Document:

kl01034_ex4-3.htm

    
      

    

     

    Exhibit 4.3

     

    TECHNOLOGY LICENSE
AGREEMENT

     

    CONFIDENTIAL TREATMENT
REQUESTED

    

    INFORMATION
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED IS OMITTED AND IS IDENTIFIED
BY THREE ASTERISKS, AS FOLLOWS “* * *”, AN UNREDACTED VERSION OF THIS DOCUMENT
HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.

    

    
      	
              BETWEEN
      :

            	
              NATIONAL RESEARCH COUNCIL OF
      CANADA, whose head office address is:

              1200
      Montreal Road

              Ottawa,
      Ontario KIA 0R6

              (through
      its Institute, whose name and address are:

              Institute
      for Biological Sciences 1200 Montreal Road, Building M-54 Ottawa, Ontario
      K1A 0R6

            	
              (called
      “NRC”)

              (called
      the “Institute”)

            

    

    

    
      	
              AND
      :

               

            	
              HELIX
      BIOPHARMA CORPORATION

              a
      corporation under the laws of Ontario, Canada whose head office address
      is:

              3-305
      Industrial Parkway South,

              Aurora
      ON Canada L4G 6X7

            	
              (called
      the “Licensee”)

            

    

     

    
          WHEREAS

       

    

    
      	
               
      

            	
              (a)

            	
              NRC
      owns or controls certain technology which is subject to intellectual
      property rights, including without limitation inventions (which may be
      protected by patents), copyright, trade secrets, know-how, and information
      that is confidential.

            

    

     

    
      	
               
      

            	
              (b)

            	
              NRC
      and the Licensee desire to enter into a licence agreement that will permit
      the technology to be used for commercial
  purposes.

            

    

     

     

    
      
        
          

        

      

       

      

    

    IN CONSIDERATION of the
following terms, conditions, promises, and payments, the parties agree as
follows:

     

     

    
      1.0  DEFINITIONS IN THIS
AGREEMENT

    

     

    For all
purposes of this Agreement the following terms, in singular or plural form as
appropriate to the context, are defined as follows:

     

    
      	
              1.1  

            	
              “NRC Technology” means
      the inventions (not necessarily patentable), trade secrets, know-how,
      Software, designs, written works, samples, biological materials, and
      technical information (confidential or not) relating to the “*** Antibody
      patent application” (NRC case # ***) tentatively
  entitled:

            

    

     

    “An Antibody Fragment, and
Derivatives Thereof, for the Detection and Treatment of Lung
Adenocarcinoma”,

    ***

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              1.2  

            	
              “Licensee Technology’
      means the inventions (not necessarily patentable), patent(s), trade
      secrets, know-how, software, designs, written works, samples, biological
      materials, and technical information (confidential or not) relating to
      Helix Biopharma Proprietary Compound named “DOS47” and related compounds
      as described by US application # 20040115186 including any improvements,
      continuation, divisional applications derived from
  it.

            

    

     

    
      	
              1.3  

            	
              “Foreground Technology”
      means the inventions (not necessarily patentable), patent(s),
      including any improvements, continuation, divisional applications derived
      from such patent(s), trade secrets, know-how, software, designs, written
      works, samples, biological materials, and technical information
      (confidential or not) relating to novel molecules resulting from the
      combination of the NRC Technology and the Licensee Technology. Such
      Foreground Technology is proprietary to
NRC.

            

    

     

    
      	
              1.4  

            	
              “Patents” means the
      following patents and patent applications, plus any divisions,
      continuations, continuations-in-part, re-issues, and extensions of these
      patents and patent applications plus any other patents and patent
      applications in countries within the Territory, covering essentially the
      same inventions or claiming priority of patenting rights from any other
      patent application within the Patent
entitled:

            

    

     

    An Antibody Fragment, and
Derivatives Thereof, for the Detection and Treatment of Lung
Adenocarcinoma”,

    ***.

     

    NRC
currently holds no other patents or patent applications in relation to the NRC
Technology. If NRC does apply for such Patents, the licence granted by this
Agreement covers these patents, specifically.

     

    
      	
              1.5  

            	
              “NRC Intellectual
      Property Rights” means Patents and other exclusionary rights in respect of
      the NRC Technology, and rights in respect of Confidential information
      included in the NRC Technology.

            

    

     

    
      	
              1.6  

            	
              “NRC’s Internal Purposes”
      means research and development within NRC’s laboratories and the
      provision of services to NRC’s customers, conducted in such a way as to
      avoid the disclosure of either confidential information of the Licensee or
      confidential information of NRC which is deliverable under this Agreement
      and whose disclosure would deprive the Licensee of some significant
      advantage intended by this
Agreement.

            

    

     

    
      	
              1.7  

            	
              “Licensee’s Internal
      Purposes” means research and development within Licensee’s
      laboratories conducted in such a way as to avoid the disclosure of
      Confidential information of NRC whose disclosure would deprive NRC of some
      significant advantage intended by this
  Agreement.

            

    

     

    
      	
              1.8  

            	
              “Product” means any
      thing (including equipment, system, device, component, chemical, molecule,
      database, or software) that incorporates or embodies or is derived from
      any part of the Foreground Technology (including all modifications made by
      the Licensee or NRC), or that results from practicing or using the
      Foreground Technology, and also any document that relates to the
      Foreground Technology.

            

    

     

    
      	
              1.9  

            	
              Service” means any
      service to third parties, not provided free, that is provided by using any
      part of the Foreground Technology (including all modifications made by the
      Licensee or NRC), or by using a Product, or that relates to a Product,
      including (without limiting the generality of the foregoing)
      customization, maintenance, installation, training, consulting, testing,
      operating, dissemination of advertising or publicity, production,
      packaging and distribution.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      	
              1.10  

            	
              “Sale” means every
      disposition of a Product, including selling, renting, leasing, licensing,
      lending, and bartering of a Product.  It also means every
      instance of providing Service. It is considered to occur when a Product or
      Service is delivered or an invoice is issued, whichever occurs first. A
      Sale exists irrespective of the collection of any debt (regardless of any
      accounting principle), but not if money received is refunded. “Sell”, and
      “Sold” have corresponding meanings.

            

    

     

    
      	
              1.11  

            	
              “Sales Revenue” means
      the gross price billed by the Licensee or sub-licensee to a purchaser on
      account of every Sale of a Product or Service, including recurring and
      deferred payments when received, less the following
      deductions:

            

    

    
      	
              (a)  

            	
              rebates
      granted and taken, except rebates granted wholly or partially in
      consideration of a third party’s agreement to purchase anything that is
      not a Product or Service as defined in this
  Agreement;

            

    

    
      	
              (b)  

            	
              trade,
      promotional, quantity or cash discounts actually allowed and taken, not
      exceeding amounts that are customary in the
  trade;

            

    

    
      	
              (c)  

            	
              amounts
      repaid or credited by reason of rejections or returns of Products, or as
      retroactive price reductions;

            

    

    
      	
              (d)  

            	
              custom
      duties, excise taxes, sales taxes, value-added taxes and any compulsory
      payments made to government authorities, if separately stated on an
      invoice with the intention that costs incurred by the Licensee will be
      recovered from the invoiced person,
and

            

    

    
      	
              (e)  

            	
              actual
      shipping and insurance costs in transporting Products to third parties if
      separately stated on an invoice with the intention that costs incurred by
      the Licensee will be recovered from the invoiced
  person.

            

    

     

    If
Products or Services are bartered for goods or services, or are disposed of
through a transaction that is not at Arm’s Length, the Sales Revenue shall be
calculated as above, using the average of gross prices billed in typical recent
Sales of equivalent Products or Services, and if there are no such Sales, then
it shall be deemed to be the fair market value (having regard to the Licensee’s
advertised prices and prices of near equivalents in the market).

     

    If a
Product is incorporated as part of another article, the Licensee shall price the
Product separately on an invoice. When a distinct price for a Product is not
invoiced, or when the price stated is not a reasonable price, the Sales Revenue
shall be calculated as above, using the average of net prices billed in typical
recent Sales of equivalent Products, and if there are no such Sales, then the
Sales Revenue for the Product shall be deemed to be the Sales Revenue for the
article multiplied by the ratio of the manufacturing cost of the Product to the
manufacturing cost of the article. The Licensee shall be responsible for
providing satisfactory evidence of manufacturing costs. This paragraph does not
apply to Services, and no adjustment is allowed to the net price billed for a
Service.

     

    
      	
              1.12  

            	
              “Other Revenue” means
      all payments, and the value of other consideration, which the Licensee
      receives in relation to sub-licences, other than royalties from Sales of
      Products or Services by the sub-licensee.  This includes,
      without limitation, initial fees, milestone payments, bonuses, periodic
      fees, fees for consulting, fees for upgrades, dividends, and the value of
      equity.

