Exhibit
      4.1

     

    AMENDMENT
      NO. 4 TO SECURITIES PURCHASE AGREEMENT
      AND
      REGISTRATION RIGHTS AGREEMENT

     

    


     

    This
      AMENDMENT NO. 4 TO SECURITIES PURCHASE AGREEMENT AND REGISTRATION RIGHTS
      AGREEMENT (this “Amendment”) is made and entered into as of January 19, 2006, by
      and among Generex Biotechnology Corporation, a Delaware corporation (“Generex”),
      and the stockholders identified on the signature pages hereto (each, a
“Purchaser” and, collectively, the “Purchasers”).

     

    RECITALS

     

    


     

    	1.  	
            Generex
              and the Purchasers are parties to a Securities Purchase Agreement,
              dated
              as of November 10, 2004 (as amended by Amendment No. 1 (as hereinafter
              defined) and Amendment No. 2 (as hereinafter defined), the “Purchase
              Agreement”), pursuant to which Generex issued and sold to the Purchasers
              an aggregate of $4,000,000 of Debentures and certain Warrants (each
              as
              defined in the Purchase Agreement). Capitalized terms used and not
              defined
              in this Amendment but defined in the Purchase Agreement shall have
              the
              respective meanings set forth in the Purchase Agreement.
              

          


     

    	2.  	
            In
              addition to the Debentures and Warrants, under the Purchase Agreement
              Generex issued and sold to the Purchasers Additional Investment Rights,
              pursuant to which the holders thereof had the right to purchase up
              to an
              additional aggregate principal amount of Debentures equal to the principal
              amount of $4,000,000 of Debentures (collectively, the “AIR Debentures”),
              together with additional Warrants to purchase up to a number of shares
              of
              Generex’s Common Stock equal to 100% of the shares issuable upon
              conversion of such AIR Debentures so purchased (collectively, the “AIR
              Warrants”).

          


     

    	3.  	
            In
              connection with the Purchase Agreement, Generex and the Purchasers
              entered
              into a Registration Rights Agreement, dated as of November 10, 2004
              (as
              amended by Amendment No. 1 (as hereinafter defined) and Amendment No.
              2
              (as hereinafter defined), the “Registration Rights Agreement”), pursuant
              to which Generex undertook certain registration obligations to the
              Purchasers.

          


     

    	4.  	
            In
              connection with that certain Amendment No. 1 to Securities Purchase
              Agreement and Registration Rights Agreement, dated as of June 15, 2005,
              by
              and among Generex and the Purchasers (“Amendment No. 1”), the Purchasers
              exercised an aggregate of $2,000,000 of Additional Investment Rights
              and
              Generex agreed to issue to the Purchasers further Additional Investment
              Rights (the “Amendment No. 1 AIR”) for an aggregate principal amount of
              $2,000,000 AIR Debentures, together with additional Warrants to purchase
              up to a number of shares of Generex’s Common Stock equal to 100% of the
              shares issuable upon conversion of such AIR Debentures so purchased.
              

          


     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

    	5.  	
            In
              connection with that certain Amendment No. 2 to Securities Purchase
              Agreement and Registration Rights Agreement, dated as of September
              8,
              2005, by and among Generex and the Purchasers (“Amendment No. 2”), the
              Purchasers exercised an aggregate of $2,000,000 of Additional Investment
              Rights and Generex agreed to issue to the Purchasers further Additional
              Investment Rights (the “Amendment No. 2 AIR”) for an aggregate principal
              amount of $2,000,000 AIR Debentures, together with additional Warrants
              to
              purchase up to a number of shares of Generex’s Common Stock equal to 100%
              of the shares issuable upon conversion of such AIR Debentures so
              purchased. 

          


     

    	6.  	
            In
              connection with that certain Amendment No. 3 to Securities Purchase
              Agreement and Registration Rights Agreement, dated as of December 4,
              2005,
              by and among Generex and the Purchasers (“Amendment No. 3”), the
              Purchasers exercised an aggregate of $4,000,000 of Additional Investment
              Rights and Generex agreed to issue to the Purchasers further Additional
              Investment Rights (the “Amendment No. 3 AIR” and together with the
              Amendment No. 1 AIR and the Amendment No. 2 AIR, the “Additional
              Investment Rights”) for an aggregate principal amount of $4,000,000 AIR
              Debentures, together with additional Warrants to purchase up to a number
              of shares of Generex’s Common Stock equal to 100% of the shares issuable
              upon conversion of such AIR Debentures so
              purchased.

