EXHIBIT
      10.10

     

    
      Portions
        herein identified by [***] have been omitted
        pursuant to a request for confidential treatment and have been filed separately
        with the 

      Commission
        pursuant to Rule 406 of the Securities Act
        of 1933, as amended.

       

    

    LICENSE
      AGREEMENT

    


    


    


    between

    


    


    Cougar
      Biotechnology Inc.

    10940
      Wilshire Blvd., Suite 600

    Los
      Angeles, CA 90024

    USA

    


    (Referred
      to as Cougar)

    


    


    and

    


    


    LEO
      Pharma A/S

    Industriparken
      55

    2750
      Ballerup

    Denmark

    


    (Referred
      to as LEO)

    


    


    (LEO
      and
      Cougar are hereinafter collectively referred to as the Parties and individually
      as a Party)

     

    
      
        
        

      

      
        1

        
          

        

      

      
        
        

      

    

    


    TABLE
      OF
      CONTENTS

    

      
        	
                1.
                  DEFINITIONS

              	
                3

              
	 	 
	
                2.
                  GRANT OF LICENSE

              	
                5

              
	 	 
	
                3.
                  OBLIGATIONS OF COUGAR

              	
                5

              
	 	 
	
                4.
                  ROYALTIES AND OTHER CONSIDERATION

              	
                6

              
	 	 
	
                5.
                  OWNERSHIP AND PROSECUTION OF PATENT RIGHTS

              	
                8

              
	 	 
	
                6.
                  INFRINGEMENT OF THE PATENT RIGHTS BY A THIRD PARTY

              	
                8

              
	 	 
	
                7.
                  INFRINGEMENT OF A THIRD PARTY’S RIGHT BY THE PATENT RIGHTS OR A
                  PRODUCT

              	
                9

              
	 	 
	
                8.
                  WARRANTIES

              	
                10

              
	 	 
	
                9.
                  INDEMNIFICATION

              	
                10

              
	 	 
	
                11.
                  CONFIDENTIALITY

              	
                12

              
	 	 
	
                12.
                  SUBLICENSING AND ASSIGNMENT

              	
                13

              
	 	 
	
                13.
                  TERM AND TERMINATION

              	
                13

              
	 	 
	
                14.
                  RIGHTS AND OBLIGATIONS AFTER TERMINATION OF THE AGREEMENT

              	
                14

              
	 	 
	
                15.
                  GOVERNING LAW AND VENUE

              	
                14

              
	 	 
	
                16.
                  FORCE MAJEURE

              	
                15

              
	 	 
	
                17.
                  MISCELLANEOUS

              	
                15

              
	 	 
	
                18.
                  PAYMENTS, NOTICES AND OTHER COMMUNICATIONS

              	
                16

              


      



     

    
      
        
        

      

      
        2

        
          

        

      

      
        
        

      

    

     

    This
      Agreement (hereinafter referred to as this "Agreement"), effective as of this
      June 27, 2005 (the ”Effective Date”), is entered into by and between LEO Pharma
      A/S, a corporation having its principal office at Industriparken 55, 2750
      Ballerup, Denmark (hereinafter referred to as “LEO”), and Cougar Biotechnology
      Inc., a corporation duly organized and existing under the laws of the State
      of
      California with head quarters at 10940 Wilshire Blvd., Suite 600, Los Angeles,
      CA 90024, USA (”Cougar”).

    


    WHEREAS

    LEO
      Pharma A/S is the sole owner of Patent Rights, Know-how and Regulatory
      Information relating to Seocalcitol

    


    WHEREAS

    Cougar
      wishes to license such Patent Rights, Know-how and Regulatory Information from
      LEO

    


    NOW
      THEREFORE

    The
      Parties have agreed as follows:

     

    1.
      DEFINITIONS

     

    “Affiliate”
      shall mean with respect to either Party, any entity that directly or indirectly
      controls, is controlled by, or is under common control with such
      Party.

    


    “Commercially
      Reasonable and Diligent Efforts” shall mean such diligent and conscientious
      endeavors as, consistent with standards of good faith and reasonableness under
      the attendant circumstances, are appropriate to attempt to accomplish the stated
      result and which include a thorough, vigorous and diligent program for
      exploitation of the Patent Rights as timely and efficiently as possible. Such
      program shall include the clinical development, including research and
      development, manufacturing, laboratory and clinical testing as well as marketing
      using such efforts and resources as are commonly used in the pharmaceutical
      industry for an ethical drug of similar commercial potential at a similar stage
      in its lifecycle, taking into consideration its safety and efficacy, its cost
      to
      develop, the competitiveness of alternative products, its proprietary position,
      the likelihood of regulatory approval, its profitability and all other relevant
      factors.

    


    “Epi-Seocalcitol”
      shall mean the active substance known under the chemical name
      1(S),3(R)-dihydroxy-20(S)-(5’-ethyl-5’-hydroxy-hepta-1’(E), 3’(E) -
      dien-1’-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene, which is an analogue of
      vitamin D.

    


    “Field
      of
      Use” shall mean all uses.

    


    “Know-how”
      shall mean all information regarding Seocalcitol and other compounds and uses
      covered by Patent Rights (except information contained in the Patent Rights
      and
      Regulatory Information) such as but not limited to reports, protocols,
      publications, trade secrets, manufacturing information, data, compounds,
      processes, formulae, formulations, materials, devices, systems, biological
      samples, tissues, intermediates, notes, records, confidential information,
      whether in written or verbal form (other than as disclosed in the Patent Rights
      or Regulatory Information) which LEO has the right to disclose to
      Cougar.

     

    
      
        
        

      

      
        3

        
          

        

      

      
        
        

      

    

    


    “Net
      Sales” shall mean the total gross receipts for sales of Product(s) to the market
      by or on behalf of Cougar or any of its sublicensees, whether invoiced or not,
      less only the sum of the following: (a) usual trade discounts to customers;(b)
      sales, tariff duties and/or use taxes directly imposed and with reference to
      particular sales; (c) outbound transportation prepaid or allowed and
      transportation insurance; (d) amounts allowed or credited on returns; (e) bad
      debt deductions actually written off during the accounting period; (f) sales
      commissions; and (g) packaging and freight charges.

    


    “New
      Drug
      Application” shall mean a New Drug Application as defined in 21 C.F.R. § 314.50
      et. seq. and filed with the Food and Drug Administration in compliance with
      applicable laws and regulations to obtain approval to market a pharmaceutical
      product in the United States.

    


    “Patent
      Rights” shall mean all patents and patent applications that include Seocalcitol
      or its manufacture or use owned or controlled by LEO prior to or during the
      term
      of this Agreement and include:

    


    
      	
            	i)	
              those
                patents and patent applications listed in the enclosed Appendix A;
                and

            


    

    
      	
            	ii)	
              any
                other United States or foreign patent applications or patents that
                claim
                priority to any of the patents or applications listed in Appendix
                A and
                Appendix B, together with any and all patents issuing thereon, including
                continuations, continuations-in-part, divisionals, reexaminations,
                extensions, and reissue applications and any United States or foreign
                patents granted upon such applications, all of which shall be deemed
                added
                to Appendix A and Appendix B. 

            


    

     

    “Product”
      shall mean any pharmaceutical product based on the Patent Rights, the Know-how
      or the Regulatory Information, including Seocalcitol, whether alone or in
      combination with other active or inactive ingredients, and any salts or
      derivatives of such Product and shall include combination products.


    


    “Regulatory
      Information” shall include all data, information, submissions and rights related
      to preparing for and seeking regulatory approval for a Product in the Territory,
      including but not limited to Orphan Drug Designations, pre-clinical or clinical
      protocols and data resulting from or relating to pre-clinical or clinical trials
      and all Investigational New Drug Applications ("INDs"), New Drug Applications
      ("NDAs") and and their non-US counterparts existing prior to or during the
      term
      as specified in Appendix C..

    


    “Seocalcitol”
      shall mean the active substance known under the chemical name
      1(S),3(R)-dihydroxy-20(R)-(5’-ethyl-5’-hydroxy-hepta-1’(E), 3’(E) -
      dien-1’-yl)-9,10-secopregna-5(Z),7(E),10(19)-triene, which is an analogue of
      vitamin D.

    


    “Territory”
      shall mean the world.

    


    “Third
      Party” means any party other than LEO, Cougar and their respective
      Affiliates.

     

    
      
        
        

      

      
        4

        
          

        

      

      
        
        

      

    

    


    2.
      GRANT
      OF LICENSE

     

    2.1.1
      Exclusivity. 

    Subject
      to all of the terms and conditions of this Agreement, and as of the Effective
      Date, LEO hereby grants to Cougar an exclusive license to and under the Patent
      Rights listed in Appendix A, Regulatory Information and Know-how to a) make,
      have made, use, lease, sell, and/or import the Product in the Field, in the
      Territory; and b) to sublicense to third parties the rights granted under
      subsection (a) of this Section 2.1.1. 

    


    2.1.2
      Exclusivity to Epi-Seocalcitol.

    Subject
      to all of the terms and conditions of this Agreement, and as of the Effective
      Date, LEO hereby grants to Cougar an exclusive license to the rights pertaining
      to Epi-Seocalcitol under the Patent Rights listed in Appendix B, Regulatory
      Information and Know-how to a) make, have made, use, lease, sell, and/or import
      the Product in the Field, in the Territory; and b) to sublicense to third
      parties the rights granted under subsection (a) of this Section 2.1.2.


    


    2.2
      Research. 

    Notwithstanding
      the license being exclusive, LEO is not prevented from use of the Patent Rights
      and the Know-how in connection with its own internal research and development
      activities irrespective of field or area.

    


    2.3
      No
      warranty. 

    LEO
      does
      not warrant that the Patent Rights, to the extent such rights have not been
      issued at the time of this Agreement entering into force, will be
      issued.

     

    3.
      OBLIGATIONS OF COUGAR

     

    3.1
      Product

    Cougar
      covenants to LEO that it will use Commercially Reasonable and Diligent Efforts
      to develop, market, promote and sell a Product. Cougar shall notify LEO of
      any
      launch of a Product.

    


    In
      the
      event of Cougar deciding not to exploit the Patent Rights, Know-how or
      Regulatory Information further for at least one Product, Cougar shall without
      undue delay inform LEO of its decision and Cougar shall hereafter be entitled
      to
      terminate this Agreement. In addition, in the event that Cougar is finally
      judicially determined to be in breach of the above covenant, then LEO shall
      thereafter be entitled to terminate this Agreement.

    


    3.2
      Development Plan and Progress Report

    Cougar
      shall within six month from the execution of this Agreement provide LEO with
      a
      full development plan. The development plan shall inter
      alia
      include
      tentative dates for the milestones mentioned in Section 4.1 (b) to 4.1 (f).
      Also
      this plan is to be updated yearly by Cougar and forwarded to LEO.

    


    Cougar
      shall provide LEO with a yearly progress report on the status of the commercial
      development of the Patent Rights and the Know-how. This yearly progress report
      shall be due every year on the anniversary of the commencement of this
      Agreement.

     

    
      
        
        

      

      
        5

        
          

        

      

      
        
        

      

    

    


    3.3
      Trademarks etc.

    Cougar
      shall not in any way use directly or indirectly the name, logo or other marks
      of
      LEO or any adaptation of them in any marketing, advertising, promotional or
      sales literature without the prior written consent of LEO.

    


    Cougar
      is, however, entitled to use the name Seocalcitol in connection with the Patent
      Rights and a Product.

    


    4.
      ROYALTIES AND OTHER CONSIDERATION

     

    4.1
      Consideration for the license

    In
      consideration of the rights granted under this Agreement Cougar shall pay to
      LEO
      the following:

    


    
      	 	
              (a)

            	
              
                Two
                  hundred fifty thousand Dollars (USD250,000) upon commencement
                  of this Agreement;

              

            


    

    


    
      	 	
              (b)

            	
              [***] upon
                completion of a Cougar sponsored (or sublicensee sponsored) Phase
                II Proof
                of Concept trial with a Product that achieves its primary endpoint
                as
                defined in the study protocol;

            


    

    


    
      	 	
              (c)

            	
              [***] upon
                the dosing of the first patient with a Product in a Cougar sponsored
                (or
                sublicensee sponsored) pivotal Phase III clinical trial;
                

            


    

    


    
      	 	
              (d)

            	
              [***] upon
                submission of the first Cougar sponsored (or sublicensee sponsored)
                New
                Drug Application by the Food and Drug Administration with a Product;
                

            


    

    


    
      	 	
              (e)

            	
              [***] upon
                the final approval by the Food and Drug Administration of the first
                Cougar
                sponsored (or sublicensee sponsored) New Drug Application for a Product;
                and

            


    

    


    
      	 	
              (f)

            	
              [***] upon
                the first final approval by the applicable regulatory agency in the
                European Union of the first Cougar sponsored (or sublicensee sponsored)
                application for a Product.