            

    

     

    
      	
              1.13  

            	
              “Reporting Date(s)” is
      (are) the date(s) in every year up to which royalties since the last
      Reporting Date are calculated as follows: January 31 and July
      31.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    
      	
              1.14  

            	
              “Affiliate” is a
      corporation of which more than 20% of the voting shares are owned by the
      Licensee, or which owns more than 20% of the voting shares of the
      Licensee, or of which more than 50% of the voting shares are owned by
      another Affiliate or if it owns more than 50% of another
      Affiliate.

            

    

     

    
      	
              1.15  

            	
              “Arm’s length” has the
      meaning as used for purposes of the Income Tax Act of
      Canada, and is not limited to the same meaning as being an
      Affiliate.

            

    

     

    
      	
              1.16  

            	
              “Territory means
      worldwide.

            

    

     

     

    
      	
              2.0  

            	
              GRANT OF
      LICENCE

            

    

     

    
      	
              2.1  

            	
              Grant:  NRC
      grants to the Licensee a licence of NRC’s Intellectual Property Rights and
      the Patents, for the Licensee’s Internal Purposes.  NRC also
      grants to the Licensee a licence of the Foreground Technology effective
      throughout the Territory:

            

    

    
      	
              (a)  

            	
              to
      reproduce, make, use, import and Sell any Product and export any Product
      to any place within the Territory;

            

    

    
      	
              (b)  

            	
              to
      engage contractors to reproduce or make any Product to be used or sold by
      the Licensee;

            

    

    
      	
              (c)  

            	
              to
      Sell any Service.

            

    

     

    
      	
              2.2  

            	
              Field of
      Use:  The Licensee shall not deaf in any manner with
      Product, Services or Foreground Technology except as authorized under this
      Agreement for applications within the Territory and within the authorized
      field of use, which is: therapeutic and diagnostic applications for
      humans.

            

    

     

    
      	
              2.3  

            	
              Exclusivity:  The
      rights granted to the Licensee by way of licence under this Agreement
      are:

            

    

    
      	
              (a)  

            	
              non-exclusive,
      for Licensee’s Internal Purposes, with respect to NRC Technology and the
      Patents;

            

    

    
      	
              (b)  

            	
              exclusive,
      with respect to Foreground Technology and to any patent relying on
      Foreground Technology.

            

    

     

    
      	
              2.4  

            	
              Sub-licensing:  The
      Licensee may sub-license the rights granted by this Agreement with respect
      to Foreground Technology to:

            

    

    
      	
              (a)  

            	
              purchasers
      of a Product, as needed to permit normal use of a Product by an end- user
      and such sub-licences survive termination of this
    Agreement;

            

    

    
      	
              (b)  

            	
              any
      other person, on terms approved by NRC in writing in
    advance.

            

    

     

    
      	
              2.5  

            	
              Canadian
      Content:  The Licensee shall perform all manufacturing of
      Products in Canada, and shall use Canadian-made materials in Products to
      the extent that they are reasonably available.  Canadian-based
      sub-licensees shall be subject to the same
      requirement.  Foreign-based sub-licensees are not so restricted,
      but they shall not be permitted to sell Products that will be imported
      into Canada.

            

    

     

    
      	
              2.6  

            	
              Delivery:  NRC
      shall give the Licensee a copy of all of NRC’s
  relevant:

            

    

    
      	
              (a)  

            	
              Patents,
      including the latest draft of any applications that have not matured into
      patents;

            

    

    
      	
              (b)  

            	
              documentation
      that is reasonably necessary for an understanding of the NRC Technology,
      to the extent that it exists;

            

    

    
      	
              (c)  

            	
              samples,
      in reasonable quantities, of materials illustrating the NRC
      Technology.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    The
Licensee shall be conclusively deemed to have received all necessary delivery
under this paragraph if the Licensee has not notified NRC, within 60 days after
the effective date of this Agreement that delivery is lacking.

     

    
      	
              3.0  

            	
              FEES AND
      ROYALTIES

            

    

     

    
      	
              3.1  

            	
              Licence
      Fee:  As consideration for the grant of the licence,
      immediately upon receiving a fully signed original of this Agreement the
      Licensee shall pay NRC the sum of *** plus applicable
    taxes.

            

    

     

    
      	
              3.2  

            	
              Licensee’s
      Royalty:  The Licensee shall pay to NRC royalties for all
      Sales of Products and Services as follows: *** of Sales
      Revenue.

            

    

     

    The
Parties shall mutually agree on an approach to establish a reduced royalty rate
if a Licensed Product uses one or more additional technologies licensed from a
third and unrelated party, based on the material contribution of the NRC
technology to the composition of the final, licensed product (so-called ‘Royalties stacking
provision’).

     

    Under
such circumstances, however, the reduced royalty rate for such Licensed Product
shall not be less than *** of Sales Revenue.

     

    
      	
              3.3  

            	
              Milestone
      payments:

            

    

     

    For the development of the first
Licensed Product:

     

    
      	
               
      

            	
              –

            	
              A
      milestone payment of twenty five thousand dollars (CAN $25,000) upon
      successful completion of Phase I clinical trials as confirmed by a
      regulatory authority (e.g.: United States Food and Drug
      Administration).

            

    

     

    
      	
               
      

            	
              –

            	
              A
      milestone payment of fifty thousand dollars (CAN $50,000) upon successful
      completion of Phase Ilb clinical trials as confirmed by a regulatory
      authority.

            

    

     

    
      	
               
      

            	
              –

            	
              A
      milestone payment of one hundred and twenty five thousand dollars (CAN
      $125,000) upon successful completion of Phase Ill clinical trials as
      confirmed by a regulatory
authority.

            

    

     

    
      	
               
      

            	
              –

            	
              A
      milestone payment of two hundred thousand dollars (CAN $200,000) upon
      receipt of market approval by a regulatory
  authority.

            

    

     

    For
the development of each subsequent Licensed Products

     

    
      	
               
      

            	
              –

            	
              A
      milestone payment of two hundred thousand dollars (CAN $200,000) upon
      receipt of market approval by a regulatory
  authority.

            

    

     

    
      	
              3.4  

            	
              Royalty for Unauthorized
      Sales:  Without implying any waiver of NRC’s rights to
      enforce limitations in this Agreement or to seek damages for breach of
      this Agreement, the Licensee shall pay to NRC, without further demand by
      NRC, royalties on Sales of Products or Services which are not authorized
      with respect to Territory or Field of
Use.

            

    

     

    
      	
              3.5  

            	
              Other
      Revenue:  The Licensee shall pay to NRC *** of Other
      Revenue.

            

    

     

    
      	
              3.6  

            	
              Minimum Annual
      Royalty:  The Licensee shall pay NRC a Minimum Annual
      Royalty (“MAR”) according to the following schedule (with tax to be
      added), regardless of whether 

            

    

     

     

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    NRC issues an invoice for the MAR.  The MAR becomes
overdue, and subject to interest on overdue payments, on the date stated here,
regardless of whether that is a Reporting Date and regardless of when the next
royalty payment and statement are due. MAR payments shall be credited against
royalties and shares of Other Revenue, payable to NRC for the same period by the
Licensee and by any sub-licensee.

     

    The
Minimum Annual Royalty is: *** per calendar year, owed if no research
collaboration agreement is in place between Collaborator and NRC in a given
calendar year, when the license is in full force. Royalties owed in a given
calendar year are to be applied against this Minimum Annual
Royalty.

     

    
      	
              3.7  

            	
              Sub-Licensee’s
      Royalty:  the Licensee shall be responsible for paying
      NRC the same royalties that would be payable if Sales by the sub-licensee
      were Sales by the Licensee.

            

    

    
      	
              (a)  

            	
              Licensee
      shall require the sub-licensee to pay directly to NRC royalties for all
      Sales of Products and Services by the sub-licence royalties as if Sales of
      Products and Services by the sub-licensee were Sales of Products and
      Services by the Licensee;

            

    

    
      	
              (b)  

            	
              Licensee
      guarantees the payments required from the
  sub-licensee.

            

    

     

    
      	
              3.8  

            	
              Tax:  The
      Goods and Services Tax, or Harmonized Sales Tax, or Quebec Sales Tax, is
      applicable to payments required by this Agreement, depending on the
      residence of the Licensee or sub-licensee, while none of those taxes
      normally applies to foreign-based payers. It is the responsibility of the
      payer, whether Licensee or sub-licensee, to determine tax status and to
      pay the applicable tax.  NRC’s GST and HST registration number
      is 121 491 807.  NRC’s QST registration number is 1006 178
      088.