          


     

    	7.  	
            Generex
              and the Purchasers now wish to further modify certain of the terms
              of the
              Purchase Agreement, Registration Rights Agreement, Additional Investment
              Rights and AIR Debentures.

          


     

    NOW,
      THEREFORE, in consideration of the foregoing Recitals and other good and
      valuable consideration, the receipt and sufficiency of which are hereby
      acknowledged, Generex and each Purchaser, severally and not jointly, agree
      as
      follows:

     

    1. Additional
      Investment Rights.
      Subject
      to the terms hereof, each Purchaser agrees to exercise 100% of its Additional
      Investment Rights (pertaining to an aggregate of $4,000,000 of AIR Debentures
      and accompanying AIR Warrants) on the Business Day following the date of this
      Amendment. 

     

    
      
         

      

      
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    	1.1.  	
            In
              consideration for such exercise, Generex agrees that the “Initial Exercise
              Date” under each of the Additional Investment Rights shall be amended to
              be January 19, 2006.

          


     

    	1.2.  	
            In
              consideration for such exercise, Generex agrees that the “Conversion
              Price” under the AIR Debentures issuable upon such exercise (the
              “Amendment No. 4 AIR Debentures”) shall not equal $1.25, but shall equal
              $1.05 (subject to adjustment as set forth in the Amendment No. 4 AIR
              Debentures).

          


     

    	1.3.  	
            In
              consideration for such exercise, Generex agrees that the “Exercise Price”
              under the AIR Warrants issuable upon such exercise (the “Amendment No. 4
              AIR Warrants”) shall not equal $1.25, but shall equal $1.05 (subject to
              adjustment as set forth in the Amendment No. 4 AIR
              Warrants).

          


     

    	1.4.  	
            In
              further consideration for the exercise of the Additional Investment
              Right
              herein contemplated, Generex will issue and deliver to each Purchaser
              a
              further Additional Investment Right in the form of Exhibit A (which
              is
              substantially the same in form as the existing Additional Investment
              Rights) (each an “Amendment No. 4 Additional AIR” and collectively, the
              “Amendment No. 4 Additional AIRs”), pursuant to which each Purchaser will
              have the right to acquire detachable units consisting of (a) additional
              AIR Debentures in principal amount equal to the principal amount of
              AIR
              Debentures issuable upon the portion of the Additional Investment Right
              to
              be exercised by each such Purchaser under Section 1 (such additional
              AIR
              Debentures, the “Amendment No. 4 Additional AIR Debentures”) and (b)
              additional AIR Warrants entitling the holder thereof to purchase a
              number
              of shares of Common Stock equal to 100% of the shares of Common Stock
              issuable upon an assumed conversion in full (without regard to any
              restrictions on conversion therein contained) at a $1.25 Conversion
              Price
              (subject to adjustment as set forth therein) of the Amendment No. 4
              AIR
              Debentures contemplated in clause (a) above, at an exercise price equal
              to
              the “AIR Warrant Exercise Price” (as such term is defined in the
              Additional Investment Rights) (collectively, the “Amendment No. 4
              Additional AIR Warrants”). The “conversion price” of the Amendment No. 4
              Additional AIR Debentures will equal $1.25, subject to adjustment in
              accordance with the terms thereof.

          


     

     

    	2.  	
            Antidilution
              Provisions of Existing Securities.
              Except as specified in Sections 1.2 and 1.3, no adjustment will be
              made to
              the conversion or exercise price of the existing Warrants, Debentures
              and
              any other outstanding securities of Generex as a result of the issuance
              of
              the Amendment No. 4 AIR Debentures and Amendment No. 4 AIR Warrants
              with
              the modified conversion price as contemplated by Sections 1.2 and 1.3.
              Accordingly, each Purchaser severally agrees that the issuance of the
              Amendment No. 4 AIR Debentures and Amendment No. 4 AIR Warrants under
              Sections 1.2 and 1.3 will not be a “Dilutive Issuance” under section 3(b)
              of the Warrants or section 5(b) of the Debentures. Purchasers are not
              hereby waiving any other reductions to the exercise or conversion price
              of
              any of their respective Generex securities that may result from any
              other
              events or circumstances. 

          


     

    
      
         

      

      
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    	3.  	
            Registration
              Rights.
              To ensure that the registration rights of the Purchasers are not adversely
              affected as a result of the transactions contemplated by this Amendment
              and to provide registration rights consistent with the existing
              registration rights in respect of the securities issuable upon exercise
              of
              the Amendment No. 4 Additional AIR, Amendment No. 4 AIR Debentures
              and
              Amendment No. 4 AIR Warrants, the parties agree as follows with respect
              to
              registration rights:

          


     

    	3.1.  	
            The
              definition of “Additional Investment Right” under the Purchase Agreement
              is hereby amended to include the Amendment No. 4 Additional
              AIRs.

