Exhibit
__

     

    
      SETTLEMENT
AGREEMENT AND MUTUAL RELEASE

      


      WHEREAS, the undersigned are parties to
the Delaware Court of Chancery action captioned In re: Transkaryotic Therapies,
Inc., C.A. No. 2776-CC (the “Consolidated Action”) and wish to settle the
Consolidated Action on the terms and conditions set forth in this Settlement
Agreement and Mutual Release (the “Agreement”),

       

      IT IS HEREBY AGREED AS
FOLLOWS:

       

      1. Settlement
Amount.  Shire Human
Genetic Therapies, Inc., a Delaware corporation formerly known as Transkaryotic
Therapies, Inc. (“TKT”), shall pay, or shall cause an entity incorporated or
otherwise organized in the United States to pay, to each of the entities listed
in the first column of Exhibit A hereto (the “Payees”) the amount set forth for
each such Payee in the second column of that Exhibit (the “Settlement
Amount”).  Each Settlement Amount of $50.00  per share
 represents $37.00 per share in proceeds from the sale of TKT stock and
$13.00 per share in interest for each share of TKT stock at issue in the
Consolidated Action and the collective payment of those Settlement Amounts is
made in full satisfaction of all claims asserted in that litigation. TKT shall
deliver the entire amount of each Payee’s Settlement Amount in accordance with
the wire transfer instructions to be provided to counsel for TKT, such
instructions to be provided within one business day of the execution of this
Agreement by all signatories.   It is agreed that the Settlement
Amount shall be allocated for tax purposes as being $37.00 in
proceeds from the sale of TKT stock and $13.00 per share in interest, and
that no party shall take any position or action inconsistent with such
treatment on a tax return.

       

      2.  Dismissal
of the Action/Payment of Settlement Amount.   Within one
business day of execution of this Agreement by all signatories, counsel for TKT
shall present to the Court of Chancery the order attached to this Agreement as
Exhibit B hereto (the “Order”) and advise the 

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

       

      Chancellor
that the parties have reached a global settlement of the Consolidated Action and
are jointly seeking the Court’s expedited approval of the Order (which will
authorize the dismissal of the Consolidated Action pursuant to 8 Del.C. §
262(k)).  By November 7, 2008, provided that the Court shall have
entered the Order on or before such date, TKT shall cause the following events
to occur simultaneously:

                

      
        	 	(a) 	payment
      of the Settlement Amount due to each Payee, as set forth above;
    and
	 	 	 
	
                 
      

              	
                (b)

              	
                filing
      of a stipulation of dismissal in the form attached as Exhibit C hereto
      (the “Dismissal”), with electronic signatures of counsel for the
      plaintiffs/petitioners in the Consolidated
  Action.

              


      

      


      In the
event the Court declines to enter the Order by November 7, 2008, this Agreement
shall become null and void for all purposes, the Dismissal shall not be filed,
and the Consolidated Action shall proceed as if this Agreement had not been
entered into.

       

                 3.  Mutual
Releases.
  Upon receipt of the Settlement Amounts by each of the
entities listed on Exhibit A, the following mutual releases shall take effect
without further action by any party:

       

      
        	
                 
      

              	
                (a)

              	
                Each
      Payee (including without limitation each plaintiff/petitioner in the
      Consolidated Action) and their respective heirs, successors, assigns,
      affiliates, parents and indirect parents, subsidiaries and indirect
      subsidiaries, officers, directors, stockholders, agents, partners,
      members, principals and counsel hereby releases each of the defendants in
      the Consolidated Action (the “Defendants”) and their heirs, successors,
      assigns, affiliates, parents and indirect parents, subsidiaries and
      indirect subsidiaries, officers, directors, stockholders, agents,
      partners, members, principals and counsel from any and all actions, causes
      of action, claims and demands for, upon or by reason of any loss, damage,
      injury, cost or expense whatsoever, in connection with or related to the
      Consolidated Action, whether in law or equity and whether based on any
      state law, federal law, foreign law or common law right of action or
      otherwise, foreseen or unforeseen, matured or unmatured, known or unknown,
      accrued or not accrued; and