            

    

     

    
      	
              3.9  

            	
              Interest:  In
      lieu of the regulation that requires NRC to charge interest on overdue
      amounts at a rate based on variable central-bank rates, interest at one
      percent (1%) per month compounded monthly (annual rate of 12.68%) must be
      paid on overdue amounts from the date when payment is due until the date
      it is received by NRC.  NRC may revise that rate upon two (2)
      months’ notice. An administrative charge of $25 will be invoiced for any
      cheque, which is refused payment by the financial institution on which it
      is drawn.

            

    

     

    
      	
              3.10  

            	
              Delinquent
      Accounts:  NRC may use a collection agency to collect any
      debt arising under this Agreement, and NRC may obtain a set-off of the
      debt against any other money payable by the Government of Canada to the
      Licensee.  The costs and fees of collection agencies shall be
      added to the debt payable to NRC.

            

    

     

    
      	
              3.11  

            	
              Statements:  The
      Licensee must deliver royalty statements to NRC within sixty (60) days
      after each Reporting Date, even if no Products or Services were
      Sold.  NRC may provide a form for royalty statements, which the
      Licensee must use.  Royalty statements must be certified
      accurate and correct by the Chief Financial Officer or some other senior
      officer of the Licensee, and must include the following information for
      the period up to the Reporting Date or since the last Reporting
      Date:

            

    

    
      	
              (a)  

            	
              the
      quantity of Products made by or for the
  Licensee;

            

    

    
      	
              (b)  

            	
              the
      quantity, and the Sales Revenue, for Products Sold at Arm’s
      Length;

            

    

    
      	
              (c)  

            	
              the
      quantity of Products disposed of at other than Arm’s Length or by barter,
      the persons to whom disposed, and the basis for the
    royalties;

            

    

    
      	
              (d)  

            	
              Sales
      Revenue from Services Sold;

            

    

    
      	
              (e)  

            	
              a
      calculation of the royalties due to
NRC;

            

    

    
      	
              (f)  

            	
              a
      projection of Sales of Products and Services for the periods to be covered
      in the next two royalty statements;

            

    

    
      	
              (g)  

            	
              where
      applicable, identical information as in (a) to (f) from the
      sub-licensee.

            

    

     

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              3.12  

            	
              Currency
      Translation:  Sales Revenue and Other Revenue, and any
      fixed payment to NRC required by this Agreement, when required to be
      converted to Canadian dollars, shall be converted using the Bank of Canada
      monthly exchange rate for the last month of the reporting
      period.  This currency information is available at the Bank of
      Canada website:
      http://bank-banque-canada.ca/english/xrate/htm.  If payments to
      NRC are required to be made in U.S. dollars, the conversion shall be the
      rate of exchange in a major financial market, as published (errors
      excluded) in a widely distributed Canadian or U.S. newspaper on the last
      date of the reporting period, or within the seven preceding
      days.  The basis of all conversions shall be stated in the
      royalty statement submitted to NRC, accompanied by a printed copy of the
      published basis of that conversion.

            

    

     

    
      	
              3.13  

            	
              Remittances:  Royalty
      statements must be accompanied by a remittance of the royalties due, in
      Canadian or U.S. funds payable at par at Ottawa, Ontario, Canada.
      Remittances can be made either by a bank transfer to an account which NRC
      will designate if asked, or by a cheque payable to: “Receiver General -
      National Research Council”, indicating on the cheque the reference number
      (if any) appearing on the first page of this
  Agreement.

            

    

    Cheques
must be addressed to:

    
      	
               
      

            	
              - NRC -
      Accounts Receivable, at the NRC head office address stated above
      (on page 1);

            

    

     

    A copy of
the royalty
statement must be sent to:

    
      	
               
      

            	
              - NRC -
      Intellectual Property Services, at the NRC head office address
      stated above (on page 1);

            

    

    and
to:

     

    
      	
               
      

            	
              - the Institute,
      at its address stated above (on page
1).

            

    

     

    
      	
              3.14  

            	
              Records:  The
      Licensee shall, and shall require sub-licensees
  to:

            

    

    
      	
              (a)  

            	
              keep
      accurate, detailed and complete records in accordance with generally
      accepted accounting principles, at its expense, which shall be retained
      and available at its principal place of business in respect of Products
      and Services, and the basis of any Other Revenue which may require a
      payment to NRC;

            

    

    
      	
              (b)  

            	
              provide
      NRC, upon request and without charge, with annual Financial Statements
      (prepared by an external auditor, if available) that will verify the Sales
      Revenue derived from Products and
Services;

            

    

    
      	
              (c)  

            	
              keep
      all the records intact for a period of not less than three (3)
      years.

            

    

     

    
      	
              3.15  

            	
              NRC’s
      Audits:  The Licensee shall make all relevant records
      available at its premises during normal business hours, upon reasonable
      notice, and permit NRC and its authorized representatives to audit,
      inspect, and copy the records.  In such circumstances, the
      Licensee shall afford all facilities and collaboration to NRC and its
      authorized representatives, and furnish all information necessary to the
      understanding of the records.  If NRC’s audit reveals that
      payments made by the Licensee are less than eight-tenths (80%) of the
      amount that should have been paid, the Licensee shall reimburse NRC’s cost
      of the audit which becomes a debt due immediately to NRC, along with a
      debt of the shortfall in royalties and share of Other Revenue with
      interest from the date on which the payments should have been
      made.  If the Licensee presents obstacles to the audit, such
      that a Chartered Accountant makes an affidavit that the audit is
      impossible or impractical, the Licensee shall be deemed by this clause to
      have agreed that NRC may estimate a fair value of the royalties and share
      of Other Revenue payable, based on the best information available, and the
      Licensee shall pay that amount to NRC immediately together with interest
      from the date on which the payments should have been
  made.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              3.16  

            	
              Licensee’s
      Audits:  At its option, NRC shall be entitled to an audit
      of Other Revenue and of the Sales Revenue from the Sale of Products and
      Services as part of the Licensee’s regular audit, at no cost to
      NRC.  When NRC gives reasonable advance notice of requiring that
      audit, the Licensee will provide NRC with an audited statement prepared by
      an external auditor that will verify Other Revenue and the Sales Revenue
      derived from the Sales of Products and Services in any year for which an
      audit has not been completed at the time NRC gives notice.  If
      the audit reveals a shortfall in what was paid to NRC, the Licensee shall
      pay the shortfall amount to NRC immediately, with interest from the date
      on which the payments should have been made.  If the audit
      reveals that payments made by the Licensee are not less than eight-tenths
      (80%) of the amount that should have been paid, NRC shall reimburse the
      Licensee for any incremental costs of the additional part of the
      audit.

            

    

     

    
      	
              3.17  

            	
              Continuing
      Rights:  The rights granted in the preceding three (3)
      paragraphs shall survive the termination of this Agreement for a period of
      three (3) years.

            

    

     

    
      	
              3.18  

            	
              Allocation To
      Technology:  If requested, the Licensee shall cooperate
      with NRC in providing information about a reasonable allocation of the
      Licensee’s Sales Revenue and Other Revenue, and therefore of royalties,
      amongst the various elements of the Products or Services, which is
      information that NRC requires for allocating shares of royalties amongst
      the creators pursuant to NRC’s Awards
Policy.

            

    

     

    
      	
              4.0  

            	
              INTELLECTUAL
      PROPERTY

            

    

     

    
      	
              4.1  

            	
              Patenting
      Responsibility:  NRC shall bear the responsibility and
      pay the cost to obtain and maintain Patents in the countries that NRC
      chooses to file an application directly or through the national phase of a
      PCT application.  NRC shall use reasonable efforts to obtain
      those Patents and shall not allow those Patents to lapse for failure to
      comply with maintenance obligations.  If applications (including
      the national phase of a PCT application) could be filed in countries,
      which NRC has not chosen, they may be requested by the Licensee and shall
      be filed by NRC if the Licensee bears all expenses including without
      limitation the cost of maintaining those
  Patents.

            

    

     

    
      	
              4.2  

            	
              Sharing Patent
      Costs:  The Licensee shall reimburse NRC, promptly on the
      receipt of an invoice for twenty five per cent (25%) of NRC’s internal
      costs (to the extent reasonable) and disbursements related to obtaining
      and maintaining the Patents.  This includes costs and
      disbursements incurred before this Agreement was in
  effect.

            

    

     

    
      	
              5.0  

            	
              TECHNICAL
      ASSISTANCE

            

    

     

    
      	
              5.1  

            	
              No
      Assistance:  NRC is not obliged to provide the Licensee
      with technical assistance relating to the NRC Technology or the
      Product.  NRC may, at its sole discretion, supply technical
      assistance under separate contracts, in accordance with NRC’s customary
      terms and standard rates.