            


    

    


    Payment
      shall be made within 15 (fifteen) working days from the date mentioned in the
      relevant section by bank transfer to such bank account as designated by LEO
      in
      writing.

    


    4.2
      Royalty

    4.2.1  Cougar
      shall pay to LEO a royalty equal to [***] of Net Sales by Cougar of Product
      during the term of the license. In the event that Cougar sublicenses the
      license, Cougar shall pay to LEO an amount equal to [***]% of the royalties
      received by Cougar from sales of Products by any sublicense, of Product in
      such
      country where said sale occurred, however no less than [***] % of Net Sales
      by such sublicense. It is understood that the primary consideration for the
      royalty payment is the transfer of Regulatory Information to Cougar, and that
      the payment of the portion of the royalty which represents the consideration
      for
      transfer of the Patent Rights is being apportioned over the term of the license
      for the convenience of the parties.

     

    
      
        
        

      

      
        6

        
          

        

      

      
        
        

      

    

    


    4.2.2 The
      royalty shall be payable upon each 31 March, 30 June, 20 September and 31
      December.

    


    4.2.3  Each
      payment shall be accompanied by a statement containing item description,
      quantity sold, sales value and currency. 

    


    4.2.4 Cougar
      shall keep complete and accurate books and records in respect of all payments
      made in accordance with this Agreement, and LEO shall be entitled to inspect
      such books and records upon reasonable notice and during normal business
      hours.

    


    4.2.5 The
      sale
      of a Product, whether by Cougar or its sublicensees, shall be counted only
      once
      in calculating Net Sales for royalty payments, and will be counted upon the
      first delivery or invoice. No multiple royalties shall be payable because any
      Products, their manufacture, use, lease or sale are or shall be covered by
      more
      than one patent application, patent or certificate of registration licensed
      under this Agreement. 

    


    4.2.6  In
      the
      event that a Product is sold in the form of a combination product containing
      one
      or more products or technologies which are themselves not a Product, the Net
      Sales for such combination product shall be calculated by multiplying the sales
      price of such combination product by the fraction A/(A+B) where A is the invoice
      price of the Product or fair market value of the Product and B is the total
      invoice price of the other products or technologies or the fair market value
      of
      the other products or technologies. In the case of a combination product which
      includes one or more Products, the Net Sales for such combination product upon
      which the royalty due to LEO is based shall not be less than the normal
      aggregate Net Sales for such Product. 

    


    4.2.7 (i)
      With
      respect to Products used to treat tumors or cancer, to the extent that Cougar
      or
      its sublicensee is required by order or judgment of any court in any
      jurisdiction, or if Cougar determines in its reasonable discretion that it
      is
      necessary, to obtain a license from a third party in order to practice the
      Patent Rights, the Know-how or the Regulatory Information, then [***]
      percent [***] of the royalties payable under such license in such
      jurisdiction may be deducted from royalties otherwise payable to LEO. (ii)
      With
      respect to Products used to treat diseases other than tumors or cancer, to
      the
      extent that Cougar or its sublicensee is required by order or judgment of any
      court in any jurisdiction, or if Cougar and LEO together agree that it is
      necessary to obtain a license from a third party in order to practice the Patent
      Rights, the Know-how or the Regulatory Information, then [***]
      percent [***] of the royalties payable under such license in such
      jurisdiction may be deducted from royalties otherwise payable to
      LEO.

    


    4.2.8 Should
      a
      compulsory license required by law be granted to a Third Party in any country
      of
      the Territory under Patent Rights licensed hereunder to Cougar, then the Royalty
      Rate payable under Section 4.2.1 shall be adjusted to match any lower rate
      granted to the Third Party for such country. 

    


    4.3
      Method of payment

    Any
      payment made in accordance with this Agreement shall be made by bank transfer
      to
      such bank account as designated by LEO in writing.

     

    
      
        
        

      

      
        7

        
          

        

      

      
        
        

      

    

    


    4.4
      Taxes

    All
      payments made in accordance with this Agreement are exclusive of value added
      tax, and when making a payment Cougar shall also pay any value added tax
      payable. 

    


    All
      taxes
      to be paid by Cougar as a consequence of this Agreement are of no relevance
      to
      LEO.

    


    5.
      OWNERSHIP AND PROSECUTION OF PATENT RIGHTS

     

    5.1
      Ownership

    LEO
      shall
      remain the full owner of the Patent Rights and has full control over the Patent
      Rights. However, upon request from Cougar, LEO shall be obliged to perform
      the
      necessary actions in order to maintain the Patent Rights and to file or
      prosecute patent applications relating to the Patent Rights. LEO will take
      into
      account the comments and requests of Cougar with respect thereto, and both
      parties agree to provide reasonable cooperation to each other to facilitate
      the
      application and prosecution of Patent Rights. 

    


    LEO
      agrees to keep Cougar reasonably well informed with respect to the status and
      progress of any such applications, prosecutions and maintenance activities
      and
      to consult in good faith with Cougar and take into account Cougar’s comments and
      requests with respect thereto. 

    


    Prior
      to
      any abandonment of any patents or patent applications in the Patent Rights,
      LEO
      shall give Cougar at least sixty (60) days notice and a reasonable opportunity
      to take over prosecution of such Patent Rights. In such event, Cougar shall
      have
      the right, but not the obligation, to commence or continue such prosecution
      and
      to maintain any such Patent Rights under its own control and at its expense
      and
      LEO shall then have no further rights in such application or patent. The Parties
      agree to cooperate in such activities including execution of any assignments
      or
      other documents necessary to enable Cougar to obtain and retain sole ownership
      and control of such Patent Rights. LEO agrees to be named as a party on any
      document or legal action desired or necessary to prosecute or enforce Patent
      Rights.

    


    5.2
      Costs

    All
      costs
      in relation to the maintenance of the Patent Rights shall be borne by
      Cougar.

    


    6.
      INFRINGEMENT OF THE PATENT RIGHTS BY A THIRD PARTY

     

    6.1
      Information and consultation

    Cougar
      and LEO shall promptly provide written notice, to the other Party, of any
      alleged infringement by a Third Party of the Patent Rights and provide such
      other Party with any available evidence of such infringement. LEO and Cougar
      shall consult one another in a timely manner concerning any appropriate response
      to the infringement.

    


    6.2.
      Prosecution and/or defence.

    LEO
      is
      entitled, at its sole discretion, to respond to an alleged infringement of
      the
      Patent Rights. However, during the term of this Agreement, LEO shall upon
      request from Cougar be obliged to prosecute and/or defend any infringement
      of
      the Patent Rights, and, using counsel acceptable to both Cougar and LEO. Cougar
      shall have the right to participate in all aspects of the action. All costs
      in
      relation to prosecution and/or defence of the Patent Rights initiated upon
      the
      request of Cougar shall be borne by Cougar, and any recovery of damages shall
      be
      retained entirely by Cougar.

     

    
      
        
        

      

      
        8

        
          

        

      

      
        
        

      

    

    


    6.3
      Cooperation

    In
      any
      suit to enforce and/or defend the Patent Rights pursuant to this Agreement,
      Cougar and LEO shall cooperate in all respects and, to the extent possible,
      have
      its employees testify when requested and make available relevant records,
      papers, information, samples, specimens, and the like.

    


    7.
      INFRINGEMENT OF A THIRD PARTY’S RIGHT BY THE PATENT RIGHTS OR A
      PRODUCT

     

    7.1
      Information and consultation

    Cougar
      and LEO shall promptly provide written notice, to the other Party, of any
      alleged infringement of a Third Party by the Patent Rights or a Product and
      provide such other Party with any available evidence of such infringement.
      LEO
      and Cougar shall consult one another in a timely manner concerning any
      appropriate response to the infringement.

    


    7.2
      Modification of Products

    Cougar
      may, in its sole discretion, modify the Product to avoid such infringement.
      

    


    7.3
      Defence by Cougar.

    In
      the
      event that a claim or suit is asserted or brought against Cougar alleging that
      the manufacture or sale of any Product by Cougar, an Affiliate of Cougar, or
      any
      sublicensee, or the use of such Product by any customer of any of the foregoing,
      infringes proprietary rights of a third party, Cougar shall give written notice
      thereof to LEO. Any such claim or suit shall be handled by Cougar at the
      discretion of Cougar, and all costs in relation to the claim or suit shall
      be
      borne by Cougar. LEO shall to a reasonable extent and at the expense of Cougar
      assist Cougar in the defence of such claim or suit. 

    


    7.4
      Defence by LEO

    In
      the
      event that a claim or suit is asserted or brought against LEO alleging that
      the
      Patent Rights interfere with proprietary rights of a third party, LEO shall
      give
      written notice thereof to Cougar. Any such claim or suit shall be handled by
      LEO
      at the discretion of LEO. Cougar shall to a reasonable extent assist LEO in
      the
      defence of such claim or suit, and Cougar shall have the right to participate
      in
      all aspects of the action. All costs in relation to such claim or suit shall
      be
      borne by Cougar regardless of whether Cougar chooses to participate in the
      defence or not. Notwithstanding the aforementioned LEO shall bear all costs
      related to such claims or suits bought against LEO related to LEO exploitation
      or use of the Patent Rights prior to the Effective Date or claims or suits
      bought against LEO related to LEO research activities performed after the
      Effective Date pursuant to Article 2.2 above.

     

    
      
        
        

      

      
        9

        
          

        

      

      
        
        

      

    

    


    8.
      WARRANTIES

     

    8.1
      To the
      best of its knowledge, LEO warrants that LEO is the owner of the Patent Rights
      and that Patent Rights do not infringe or violate any patent right(s) or other
      proprietary right(s) of any third party.

    


    8.2
      To the
      best of its knowledge, LEO has all right, title, and interest in and to the
      Patent Rights and Know-how, including the exclusive, absolute, irrevocable
      right, title and interest thereto, free and clear of all liens, charges,
      encumbrances or other restrictions or limitations of any kind
      whatsoever.

     

    8.3
      There
      are no licenses, options, disputes, royalty obligations or proceedings relating
      to, affecting, or limiting the rights of LEO or the rights of the Cougar under
      this Agreement, or which may lead to a claim of infringement or invalidity
      regarding, any part or all of the Patent Rights or Know How or their use.


    


    8.3.1
      To the
      best knowledge of LEO, there are no restrictions, liens or claims relating
      to,
      affecting, or limiting the rights of LEO or the rights of the Cougar under
      this
      Agreement, or which may lead to a claim of infringement or invalidity regarding,
      any part or all of the Patent Rights or Know How or their use. 

    


    8.4
      To the
      best knowledge of LEO, there is no claim, pending or threatened, of
      infringement, interference or invalidity regarding any part or all of the Patent
      Rights or Know-how or their use. 

    


    8.5
      Exhibit
      A sets forth all the Patent Rights,.

    


    8.6
      To the
      best knowledge of LEO, there are no inventors of Patent Rights other than those
      listed as inventors on the patent filings.

    


    8.7
      To the
      best of its knowledge, LEO has provided Cougar with copies of all documents
      reflecting support or funding for all or part of the research leading to Patent
      Rights and Know-how, and has listed all funding agencies on Exhibit B.


    


    8.8
      To the
      best of its knowledge, LEO has advised Cougar of all material adverse affects
      or
      significant risks associated with the use of Seocalcitol. 

    


    9.
      INDEMNIFICATION 

     

    9.1
      Indemnification by Cougar: 

    Cougar
      agrees to indemnify, defend and hold LEO, including its Affiliates, respective
      employees and agents, harmless against all costs, claims, suits, expenses
      (including reasonable legal fees) and damages to the extent such
      claims:

    


    
      	 	
              (a)

            	
              arise
                or result from Cougar‘s activities under this Agreement, including but not
                limited to infringement of third party’s rights; or
                

            


    

    


    
      	 	
              (b)

            	
              are
                due to negligence or wilful misconduct by Cougar; or
                

            


    

     

     

    
      
        
        

      

      
        10

        
          

        

      

      
        
        

      

    

     

    
      	 	
              (c)

            	
              arise
                out of the possession, manufacture, use, sale, administration etc.
                of a
                Product by Cougar.

            


    

     

    9.2
      Cougar
shall
      procure and maintain commercial general liability insurance, including without
      limitation, product liability insurance, in amounts customary in the relevant
      industry in which Cougar commercially exploits Product. Such insurance coverage
      shall extend to indemnities of Cougar and LEO shall be named as an insured.
      Insurance coverage shall be obtained through insurance carriers reasonably
      acceptable to LEO. Product liability insurance shall be maintained prior to
      the
      first commercial sale of Product and shall be continued for a commercially
      reasonable amount of time after the expiration of this Agreement.