              


      

       

      
        
          
          

        

        
          2

          
            

          

        

        
          
          

        

      

       

      
        	
                 
      

              	
                (b)

              	
                Each
      of the Defendants and their respective heirs, successors, assigns,
      affiliates, parents and indirect parents, subsidiaries and indirect
      subsidiaries, officers, directors, stockholders, agents, partners,
      members, principals and counsel hereby releases each of the
      plaintiffs/petitioners in the Consolidated Action and their heirs,
      successors, assigns, affiliates, parents and indirect parents,
      subsidiaries and indirect subsidiaries, officers, directors, stockholders,
      agents, partners, members, principals and counsel from any and all
      actions, causes of action, claims and demands for, upon or by reason of
      any loss, damage, injury, cost or expense whatsoever, in connection with
      or related to the Consolidated Action, whether in law or equity and
      whether based on any state law, federal law, foreign law or common law
      right of action or otherwise, foreseen or unforeseen, matured or
      unmatured, known or unknown, accrued or not
  accrued.

              


      

      


      4.  Authority/Binding
Effect.   Each party hereto represents that the person
executing this Agreement on that party’s behalf has been duly authorized to do
so and that the party for whom such person is acting will be fully and legally
bound by such execution of this document.  This Agreement shall be
binding upon and shall inure to the benefit of the successors, heirs, assigns
and affiliates of the parties hereto.

       

      5. No
Admission of Liability.  The
parties agree that this Agreement shall not be deemed or construed to be an
admission or evidence of any violation of any statute or law or of any liability
or wrongdoing or of the truth of any of the claims or allegations alleged in the
Consolidated Action or as a waiver of any defenses thereto.

       

      6.  Counterparts.   This
Agreement may be executed in counterparts, and facsimile or electronic
signatures of the parties shall be treated for all purposes as original
signatures, but shall not be effective against any party until executed by all
parties.

       

      7.  No
Modification.   No modification or waiver of any provision of
this Agreement shall be effective unless the same shall be in writing and signed
by all parties hereto.

       

      
        
          
          

        

        
          3

          
            

          

        

        
          
          

        

      

       

      8.  Governing
Law; Jurisdiction.  This Agreement
shall be governed by the laws of Delaware without regard to principles of
conflicts of law.  The Court of Chancery of the State of Delaware
shall have exclusive jurisdiction to hear any matters arising out of this
Agreement, and the parties hereby express their intent that the Court of
Chancery shall be the appropriate forum for any such matters.  It is
further agreed that the party who prevails in any such proceeding shall be
entitled to recover from the non-prevailing party all reasonable costs and
attorney’s fees incurred in that regard.

      


      [SIGNATURE
PAGES FOLLOW]

       

       

      
        
          
          

        

        
          4

          
            

          

        

        
          
          

        

      

      
         

        
          	
                  SHIRE
      HUMAN GENETIC THERAPIES, INC. 

                  f/k/a
      TRANSKARYOTIC THERAPIES, INC.

                	 	 	SHIRE
      PLC	 
	 	 	 	 	 
	By:	
                   

                	 	 	By:	
                   

                	 
	 	
                  Title:

                	 	 	 	
                  Title:

                	 
	 	
                  Date:  
      November ___, 2008

                	 	 	 	
                  Date:  
      November ___, 2008

                	 


        

         

         

        
          
            
              	
                      DR.
      DENNIS LANGER

                    	 	 	 	 
	 	 	 	 	 
	 	 	 	 	 	 	 
	By:	
                       

                    	 	 	 	
                       

                    	 
	 	
                      Title:

                    	 	 	 	
                       

                    	 
	 	
                      Date:  
      November ___, 2008

                    	 	 	 	
                       

                    	 


            

             

            
              
                 

                
                  	
                          HIGH
      RIVER LIMITED PARTNERSHIP

                        	 	 	ICAHN
      PARTNERS MASTER FUND L.P.	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                           

                        	 	 	By:	
                           

                        	 
	 	
                          Title:

                        	 	 	 	
                          Title:

                        	 
	 	
                          Date:  
      November ___, 2008

                        	 	 	 	
                          Date:  
      November ___, 2008

                        	 


                

                 

                
                  
                     

                    
                      	
                              ICAHN
      PARTNERS, L.P.