            

    

     

    
      	
              5.2  

            	
              NRC’s
      Improvements:  In the event that NRC produces additions
      or changes to the NRC Technology or to the Foreground Technology, which by
      their nature could not be used without some use of the NRC Technology or
      the Foreground Technology, NRC shall inform the Licensee and, the
      additions or changes shall be regarded as part of the NRC Technology or
      the Foreground Technology for all purposes of this
    Agreement.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              5.3  

            	
              Licensee’s Improvements or
      Additions:  In the event that the Licensee produces
      additions or changes to the NRC Technology or the Foreground Technology,
      which by their nature could not be made or used without some use of the
      NRC Technology or the Foreground Technology, the Licensee shall provide
      NRC, within ninety (90) days from the time the additions or changes have
      been made, with all available technical information concerning them,
      including source code if software is involved, and shall be deemed to
      license NRC to use them for NRC’s Internal Research Purposes at no cost to
      NRC.

            

    

     

    
      	
              5.4  

            	
              Grant
      Back:  Upon Termination of this Agreement, the Licensee
      shall be deemed to have granted to NRC, and shall execute any documents
      reasonably required by NRC as additional evidence of this, a
      non-exclusive, unconditional, irrevocable, perpetual royalty- free
      licence, including the right to sub-license, to make, use or sell articles
      incorporating any additions and changes made by the Licensee which were
      required by the preceding paragraph to be reported to NRC, whether
      patentable or unpatentable, without any obligation to account to the
      Licensee.

            

    

     

    
      	
              6.0  

            	
              CONFIDENTIALITY

            

    

     

    
      	
              6.1  

            	
              What
      is Confidential:  The NRC Technology and the Foreground
      Technology are confidential to NRC except for published elements and
      elements which NRC states in writing to be not confidential. Software
      source code is confidential to NRC.  The Licensee’s derivative
      software is confidential to the Licensee, unless the Licensee states
      otherwise in writing. Any documents of either party, marked
      ‘Confidential”, “Protected’’, “Proprietary”, or similar words, are
      confidential to that party.

            

    

     

    
      	
              6.2  

            	
              Obligations of
      Confidentiality:  Except to the extent expressly
      authorized in this Agreement, each party shall, until five years after the
      expiration date defined in paragraph 11.1, protect the other party’s
      confidential information with some degree of care as it uses to protect
      its own confidential information, but not less than a reasonable degree of
      care, and shall not use such information for purposes other than those
      contemplated by this Agreement.  Disclosure of information by a
      receiving party is permitted to the extent that it can be proved to
      be:

            

    

    
      	
              (a)  

            	
              independently
      developed by the receiving party without reference to or use of the
      confidential information of the other
party;

            

    

    
      	
              (b)  

            	
              received
      from the third party without breach of any obligation of
      confidentiality;

            

    

    
      	
              (c)  

            	
              in
      the public domain at the time of its disclosure or that later becomes
      publicly available without breach of this
  Agreement;

            

    

    
      	
              (d)  

            	
              required
      to be disclosed by law, including in the case of NRC, the Access to Information Act,
      provided that the receiving first provides the disclosing party
      with notice of such requirements and of its intent to disclose the
      information; or

            

    

    
      	
              (e)  

            	
              required
      in order to comply with applicable rules and regulations of any stock
      exchange on which the Licensee’s shares are
  listed.

            

    

     

    
      	
              6.3  

            	
              If Confidentiality
      Lost:  This Agreement remains in effect regardless of any
      loss of confidentiality of the NRC Technology or the Foreground Technology
      at any time for
      any reason, although each party retains the right to terminate this
      Agreement for a breach by the other
party.

            

    

     

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              7.0  

            	
              DILIGENT
      EXPLOITATION

            

    

     

    
      	
              7.1  

            	
              Requiring
      Diligence:  The licence granted by this Agreement is
      conditional upon diligent exploitation of the rights granted to the
      Licensee, in a manner likely to satisfy the demand for the Products and
      Services in relation to all reasonable applications, and to adequately
      serve the Licensee’s customers, throughout the Territory.  If
      NRC suspects a lack of diligence, NRC will give written notice to the
      Licensee, inviting the Licensee to explain to the satisfaction of NRC, in
      writing within six (6) months, why the level of exploitation should be
      considered satisfactory. Diligence will be judged without regard to
      royalties or minimum royalties paid.  NRC reserves the right to
      find a lack of diligence after the six-months’ notice and after having
      studied any response made by the Licensee, and this decision shall be
      conclusive, subject only to the dispute resolution provisions of this
      Agreement.

            

    

     

    
      	
              7.2  

            	
              Consequences of Lack of
      Diligence:  On a country-by-country basis, or in all
      countries at the same time, when NRC finds a lack of diligence in
      accordance with the preceding paragraph, NRC has the right
    to:

            

    

    
      	
              (a)  

            	
              convert
      any exclusivity to non-exclusivity in a
country,

            

    

    
      	
              (b)  

            	
              terminate
      the licence entirely in respect of a country,
or

            

    

    
      	
              (c)  

            	
              modify
      the field of use.

            

    

     

    NRC shall
not exercise those rights before six (6) years or the date of entry into Phase 1
clinical trials in humans as formally evidenced by a national regulatory
authority having jurisdiction on such matters, but NRC’s demand for
justification can be made earlier.

     

    
      	
              7.3  

            	
              Multiple
      Occurrences:  The procedure for challenging diligence,
      and the consequences, may be invoked more than
  once.

            

    

     

    
      	
              8.0  

            	
              USE OF NRC’S
      NAME

            

    

     

    
      	
              8.1  

            	
              Control of
      Use:  NRC reserves the right, in its sole discretion, to
      control any unauthorized use of its name and may notify the Licensee that
      it must immediately cease using the name, including any abbreviations,
      words, or images that imply an association with NRC.  Upon
      receipt of such notification, the Licensee must use its best efforts to
      withdraw from circulation any written material that represents an
      unauthorized use.

            

    

     

    
      	
              8.2  

            	
              Authorized
      Use:  Notwithstanding any other provision of this
      Agreement, NRC hereby authorizes the Licensee, and the Licensee agrees to
      take all reasonable opportunities, such as in sales literature or press
      releases, to acknowledge NRC as the source of the NRC Technology, but not
      so as to imply, in any such acknowledgment, that NRC endorses or approves
      any Product or Service offered for Sale by the
  Licensee.

            

    

     

    
      	
              9.0  

            	
              WARRANTIFS,
      DISCLAIMERS AND INDEMNITIES

            

    

     

    
      	
              9.1  

            	
              Warranty of Licensing
      Rights:  NRC warrants that it has not previously granted
      any rights that would conflict with the rights granted by this
      Agreement.  NRC warrants that it is either the owner or the
      licensee (with power to sub-license) of Patents licensed by this
      Agreement.

            

    

     

    
      	
              9.2  

            	
              No Implied
      Warranties:  Except for representations, warranties or
      conditions expressly made in this Agreement, the NRC Technology and the
      Foreground Technology are supplied and licensed on an as is” basis, and
      there are no representations, warranties or conditions, express or implied
      by statute, including without limitation any with respect
    to:

            

    

    
       

       

      
        
          
          

        

        
          
          

          
            

          

        

        
          
          

        

      

       

                      
(a)  market
readiness, merchantability, or fitness for any use or
purpose;

    

    
      	
              (b)  

            	
              operational
      state, character, quality, or freedom from
  defects;

            

    

    
      	
              (c)  

            	
              non-infringement
      of rights of third parties under present or future
  patents.

            

    

     

    
      	
              9.3  

            	
              No Contestation of
      Validity:  The Licensee acknowledges the validity of the
      Patents and copyright licensed hereunder and agrees not to contest such
      validity during the life of this Agreement, either directly or indirectly
      by assisting other parties.  This clause is not operational
      under U.S. law.

            

    

     

    
      	
              9.4  

            	
              Limited
      Damages:  NRC shall not be liable, in any event, for
      consequential or incidental damages, or loss of income, arising from the
      possession or use of anything licensed or conveyed pursuant to this
      Agreement.

            

    

     

    
      	
              9.5  

            	
              Indemnity:  NRC
      rejects all liability and responsibility relating to the consequences of
      using the Products or providing Services.  The Licensee shall
      indemnify and save harmless NRC, its employees and agents from and
      against, and be responsible for:

            

    

    
      	
              (a)  

            	
              all
      claims, demands, losses, damages, costs including solicitor and client
      costs, actions, suits or proceedings brought by any third party, that are
      in any manner based upon, arising out of, related to, occasioned by, or
      attributable to:

            

    

    
      	
              (b)  

            	
              the
      manufacturing, distribution, shipment, offering for Sale, Sale, or use of
      Products, Services or the Foreground Technology;
  and

            

    

    
      	
              (c)  

            	
              product
      liability and infringement of intellectual property rights other than
      copyright;

            

    

    
      	
              (d)  

            	
              other
      costs, including extra-judicial costs, of NRC defending any such action or
      proceeding, which NRC shall have the right to defend with counsel of its
      choice.