    


    9.3
      Indemnification by LEO: 

    LEO
      agrees to indemnify, defend and hold Cougar, including its Affiliates,
      respective employees and agents, harmless against all costs, claims, suits,
      expenses (including reasonable legal fees) and damages to the extent such
      claims:

    


    (a) arise
      from the breach of any representation or warranty of LEO hereunder;
      or

    


    (b) are
      due
      to negligence or wilful misconduct by LEO.

    


    10.
      REGULATORY INFORMATION

    


    10.1
      Information following the Effective Date

    To
      the
      extent legally possible, LEO shall within three (3) months following the
      Effective Date provide Cougar with and give Cougar access to the documents
      mentioned in Appendix C, which are related to the following: (i) copies of
      all
      regulatory submissions, (ii) copies of all reports pertaining to clinical trials
      (excluding the following 3 unfinished reports: EBC 9609, EBC 9702 (an interim
      report will be provided for this study) and EBC 9802,), (iii) CIOMS reports
      from
      all clinical trials conducted by LEO, (iv) copies of all preclinical reports,
      (v) access to physicians, CROs and health care administrators involved in trials
      as able to do so involved in trials, (vi) all drug manufacture files along
      with
      the right to use the manufacturing process, (vii) and all other Regulatory
      Information that Cougar may reasonably request from LEO pertaining to
      Seocalcitol as specified in Appendix C. In addition, LEO shall cross reference
      or assign all regulatory filings covering Seocalcitol as specified in Appendix
      C
      at Cougar’s request. Notwithstanding the aforementioned Cougar may at any time
      during the term of this Agreement request access to all the data kept by LEO
      as
      mentioned above in this Clause 10.1

    


    10.2
      Subsequent information 

    Within
      eighteen (18) months following the Effective Date LEO shall deliver the
      remaining documents mentioned in Appendix C, which are related to the following:
      (i) copies of all patient records, (ii) copies of trial master file material,
      (iii) copies of CT scans, (iv) copies of electronic (raw) data of trials, incl.
      adverse event reports and statistical files, (v) final reports of the EBC 9609,
      EBC 9702 and EBC 9802 trials as mentioned above in Clause 10.1. Cougar
      acknowledges and accepts that the amount of documentation prevents LEO from
      undertaking any legal obligation to supply the entire or the majority part
      of
      the documentation at an earlier date than 18 months from the Effective Date.
      However, as a sign of its good faith LEO will within the above-mentioned 18
      months period, to the extent practically possible, upon request from Cougar
      and
      subject to 6 months prior notice in respect of each such request from Cougar
      use
      it reasonable endeavours to execute and deliver to Cougar specified documents
      as
      Cougar may request from LEO. Furthermore, LEO shall, at any time, reasonably
      cooperate with Cougar and provide Cougar with such assistance as reasonably
      may
      be requested by Cougar, including with respect to the transfer of clinical
      data
      and filings with the FDA. Should Cougar inform LEO that any specific
      documentation is needed for regulatory purposes (US or international), LEO
      will
      allow a representative of Cougar to have access to such documentation at
      LEO.

    The
      provision of such information (as paper copies) shall be at the expense of
      Cougar, who shall cover all external costs related hereto up to a maximum amount
      of [***]. Notwithstanding the aforementioned Cougar may at any time during
      the term of this Agreement request access to all the data kept by LEO as
      mentioned above in this Clause 10.2.

     

    
      
        
        

      

      
        11

        
          

        

      

      
        
        

      

    

    


    10.3
      Transfer of materials

    During
      the term of this Agreement, LEO shall provide Cougar with remaining drug
      substance and manufacturing intermediates according to a separate Material
      Transfer Agreement. 

    


    11.
      CONFIDENTIALITY

     

    11.1
      Confidential Information

    “Confidential
      Information” means any proprietary or confidential information relating to the
      Patent Rights, Regulatory Information and the Know-how including but not limited
      to patent prosecution documents relating to Patent Rights, commercial
      information, techniques, data or other information, whether in verbal or written
      form disclosed by one Party to the other. Cougar and LEO agree that they will
      not use the Confidential Information for any purpose unrelated to this
      Agreement, and will hold it in confidence during the term of this Agreement
      and
      for a period of five (5) years after the termination or expiration date of
      this
      Agreement. The Parties shall exercise with respect to the Confidential
      Information the same degree of care as the Parties exercise with respect to
      its
      own confidential or proprietary information of a similar nature, and shall
      not
      disclose it or permit its disclosure to any third party (except to those of
      its
      employees, consultants, or agents who are bound by the same obligation of
      confidentiality pursuant to this Agreement). However, such undertaking of
      confidentiality by the Party shall not apply to any information or data
      which:

    


    11.1.1 Party
      receives at any time from a third-party lawfully in possession of same and
      having the right to disclose same.

    


    11.1.2 Is,
      as of
      the date of this Agreement, in the public domain, or subsequently enters the
      public domain through no fault of Party.

    


    11.1.3 Is
      independently developed by Party as demonstrated by written evidence without
      reference to information disclosed by the other Party.

    


    11.1.4 Is
      disclosed pursuant to the prior written approval of the original disclosing
      Party.

    


    11.1.5 Is
      required to be disclosed pursuant to law or legal process (including, without
      limitation, to a governmental authority) provided, in the case of disclosure
      pursuant to legal process, reasonable notice of the impending disclosure is
      provided to a Party and the Party has agreed to such disclosure in writing
      or
      has exhausted its right to contest such disclosure.

     

    
      
        
        

      

      
        12

        
          

        

      

      
        
        

      

    

    


    11.2
      Ownership of information

    Any
      and
      all information supplied by LEO under the Agreement shall be and remain the
      sole
      and exclusive property of LEO unless otherwise disposed of under this Agreement
      and Cougar
      shall
      upon the request of LEO return the same and all copies thereof to LEO except
      one
      copy to be retained for legal purposes.

    


    12.
      SUBLICENSING AND ASSIGNMENT

     

    12.1
      Sublicensing

    12.1.1
      Cougar
      shall be entitled to sublicense the license granted in this Agreement in its
      reasonable discretion. Cougar assumes, however, full responsibility in respect
      of any breach of this Agreement by a sublicense, and all activities of any
      sub-licensee will be considered activities of Cougar. Cougar undertakes to
      keep
      LEO informed of all sub-licensees.

    


    12.1.2
      Upon
      termination of this Agreement other than by expiration in accordance with
      Section 13.2 or by termination caused by any act or omissions attributable
      to Cougar in accordance with Section 13.3 or 13.4 LEO agrees that any and all
      sublicenses survive such termination, unless the sublicense in the opinion
      of
      LEO represents a commercial or legal conflict to LEO. Upon termination LEO
      shall
      enter into separate agreements with relevant sub-licensees on terms and
      conditions equal to the previous agreements between the sub-licensee and Cougar
      and agreements between Cougar and sub-licensees existing at the time of
      termination of this Agreement shall be terminated with immediate effect.
      However, LEO shall not be required to take on any additional obligations or
      restrictions in its agreement with sub-licensee not already imposed on LEO
      by
      this Agreement. Notwithstanding the foregoing, if Cougar believes that LEO
      has
      terminated this Agreement for the primary purpose of doing business directly
      with the sublicensee, the termination may be disputed under the provisions
      of
      Section 15.

    


    12.2
      Assignment

    This
      Agreement and the rights and duties appertaining hereto may not be assigned
      by
      either party without first obtaining the written consent of the other which
      consent shall not be unreasonably withheld. Notwithstanding the foregoing,
      Cougar may assign this Agreement without the consent of LEO (i) to a purchaser,
      merging or consolidating corporation, or acquiror of substantially all of the
      Cougar's assets or business and/or pursuant to any reorganization qualifying
      under Section 368 of the Internal Revenue Code of 1986 as amended, as may be
      in
      effect at such time, or (ii) to an Affiliate of Cougar. In either such case,
      Cougar shall notify Licensor in writing within thirty (30) days of such
      assignment. 

    


    13.
      TERM
      AND TERMINATION

     

    13.1
      Commencement

    This
      Agreement will come into force on the Effective Date.

    


    13.2
      Expiration

    The
      term
      of this Agreement shall expire upon the later to occur of 

    


    (a)
      twenty (20) years from commencement

    


    (b)
      the
      expiration of the last patent contained in the Patent Rights

     

    
      
        
        

      

      
        13

        
          

        

      

      
        
        

      

    

    


    13.3
      Termination due to Breach:
      

    Material
      failure or breach by either Party to comply with any of the obligations and
      conditions of this Agreement unless such failure is caused by applicable laws
      or
      regulations, shall entitle the other Party to give to the Party in default
      notice requiring it to remedy such failure or breach. If such failure or breach
      is not remedied within ninety (90) days after receipt of such notice (or in
      the
      case of a failure or breach not capable of being remedied within such ninety
      (90) days period, the Party in default has failed within such period to commence
      and diligently continue actions to cure such failure or breach), the notifying
      Party shall be entitled to terminate this Agreement by giving notice to take
      effect immediately. Notwithstanding the above, if the Party whose rights are
      being terminated disputes such termination, the Agreement shall remaining effect
      until the dispute is resolved, including through any necessary legal processes.
      

    


    13.4
      Termination due to Bankruptcy:
      

    In
      the
      event of Cougar assigning or making any composition or sequestration of assets
      for the benefit of creditors, becoming insolvent, going into liquidation,
      becoming bankrupt, being placed in receivership or provisional administration,
      or dissolving, LEO may at its option terminate this Agreement forthwith by
      notice in writing.

    


    13.5
      Termination due to ceasing of exploitation

    LEO
      shall
      be entitled to terminate this Agreement in the event that (a) Cougar informs
      LEO
      in writing of its intent not to proceed with the commercial development of
      at
      least one Product or (b) Cougar is finally judicially determined to not be
      using
      Commercially Reasonable and Diligent Efforts to develop, market, promote and
      sell a Product.

    


    13.6
      Non-compensation

    No
      compensation shall be paid by LEO to Cougar as a consequence of justifiable
      termination on the part of LEO in accordance with articles
      13.3-13-5.

    


    14.
      RIGHTS AND OBLIGATIONS AFTER TERMINATION OF THE AGREEMENT

     

    Upon
      expiration of this Agreement according to Section 13.2, Cougar shall be granted
      a royalty-free, perpetual and worldwide license to the Patent Rights, the
      Know-how and the Regulatory Information. Termination or expiration of this
      Agreement shall not release either Party from any obligation arising prior
      to
      such termination.

    


    15.
      GOVERNING LAW AND VENUE

     

    Any
      dispute arising out of or in connection with this Agreement, including any
      question regarding their existence, validity or termination, shall be finally
      solved under the Rules of Arbitration of the International Chamber of Commerce,
      which Rules are deemed to be incorporated by reference into this clause. The
      number of arbitrators shall be three. The seat, or legal place, of arbitration
      shall be Berlin, Germany. The language to be used in the arbitration shall
      be
      English. The governing law of this Agreement shall be the substantive law of
      Germany.

     

    
      
        
        

      

      
        14

        
          

        

      

      
        
        

      

    

    


    16.
      FORCE
      MAJEURE

     

    Neither
      Party shall be liable for the non-performance of its obligations set forth
      in
      this Agreement and no Party shall be deemed in breach of its obligations if
      such
      non-performance is due to force majeure, i.e. natural disaster, strikes, civil
      war or other circumstances beyond the reasonable control of such Party, provided
      such force majeure cannot be overcome by exercising due diligence and provided
      that the Party failing to perform its obligations notifies the other Party
      as
      soon as possible of the occurrence. However, if the force majeure persists
      for a
      period of more than four (4) months, the non-failing Party shall be entitled
      to
      terminate this Agreement with two (2) months’ prior written notice.

    


    17.
      MISCELLANEOUS

     

    17.1
      Notices:
      

    Any
      notice required or provided for by the terms of this Agreement shall be in
      English and in writing and shall be sent by registered airmail or by facsimile
      properly addressed in accordance with the above addresses or to such other
      addresses as the parties may at a later date advise. Such notice can also be
      sent electronically but must then be followed by a notice by registered airmail.
      The effective date of a notice shall be the date of sending such notice.


    


    17.2
      Waiver

    The
      waiver by either Party of any breach by the other Party of any of the provisions
      of this Agreement shall not be deemed to be a waiver of any subsequent or
      continuing breach of this Agreement. 

