its obligation to purchase
                Product
                hereunder from SANQUIN (or its successor) upon the following terms
                and
                conditions (for purposes of clarity, following a Change in Control,
                LEVPHARMA may independently engage a third party to manufacture and
                deliver quantities of Product in excess of the minimum purchase commitment
                required under this Amendment still being supplied by SANQUIN or
                its
                successor, in which event LEVPHARMA shall not be obligated to make
                the
                following payments to SANQUIN for as long as LEVPHARMA continues
                to order
                the quantities as contemplated under the minimum purchase commitment
                from
                SANQUIN or its successor:

            


    

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      	 	
              Ø

            	
              Upon
                actually exercising the right to transfer the Technology outside
                SANQUIN
                (or any resulting successor company) which results in the termination
                of
                SANQUIN’s manufacturing obligations hereunder, LEVPHARMA will make a
                down-payment to SANQUIN (or any resulting successor company) of *
                *
                * euro.
                This down-payment shall be applied against all future royalties or
                license
                fees for which LEVPHARMA may be liable pursuant to this paragraph.
                Should
                the Change of Control event triggering LEVPHARMA to exercise the
                right to
                transfer the Technology outside SANQUIN (or any resulting successor
                company) take place before * * *, then LEVPHARMA may, at LEVPHARMA’s sole
                discretion, make this down-payment by electing to forgive some or
                all of
                any outstanding indebtedness of SANQUIN pursuant to the loan arrangement
                contemplated in Section 4.1(c) of this Amendment. Should the Change
                of
                Control event triggering LEVPHARMA to exercise the right to transfer
                the
                Technology outside SANQUIN (or any resulting successor company) take
                place
                after * * *, then LEVPHARMA shall * * * of
                this Amendment and make this down-payment of * *
                *.

            


    

    


    
      	 	
              Ø

            	
              SANQUIN
                (or any resulting successor company) shall work in good faith with
                LEVPHARMA to actually effect such a transfer of the Technology. SANQUIN
                (or any resulting successor company) shall continue to supply the
                Product
                under the terms of the Agreement as amended until such transfer is
                complete and approved by the Regulatory Authorities.
                

            


    

    
      	 	
              Ø

            	
              Upon
                the first anniversary of the Regulatory Approval of the transfer
                of the
                Technology, and upon every anniversary thereafter for a period of
                * *
                * 
                years, LEVPHARMA shall pay to SANQUIN (or any resulting successor
                company)
                a minimum annual royalty of * * * euro.

            


    

    
      	 	
              Ø

            	
              In
                addition, LEVPHARMA shall pay a running royalty for a period of *
                *
                * years
                from the first anniversary of the Regulatory Approval of the Technology
                transfer of * * * 
                on
                net sales of Product that was manufactured outside SANQUIN (or any
                resulting successor company), to be applied against any minimum annual
                royalties.

            


    

    
      	 	
              Ø

            	
              In
                the event LEVPHARMA transfers the Technology to a third party manufacturer
                for the purpose of reducing the quantity of Product LEVPHARMA purchases
                from SANQUIN (but not terminating such relationship), the amounts
                specified above shall be adjusted on a pro-rata
                basis to reflect the reduction in Product purchased by LEVPHARMA
                hereunder. 

            


    

    


    d) 
      For
      purposes of this Agreement, a “Change in Control” shall mean:

    i. the
      sale,
      lease, transfer, conveyance, or other disposition of all or substantially all
      of
      SANQUIN’s assets;

    ii. a
      merger,
      consolidation, reorganization or other similar transaction that results in
      SANQUIN retaining less than 50%
      ownership of the entity that survives the transaction or otherwise has the
      effect of SANQUIN not being the surviving
      entity in such transaction;

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    iii. the
      sale
      of greater than 40% of the voting equity interests of SANQUIN to one or more
      third parties; 

    iv. approval
      by SANQUIN’s Board of a plan of complete liquidation; or 

    v. the
      individuals constituting the Board of SANQUIN as of the date of this Agreement
      (the “Incumbent Board”) cease for any reason to constitute at least 1/2 of the
      members of the Board; provided, however, that if the election, or nomination
      for
      election of any new director was approved by a vote of the Incumbent Board,
      such
      new director shall be considered a member of the Incumbent Board.