            

    

     

    This
clause shall survive expiration or termination of this Agreement.

     

    
      	
              10.0  

            	
              INFRINGFMENT
      LITIGATION

            

    

     

    
      	
              10.1  

            	
              Initial
      Consultation:  If the Licensee receives or become aware
      of any claim or assertion by a third party that any activities by the
      Licensee under this Agreement constitute an infringement or other
      violation of a third party’s patents or other intellectual property, the
      Licensee shall notify NRC and shall provide NRC with all details relating
      to the allegation.  The parties shall promptly enter into
      discussions with the third party to determine the extent and validity of
      the infringement and the parties mutually agreed course of action. Each
      party will absorb its own costs of the
  discussions.

            

    

     

    
      	
              10.2  

            	
              Negotiation:  The
      parties may negotiate with a third party to obtain any additional rights
      required, such as may arise if a third party’s patent
      emerges.  Each party will absorb its own costs of
      negotiation.  If those additional rights require payment, the
      parties will negotiate for a reduction in royalties payable to NRC, and
      failing agreement within sixty (60) days, either party may invoke the
      arbitration procedure in this Agreement to settle the amount of the
      reduction of the royalty.

            

    

     

    
      	
              10.3  

            	
              Legal
      Action:  The parties may agree to jointly defend or
      pursue litigation, but neither party shall bind or commit the other party
      to any course of action which involves liability for legal costs, expenses
      or damages.  If the parties fail to agree, within a reasonable
      time having regard to the normal progress of litigation, as to any course
      of action which might be jointly taken, either party may take or defend
      proceedings alone, if legally entitled to act alone, and shall be entitled
      to retain any amount awarded to it by a court, or paid to it as a
      settlement by the third party, and the excess of that amount over costs
      

            

    

     

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    reasonably incurred by both parties for the settlement or
litigation, shall be regarded as Sales Revenue of a sub-licensee for the purpose
of calculating royalties.  If one party wishes to act alone but
formalities require participation of the other party, the other party shall join
in the proceeding to the extent necessary for formalities.  Each party
will cooperate with the other in making available all necessary documents and
witnesses for any legal proceeding, without fees.  A party proceeding
alone (or with one party as a formality) shall indemnify the other party for
reasonable legal costs for representation that is reasonably necessary, and for
any court-ordered payments.

     

    
      	
              10.4  

            	
              Damages for
      Infringement:  If the parties (and not with one party
      participating only as a formality) have jointly pursued an infringer by
      litigation and the Licensee obtains money from the infringer as a
      settlement or by court order, the excess of that money above the
      Licensee’s costs that were reasonably incurred for the settlement or
      litigation, shall be regarded as Other Revenue in relation to a
      sub-licence.

            

    

     

     

    
      	
              11.0  

            	
              DURATION AND
      TERMINATION

            

    

     

    
      	
              11.1  

            	
              Expiration:  This
      Agreement shall become effective when it has been signed by both parties.
      Unless terminated earlier, this Agreement shall terminate when the last
      patent right related to the Foreground Technology expires, on a
      country-by-country basis.

            

    

     

    
      	
              11.2  

            	
              Termination by Either Party for
      Default or Breach:  In the event that one party defaults
      or breaches any of the provisions of this agreement, the other party shall
      have the right to terminate this Agreement by giving written notice to the
      defaulting party, but this act shall not prejudice the right of NRC to
      recover any fee due at the time of such termination and shall not
      prejudice any cause of action or claim of NRC accrued or to accrue on
      account of any breach or default by the Licensee.  However, if
      the defaulting party cures the breach within sixty (60) days after the
      notice is given, this Agreement shall continue in full force and
      effect.

            

    

     

    
      	
              11.3  

            	
              Termination by
      NRC:  This Agreement, at the option of NRC, may be
      terminated forthwith by NRC if the Licensee becomes bankrupt, or
      insolvent, or has a receiver appointed to continue its operations, or
      passes a resolution for winding up, or takes the benefit of any statute
      relating to bankrupt or insolvent debtors or the orderly payment of
      debts.

            

    

     

    
      	
              11.4  

            	
              Procedure on
      Termination:  Upon termination the Licensee
      shall:

            

    

    
      	
              (a)  

            	
              deliver
      a detailed statement to NRC of the inventory of all Products then existing
      and not Sold by the Licensee as at that
date;

            

    

    
      	
              (b)  

            	
              retain
      the right to Sell Products then existing and shall pay royalties (but not
      MAR) to NRC as Products are Sold for a period of one year provided that
      any remaining inventory of Products shall be destroyed by the License at
      the end of that year;

            

    

    
      	
              (c)  

            	
              retain
      the right to deliver Services for which a contractual commitment has been
      made before the Termination, for a period of one year, subject to the
      continued obligation to pay Royalties on the Sales Revenue for those
      services; and

            

    

    
      	
              (d)  

            	
              cease
      any other use of the NRC Technology and the Foreground Technology unless
      the NRC Technology and the Foreground Technology, in total, has then
      become part of the public domain other than through any act or omission
      of the
      Licensee.

            

    

     

    
      	
              11.5  

            	
              Accrued
      Obligations:  Termination does not release a party from
      any obligations, which accrued while this Agreement was in force or upon
      its termination.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              12.0  

            	
              LAW AND
      DISPUTES

            

    

     

    
      	
              12.1  

            	
              Choice of
      Law:  This Agreement shall be interpreted according to
      the laws of the Province of Ontario and the laws of Canada in force
      there.

            

    

     

    
      	
              12.2  

            	
              Courts:  Any
      litigation concerning this Agreement, including litigation arising from
      arbitration, shall be brought only in a court which has ordinary
      jurisdiction over the defendant on the basis of residence, and the
      residence of NRC for this purpose shall be regarded as the location of the
      Institute.

            

    

     

    
      	
              12.3  

            	
              Dispute
      Resolution:  Both parties will use reasonable efforts to
      reach an amicable negotiated settlement of any dispute concerning the
      interpretation or operation of this Agreement.  Disputes
      concerning this Agreement shall not be litigated.  If
      negotiation fails to resolve a dispute within sixty (60) days, either
      party can require non-binding mediation, whereupon the parties shall
      jointly appoint one impartial expert mediator to mediate according to
      mutually agreed procedures.  If a party refuses to effectively
      participate in mediation, or if mediation continues for more than sixty
      (60) days, either party can require binding arbitration under the Commercial Arbitration Act
      of Canada, whereupon the parties shall attempt to jointly appoint
      one impartial expert arbitrator.  If the parties cannot agree
      within thirty (30) days on the choice of an arbitrator, each party shall
      appoint its own arbitrator and those arbitrators shall jointly appoint a
      chairperson of an arbitral tribunal.  An arbitral award shall
      not include punitive damages, or interim measures.  Each party
      shall pay its own costs and an equal share of all other costs of mediation
      and arbitration, except for the exceptional circumstance in which an
      arbitral award may require the payment of all costs by a party who has
      brought a plainly frivolous dispute.  Unless otherwise agreed by
      the parties when the occasion arises, mediation and arbitration shall be
      held in the city where the Institute is located.  This provision
      survives the Termination of this
Agreement.

            

    

     

    
      	
              13.0  

            	
              GENERAL TERMS AND
      CONDITIONS

            

    

     

    
      	
              13.1  

            	
              Entire
      Agreement:  This Agreement represents the entire
      understanding between the parties as of the effective date hereof, and
      supersedes all prior communications, negotiations and agreements, written
      or oral, concerning the NRC Technology and the Foreground
      Technology.

            

    

     

    
      	
              13.2  

            	
              Limits of
      Agreement:  For greater certainty, the parties agree that
      this is not an assignment of ownership of copyright or of patent rights,
      but merely a licence.  This Agreement shall not be construed as
      creating the relationship of principal and agent, employer and employee,
      partnership, or joint venture.

            

    

     

    
      	
              13.3  

            	
              Amendments: This
      Agreement may only be amended by an agreement in writing, signed by the
      parties, expressly referring to this
Agreement.

            

    

     

    
      	
              13.4  

            	
              Severance:  If
      any provision in this Agreement is found, by a court or arbitration, to be
      wholly or partly invalid, illegal or unenforceable in any respect, the
      remainder of this Agreement shall remain enforceable and this Agreement
      shall be construed as if that provision had never existed.  The
      request to initial each page is not a condition of this
      Agreement.