    


    17.3
      Entire Agreement

    The
      Agreement constitutes the entire understanding between the Parties with respect
      to the subject matter addressed herein and supersedes all prior agreements,
      written or oral, between the Parties relating to the subject matter of the
      Agreement.

    


    17.4
      Amendments

    The
      Agreement may not be modified, changed or discharged, fully or in part, except
      by an agreement in writing signed by the Parties.

    


    17.5
      Severability

    In
      the
      event that any of the provisions of the Agreement are held by the court of
      the
      competent jurisdiction to be invalid, void or otherwise unenforceable, the
      remaining parts of the Agreement shall remain in force and the provision in
      question shall be construed as to conform to applicable law.

    


    If
      an
      exclusive license is incompatible with applicable antitrust and/or competitive
      law, the Parties agree that this Agreement shall be transformed into a simple
      license, and that the remainder of the Agreement shall remain unamended. The
      Parties agree to negotiate in good faith the size of the royalty in case the
      license is transformed into a simple license. 

    


    17.6
      Changes in Mandatory Law:

    The
      Parties are obliged to accept changes in the Agreement made in order to comply
      with changes in mandatory law affecting this Agreement.

     

    
      
        
        

      

      
        15

        
          

        

      

      
        
        

      

    

    


    18.
      PAYMENTS,
      NOTICES AND OTHER COMMUNICATIONS

     

    Any
      payment, notice or other communication required or permitted to be given
      pursuant to this Agreement shall be in writing and sent by certified first
      class
      mail, postage prepaid, by hand delivery or by facsimile if confirmed in writing,
      in each case effective upon receipt, at the addresses below or as otherwise
      designated by written notice given to the other party:

     

    In
      the
      case of LEO:

    


    Industriparken
      55

    2750
      Ballerup

    Denmark

    Attention:
      Executive Vice President R & D Poul Rasmussen

    Tel.:
      +45
      4492 3800

    Fax:
      +45
      7226 3320

    


    In
      the
      case of Cougar:

     

    Cougar
      Biotechnology Inc.

    10940
      Wilshire Blvd., Suite 600

    Los
      Angeles, CA 90024

    USA
      

    Attn:
      CEO/President Alan Auerbach

    Tel:
      +1
      310-443-4209

    Fax:
      +1
      310 443 4210

    


    


    Agreed
      and accepted:

    

      
        	
                COUGAR
                  Biotechnology Inc

              	
                LEO
                  Pharma A/S

              
	 	 
	
                Date: 
                  June 27, 2005

              	
                Date: 
                  June 20, 2005

              
	 	 
	 	 
	
                /s/
                  Alan Auerbach

              	
                /s/
                  Paul Rasmussen

              
	
                Name 
                  Alan Auerbach

              	
                Paul
                  Rasmussen

              
	
                Title  
                  Chief Executive

                          
                  Officer and President

              	
                Executive
                  Vice President R & D

              


      

    

    


    

       

    

    
      
        
        

      

      
        16

        
          

        

      

      
        
        

      

    


    Appendix
      A

    


    List
      of
      Patents and Patent Applications

    


    


    Seocalcitol
      compound

    


    Country Patent/Application
      No. Filing
      date Expiry
      date Status

     

    
      
        	
                Country

              	
                Patent/Application
                  No.

              	
                Filing
                  date

              	
                Expiry
                  date

              	
                Status

              
	
                Australia

              	
                630227

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Austria1

              	
                E112556

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Belgium1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Canada

              	
                2,057,048

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Denmark1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Finland

              	
                93724

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                France1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Germany1

              	
                69013155.0

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Ireland

              	
                64889

              	
                26.06.90

              	
                26.06.10

              	
                granted

              
	
                Italy1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Japan

              	
                2807087

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Rep.
                  Korea

              	
                195547

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Luxembourg1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Netherlands1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                New
                  Zealand

              	
                234326

              	
                02.07.90

              	
                02.07.10

              	
                granted

              
	
                Philippines

              	
                27301

              	
                10.07.90

              	
                04.05.10

              	
                granted

              
	
                South
                  Africa

              	
                90/5094

              	
                29.06.90

              	
                29.06.10

              	
                granted

              
	
                Spain1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Sweden1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                Switzerland1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                UK1

              	
                482
                  100

              	
                04.07.90

              	
                04.07.10

              	
                granted

              
	
                USA

              	
                5,190,935

              	
                04.07.90

              	
                04.07.10

              	
                granted

              


      

       

    

    
      	1.	
              Validated
                European patent

            


    

    


    Composition
      comprising solubilized seocalcitol

     

    
      
        	
                Country

              	
                Patent/Application
                  No. 

              	
                Filing
                  date

              	
                Expiry
                  date

              	
                Status

              
	
                Australia

              	
                768785

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Austria1

              	
                E245968

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Belgium1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Canada

              	
                2,369,587

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                China

              	
                00807011.3

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                Cyprus1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Czech
                  Rep.

              	
                PV
                  2001-3665

              	
                05.04.2000

              	 	
                abandoned

              
	
                Denmark1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Finland1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                France1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Germany1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Greece1

              	
                20030403954

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Hong
                  Kong

              	
                03101869.3

              	
                14.03.2003

              	
                05.04.20

              	
                pending

              
	
                Hungary

              	
                P0203903

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                Ireland1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Italy1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Japan

              	
                2000-610445

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                Rep.
                  Korea

              	
                1020017013042

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                Luxembourg1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Netherlands1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                New
                  Zealand

              	
                514604

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Poland

              	
                P-356968

              	
                05.04.2000

              	
                05.04.20

              	
                pending

              
	
                Portugal1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Romania1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Russia

              	
                2001130462

              	
                05.04.2000

              	 	
                abandoned

              
	
                Spain1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Sweden1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                Switzerland1

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                UK1 

              	
                1
                  171 100

              	
                05.04.2000

              	
                05.04.20

              	
                granted

              
	
                USA

              	
                09/958,648

              	
                05.04.2000

              	 	
                abandoned

              


      

       

    

    
      	1.	
              Validated
                European patent

            


    

    


    


    
      
        
        

      

      
        17

        
          

        

      

      
        
        

      

    

    


    Appendix
      B

    


    List
      of
      Patents and Patent Applications

    


    


    Epi-seocalcitol
      compound

     

    
      
        	
                Country

              	
                Patent/Application
                  No.

              	
                Filing
                  date

              	
                Expiry
                  date

              	
                Status

              
	
                Australia

              	
                722659

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Austria1

              	
                E216361

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Belgium1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Canada

              	
                2,266,479

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                China

              	
                97198407.7

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Czech
                  Rep.

              	
                290933

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Denmark1

              	
                937038

              	
                27.10.97

              	
                27.1017

              	
                granted

              
	
                Finland1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                France

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Germany1

              	
                69712086

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Greece1

              	
                20020402022

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Hong
                  Kong

              	
                1022298

              	
                29.02.00

              	
                27.10.17

              	
                granted

              
	
                Hungary

              	
                P9904333

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                Ireland1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Italy1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Japan

              	
                519931/1998

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                Rep.
                  Korea

              	
                1019997002315

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                Luxembourg1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Netherlands1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                New
                  Zealand

              	
                334328

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Poland

              	
                P.333068

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                Portugal1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Romania

              	
                99-00325

              	
                27.10.97

              	
                27.10.17

              	
                pending

              
	
                Russia

              	
                2183622

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Spain1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Sweden1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                Switzerland

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                UK1

              	
                937038

              	
                27.10.97

              	
                27.10.17

              	
                granted

              
	
                USA

              	
                6,310,226

              	
                27.10.97

              	
                27.10.17

              	
                granted

              


      

       

    

    
      	1.	
              Validated
                European patent

            


    

    


    The
      exclusive license granted to Cougar are limited to the rights pertaining to
      epi-seocalcitol under the above Patent Rights and Patent applications. All
      other
      rights under the above Patents and patent application shall remain the exclusive
      property of LEO.

     

     

    
      
         

      

      
        18

        
          

        

      

      
         

      

    

    Appendix
      C

     

    
      Regulatory
        Information

      


    

    

      
        	
                Title

              	 	
                Doc
                  ID (Availability)

              	 	
                Date

              
	
                Chemistry

              	 	 	 	 
	 	 	 	 	 
	
                Analytics

              	 	 	 	 
	
                2003

              	 	
                YES

              	 	 
	
                1992

              	 	
                YES

              	 	 
	
                1993

              	 	
                YES

              	 	 
	 	 	
                YES

              	 	 
	
                1992

              	 	
                YES

              	 	 
	
                EB1089,
                  Hygroscopicity

              	 	
                Report
                  no 18-RL 9817 (BLO)

              	 	
                1998

              
	
                EB1089,
                  Octanol/Water Partition Coefficient

              	 	
                Report
                  no 18-RC 9806 (CBO)

              	 	
                1998

              
	
                EB1089,
                  Oploselighed i vand

              	 	
                Report
                  no 18-RL 9220(BLO)

              	 	
                1992

              
	
                Seocalcitol,
                  EB1089, Internal Preformulation Report

              	 	
                Report
                  no 18-RL 008 draft

              	 	
                2003

              
	
                EB1089,
                  Response Factor for Pre-EB1089 (EB 1286) at 232 and at 264
                  nm

              	 	
                Report
                  no 18-RD 9205 (BLO)

              	 	
                1992

              
	 	 	 	 	 
	
                Seocalcitol,
                  EB1089, Impurity Profiles of Seocalcitol

              	 	
                Report
                  no 181-RH 0310 1st.rev.
                  (LMH)

              	 	
                2003

              
	
                EB1089
                  Specification

              	 	
                Specification
                  no 18-FL 0001 (BLO)

              	 	
                2000

              
	
                Seocalcitol,
                  EB1089, Justification of PSecification

              	 	
                Report
                  no 18-RL 0284 (BLO)

              	 	
                2002

              
	 	 	 	 	 
	
                Seocalcitol,
                  EB1089, HPLC Identification, Assay and determination of Related
                  Substances

              	 	
                Method
                  no 18-FL 0007 1st.rev.
                  (LMH)

              	 	
                2003

              
	
                Seocalcitol,
                  EB1089, Validation of Method 18-FL 0007: HPLC identification, Assay
                  and
                  determination of Related Substances

              	 	
                Report
                  no 181-RE 0309 1st.rev.
                  (KEL)

              	 	
                2003

              
	
                EB1089,
                  HPLC Identification, Assay and Determination of Related
                  Compounds

              	 	
                Method
                  no 18-FL 9106, 2nd
                  revision (BLO)

              	 	
                1994

              
	
                EB
                  1089, Validation of the Method for Identification, Assay and Determination
                  of Related Compounds (18-FL 9106)

              	 	
                Report
                  no 18-RL 9230 (LDS)

              	 	
                1992

              
	
                EB1089,
                  Determination of 9-Acetylanthracene

              	 	
                Method
                  no 18-FL 9808 (BLO)

              	 	
                1998

              
	
                EB1089,
                  Validation of the Method for Determination of 9-Acetylantracene
                  (18-FL
                  9808)

              	 	
                Report
                  no 18-RL 9812 (BLO)

              	 	
                1998

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                EB1089,
                  Related compounds, thin-layer chromatographic method

              	 	
                Method
                  no 18-FL 9107, 1st
                  rev (BLO)

              	 	
                1996

              
	
                EB1089
                  Validation of Thin-layer Chromatographic Method for Determination
                  of
                  Related Compounds (18-FL 9107)

              	 	
                Report
                  no 18-RL 9402 (BLO)

              	 	
                1994

              
	
                EB1089,
                  Validation of Thin-layer Chromatographic Method for Determination
                  of
                  Relaed Compounds (18-FL 9107)

              	 	
                Report
                  no 18-RL 9407 (BLO)

              	 	
                1994

              
	
                EB1089,
                  Gas Chromatographic Determination of Residual Solvents

              	 	
                Method
                  no F75-BBJ 9810 (BBJ)->afd. 751 NRA/BBJ

              	 	 
	 	 	 	 	 
	
                Seocalcitol,
                  EB1089, Reference Substance Y19

              	 	
                Report
                  no 18-RL 0007, 1st.rev
                  (BLO)

              	 	
                2003

              
	
                EB1089,
                  Batch Analyses

              	 	
                Table
                  no 18-TL 0020 (BLO)

              	 	
                2000

              
	
                EB1089
                  Batch Survey

              	 	
                Table
                  no 181-TH 0301 (LMH)

              	 	
                2003

              
	
                EB1089
                  Batch Survey

              	 	
                Table
                  no 181-TH 0302 (LMH)

              	 	
                2003

              
	
                EB1089
                  Batch Survey

              	 	
                Table
                  no 181-TH 0303 (LMH)