          


     

    	3.2.  	
            The
              definition of “Additional Investment Right Securities” under the Purchase
              Agreement is hereby amended to include the Amendment No. 4 Additional
              AIR
              Debentures and Amendment No. 4 Additional AIR Warrants and the Amendment
              No. 4 Underlying Shares (as hereinafter defined) issuable in connection
              therewith.

          


     

    	3.3.  	
            The
              parties hereby confirm that the definition of “Registrable Securities”
              under the Registration Rights Agreement includes (a) the additional
              shares
              of Common Stock as may be issuable upon a conversion of the Amendment
              No.
              4 AIR Debentures, (b) the additional shares of Common Stock as may
              be
              issuable upon an exercise of the Amendment No. 4 AIR Warrants, and
              (c) the
              Additional Investment Right Securities contemplated in Section
              3.2.

          


     

    	3.4.  	
            Generex
              will prepare and file a registration statement to cover all shares
              of
              Common Stock issuable under the Additional Investment Rights, including
              shares of Common Stock issuable upon conversion of the Amendment No.
              4
              Additional AIR Debentures and the Common Stock issuable upon the exercise
              of the Amendment No. 4 Additional AIR Warrants.


          


     

    	3.5.  	
            The
              registration statement contemplated in Section 3.4 will constitute
              a
              “Registration Statement” under the Registration Rights Agreement, afforded
              all of the rights and obligations of and upon each of Generex and the
              “Purchasers” thereunder, including Sections 2(b) and 3(c) thereof. With
              respect to the Registration Statement contemplated by Section 3.4,
              the
              Filing Date shall be January 26, 2006. The calculation of the
              Effectiveness Date with respect to the Registration Statement contemplated
              by Section 3.4 shall be the same as for the initial Registration Statement
              under the Registration Rights Agreement. In addition, such Registration
              Statement may include some or all of the shares set forth in Schedule
              3.5
              hereto, in addition to the shares referenced in Section 3.4 above.
              

          


     

     

    	4.  	
            Representation
              and Warranties of Generex.
              Generex hereby represents and warrants to each Purchaser as follows,
              except as may be set forth on the Additional Disclosure Schedules
              hereto:

          


     

     

    
      
         

      

      
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    (a)  Authorization;
      Enforcement.
      Generex
      has the requisite corporate power and authority to enter into and to consummate
      the transactions contemplated by this Amendment and each other Transaction
      Document (as hereinafter defined) and to carry out its obligations under each.
      The execution and delivery of each Transaction Document by Generex and the
      consummation by it of the transactions contemplated thereby have been duly
      authorized by all necessary action on the part of Generex and no further action
      is required by Generex in connection therewith other than the Required Approvals
      (as hereinafter defined). Each of this Amendment, the Amendment No. 4 Additional
      AIRs, the Amendment No. 4 AIR Debentures, the Amendment No. 4 AIR Warrants,
      the
      Amendment No. 4 Additional AIR Debentures and Amendment No. 4 Additional AIR
      Warrants (collectively, the “Transaction Documents”) has been (or upon delivery
      will have been) duly executed by Generex and, when delivered in accordance
      with
      the terms hereof, will constitute the valid and binding obligation of Generex,
      enforceable against Generex in accordance with their respective terms except
      (i)
      as limited by applicable bankruptcy, insolvency, reorganization, moratorium
      and
      other laws of general application affecting enforcement of creditors’ rights
      generally and (ii) as limited by laws relating to the availability of specific
      performance, injunctive relief or other equitable remedies.

     

    (b)  No
      Conflicts.
      The
      execution, delivery and performance of the Transaction Documents by Generex
      and
      the consummation by Generex of the other transactions contemplated thereby
      do
      not and will not: (i) conflict with or violate any provision of Generex’s or any
      Subsidiary’s certificate or articles of incorporation, bylaws or other
      organizational or charter documents, or (ii) conflict with, or constitute a
      default (or an event that with notice or lapse of time or both would become
      a
      default) under, result in the creation of any Lien upon any of the properties
      or
      assets of Generex or any Subsidiary, or give to others any rights of
      termination, amendment, acceleration or cancellation (with or without notice,
      lapse of time or both) of, any agreement, credit facility, debt or other
      instrument (evidencing a Company or Subsidiary debt or otherwise) or other
      understanding to which Generex or any Subsidiary is a party or by which any
      property or asset of Generex or any Subsidiary is bound or affected, or (iii)
      subject to the Required Approvals, conflict with or result in a violation of
      any
      law, rule, regulation, order, judgment, injunction, decree or other restriction
      of any court or governmental authority to which Generex or a Subsidiary is
      subject (including federal and state securities laws and regulations), or by
      which any property or asset of Generex or a Subsidiary is bound or affected,
      or
      (iv) conflict with or result in a violation of the rules or regulations of
      the
      Nasdaq Stock Market.