            

    

     

    
      	
              13.5  

            	
              Waiver:  Failure
      by either party to assert rights arising from any breach or default of
      this Agreement, or acceptance of payments, shall not be regarded as a
      waiver of rights.  No failure to assert rights, no waiver, and
      no toleration implies any continuing or future waiver of
      rights.

            

    

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    
      	
              13.6  

            	
              Assignment:  This
      Agreement is personal to the parties, so that neither its assignment, nor
      its assumption by a corporation formed by amalgamation with a party is
      valid without the other party’s written
consent.

            

    

     

    
      	
              13.7  

            	
              Force
      Majeure:  Neither party shall be responsible or liable to
      the other for failure or delay in the performance of this Agreement due to
      war, fire, accident or other casualty, labour disturbance, act of the
      public enemy, act of God, or any other contingency beyond that party’s
      reasonable control.  In the event of applicability of this
      paragraph, the party affected by such force majeure shall use its best
      efforts to eliminate, cure and overcome any such causes and resume
      performance of its obligations as soon as
  possible.

            

    

     

    
      	
              13.8  

            	
              Notices:  Any
      notice contemplated by this Agreement, unless a different address is
      subsequently notified by one Party to the other in writing, must be sent
      to the address stated at the beginning of this Agreement where the Parties
      are identified, by:

            

    

    
      	
              (a)  

            	
              registered
      mail, and then it is deemed to be an effective notice five (5) days after
      it is sent,

            

    

    
      	
              (b)  

            	
              courier,
      and then it is an effective notice only when acknowledged by an official
      receipt, or

            

    

    
      	
              (c)  

            	
              by
      personal delivery to the office of the chief executive officer of the
      Party, and then it is an effective notice only when acknowledged by a
      signature of either that person or a person with apparent authority to
      receive messages.

            

    

     

     

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

    
 

    

    
      	
              SIGNED by the Licensee
      in duplicate at              
      Aurora,
      Canada               ,
      Canada:

            
	 
      	
              HELIX
      BIOPHARMA CORPORATION

            
	
              Date       April 27,
      2005         
                                                 

            	
              Per:  /s/ Donald
      Segal                                                                     

            
	 
	
                                           Name and title: Donald
      Segal, President

            
	 
	 
	
              SIGNED by NRC in
      duplicate at Ottawa, Canada:

            
	 
      	
              NATIONAL
      RESEARCH COUNCIL OF CANADA

            
	
              Date       April 28,
      2005          
                                                 

            	
              Per: /s/ Dr. Gabrielle
      Adams                                                                     

            
	 
	
                                                 Name and title: Dr.
      Gabrielle Adams

                                                   
      Director General NRC-Institute for Biological
  Scienceskl01034_ex4-4.htm

    
      

    

     

    Exhibit
4.4

    

    

    

    Material
Transfer

    

    and

    

    License
Option Agreement

    

    

    

    

    

    between

    

    Helix
BioPharma Corporation

    

    and

    

    Schering
Corporation

    

    

    

    

    

    December
2000

    

    CONFIDENTIAL TREATMENT
REQUESTED

     

    INFORMATION
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED IS OMITTED AND IS IDENTIFIED
BY THREE ASTERISKS, AS FOLLOWS “* * *”, AN UNREDACTED VERSION OF THIS DOCUMENT
HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    MATERIAL TRANSFER &
LICENSE OPTION AGREEMENT

    

    This
Agreement, effective the latest of the signature dates, is by and between the
following parties:

    

    Helix
BioPharma Corp., having a principal place of business at 3-305 Industrial
Parkway South, Aurora, Ontario  L4G 6X7, Canada (hereinafter referred
to as “Helix”); and

    

    Schering
Corporation, having a principal place of business at 2000 Galloping Hill Road,
Kenilworth, New Jersey 07033 (hereinafter referred to as
“Schering”).

    

    WHEREAS,
Schering has developed certain Material and Proprietary Information (each as
defined below) and desires to protect its proprietary rights in and to the
Material and Proprietary Information;

    

    WHEREAS,
Helix has developed certain Proprietary Information, which includes the Biphasix
Technology (as defined below), and desires to protect its proprietary rights in
and to the Proprietary Information;

    

    WHEREAS
Helix desires to obtain quantities of the Material from Schering for use in the
development of a topical formulation using Helix’ proprietary Biphasix
technology; and

    

    WHEREAS
Schering, being the owner of the entire right, title and interest in the
Material, is willing to provide Helix with the Material for the sole purpose of
conducting such Development Program;

    

    NOW,
THEREFORE, in consideration of the transfer of Material to Helix and to protect
the interests and rights of Schering and Helix, the parties have agreed to the
following:

    

    1.         Definitions:

    

    “Affiliate” shall mean any individual
or entity directly or indirectly controlling, controlled by or under common
control with, a party to this Agreement.  For purposes of this
Agreement, the direct or indirect ownership of fifty percent (50%) or more of
the outstanding voting securities of an entity, or right to receive fifty
percent (50%) or more of the profits or earning of an entity shall be deemed to
constitute control.  Such other relationship as in fact results in
actual control over the management, business and affairs of an entity shall also
be deemed to constitute control.

    

    “Agreement Product” shall mean a
topical formulation of interferon alpha-2b, recombinant, formulated using
Biphasix Technology.

    

    “Biphasix Technology” shall mean the
Helix Patents, the subject matter claimed in the Helix Patents and all of Helix’
know-how related to the practice of such subject matter.

    

    “Development Program” shall mean all
the work necessary to prepare a dossier that would be acceptable to the Canadian
Health Protection Branch (“Health Canada”), the European Union’s Committee for
Proprietary Medicinal Products (“CPMP”) and the US Food and Drug Administration
(“FDA”) for regulatory approval of the Agreement Product for the treatment of

     

     

    
      
        1

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    genital
warts due to HPV infection (the “Primary Indication”) and cervical dysplasia
(the “Secondary Indication”).   The Development Program shall
include, without limitation all preclinical, clinical, pharmacokinetic and
toxicology studies necessary to support such regulatory approvals for the
Agreement Product.

    

    “Helix Patents” shall mean the U.S.
patent applications and patents listed on Exhibit A and all divisions,
continuations, continuations-in-part, reexaminations, reissues, extensions,
registrations and supplementary protection certificates thereof, and all
corresponding foreign patent applications and patents.

    

    “Material” shall mean interferon
alpha-2b, recombinant, meeting the specifications identified in Exhibit
B.

    

    “Proprietary Information” shall mean
know-how and data, as well as trade secrets, technical information, tangible
materials, records and other proprietary technology belonging to one party which
is provided to the other party pursuant to this Agreement.  Schering’s
Proprietary Information shall include, without limitation, any of Schering’s
assays, test procedures, specifications, reference standards, data, processes or
methods relating to the Material or its use, which may be provided to Helix
under this Agreement.  Helix’s Proprietary Information shall include,
without limitation, all assays, test procedures, specifications, reference
standards, data, processes or methods relating to the Biphasix Technology or its
use, which may be provided to Schering under this Agreement.

    

    2. Schering shall provide to Helix,
without charge, sufficient quantities of the Material to enable Helix to conduct
the Development Program; provided that Schering’s obligation to provide Material
shall not exceed an aggregate total of *** without Schering’s prior written
approval.  The Material shall be manufactured in compliance with
current Good Manufacturing Practices (as established pursuant to the U.S. Food,
Drug and Cosmetics Act or otherwise by the U.S. Food and Drug
Administration).  The Material is owned by Schering and shall remain
the property of Schering.  Helix shall be responsible for the control
of the Material, which shall be stored in a locked, secured area, and shall not
distribute or release the Material to any third party, except as necessary for
the performance of the Development Program, without the prior written permission
of Schering.

    

    3.      The Material
shall be used by Helix solely in performance of the Development Program and
Helix shall not use any of the Material for any other purpose without the prior
written approval of Schering.  The Development Program shall be
conducted by Helix in accordance with the plan described in Exhibit C, which
shall be reviewed and approved in advance by Schering.  Any material
changes to the Development Program shall require Schering’s prior written
approval.  Helix shall use diligent efforts to conduct the Development
Program and maintain records and data during and after the term or early
termination of this Agreement in compliance with all applicable legal and
regulatory requirements, including without limitation, any applicable
requirements of the FDA.  Helix shall be solely responsible for the
costs and expenses of performing the Development Program.

    

    4. This Agreement, including the resulting
transfer of Material, constitutes the grant of the limited right to Helix to use
the Material solely to conduct the Development Program.  Helix shall
have no right to sublicense, assign or transfer any of its rights in the
Material to any third

     

     

    
      
        2

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    party.  Schering
shall be free, in its sole discretion, to use the Material for its own purposes
and to distribute the Material to other parties.