              	 	
                2003

              
	 	 	 	 	 
	
                Seocalcitol,
                  EB1089, Stability Summary

              	 	
                Report
                  no 181-RH 0306 1st.rev.
                  (LMH)

              	 	
                2003

              
	
                EB1089,
                  Stability in propylene glycol-buffer solution, 12 months

              	 	
                Report
                  no 18-RL 9223 (BLO)

              	 	
                1992

              
	
                EB1089,
                  stabilitet I tynd cocosolie, I soyaolie og I jordnodolie

              	 	
                Report
                  no 18-RL 9321 (BLO)

              	 	
                1993

              
	
                EB1089,
                  Stability in propylene glycol and propylene glycol buffer solution,
                  preliminary results

              	 	
                Report
                  no 18-RL 9109 (BLO)

              	 	
                1991

              
	
                EB1089,
                  Stability in solution, pH 3-8

              	 	
                Report
                  no 18-RL 9120 (BLO)

              	 	
                1991

              
	
                EB1089,
                  Stability of EB 1089 in Simulated Gastric Acid

              	 	
                Report
                  no 18-RD 9310 (BLO)

              	 	
                1993

              
	
                EB1089,
                  Three Years Stability Studies on the Drug Substance

              	 	
                Report
                  no 18-RL 9739 (BLO)

              	 	
                1997

              
	
                Seocalcitol,
                  EB1089, Three Years Stability Studies on the Drug
                  Substance

              	 	
                Report
                  no 18-RL 0108 (BLO)

              	 	
                2001

              
	
                Seocalcitol,
                  EB1089, Three Years Stability Study on Drug Substance

              	 	
                Report
                  no 18-RH 0302 (LMH)

              	 	
                2003

              
	
                Seocalcitol
                  (EB1089), Light Stability Studies ont eh Drug Substances in
                  Solution

              	 	
                Report
                  no 18-RC 0206 (CBO)

              	 	
                2002

              
	
                Seocalcitol
                  EB1089, Oxidation with Hydrogen Peroxide

              	 	
                Report
                  no 18-RH 0309 1st.rev.
                  (LMH)

              	 	
                2003

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                Seocalcitol
                  (EB1089) Capsules 5μg. Uniformity of Content

              	 	
                Method
                  no 18-FS 0001, 2nd
                  rev (BLO)

              	 	
                2003

              
	 	 	 	 	 
	
                Biological

              	 	 	 	 
	
                EB1089,
                  Pharmacological aspects I: effects on cancer cells in
                  vitro.

              	 	
                R07-94/12
                  (CMH)

              	 	
                10.08.94

              
	
                EB1089,
                  Pharmacological aspects II: effects on skin cells in
                  vitro.

              	 	
                R07-94/13
                  (CMH)

              	 	
                10.08.94

              
	
                EB1089,
                  Pharmacological aspects III: affinity for the vitamin D receptor,
                  binding
                  to DBP and preliminary in vivo pharmacokinetics

              	 	
                R07-94/14
                  (CMH)

              	 	
                15.08.94

              
	
                Effect
                  of 1alpha,25(OH)2D3, CB1093, EB1089 and MC1288 on anchorage-independent
                  growth of human breast cancer cells in vitro.

              	 	
                R07-98/02
                  (CMH)

              	 	
                20.01.98

              
	
                Effects
                  of 1alpha,25(OH)2D3 and EB1089 on proliferation and colony formation
                  of
                  human mammary tumour cells.

              	 	
                R07-92/11
                  (CMH)

              	 	
                13.07.92

              
	
                Effects
                  of 1alpha,25(OH)2D3 and EB1089 on tumour cell invasion in vitro
                  assessed
                  by the Boyden Chamber Invasion Assay.

              	 	
                R07-92/17
                  (CMH)

              	 	
                18.12.92

              
	
                Effects
                  of cyanoguanidine and vitamin D compounds on two lung cancer cell
                  lines

              	 	
                R07-96/03
                  (CMH)

              	 	
                05.02.96

              
	
                Expression
                  of adhesion molecules on the surface of human melanoma cells in
                  vitro.

              	 	
                R07-96/05
                  (CMH)

              	 	
                20.02.96

              
	
                In
                  vitro effects of vitamin D analogues on the invasion of metastatic
                  mammary
                  carcinoma cells.

              	 	
                7-93/12
                  (CMH)

              	 	
                05.10.93

              
	 	 	 	 	 
	
                Pharmaceutical

              	 	 	 	 
	
                Capsules

              	 	 	 	 
	
                Seocalcitol
                  Capsules 5mcg homogenity of solution during production

              	 	
                9-KFI\000704A/biw
                  (KFI)

              	 	
                04.07.00

              
	
                Capsules
                  - stability

              	 	 	 	 
	
                EB1089
                  (Seocalcitol) capsules 0.25mcg + 1mcg (enteric coated)-Stress Testing,
                  Accelerated and Long Term Stability

              	 	
                9-IVA/000911D/stm
                  (KFI)

              	 	
                11.09.00

              
	
                Seocalcitol
                  Capsules 10mcg, 20mcg (Enteric Coated), Accelerated and Long Term
                  Stability

              	 	
                9-VIJ\011003A/biw

              	 	
                03.10.01

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                Seocalcitol
                  Capsules 5mcg (Enteric Coated), Accelerated and Long Term
                  Stability

              	 	
                9-VIJ\021004A/biw

              	 	
                04.10.02

              
	
                Seocalcitol
                  Capsules 5mcg. Size 3, Long Term, Intermediate and Accelerated
                  Storage
                  Conditions

              	 	
                92-VIJ\030626A/biw

              	 	
                26.06.03

              
	
                Seocalcitol
                  Capsules 5 mcg size 3, Stability Summary and Conclusion

              	 	
                92-VIJ\030310B/biw

              	 	
                10.03.03

              
	
                EB1089
                  solution for capsules 100 mcg/g Stability of solution before
                  encapsulation

              	 	
                9-KFI\970312A/stm
                  (KFI)

              	 	
                12.03.97

              
	
                Seocalcitol
                  Solution for Capsules 50 mcg/g, Stability of solution before
                  encapsulation

              	 	
                9-VIJ\020206A/biw

              	 	
                06.02.02

              
	
                Seocalcitol
                  Capsules Placebo, Accelerated and Long Term stability

              	 	
                9-SEJ\031210A/biw

              	 	
                10.12.03

              
	
                Capsules
                  - methods

              	 	 	 	 
	
                9-1240-3
                  EB1089 Capsules 0.25mcg Assay and Identification of EB1089 by
                  HPLC

              	 	
                9-960812C.KF/bw
                  (KFI)

              	 	
                12.08.96

              
	
                9-1238-3
                  EB1089 Capsules 1mcg Assay and Identification of EB1089 by
                  HPLC

              	 	
                9-960812D.KF/bw
                  (KFI)

              	 	
                12.08.96

              
	
                9-1275-5
                  EB1089 Capsules 5mcg Assay and Identification of EB1089 by
                  HPLC

              	 	
                9-KFI\000821A/biw
                  (KFI)

              	 	
                21.08.00

              
	
                9-1320-1
                  EB1089 Capsules 10mcg + 20mcg Assay and Identification of EB1089
                  by
                  HPLC

              	 	
                9-960812B.KF/bw
                  (KFI)

              	 	
                12.08.96

              
	
                9-1534-1
                  EB1089 oil solution, Cleaning Validation, HPLC assay of
                  EB1089

              	 	
                9-KFI\990520A/biw
                  (KFI)

              	 	
                20.05.99

              
	
                Capsules
                  - validation

              	 	 	 	 
	
                EB1089
                  Capsules 1mcg Validation of the HPLC method for assay and identification
                  of EB1089 (9-1238)

              	 	
                9-950116B.IM/bl
                  (KFI)

              	 	
                16.01.95

              
	
                EB1089
                  Capsules 10mcg + 20mcg Validation of the HPLC method for assay
                  and
                  identification of EB1089 (9-1275 and 9-1320)

              	 	
                9-KFI/961111A/bly
                  (KFI)

              	 	
                11.11.96

              
	
                EB1089
                  oil solution, Cleaning Validation Validation of the HPLC method
                  for assay
                  of EB1089 (9-1534-1)

              	 	
                9-KFI\990520B/kfi
                  (KFI)

              	 	
                20.05.99

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                Pharmacological

              	 	 	 	 
	
                EB1089,
                  Pharmacological aspects IV: effects on calcium metabolism in
                  rats

              	 	
                R07-94/15
                  (CMH)

              	 	
                17.08.94

              
	
                EB1089,
                  Pharmacological aspects V: studies involving external
                  collaboration

              	 	
                R07-94/16
                  (CMH)

              	 	
                24.08.94

              
	
                Xenografting
                  of MCF-7 human breast carcinoma cells to nude mice. Effect of oral
                  treatment with EB1089 from day of grafting

              	 	
                35-95/08
                  (EBR)

              	 	
                10.12.95

              
	
                Test
                  of three possible vehicles for vitamin D analogues in vivo using
                  EB1089 as
                  model compound.

              	 	
                35-97/05
                  (EBR)

              	 	
                11.06.97

              
	 	 	 	 	 
	
                Pharmacokinetics

              	 	 	 	 
	
                Pharmacokinetics
                  study on [14C]EB1089 in female rats

              	 	
                35-93/01
                  (AMK)

              	 	
                1993-08-13

              
	
                Oral
                  absorption of [14C]EB1089 studied in one female and one male
                  minipig

              	 	
                36-94/04
                  (AMK)

              	 	
                1994-08-31

              
	
                [3H]
                  EB1089 oral absorption and bioavailability in minipigs of [3H]EB1089
                  from
                  an enteric coated capsule and a propylene glycol solution

              	 	
                36-94/11
                  (AMK)

              	 	
                1995-06-30

              
	
                Pharmacokinetic
                  study on [14C]EB1089 in male rats

              	 	
                36-95/05
                  (AMK)

              	 	
                1996-01-26

              
	
                Toxicokinetics
                  of EB1089-000 in minipigs

              	 	
                36-99/13
                  (AMK)

              	 	
                1999-10-25

              
	
                EB1089-000.
                  Oral bioavailability in female minipigs of EB1089 after administration
                  of
                  four different capsule formulations.

              	 	
                36-00/13
                  (AMK)

              	 	
                2000-11-15

              
	
                EB1089-000.
                  Toxicokinetics after oral administration of EB1089 capsules to
                  male and
                  female minipigs.

              	 	
                36-00/14
                  (AMK)

              	 	
                2000-11-21

              
	
                EB1089-000
                   (Seocalcitol). Pharmacokinetics in male rats after single and
                  repeated
                  oral administration

              	 	
                36-00/18
                  (AMK)

              	 	
                2000-12-14

              
	
                EB1089-000
                  (Seocalcitol). Pharmacokinetics in female rats after single and
                  repeated
                  oral administration.

              	 	
                36-00/19
                  (AMK)

              	 	
                2000-12-14

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                Quantification
                  of Seocalcitol in serum samples originating from the study: Seocalcitol.
                  A
                  pilot phase I, open-label, randomised, balanced, single oral dose,
                  two-period cross-over study to investigate the pharmacokinetic
                  of single
                  oral doses of Seocalcitol capsules at two dose levels in healthy
                  male
                  subjects.

              	 	
                36-01/12
                  (AMK)

              	 	
                2001-06-11

              
	
                Quantification
                  of Seocalcitol in serum samples originating from the GCP-study:
                  Seocalcitol - A Phase I, open-label, randomised, balanced, three-period
                  cross-over study to investigate the bioavailability and bioequivalence
                  of
                  single oral doses of Seocalcitol in three different formulations
                  in
                  healthy male subjects

              	 	
                361-02/17
                  (AMK)

              	 	
                2002-08-22

              
	
                Absorption
                  and excretion of 3H-EB1089 in rats

              	 	
                361-02/24
                  (AGL)

              	 	
                2002-12-02

              
	
                Absorption
                  and excretion of 3H-EB1089 in minipigs

              	 	
                361-03/19
                  (VHS)

              	 	
                2003-12-18

              
	
                Pharmacokinetic
                  study on [14C]EB1089 in female rats

              	 	
                35-93/01
                  (AMK)

              	 	 
	
                Pharmacokinetic
                  study on [14C]EB1089 in male rats

              	 	
                36-95/05
                  (AMK)

              	 	 
	
                [3H]EB1089
                  oral absorption and bioavailability in minipigs of [3H]EB1089 from
                  an
                  enteric coated capsule and a propylene glycol solution

              	 	
                36-94/11
                  (AMK)

              	 	 
	
                Oral
                  absorption of [14C]EB1089 studied in one female and one male
                  minipig

              	 	
                36-94/04
                  (AMK)

              	 	 
	
                Pharmacokinetic
                  studies on [14C]EB1089 in one female and one male minipig, 20mcg/kg
                  i.v.
                  and 40mcg/kg p.o.