                               

                            	 	 	VIKING
      GLOBAL EQUITIES LP	 
	 	 	 	 	 
	By:	
                               

                            	 	 	By:	
                               

                            	 
	 	
                              Title:

                            	 	 	 	
                              Title:

                            	 
	 	
                              Date:  
      November ___, 2008

                            	 	 	 	
                              Date:  
      November ___, 2008

                            	 


                    

                    
                       

                      
                        
                           

                          
                            	
                                    VGE
      III PORTFOLIO LTD.

                                  	 	 	CR
      INTRINSIC INVESTMENTS, LLC	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                                     

                                  	 	 	By:	
                                     

                                  	 
	 	
                                    Title:

                                  	 	 	 	
                                    Title:

                                  	 
	 	
                                    Date:  
      November ___, 2008

                                  	 	 	 	
                                    Date:  
      November ___, 2008

                                  	 


                          

                          
                             

                            
                              
                                 

                                
                                  	
                                          SIGMA
      CAPITAL ASSOCIATES, LLC

                                        	 	 	MILLENCO,
      LLC	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                                           

                                        	 	 	By:	
                                           

                                        	 
	 	
                                          Title:

                                        	 	 	 	
                                          Title:

                                        	 
	 	
                                          Date:  
      November ___, 2008

                                        	 	 	 	
                                          Date:  
      November ___, 2008

                                        	 


                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

       

      
        
          
          

        

        
          5

          
            

          

        

        
          
          

        

        
          
             

            
              	 	 	 	 	 
	
                      PORTER
      ORLIN LLC

                    	 	 	ATTICUS
      CAPITAL LP	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                       

                    	 	 	By:	
                       

                    	 
	 	
                      Title:

                    	 	 	 	
                      Title:

                    	 
	 	
                      Date:  
      November ___, 2008

                    	 	 	 	
                      Date:  
      November ___, 2008

                    	 


            

             

            
              
                 

                
                  	 	 	 	 	 
	
                          ROSLYN
      M. ORLIN

                        	 	 	
                          DEEPHAVEN
      EVENT TRADING, LTD.

                        	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                           

                        	 	 	By:	
                           

                        	 
	 	
                          Title:

                        	 	 	 	
                          Title:

                        	 
	 	
                          Date:  
      November ___, 2008

                        	 	 	 	
                          Date:  
      November ___, 2008

                        	 


                

                 

                
                  
                     

                    
                      	
                              DEEPHAVEN
      GROWTH OPPORTUNITIES TRADING, LTD.

                            	 	 	
                              MA
      DEEP EVENT TRADING, LTD.

                            	 
	 	 	 	 	 
	 	 	 	 	 
	By:	
                               

                            	 	 	By:	
                               

                            	 
	 	
                              Title:

                            	 	 	 	
                              Title:

                            	 
	 	
                              Date:  
      November ___, 2008

                            	 	 	 	
                              Date:  
      November ___, 2008

                            	 


                    

                     

                  

                

              

            

          

        

      

      


      EXECUTION
OF AGREEMENT

      BY NON-PARTY
STOCKHOLDER:

      


      ING
CAPITAL LLC hereby acknowledges that, although it is not a party to the
Consolidated Action, its execution of this Settlement Agreement and Mutual
Release constitutes its express agreement to be bound by the all of the terms
and conditions set forth above as if it were such a party, and that its receipt
of a Settlement Amount (as reflected on Schedule A hereto) is conditioned upon
its agreement to be so bound.