    

    5.      In
consideration for the supplies of Material being provided by Schering hereunder,
Helix hereby grants to Schering an exclusive option and right of first refusal
to obtain a worldwide, exclusive license to make, have made, import, export,
use, offer for sale and sell pharmaceutical products containing alpha interferon
in combination with the Biphasix Technology, including without limitation, the
Agreement Product (the “Option”).  Schering may exercise the Option,
in its sole discretion, at any time during the Option Period (as defined below),
by providing Helix with written notice to that effect.  The “Option
Period” shall mean the period extending from the Effective Date until the date
which is sixty (60) days after Schering receives notice, as required under
Section 8(a), of the successful completion of Phase III clinical trials for the
Agreement Product under the Development Program.

    

    (a)   
Upon
exercising the Option, the parties shall have a period of ninety (90) days (the
“Negotiation Period”) to negotiate in good faith and enter into a mutually
acceptable license agreement for the Agreement Product (the License
Agreement”).  The License Agreement shall incorporate the basic
business terms set forth in Exhibit D, and such other terms and conditions,
consistent with the basic business terms, as are reasonable and customary in the
industry for such agreements.

     

    (b)   
Schering
shall have no obligation to enter into the License Agreement (nor any obligation
to make a determination of whether to enter into the License Agreement) prior to
its exercising the Option in accordance with this Section 5.

     

    (c)   
In the
event that Schering does not exercise the Option during the Option Period, then
the Option shall expire upon expiration of the Option Period.

     

    (d)   
During
the Option Period and the Negotiation Period, Helix shall not grant or offer to
grant a license, or assign, transfer or otherwise convey any rights, title or
interest in or to the Agreement Product, or under any patent applications or
patents owned or controlled by Helix which have claims covering the Agreement
Product, its manufacture or use, to any third party.  In addition,
during the Option Period and the Negotiation Period, Helix will not discuss or
evaluate a possible business relationship with any third party, or grant any
licenses or other rights to any third party, relating to the use of Biphasix
Technology in combination with  alpha interferon, nor enter into or
make any understandings or agreements with a third party which would otherwise
diminish the rights granted to Schering under this Agreement, without the prior
written consent of Schering.  Nothing herein shall be construed as
limiting Helix’ right to use the Biphasix Technology in connection with
compounds other than alpha interferon, or to make the Biphasix Technology
available to third parties for use in combination with compounds other than
alpha interferon.

     

    

    6.     
Each
party shall preserve any and all Proprietary Information received from the other
party as confidential and shall not use any such Proprietary Information except
as necessary to conduct the Development Program or as otherwise expressly
permitted hereunder.  The obligations of confidentiality and non-use
under this Agreement shall continue for a period of ten (10) years after the
expiration or termination of this Agreement, at which time it will
cease.  In the event the Proprietary Information is disclosed to the
receiving party in a manner other than in 

     

     

     

    
      
        3

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

    writing,
it shall be reduced to written form, marked “Confidential” and transmitted to
the receiving party within fifteen (15) business days of the initial
disclosure.  These confidentiality and non-use restrictions shall not
apply to any Proprietary Information:

    

    (a)  
which is
known by the receiving party prior to its communication by the disclosing party,
as evidenced by the receiving party’s written business records;

     

    (b)  
which is
a matter of public knowledge at the time of such disclosure by the disclosing
party;

     

    (c)  
which is
a matter of public knowledge, without fault on the part of the receiving party,
subsequent to disclosure by the disclosing party.

     

    (d)  
which is
disclosed to the receiving party by a third party lawfully having possession of
such Proprietary Information without an obligation of confidentiality to the
disclosing party;

     

    (e)  
which is
independently developed by the receiving party, or its parent corporation or
their respective Affiliates, without the aid, application or use of the
disclosing party’s Proprietary Information (and/or in the case of Helix the
Material) provided to the receiving party hereunder (and such independent
development can be properly demonstrated by the receiving party);
or

     

    (f)  
which is
required by law, regulation, rule, act, or order of any governmental authority
or agency to be disclosed; provided, however, that the
party required to disclose immediately notify the other party upon receiving
notice of requirement to disclose.

     

    

    7.     
Helix
shall use the Material in compliance with Good Laboratory Practices and Good
Clinical Practices (as set forth in the ICH guidelines) and all applicable laws,
rules and governmental regulations.  Helix represents and warrants
that it will not use in any capacity, in connection with the activities to be
performed under this Agreement, any individual or entity who has been debarred
pursuant to the Federal Food, Drug and Cosmetic Act, as amended.  THE
MATERIAL IS PROVIDED WITHOUT WARRANTY OF MERCHANTABILITY OR FITNESS FOR A
PARTICULAR PURPOSE OR ANY OTHER WARRANTY, EXPRESS OR
IMPLIED.  SCHERING MAKES NO REPRESENTATION OR WARRANTY THAT USE OF THE
MATERIAL WILL NOT INFRINGE ANY PATENT OR OTHER PROPRIETARY RIGHT OF ANY THIRD
PARTY.

    

    8. Helix shall keep Schering informed of
the progress of the Development Program by providing semi-annual written reports
containing sufficient information to enable Schering to monitor the progress and
outcome of the Development Program. Helix shall provide Schering with a written
final report within sixty (60) days after completion of the Development Program
or termination of this Agreement.

    

    (a)   
Helix
shall provide written notice to Schering upon the successful completion of Phase
III clinical trials for the Agreement Product.  Such notice shall
include a detailed report of the data and results of all pre-clinical, clinical
and toxicology studies involving the Agreement Product sufficient to enable
Schering to independently 

     

     

    
      
        4

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    evaluate
the outcome of such studies.  The Option Period described in Section 5
shall begin upon receipt by Schering of such notice.

    

    (b)   
During
the Option Period Schering will be permitted to conduct a due diligence review
of the Agreement Product and the Development Program to enable it to determine
whether or not to exercise the Option.  Upon request, Helix shall
provide Schering with reasonable cooperation in the performance of such due
diligence, which shall include providing Schering access to any additional data,
information and results relating to the results of the Development Program which
may be reasonably necessary to complete the diligence evaluation.

    

    9. Any new invention, development,
biological material or discovery, whether patentable or not, resulting from the
performance of the Development Program, or from the use of Schering’s
Proprietary Information or the Material by Helix in connection therewith, or
otherwise relating to the Agreement Product shall be promptly disclosed in
writing to Schering (individually and collectively referred to herein as
“Invention”).  The parties acknowledge and agree that all rights,
title and interest in and to any Inventions shall be governed by the following
terms:

    
      	
                      (i)  

            	
              Inventions
      that relate solely to alpha interferon and/or the Material shall be solely
      owned by Schering (“Schering
Inventions”);

            

    

     

    
      	
              (ii)  

            	
              Inventions
      that relate solely to the Biphasix Technology shall be solely owned by
      Helix (“Helix Inventions”); and

            

    

     

    
      	
              (iii)  

            	
              Inventions
      which relate to the combination of the Biphasix Technology with alpha
      interferon and/or the Material shall be jointly owned by the parties
      (“Joint Inventions”), subject to the terms and conditions set forth
      herein.

            

    

     

    

    (a)   
Each of
Schering and Helix shall have sole responsibility, at such party’s sole
discretion and expense, for the preparation, filing, prosecution, maintenance,
enforcement and defense of patent applications and patents claiming Schering
Inventions or Helix Inventions, respectively.  The other party shall,
upon request, reasonably assist such party in connection with such
activities.  Reasonable assistance shall include causing the execution
of any patent assignments or other documents necessary to perfect the requesting
party’s title to the Schering Invention or Helix Invention as
applicable.

     

    (b)   
In the
event of any patentable Joint Invention, the parties shall consult and agree
upon mutually acceptable procedures and allocate responsibility for the
preparation, filing, prosecution, maintenance, enforcement and defense of patent
applications and patents.

     

    (c)   
Except as
expressly set forth herein, nothing contained in this Agreement shall be deemed
to grant or create either directly or by implication, estoppel or otherwise any
license, title or other rights under any patents, patent applications or other
proprietary interests to any materials, inventions or discoveries of either
party.