              	 	
                36-94/06
                  (AMK)

              	 	 
	
                Toxicokinetics
                  of EB1089-000 in minipigs

              	 	
                36-99/13
                  (AMK)

              	 	 
	
                EB1089,
                  Pharmacological aspects III: affinity for the vitamin D receptor,
                  binding
                  to DBP and preliminary in vivo pharmacokinetics.

              	 	
                R07-94/14
                  (CMH)

              	 	 
	
                EB1089.Review
                  of preclinical in vivo DMPK studies

              	 	
                36-97/10

              	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
                  Title

                	 	
                  Doc
                    ID (Availability)

                	 	
                  Date

                


        

      

      
        	
                EB1089.Pharmacokinetics
                  in mice.

              	 	
                36-93/02

              	 	 
	
                Pharmacokinetic
                  study on 14C-EB1089 in female and male minipigs.

              	 	
                36-94/07

              	 	 
	
                EB1089.
                  Whole-body autoradiography of rats after oral and intravenous
                  administration of 14C-EB1089

              	 	
                WBAR/95/01
                  (36-96/10), (AMK)

              	 	 
	 	 	 	 	 
	
                Toxicological

              	 	 	 	 
	
                Single
                  dose toxicity studies:

              	 	 	 	 
	
                EB1089
                  - Acute oral toxicity (LD50) test in mice

              	 	
                IRI
                  552372

              	 	
                1992

              
	
                EB1089
                  - Acute intravenous toxicity (LD50) test in mice

              	 	
                IRI
                  552325

              	 	
                1992

              
	
                EB1089
                  - Acute intraperitoneal toxicity (LD50) test in mice

              	 	
                IRI
                  552367

              	 	
                1992

              
	
                EB1089
                  - Single does toxicity study in rats (Non-GLP)

              	 	
                ATOX/98/02

              	 	
                1998

              
	
                EB1089
                  - The effect of intravenous injection of EB1089 on the calcium
                  homestasis
                  in rats (Non-GLP)

              	 	
                ATOX/96/05

              	 	
                1996

              
	
                EB1089
                  - Dose ranging study in mice and rats. Single does toxicity
                  (Non-GLP)

              	 	
                910220A1

              	 	
                1991

              
	
                Repeat
                  dose toxicity studies:

              	 	 	 	 
	
                EB1089
                  Capsules - 1week preliminary oral toxicity study in minipigs
                  (Non-GLP)

              	 	
                TTOX/95/06

              	 	
                1995

              
	
                EB1089
                  - 14 days intravenous toxicity study in rats

              	 	
                TTOX/96/01

              	 	
                1996

              
	
                EB1089
                  - 14 days oral toxicity study in rats fed a diet with normal or
                  low
                  calcium content

              	 	
                TTOX/96/02

              	 	
                1996

              
	
                EB1089
                  (CRC9101) - 4 week oral toxicity study in mice with 4 week recovery
                  period

              	 	
                IRI
                  450897

              	 	
                1992

              
	
                EB1089
                  - 4 weeks preliminary oral toxicity study in rats

              	 	
                920427T1

              	 	
                1993

              
	
                EB1089
                  (CRC9101) - 4 week oral toxicity study in rats with a 4 week recovery
                  period

              	 	
                IRI
                  450902

              	 	
                1992

              
	
                EB1089
                  - 4 weeks dermal toxicity study in rats

              	 	
                TTOX/95/04

              	 	
                1996

              
	
                EB1089
                  - 4 weeks preliminary oral toxicity study in minipigs

              	 	
                920527T2

              	 	
                1993

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                EB1089
                  - 13 weeks oral toxicity study in rats

              	 	
                920629T3

              	 	
                1993

              
	
                EB1089
                  - 13 weeks oral toxicity study in minipigs

              	 	
                920817T5

              	 	
                1993

              
	
                EB1089
                  - 26 weeks oral toxicity study in rats

              	 	
                940307T2

              	 	
                1995

              
	
                EB1089
                  - A 39-week oral toxicity study in minipigs

              	 	
                TTOX/97/08
                  (Scantox 24960)

              	 	
                1999

              
	
                1st
                  Amendment to TTOX/97/08

              	 	
                -

              	 	
                1999

              
	
                Genotoxicity
                  studies:

              	 	 	 	 
	
                EB1089
                  - Micronucleus test after oral administration in mice

              	 	
                920921N7

              	 	
                1993

              
	
                EB1089
                  - I.v. micronucleus test in mice

              	 	
                940627N2

              	 	
                1994

              
	
                EB1089
                  - Reverse mutation in five histidine requiring strains of Salmonella
                  typhimurium

              	 	
                GTOX/98/01
                  (Covance 339/61-D5140)

              	 	
                1998

              
	
                EB1089
                   - Induction of chromosome aberrations in cultured human peripheral
                  blood
                  lumphocytes

              	 	
                Corning
                  Hazleton 339/26-1052

              	 	
                1995

              
	
                EB1089
                  - Dose finding study concerning the bacterial fluctuation mutagenicity
                  test

              	 	
                920629N4

              	 	
                1992

              
	
                EB1089
                  - Bacterial fluctuation mutagenicity test

              	 	
                920706N5

              	 	
                1992

              
	
                EB1089
                  - Dose finding study concerning micronucleus test

              	 	
                940613N1

              	 	
                1994

              
	
                EB1089
                  - Dose finding study concerning the micronucleus test

              	 	
                920810N6

              	 	
                1992

              
	
                Carcinogenicity
                  studies:

              	 	 	 	 
	
                None

              	 	 	 	 
	
                Reproductive
                  and developmental toxicity studies:

              	 	 	 	 
	
                EB1089
                  - Effect on fertility and embryo-fetal development in rats

              	 	
                940502R1

              	 	
                1996

              
	
                EB1089
                  and 1,25-dihydroxyvitamin D3 - Effect on the maternal calcium homeostasis
                  and fetal bone formation in rats

              	 	
                RTOX/95/01

              	 	
                1996

              
	
                Local
                  tolerance studies:

              	 	 	 	 
	
                None

              	 	 	 	 
	
                Other
                  toxicity studies:

              	 	 	 	 
	
                None

              	 	 	 	 
	
                Pharmacology
                  - Safety Pharmacology studies:

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Diuretic
                  effect of EB1089-000 in rats after oral dosing for four consecutive
                  days

              	 	
                SPHA0202

              	 	
                2002

              
	 	 	 	 	 
	
                EB1089-000
                  - Influence on intestinal motility in mice. Pharmacology. Nielsen
                  CK

              	 	
                35-98/10

              	 	
                1998

              
	
                EB1089
                  - Behaviour in mice after oral dosing. Pharmacology. Nielsen
                  CK

              	 	
                35-98/03

              	 	
                1998

              
	
                EB1089
                  - Hexobarbital sleeping time in mice. Pharmacology. Nielsen
                  CK

              	 	
                35-98/06
                  (97CKN6)

              	 	
                1998

              
	
                EB1089-000
                  - Tail flick analgesia in rats. Pharmacology. Gonzalez T.

              	 	
                35-99/12

              	 	
                1999

              
	
                EB1089-000
                  - Anticonvulsive test in mice. Pharmacology. Bramm E.

              	 	
                35-99/11

              	 	
                1999

              
	 	 	 	 	 
	
                Statistical

              	 	 	 	 
	
                A
                  Meta-Analysis of the Relationship Between Dose of EB1089 and Albumin
                  Corrected Serum Calcium in Six Studies

              	 	
                17-9801/SUM
                  (SIG)

              	 	
                04.06.99

              
	 	 	 	 	 
	
                Clinical

              	 	 	 	 
	
                A
                  phase I study of oral EB1089 in patients with advanced
                  cancer

              	 	
                EBC
                  9101 UK

              	 	
                Report
                  available

              
	
                EB1089
                  in acute myeloid leucaemia and myelodysplastic syndromes - a feasibility
                  study

              	 	
                EBC
                  9402 FI

              	 	
                Report
                  available

              
	
                EB
                  1089 in pancreatic cancer

              	 	
                EBC
                  9503 UK

              	 	
                Report
                  available

              
	
                EB1089
                  in breast cancer

              	 	
                EBC
                  9504 INT

              	 	
                Report
                  available

              
	
                EB1089
                  in hepatocellular carcinoma

              	 	
                EBC
                  9505 DK

              	 	
                Report
                  available

              
	
                EB1089
                  in PTHrP suppression

              	 	
                EBC
                  9506 INT

              	 	
                Report
                  available

              
	
                EB1089
                  in colorectal cancer

              	 	
                EBC
                  9601 INT

              	 	
                Report
                  available

              
	
                EB1089
                  in myelodysplastic syndromes (MDS)

              	 	
                EBC
                  9608 UK

              	 	
                Report
                  available

              
	
                EB1089
                  and apoptosis

              	 	
                EBC
                  9609 INT

              	 	
                Report
                  not available

              
	
                EB1089
                  in multiple myeloma

              	 	
                EBC
                  9701 INT

              	 	
                Report
                  available

              
	
                EB1089
                  and apoptosis in prostate cancer

              	 	
                EBC
                  9702 CA

              	 	
                Report
                  not available

              
	
                EB1089
                  in early recurrent prostate cancer

              	 	
                EBC
                  9703 US

              	 	
                Report
                  available

              
	
                Seocalcitol
                  versus placebo in advanced hepatocellular carcinoma

              	 	
                EBC
                  9801 INT

              	 	
                Report
                  not available

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Seocalcitol
                  versus placebo in the adjuvant treatment of hepatocellular
                  carcinoma

              	 	
                EBC
                  9802 INT

              	 	
                Report
                  not available

              
	
                Seocalcitol
                  in advanced hepatocellular carcinoma: Follow-up

              	 	
                EBC
                  0303 FR

              	 	
                Report
                  not available

              
	
                A
                  phase I study of oral EB1089 in patients with psoriasis

              	 	
                EBP
                  9401 DK

              	 	
                Report
                  available

              
	
                A
                  pacebo-controlled study of EB1089 in psoriasis

              	 	
                EBP
                  9606 DK

              	 	
                Report
                  available

              
	
                Tolerability
                  and safety of EB1089 capsules in healthy subjects

              	 	
                EBV
                  9501 NL

              	 	
                Report
                  available

              
	
                Seocalcitol
                  - A pilot phase I, open-label, randomised, balanced, single oral
                  dose,
                  two-period crossover study to investigate the pharmacokinetics
                  of single
                  doses of Seocalcitol capsules at two dose levels in healthy male
                  subjects

              	 	
                EBV
                  0001 UK

              	 	
                Report
                  available

              
	
                Seocalcitol
                  - A pilot phase I, open-label, randomized, balanced, single oral
                  dose,
                  three-period crossover study to investigate the bioavailability
                  and
                  bioequivalence of single oral doses of Seocalcitol capsules in
                  three
                  different formulations in healthy male subjects

              	 	
                EBV
                  0002 UK

              	 	
                Report
                  available

              
	
                Clinical
                  other

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Copies
                  of all patient records:

                Study
                  files No binders

                EBC
                  9801 INT 273

                EBC
                  9802 INT 208

                EBC
                  9505 DK 90

                EBC
                  9506 INT 30

                EBC
                  9703 US 20

                EBC
                  9601 INT 30

                EBC
                  9701 INT 20

                EBC
                  9609 INT 18

                total
                  : 689

                 

                CRF
                  pages: 150.000

                CT
                  scans:

                EBC
                  9505 DK: approx 100

                EBC
                  9802 INT: approx 5.000

                 

                SAE
                  documentation : 15 boxes, each containing approx 10 binders - Some
                  of the
                  SAE information can be found electronically as CIOMS
                  reports

              	 	 	 	 
	
                Copies
                  of all computer data

                None
                  available due to lack of version-tracking system

              	 	 	 	 
	
                A
                  Phase I Study of Oral EB1089 in Patients with Advanced
                  Cancer

              	 	
                EBC
                  9101 UK (TOS)

              	 	
                03.09.97

              
	
                A
                  Phase I Study of EB1089 in patients with Psoriasis

              	 	
                EBP
                  9401 DK (JTU)

              	 	
                02.03.98

              
	
                EB1089
                  in Acute Myeloid Leukaemia and Myelodysplastic Syndromes - A Feasibility
                  Study

              	 	
                EBC
                  9402 FI (TOS)

              	 	
                08.09.99

              
	