      
         

        
          
             

            
              	
                       

                       

                    	 	 	ING CAPITAL
LLC	 
	 	
                       

                    	 	 	By:	
                       

                    	 
	 	
                       

                    	 	 	 	
                      Title:

                    	 
	 	
                       

                    	 	 	 	
                      Date:  
      November ___, 2008

                    	 


            

             

          

        

      

      


      
        
          
          

        

        
          6

          
            

          

        

        
          
          

        

         

      

      EXHIBIT
A

      TO

      SETTLEMENT
AGREEMENT

      AND
MUTUAL RELEASE

      


      
        	
                 

                Payees

              	
                Settlement
      Amounts

                to
      be Paid

                by
      TKT

              	
                 

                Number
      of

                TKT
      Shares Represented

              
	
                Millenco
      LLC

              	
                $164,983,550

              	
                3,299,671

              
	
                Porter
      Orlin LLC

              	
                $123,235,350

              	
                2,464,707

              
	
                Atticus
      Capital LP

              	
                $38,945,000

              	
                778,900

              
	
                Roslyn
      Orlin

              	
                $500,000

              	
                10,000

              
	
                Icahn
      Partners Master Fund L.P.

              	
                $37,595,850

              	
                751,917

              
	
                Icahn
      Partners L.P.

              	
                $34,703,950

              	
                694,079

              
	
                High
      River Limited Partnership

              	
                $18,075,000

              	
                361,500

              
	
                CR
      Intrinsic Investments, LLC

              	
                $100,628,050

              	
                2,012,561

              
	
                Sigma
      Capital Associates, LLC

              	
                $16,850,000

              	
                337,000

              
	
                VGE
      III Portfolio Ltd.

              	
                $2,735,000

              	
                54,700

              
	
                Viking
      Global Equities LP

              	
                $2,565,000

              	
                51,300

              
	
                Deephaven
      Event Trading Ltd.

              	
                $4,855,700

              	
                97,114

              
	
                Deephaven
      Growth Opportunities Trading, Ltd.

              	
                $2,960,050

              	
                59,201

              
	
                ING
      Capital LLC

              	
                $18,825,000

              	
                376,500

              


      

      


      
        
          
          

        

        
          7

          
            

          

        

        
          
          

        

      

      


      EXHIBIT
B

      TO

      SETTLEMENT
AGREEMENT

      AND
MUTUAL RELEASE

      


      IN
THE COURT OF CHANCERY OF THE STATE OF DELAWARE

      


      
        	
                 

                IN
      RE: TRANSKARYOTIC  THERAPIES, INC.

                 

              	
                )

                )

                )

                )

              	
                 

                Consolidated

                C.A.
      No. 2776-CC

              


      

      


      [PROPOSED]
ORDER

      


      WHEREAS,
this Court has been informed that the parties to the captioned action have
reached a proposed settlement (the “Settlement”); and

      


      WHEREAS,
the parties have represented to this Court that all persons listed on the duly
verified list of appraisal claimants (as filed with this Court) have agreed to
settle this action under the terms and conditions of the Settlement;
and

      


      WHEREAS,
the Court finds that these circumstances satisfy the requirements of 8 Del. C. § 262
(k);

      


      NOW,
THEREFORE, this ____ day of November, 2008, IT IS HEREBY ORDERED that this
action may be dismissed by the filing of a stipulation of dismissal pursuant to
Court of Chancery Rule 41(a)(1)(ii).

      


      
         

        
          
             

            
              	
                       

                       

                    	 	 	 	 
	 	
                       

                    	 	 	 	
                       

                    	 
	 	
                       

                    	 	 	 	
                      William
      B. Chandler, III

                    	 
	 	
                       

                    	 	 	 	
                      Chancellor

                    	 


            

             

          

        

      

       

      


      
        
          
          

        

        
          8

          
            

          

        

        
          
          

        

         

      

      EXHIBIT
C

      TO

      SETTLEMENT
AGREEMENT

      AND
MUTUAL RELEASE

      


      IN
THE COURT OF CHANCERY OF THE STATE OF DELAWARE

      


      
        	
                 

                IN
      RE: TRANSKARYOTIC  THERAPIES, INC.