     

    

     

    
      
        5

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    

     

    10.          
Helix shall notify Schering within twenty-four (24) hours after learning of any
serious and/or unexpected adverse drug reaction affecting any patient in the
Development Program.  Helix further agrees to follow up such
notification of adverse drug reaction with appropriate reports in compliance
with all applicable legal and regulatory requirements.  Helix shall
provide such notification to: Schering Corporation, 50 Lawrence Road,
Springfield, NJ  07081-3121, Attention:  Senior Director –
Medical and Safety Services, Telephone No.: (973) 921-7400, Facsimile No.: (973)
921-7424

    

    11.           Schering
shall indemnify, defend and hold harmless Helix and its Affiliates, and their
respective directors, officers, agents, and employees from and against any
demands, claims, actions, proceedings or costs of judgments which may be made or
instituted against any of them by reason of personal injury (including death) to
any person, or damage to property, to the extent caused by the use of the
Material to conduct the Development Program.  Notwithstanding the
foregoing, Schering shall have no indemnification obligation or liability and
Helix shall indemnify, defend and hold harmless Schering, its parent corporation
and Affiliates, and their respective officers, directors, agents, and employees
with respect to any demands, claims, actions, proceedings or costs of judgments
which may be made or instituted against any of them by reason of personal injury
(including death) to any person, or damage to property, to the extent caused by:
(i) failure of Helix to comply with any applicable FDA or other governmental or
state requirements, law, rules or regulations applicable to the performance of
its obligations under this Agreement; (ii) the breach by Helix of nay of its
covenants, representations or warranties under this Agreement; or (iii) a
negligent act or omission or willful misconduct by Helix, its directors,
officers, agents or employees related to the performance of the Development
Program.

    

    12.           This
Agreement shall terminate upon expiration of the Option Period.  In
addition, either party shall have the right to terminate this Agreement upon
thirty (30) days’ written notice in the event of a material breach of this
Agreement by the other party; unless the breach is cured during such thirty (30)
day period.  Notwithstanding the foregoing, Sections 6, 7, 8, 9, 10,
11, 13, 14, 15, 16 and 17, and any other applicable provisions extending into
the future shall survive the termination or expiration of this
Agreement.  Upon completion of the Development Program, or the earlier
termination of this Agreement, Helix shall cease use of and shall, at Schering’s
election, return to Schering or destroy any unused Material.  Upon
request, each of Schering and Helix shall return to the other party all copies
of the requesting party’s Proprietary Information in its possession, except for
one archival copy which may be retained by it for purposes of identifying its
obligations under this Agreement.

    

    13.           
Neither
party shall use the name of the other party (or the name of Schering, its parent
corporation or their respective Affiliates) for promotional purposes without the
prior written consent of the party whose name is proposed to be
used.  The parties agree that on or after the Effective Date that
Helix may issue an initial press release as set forth in Exhibit
E.  No other news release, publicity or other public announcement,
either written or oral, regarding the terms and/or existence of this Agreement,
or performance hereunder, shall be made by Schering or Helix without the prior
written approval of the other party; provided, however, that nothing
herein will be deemed to prevent either party from making such disclosures to
the extent required under applicable federal, state or provincial securities
laws or any rule or regulation of any nationally recognized securities exchange
(including, without limitation, the Toronto Stock Exchange), provided same is
accurate and complete.  In such event, however, the disclosing party

     

     

     

    
      
        6

      

      
        
        

        
          

        

      

      
        
        

      

    

     

     

     

    shall use
good faith efforts to consult with the other party prior to such disclosure and
where applicable, shall request confidential treatment to the extent
available.

    

    14.          
This
Agreement is not assignable by either party, whether by operation of law or
otherwise, without the prior written consent of the other party.

    

    15.          
This
Agreement shall be governed by and construed in accordance with the laws of New
York, excluding the choice of law provisions.

    

    16.           This
Agreement is intended to be severable.  Should any part or provision
of this Agreement be found to be unenforceable or invalid for any reason, the
remaining parts and provisions will remain in effect.

    

    17.          
This
Agreement constitutes the entire understanding of the parties with respect to
the subject matter hereof and hereby supersedes and replaces all prior
agreements and understandings with respect to the Material, and may be modified
only with written permission of both parties.

    

    

    IN WITNESS WHEREOF, the parties have
caused this Agreement to be executed by duly authorized representatives as of
the last date written below.

    

    HELIX
BIOPHARMA
CORP.                                                                        SCHERING
CORPORATION

    

    By:                 /s/ Donald
Segal                                   By:                 
/s/ David
Poorvin                                      

    

    Name:            Donald
Segal                                        
Name:            
David
Poorvin                                   

    

    Title:              Executive
Vice-President                                                         Title:              
Vice
President                                   

    

    Date:              December 18,
2000                                                                   
Date:             
December 13,
2000

    

     

     

     

     

    
      
        7 

      

      
         

        
          

        

      

      
         

      

    

    

    Exhibit
A

    

    

    Patents
and Patent Applications (U.S.)

    

    
      	
              Title

            	
              Application No.

            	
              Patent No. / Status

            
	
              Biphasic
      Multilamellar Lipid Vesicles

            	
              08/872,068

            	
              5,853,755

            
	
              Method
      for Preparing Biphasic Multilamellar Lipid Vesicles

            	
              09/042,097

            	
              5,993,851

            
	
              Topical
      Patch for Liposomal Drug Delivery System

            	
              08/342,962

            	
              5,718,914

            
	
              Composition
      and Method for Dermal and Transdermal Administration of a
      Cytokine

            	
              09/216,500

            	
              Pending

            
	
              Biphasic
      Lipid Vesicle Composition for Transdermal Administration of an
      Immunogen

            	
              09/141,875

            	
              5,993,852

            
	
              Composition
      for Transdermal and Dermal Administration of
    Interferon-alpha

            	
              60/195,549

            	
              Pending

            
	
              Composition
      for Transdermal Administration of Insulin

            	
              60/195,401

            	
              Pending

            
	
              Delivery
      of Polynucleotides Using Biphasic Lipid Vesicles

            	
              60/195,945

            	
              Pending

            

    

    

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    

    Exhibit
B

    

    Specification Limits/Ranges
for Material (interferon alpha-2b)

    

    ***

     

     

     

     

     

     

     

     

     

     

     

     

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    

    Exhibit
C

    

    Development
Program

    

    ***

     

     

     

     

     

     

     

     

     

     

     

     

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    

    Exhibit
D

    

    Basic Business Terms for a
License Agreement

    

     

    

    
      	
              Grant:

            	
              Exclusive
      right to make, have made, import, export, use, offer for sale and sell
      pharmaceutical formulations of alpha interferon, including without
      limitation interferon alpha-2b, utilizing the Biphasix Technology within
      the Field, with right to
sublicense.

            

    

    

    
      	
              Field:

            	
              Topical
      alpha interferon formulations

            

    

    

    Territory:               
Worldwide

    

    Duration:               
Life of patents

    

    License
fees:                         $250K             
Exercise of option (within 60 days of phase III completion)

    $500K                      NDA
filing in the US for Primary Indication

    $500K                      HRD
filing in the EU for Primary Indication

    $2.0M                      NDA
approval in the US for Primary Indication

    $1.0M                      HRD
approval in the EU for Primary Indication

    $2.0M                      NDA
approval in the US for Secondary Indication

    $1.0M                      HRD
approval in the EU for Secondary Indication

    

    $3.0M                      When
Net Sales first reach $50M/yr.

    $5.0M                      When
Net Sales first reach $100M/yr.

    $8.0M                      When
Net Sales first reach $150M/yr.

    --------

    $23.25M                  Total
fees

    

    (Each of
the above license fees shall only be payable once on the first occurrence of the
relevant triggering event.)

    

    Royalty:                
5%  on Net Sales up to $50M

    6%  on Net Sales between
$50-$100M

    7%  on Net Sales over
$100M

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    

    Exhibit
E

     

    Form of Initial Press
Release

    

     

    

    HELIX
BIOPHARMA GRANTS BIPHASTXTM LICENSE OPTION TO SCHERING-PLOUGH

    

    

    Helix
BioPharma today announced that it has signed an agreement with Schering-Plough
Corporation
of Kenilworth, N.1, which grants Schering-Plough the option to obtain an
exclusive

    worldwide
license to use Helix BioPharma's BIPHASIXTM technology in pharmaceutical
products
containing alpha interferon. As part of the license option, Schering-Plough will
supply

    Helix
BioPharma, at no charge, with a quantity of interferon alfa-2b for use in Helix
BioPharma's
planned development program for an interferon alfa-2b BIPHASIXTM cream
for

    the
treatment of genital warts and cervical dysplasia.

    

    Schering-Plough'
s option may be exercised at any time up to a specified period following the
successful
completion of Phase Ill clinical trials. Included in the option agreement are
terms for the grant
of a license to Schering-Plough that provides for milestone payments and
royalties on product
sales:

    

    "We are
very pleased to have signed this agreement with Schering-Plough, the world
leader in the
production and marketing of alpha interferon products, and we look forwardto
working with them on
this important project," said Jerome McElroy, President and Chairman of Helix
BioPharma:

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00152-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00152-of-00352.parquet"}]]