                Tolerability
                  and Safety of EB1089 Capsules in Healthy Volunteers

              	 	
                EBV
                  9501 NL (TOS)

              	 	
                24.06.98

              
	
                A
                  Placebo-Controlled Study of EB1089 in Psoriasis

              	 	
                EBP
                  9606 DK (JTU)

              	 	
                26.06.98

              
	
                EB1089
                  in Breast Cancer

              	 	
                EBC
                  9504 INT (AUJ)

              	 	
                01.03.00

              
	 	 	 	 	 
	
                Clinical
                  other

              	 	 	 	 
	
                Copies
                  of all patients records

              	 	 	 	 
	
                Copies
                  of all computer data

              	 	 	 	 
	 	 	 	 	 
	
                Copies
                  of all regulatory submissions

              	 	 	 	 
	
                US:

              	 	 	 	 
	
                · IND
                  55,250, EB1089 Capsules:

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Serial
                  No. 000: Original IND, JAN-1998

              	 	 	 	
                04-FEB-1998

              
	
                Serial
                  No. 001: IBRD-ROSTRUM appointed as US agent for LEO

              	 	 	 	
                26-FEB-1998

              
	
                Serial
                  No. 002: Protocol Amendment, EBC 9703 US

              	 	 	 	
                17-MAR-1998

              
	
                Serial
                  No. 003: Response to FDA regarding deficiencies

              	 	 	 	
                04-JUN-1998

              
	
                Serial
                  No. 004. Protocol Amendment, EBC 9706

              	 	 	 	
                04-NOV-1998

              
	
                Serial
                  No. 005: Information Amendment

              	 	 	 	
                05-APR-1999

              
	
                Serial
                  No. 006: IND Annual Report

              	 	 	 	
                05-APR-1999

              
	
                Serial
                  No. 007: IND Annual Report

              	 	 	 	
                06-APR-1999

              
	
                Serial
                  No. 008, Protocol Amendment, EBC 9703 US

              	 	 	 	
                12-JUL-1999

              
	
                Serial
                  No. 009: Information Amendment, Chemistry

              	 	 	 	
                07-SEP-1999

              
	
                Serial
                  No. 010: Information Amendment, Toxicology

              	 	 	 	
                07-SEP-1999

              
	
                Serial
                  No. 011: Protocol Amendment, New Protocol

              	 	 	 	
                28-JAN-2000

              
	
                Serial
                  No. 012: Safety Report

              	 	 	 	
                03-APR-2000

              
	
                Serial
                  No. 013: EoP2 Meeting Request

              	 	 	 	
                27-APR-2000

              
	
                Serial
                  No. 014: Safety Report

              	 	 	 	
                09-MAY-2000

              
	
                Serial
                  No. 015: Safety Report

              	 	 	 	
                22-JUN-2000

              
	
                Serial
                  No. 016: IND Annual Report

              	 	 	 	
                27-JUN-2000

              
	
                Serial
                  No. 017: Information Amendment - Pre-clinical

              	 	 	 	
                27-JUN-2000

              
	
                Serial
                  No. 018: Pre-meeting Package

              	 	 	 	
                05-JUL-2000

              
	
                Serial
                  No. 019: Information Amendment - Chemistry

              	 	 	 	
                20-JUL-2000

              
	
                Serial
                  No. 020: Safety Report

              	 	 	 	
                01-AUG-2000

              
	
                Serial
                  No. 021: Safety Report

              	 	 	 	
                20-SEP-2000

              
	
                Serial
                  No. 022: Change of Agent Name from Phoenix to MDS

              	 	 	 	
                19-OCT-2000

              
	
                Serial
                  No. 023: Safety Report

              	 	 	 	
                01-NOV-2000

              
	
                Serial
                  No. 024: Safety Report

              	 	 	 	
                14-NOV-2000

              
	
                Serial
                  No. 025: Safety Report

              	 	 	 	
                14-NOV-2000

              
	
                Serial
                  No. 026: Safety Report

              	 	 	 	
                20-NOV-2000

              
	
                Serial
                  No. 027: Safety Report

              	 	 	 	
                19-MAR-2001

              


      

      

        
          	
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                Serial
                  No. 028: Orphan Drug Petition

              	 	 	 	
                27-MAR-2001

              
	
                Serial
                  No. 029: Safety Report

              	 	 	 	
                04-APR-2001

              
	
                Serial
                  No. 030: Safety Report

              	 	 	 	
                16-APR-2001

              
	
                Serial
                  No. 031: Safety Report

              	 	 	 	
                24-APR-2001

              
	
                Serial
                  No. 032: Request for Teleconference

              	 	 	 	
                22-MAY-2001

              
	
                Serial
                  No. 033: Safety Report

              	 	 	 	
                29-MAY-2001

              
	
                Serial
                  No. 034: Safety Report

              	 	 	 	
                14-JUN-2001

              
	
                Serial
                  No. 035: Safety Report

              	 	 	 	
                27-JUL-2001

              
	
                Serial
                  No. 036: Teleconference

              	 	 	 	
                27-JUL-2001

              
	
                Serial
                  No. 037: Safety Report

              	 	 	 	
                02-AUG-2001

              
	
                Serial
                  No. 038: Safety Report

              	 	 	 	
                07-AUG-2001

              
	
                Serial
                  No. 039: IND Annual Report

              	 	 	 	
                23-AUG-2001

              
	
                Serial
                  No. 040: Safety Retort

              	 	 	 	
                04-OCT-2001

              
	
                Serial
                  No. 041: Safety Report

              	 	 	 	
                15-NOV-2001

              
	
                Serial
                  No. 042: Interim Statistical Plan

              	 	 	 	
                10-DEC-2001

              
	
                Serial
                  No. 043: Safety Resort

              	 	 	 	
                13-DEC-2001

              
	
                Serial
                  No. 044: Safety Resort

              	 	 	 	
                12-FEB-2002

              
	
                Serial
                  No. 045: Safety Resort

              	 	 	 	
                14-FEB-2002

              
	
                Serial
                  No. 046: Request for

                Teleconference

              	 	 	 	
                14-MAR-2002

              
	
                Serial
                  No. 047: Safety Resort

              	 	 	 	
                15-MAR-2002

              
	
                Serial
                  No. 048: Safety Resort

              	 	 	 	
                15-MAR-2002

              
	
                Serial
                  No. 049: Safety Resort

              	 	 	 	
                25-MAR-2002

              
	
                Serial
                  No. 050: Safety Resort

              	 	 	 	
                18-APR-2002

              
	
                Serial
                  No. 051: Safety Resort

              	 	 	 	
                18-APR-2002

              
	
                Serial
                  No. 052: Safety Resort

              	 	 	 	
                29-APR-2002

              
	
                Serial
                  No. 053: Pre-meeting Package for Teleconference

              	 	 	 	
                02-MAY-2002

              
	
                Serial
                  No. 054: Protocol Amendment

              	 	 	 	
                07-MAY-2002

              
	
                Serial
                  No. 055: Protocol Amendment, EBC 9802 INT

              	 	 	 	
                09-MAY-2002

              
	
                Serial
                  No. 056: Interim Analysis Report

              	 	 	 	
                23-MAY-2002

              
	
                Serial
                  No. 57: Withdrawal of Submission of Interim Analysis

              	 	 	 	
                06-JUN-2002

              
	
                Serial
                  No. 058: 7-day Safety Report

              	 	 	 	
                10-JUN-2002

              
	
                Serial
                  No. 059: 7-day Safety Report

              	 	
                I

              	 	
                14-JUN-2002

              
	
                Serial
                  No. 060: 7-day Safety Report

              	 	 	 	
                14-JUN-2002

              
	
                Serial
                  No. 061: 7-day Safety Report

              	 	 	 	
                24-JUN-2002

              
	
                Serial
                  No. 062: 7-day Follow-up Safety Report 

              	 	 	 	
                24-JUN-2002

              
	
                Serial
                  No. 063: IND Annual Report

              	 	 	 	
                25-JUN-2002

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Serial
                  No. 064: Information Amendment

              	 	 	 	
                12-JUL-2002

              
	
                Serial
                  No. 065: Information Amendment - Clinical

              	 	 	 	
                18-JUL-2002

              
	
                Serial
                  No. 066: Protocol Amendment, EBC 9802 INT

              	 	 	 	
                12-SEP-2002

              
	
                Serial
                  No. 068: Information Amendment, CMC

              	 	 	 	
                20-DEC-2002

              
	
                Serial
                  No. 069: Safety Report

              	 	 	 	
                30-JAN-2003

              
	
                Serial
                  No. 070: Safety Report

              	 	 	 	
                04-FEB-2003

              
	
                Serial
                  No. 072: Safety Report

              	 	 	 	
                03-MAR-2003

              
	
                Serial
                  No. 073: Safety Report

              	 	 	 	
                25-MAR-2003

              
	
                Serial
                  No. 074: Safety Report

              	 	 	 	
                14-APR-2003

              
	
                Serial
                  No. 075: Safety Report

              	 	 	 	
                14-APR-2003

              
	
                Serial
                  No. 076: Safety Resort

              	 	 	 	
                14-APR-2003

              
	
                Serial
                  No. 077: IND Annual Report

              	 	 	 	
                22-MAY-2003

              
	
                Serial
                  No. 079: Information Amendment - Chemistry

              	 	 	 	
                21-JUL-2003

              
	
                Serial
                  No. 080: Revised Investigator’s Brochure

              	 	 	 	
                21-JUL-2003

              
	
                Serial
                  No. 081: Protocol Amendment, EBC 9802 INT

              	 	 	 	
                22-JUL-2003

              
	
                Serial
                  No. 082: Safety Report

              	 	 	 	
                31-
                  JUL-2003

              
	
                Serial
                  No. 083: Safety Report

              	 	 	 	
                07-AUG-2003

              
	
                Serial
                  No. 085: Safety Report

              	 	 	 	
                02-SEP-2003

              
	
                Serial
                  No. 086: Safety Report

              	 	 	 	
                15-SEP-2003

              
	
                Serial
                  No. 087: Safety Report

              	 	 	 	
                22-SEP-2003

              
	
                Serial
                  No. 088: Safety Report

              	 	 	 	
                14-OCT-2003

              
	
                Serial
                  No. 090: Safety Report

              	 	 	 	
                24-OCT-2003

              
	
                Serial
                  No. 091: Safety Report

              	 	 	 	
                30-OCT-2003

              
	
                Serial
                  No. 092: Safety Report

              	 	 	 	
                30-OCT-2003

              
	
                Serial
                  No. 093: Safety Report

              	 	 	 	
                01-DEC-2003

              
	
                Serial
                  No. 094: Safety Report

              	 	 	 	
                01-DEC-2003

              
	
                Serial
                  No. 095: Safety Report

              	 	 	 	
                29-JAN-2004

              
	
                Serial
                  No. 096: Request for Placing IND on “Inactive” Status

              	 	 	 	
                15-MAR-2004

              
	
                Serial
                  No. 097: Request to Close IND

              	 	 	 	
                05-APR-2004

              
	
                Correspondence
                  with FDA regarding the above serial nos.