                 

              	
                )

                )

                )

                )

              	
                 

                Consolidated

                C.A.
      No. 2776-CC

              


      

       

      


      STIPULATION  OF
DISMISSAL

      


      


      Pursuant
to Court of Chancery Rule 41(a)(1)(ii) and the Order dated November ________,
2008   the captioned action is hereby dismissed with
prejudice.

      
         

        
          
             

            
              	ASHBY &
    GEDDES	 	 	POTTER ANDERSON
      & CORROON LLP	 
	 	 	 	 	 
	 	 	 	 	 
	
                      Stephen
      E. Jenkins (#2152) 

                      Steven
      T. Margolin (#3110) 

                      Lauren
      E. Maguire  (#4261) 

                      Catherine
      A. Strickler (#4310) 

                      Andrew
      D. Cordo (#4534) 

                      500
      Delaware Avenue, 8th
      Floor 

                      Wilmington,
      DE 19801 

                      (302)
      654-1888

                    	 	 	
                      Arthur
      L. Dent (#2491)

                      Bradley
      W. Voss (#4318)

                      Abigail
      M. LeGrow (#4673)

                      P.O.
      Box 951

                      1313
      N. Market Street

                      Wilmington,
      DE 19801

                      (302)
      984-6034

                    	 
	 	 	 	 	 
	Attorneys for High River
      Limited Partnership, Icahn Partners Master Fund, L.P., Icahn Partners,
      L.P., Viking Global Equities LP, VGE III Portfolio Ltd., CR Intrinsic
      Investments, LLC, and Sigma Capital Associates, LLC	 	 	Attorneys for Millenco, LLC,
      Porter Orlin LLC, Atticus Capital LP and Roslyn M. Orlin	 


            

             

          

        

      

      


      
        
          
          

        

        
          9

          
            

          

        

        
          
          

        

      

      
        
           

          
            
               

              
                	EDWARDS ANGELL PALMER &
      DODGE LLP	 	 	RICHARDS, LAYTON
      & FINGER, P.A.	 
	 	 	 	 	 
	 	 	 	 	 
	
                        

                          John
      L. Reed (#3023)

                          Denise
      Seastone Kraft  (#2778)

                          919
      North Market Street

                          15th
      Floor

                          Wilmington,
      Delaware   19801

                          (302)
      777-7770

                        

                      	 	 	
                        

                          Allen
      M. Terrell, Jr. (#709)

                          John
      D. Hendershot (#4178)

                          Charles
      A. McCauley, III (#4738)

                          One
      Rodney Square, P.O. Box 551

                          Wilmington,
      Delaware 19899-0551

                          (302)
      651-7700

                        

                      	 
	 	 	 	 	 
	Attorneys for Deephaven Event
      Trading, Ltd., Deephaven Growth Opportunities Trading, Ltd. and MA Deep
      Event Trading, Ltd.	 	 	Attorneys for Transkaryotic
      Therapies, Inc., and Shire Plc.	 


              

               

            

          

        

      

      
        
           

          
            
               

              
                	DUANE MORRIS
    LLP	 	 	
                      	 
	 	 	 	 	 
	 	 	 	 	 
	
                        

                                
                            Daniel
      V. Folt (#3143)

                            Matt
      Neiderman (#4018)

                            1100
      North Market Street

                            Suite
      1200

                            Wilmington,
      DE 19801

                            (302)
      657-4927

                          

                        

                      	 	 	
                         

                      	 
	 	 	 	 	 
	      
                        Attorneys
      for Dennis H. Langer

                      	 	 	 	 


              

               

            

          

        

      

      10