    


    9.
      Term.
      Article
      XII of the Original Agreement is hereby amended to provide that the initial
      term
      of the Agreement, as amended hereby, shall be effective through the effective
      date of this Amendment and ending on December 31, 2010. In addition, the Parties
      hereby agree to the following:

     

    a)
      LEVPHARMA shall have the absolute right to extend the initial term of this
      Agreement for up to eighteen (18) additional years by way of six (6) three
      (3)
      year renewal periods, upon the written notification by LEVPHARMA to SANQUIN
      of
      its intention to do so no later than 6 months before the expiration of the
      initial term and any subsequent renewal term of this Agreement.

     

    b)
      This
      Agreement may be further extended by the mutual written agreement of the Parties
      at any time prior to its expiration.

     

    10.
      Assignment.
      SANQUIN
      hereby consents in all respects to the assignment of the Agreement from
      LEVPHARMA to Lev Pharmaceuticals, Inc. (“LEV”) which is the parent corporation
      and sole owner of LEVPHARMA. LEVPHARMA
      hereby assigns all of its rights and obligations under the Agreement to LEV
      and
      LEV hereby assumes and agrees to perform any and all obligations and duties
      of
      LEVPHARMA under the Agreement and LEV shall have the sole responsibility for
      performing the obligations and exercising the rights of LEVPHARMA under the
      Agreement. 

     

    11.
      Full
      Force and Effect.
      Except
      to the extent the Original Agreement is modified by this Amendment, the other
      terms and provisions of the Original Agreement shall remain unmodified and
      in
      full force and effect. In the event of a conflict between the terms of the
      Original Agreement and the terms of this Amendment, the terms of this Amendment
      shall prevail. 

     

    12.
      General.
      This
      Amendment supersedes all prior arrangements and understandings between the
      Parties, written and oral, with respect to its subject matter. This Amendment
      may be executed in any number of counterparts, and each such counterpart shall
      be deemed to be an original instrument, but all such counterparts together
      shall
      constitute but one Agreement. Each party hereto represents and warrants that
      it
      has full right, power and authority to enter into this Amendment, to perform
      its
      obligations hereunder and has duly authorized its representative to execute
      this
      Amendment on its behalf.

     

    [*CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN
      PORTIONS OF THIS DOCUMENT. EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN
      AND
      REPLACED WITH AN ASTERISK [***], HAS BEEN FILED SEPARATELY WITH THE SECURITIES
      AND EXCHANGE COMMISSION.]


    
      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

    

     

    
      IN
        WITNESS WHEREOF, the Parties through their duly authorized representatives
        have
        executed this Amendment No. 3 to Distribution and Manufacturing Services
        Agreement as of the date first above written. 

    

     

    
      	 	 	 
	 	LEV
              DEVELOPMENT CORP.
	 
 	 
 	 
 
	 	By:  	/s/
              Joshua D. Schein
	 	
              
Joshua
              D. Schein, Ph.D.
	 	Chief
              Executive Officer


    

     

    
      	 	 	 
	 	LEV
              PHARMACEUTICALS, INC.
	 
 	 
 	 
 
	 	By:  	/s/
              Joshua D. Schein
	 	
              
Joshua
              D. Schein, Ph.D.
	 	
              Chief
                Executive Officer

            


    

     

    
      	 	 	 
	 	SANQUIN
              BLOOD SUPPY FOUNDATION
	 
 	 
 	 
 
	 	By:  	/s/
              T.J.F. Buunen
	 	
              
Name:
              T.J.F. Buunen
	 	Title:
              CEO