              	 	 	 	 
	 	 	 	 	 
	
                · Request
                  for Orphan Drug Designation, Hepatocellular Carcinoma

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Original
                  Application

              	 	 	 	
                18-JAN-2001

              
	
                Correspondence
                  with the FDA

              	 	 	 	 
	 	 	 	 	 
	
                · Interim
                  Analysis

              	 	 	 	 
	
                FDA
                  Information Package, Teleconference 4-JUN-2002, More Access to
                  Interim
                  Data

              	 	 	 	
                30-APR-2002

              
	
                EBC
                  9801 INT: Response to FDA Comments, Interim Analysis Plan, Hepatocellular
                  Carcinoma

              	 	 	 	
                30-APR-2002

              
	
                Statistical
                  Analysis Plan, Interim Analysis Number 1: Efficacy of Seocalcitol
                  Enteric-Coated Capsules or Placebo in Prolonging Time to Relapse
                  Following
                  Intended Curative Resection or Percutaneous Ablative Treatment
                  for
                  Hepatocellular Carcinoma

              	 	
                EBC
                  9802 INTI

              	 	
                15-AUG-2002

              
	
                Statistical
                  Analysis Plan, Interim Analysis Number 1: Seocalcitol versus Placebo
                  in
                  the Adjuvant Treatment of Hepatocellular Carcinoma

              	 	
                EBC
                  9802 INT

              	 	
                15-AUG-2002

              
	 	 	 	 	 
	
                · DMFs

              	 	 	 	 
	
                Type
                  I DMF No. 10842, Manufacturing Facilities

              	 	 	 	
                MAR-1994

              
	
                Yearly
                  updates of Type I DMF No. 10842

              	 	 	 	
                1995-1999

              
	
                Type
                  I DMF No. 11585, Facilities, Personnel and General Operating
                  Procedures

              	 	 	 	
                JUL-1995

              
	
                Yearly
                  updates of Type I DMF No. 11585

              	 	 	 	
                1996-1997

              
	
                Type
                  II DMF No. 10840, Drug Substance

              	 	 	 	
                MAR-1994

              
	
                Yearly
                  updates of Type II DMF No. 10840

              	 	 	 	
                1995-2004

              
	
                Type
                  II DMF No. 11505, Drug Product

              	 	 	 	
                MAY-1995

              
	
                Yearly
                  updates of Type II DMF No. 11505

              	 	 	 	
                1996-2004

              
	 	 	 	 	 
	
                · Miscellaneous

              	 	 	 	 
	
                Part
                  IV EBC 9703 US, Final Protocol

              	 	
                EBC
                  9703 US

              	 	
                09-DEC-1997

              
	
                Sponsor-Investigator
                  IND for

                Compassionate
                  Use (ALS)

              	 	 	 	
                09-SEP-1998

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                FDA
                  Briefing Document for EoP2 Meeting

              	 	 	 	
                30-JUN-2000

              
	
                FDA
                  Meeting Minutes, EoP2

              	 	 	 	
                11-AUG-2000

              
	
                FDA
                  Telecon Meeting Minutes

              	 	 	 	
                27-JUN-2001

              
	
                FDA
                  Telecon Meeting Minutes

              	 	 	 	
                04-JUN-2002

              
	
                Follow-up
                  Protocol Assistance, Gastro-resistant Capsules 5 mcg, Hepatocellular
                  Carcinoma

              	 	 	 	
                APR-2002

              
	
                Abbreviated
                  Clinical Study Report, EBC 9703 US: EB 1089 in Early Recurrent
                  Prostate
                  Cancer

              	 	
                EBC
                  9703 US

              	 	
                24-MAR-2004

              
	 	 	 	 	 
	
                CANADA:

              	 	 	 	 
	
                · INDs

              	 	 	 	 
	
                Pre-IND
                  Information Package: EB 1089 in PTHrP Suppression, EBC 9506
                  INT

              	 	 	 	
                JAN-1996

              
	
                Protocol
                  EBC 9506 INT: EB 1089 in PTHrP Suppression

              	 	 	 	
                AUG-1996

              
	
                Correspondence
                  with authorities regarding EBC 9506 INT

              	 	 	 	 
	
                Protocol
                  EBC 9601 INT: EB 1089 in Colorectal Cancer

              	 	 	 	
                10-JUN-1996

              
	
                Correspondence
                  with authorities regarding EBC 9601 INT

              	 	 	 	 
	
                Protocol
                  EBC 9505 DK: EB 1089 in Hepatocellular Carcinoma

              	 	 	 	
                16-JAN-1996

              
	
                Correspondence
                  with authorities regarding EBC 9505 DK

              	 	 	 	 
	
                Protocol
                  EBC 9702 CA: EB 1089 and Apoptosis in Prostate Cancer

              	 	 	 	
                27-MAR-1998

              
	
                Correspondence
                  with authorities regarding EBC 9702 CA

              	 	 	 	 
	
                Protocol
                  EBC 9801 INT: Advanced Hepatocellular Carcinoma

              	 	 	 	
                16-MAR-1999

              
	
                Correspondence
                  with authorities regarding EBC 9801 INT

              	 	 	 	 
	
                Protocol
                  EBC 9802 INT: Adjuvant Treatment of Hepatocellular
                  Carcinoma

              	 	 	 	
                19-MAY-1999

              
	
                Correspondence
                  with authorities regarding EBC 9802 INT

              	 	 	 	 
	 	 	 	 	 
	
                · Clinical
                  Trial Applications

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                  Doc
                    ID (Availability)

                	 	
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                Protocol
                  EBC 9702 CA: EB 1089 and Apoptosis in Prostate Cancer

              	 	 	 	
                27-MAR-1998

              
	
                Protocol
                  Amendment: EBC 9702 CA

              	 	 	 	
                18-OCT-2001

              
	
                Quality
                  Amendment: Extension of Shelf Life, EBC 9801 INT and EBC 9802
                  INT

              	 	 	 	
                NOV-2002

              
	
                Protocol
                  Amendment #5, 26-MAR-2003: Switch to Non-enteric Coated Capsules,
                  EBC 9801
                  INT

              	 	 	 	
                APR-2003

              
	
                Protocol
                  Amendment #7, 25-MAR-2003, EBC 9802 INT

              	 	 	 	
                APR-2003

              
	
                Quality
                  Amendment: Update to Non-enteric Coated Size 3 Capsules and Production
                  Site Change for a Contract Manufacturer, EBC 9801 INT

              	 	 	 	
                08-MAY-2003

              
	
                Correspondence
                  with authorities regarding the above

              	 	 	 	 
	
                · Miscellaneous

              	 	 	 	 
	
                Seocalcitol
                  placebo capsules: In-house approval of 36-month shelf life

              	 	
                _

              	 	
                NOV-2001

              
	
                Correspondence
                  with authorities regarding Investigator's Brochure for EB
                  1089

              	 	 	 	 
	 	 	 	 	 
	
                EU:

              	 	 	 	 
	
                · Scientific
                  Advice Request, 5 mcg Gastro-resistant Capsules, Hepatocellular
                  Carcinoma

              	 	 	 	 
	
                Correspondence
                  with EMEA

              	 	 	 	 
	
                Questions
                  Concerning the Clinical Aspects Followed by the Company's Position
                  and
                  Justification

              	 	 	 	
                31-AUG-2000

              
	
                Questions
                  Concerning the Pre-clinical Aspects Followed by the Company's Position
                  and
                  Justification

              	 	 	 	
                30-AUG-2000

              
	
                Questions
                  Concerning the Quality Aspects Followed by the Company's Position
                  and
                  Justification

              	 	 	 	
                AUG-2000

              
	
                Annex
                  1: Background Information

              	 	 	 	
                31-AUG-2000

              
	
                Annex
                  2: Quality

              	 	 	 	
                AUG-2000

              
	
                Annex
                  3: Pre-clinical

              	 	 	 	
                29-AUG-2000

              
	
                Annex
                  4: Clinical

              	 	 	 	
                31-AUG-2000

              
	
                Correspondence
                  with EMEA regarding the above

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Request
                  for Initial Multidisciplinary Scientific Advice (EBC 9801 INT:
                  Advanced
                  HCC; EBC 9802 INT: Adjuvant treatment of HCC)

              	 	 	 	
                OCT-2000

              
	
                · Orphan
                  Drug Application, Hepatocellular Carcinoma

              	 	 	 	 
	
                Correspondence
                  with EMEA

              	 	 	 	 
	
                Original
                  Application

              	 	 	 	
                MAR-2001

              
	
                Annual
                  Report, 1 Aug. 2001 - 31 July 2002

              	 	 	 	
                SEP-2002

              
	
                Annual
                  Report, 1 Aug. 2002 - 31 July 2003

              	 	 	 	
                SEP-2003

              
	 	 	 	 	 
	
                Denmark:

              	 	 	 	 
	
                Correspondence
                  with authorities regarding Clinical Trial Application, EBP 9401
                  DK
                  (Psoriasis)

              	 	 	 	 
	
                Correspondence
                  with authorities regarding Clinical Trial Application, EBC 9601
                  INT
                  (Colorectal Cancer)

              	 	 	 	 
	
                Correspondence
                  with authorities regarding Clinical Trial Application, EBC 9505
                  DK
                  (Hepatocellular Carcinoma)

              	 	 	 	 
	
                Correspondence
                  with authorities regarding Clinical Trial Application, EBC 9604
                  INT
                  (Breast Cancer)

              	 	 	 	 
	
                Correspondence
                  with authorities regarding use of EB 1089 enteric-coated capsules
                  5 mcg to
                  certain hospitals

              	 	 	 	 
	
                Correspondence
                  with authorities regarding supply of EB 1089 to few patients with
                  intestinal cancer

              	 	 	 	 
	 	 	 	 	 
	
                France:

              	 	 	 	 
	
                Notification
                  of Clinical Trial, EBC 9802 INT, France

              	 	 	 	 
	 	 	 	 	 
	
                Italy:

              	 	 	 	 
	
                Request
                  for approval of amendment to the Giudizio di Notorietà (EBC 9801 INT and
                  EBC 9802 INT), Italy

              	 	 	 	 


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                Spain:

              	 	 	 	 
	
                Clinical
                  Trial Application, Spain

              	 	 	 	
                , JUL-1999

              
	
                Chem.,
                  Pharm. and Biol. Doc. for an IND, Capsules 5 mcg and Placebo Capsules,
                  Spain

              	 	 	 	
                MAY-1999

              
	
                Renewal
                  of Clinical Trial Application

              	 	 	 	
                JUL-2001

              
	
                Renewal
                  of Clinical Trial Application, Non-enteric Coated Capsules

              	 	 	 	
                JUL-2003

              
	
                Application
                  for Use of Non-coated Capsules Size 3

                (sent
                  to Spain, Italy, France, UK and Canada)

              	 	 	 	
                28-APR-2003

              
	
                Notification
                  of Clinical Trials, EBC 9801 INT, EBC 9802 INT

              	 	 	 	
                04-DEC-2002

              
	 	 	 	 	 
	
                Sweden:

              	 	 	 	 
	
                Notification
                  of Clinical Trials, 5 mcg Enteric Coated Capsules, EBC 9701 INT,
                  Norway
                  and Sweden

              	 	 	 	
                MAR-1998

              
	
                Correspondence
                  with authorities regarding EBC 9701 TNT

              	 	 	 	 
	 	 	 	 	 
	
                UK:

              	 	 	 	 
	
                · Clinical
                  Trial Exemption, EB1089, CTX 00043/0189A

              	 	 	 	 
	
                Original
                  Application

              	 	 	 	
                DEC-1992

              
	
                Variation,
                  2 mcg and 5 mcg: EBC 9101

              	 	 	 	
                25-FEB-1993

              
	
                Variation:
                  Commencing of Study EBC 9503

              	 	 	 	
                18-SEP-1995

              
	
                Variation,
                  5 mcg: EBC 9504 INT

              	 	 	 	
                10-JAN-1996

              
	
                Variation,
                  10 μg and 20 μg: Chem./Pharm. Doc.

              	 	 	 	
                JAN-1996

              
	
                Variation,
                  1 μg: Chem./Pharm. Doc.

              	 	 	 	
                SEP-1996

              
	
                Variation,
                  5 mcg, 10 mcg and 20 mcg: EBC 9601 INT

              	 	 	 	
                21-JUN-1996

              
	
                Variation,
                  1 mcg, 5 mcg, 10 mcg and 20 mcg: EBC 9608 INT

              	 	 	 	
                04-OCT-1996

              
	
                Variation,
                  5 mcg: EBC 9506 INT

              	 	 	 	
                18-SEP-1995

              
	
                Variation:
                  Extension of Maximum Treatment Length, EBC 9503 UK

              	 	 	 	
                27-JAN-1997

              
	
                Variation,
                  5 μg: EBC 9505 DK

              	 	 	 	
                24-JUN-1997

              
	
                Variation,
                  5 μg: Protocol EBC 9609 INT

              	 	 	 	
                08-APR-1999

              
	
                Variation,
                  5 μg: EBC 9801 INT

              	 	 	 	
                12-MAY-1999

              
	
                Variation,
                  5 μg: EBC 9802 INT

              	 	 	 	
                16-JUL-1999

              


      

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

      

        
          	
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                  Date

                


        

      

      
        	
                Variation,
                  5 μg: Extension of ShelfLife

              	 	 	 	
                NOV-2002

              
	
                Variation:
                  Supporting Data, Non-enteric Coated Capsule Size 3

              	 	 	 	
                JUN-2003

              
	
                Correspondence
                  with authorities regarding all of the above

              	 	 	 	 
	 	 	 	 	 
	
                · Miscellaneous

              	 	 	 	 
	
                CTX,
                  EB 1089 Propylene Glycol-Buffer Sol., Chem. & Pharm.
                  Doe.

              	 	 	 	
                NOV-1992

              
	 	 	 	 	 
	
                Other
                  Regulatory Information

              	 	 	 	 
	
                Correspondence
                  with the World Health Organization regarding International Nonproprietary
                  Name for EB 1089

              	 	 	 	 
	 	 	 	 	 
	
                Draft
                  EU SmPC for Seocalcitol (EBC 9801 INT)

              	 	 	 	
                28-AUG-2000