     

    (c)  Filings,
      Consents and Approvals.
      Generex
      is not required to obtain any consent, waiver, authorization or order of, give
      any notice to, or make any filing or registration with, any court or other
      federal, state, local or other governmental authority or other Person in
      connection with its execution, delivery and performance of the Transaction
      Documents, other than (i) filings required pursuant to Section 7.4, (ii) the
      filing with the Commission of the Registration Statement contemplated in Section
      3.4, (iii) the notice and/or application(s) to the Nasdaq Stock Market of the
      issuance and sale of the Amendment No. 4 Additional AIR and the listing of
      the
      shares of Common Stock ultimately issuable in respect thereof for trading
      thereon in the time and manner required thereby, and (iv) the filing of Form
      D
      with the Commission and such filings as are required to be made under applicable
      state securities laws (collectively, the “Required Approvals”). 

     

    
      
         

      

      
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    (d)  Stockholder
      Approval.
      No
      approval of the stockholders of Generex is required in order for Generex to
      enter into this Amendment and to issue and deliver to the Purchasers the
      Securities (as hereinafter defined).

     

    (e)  Issuance
      of the Securities.
      The
      Amendment No. 4 AIR Debentures, Amendment No. 4 AIR Warrants, Amendment No.
      4
      Additional AIRs, Amendment No. 4 Additional AIR Debentures, Amendment No. 4
      Additional AIR Warrants, and the shares of Common Stock issuable upon the
      exercise and conversion of each the foregoing (collectively, the “Securities”)
      are duly authorized and, when issued and paid for in accordance with their
      respective terms, will be duly and validly issued, fully paid and nonassessable,
      free and clear of all Liens other than restrictions on transfer under applicable
      securities laws. Generex has reserved from its duly authorized capital stock
      a
      number of shares of Common Stock for issuance upon exercise and conversion
      of
      the Amendment No. 4 AIR Debentures, Amendment No. 4 AIR Warrants, Amendment
      No.
      4 Additional AIR Debentures and Amendment No. 4 Additional AIR Warrants, and
      as
      payment of interest in shares of Common Stock under the Amendment No. 4 AIR
      Debentures and Amendment No. 4 Additional AIR Debentures (collectively, such
      shares of Common Stock are the “Amendment No. 4 Underlying Shares”) at least
      equal to the Required Minimum on the date hereof. “Required Minimum” means, as
      of any date, the maximum aggregate number of shares of Common Stock then issued
      or potentially issuable in the future pursuant to the Transaction Documents,
      including any Amendment No. 4 Underlying Shares issuable upon exercise or
      conversion in full of all Amendment No. 4 AIR Warrants, Amendment No. 4
      Additional AIR Warrants, Amendment No. 4 AIR Debentures and Amendment No. 4
      Additional AIR Debentures (including Amendment No. 4 Underlying Shares issuable
      as payment of interest), ignoring any conversion or exercise limits set forth
      therein, and assuming that the applicable conversion and exercise prices are
      at
      all times on and after the date of determination 75% of the then conversion
      or
      exercise price on the Trading Day immediately prior to the date of
      determination.

     

    (f)  Valid
      Private Placement.
      Assuming the accuracy of the Purchasers’ representations and warranties set
      forth in Section 4.2, no registration under the Securities Act is required
      for
      the offer and sale of the Securities by Generex to the Purchasers as
      contemplated by the Transaction Documents. 

     

    (g)  Acknowledgment
      Regarding Purchaser’ Purchase of Securities.
      Generex
      acknowledges and agrees that each Purchaser is acting solely in the capacity
      of
      an arm’s length purchaser with respect to the Transaction Documents. Generex
      further acknowledges that no Purchaser is acting as a financial advisor or
      fiduciary of Generex (or in any similar capacity) with respect to any
      Transaction Document or the transactions contemplated thereby, and any advice
      given by any Purchaser or any of their respective representatives or agents
      in
      connection with the Transaction Documents and the transactions contemplated
      thereby is merely incidental to the Purchasers’ respective purchase of the
      Securities. Generex further represents that Generex’s decision to enter into the
      Transaction Documents has been based solely on the independent evaluation of
      the
      transactions contemplated thereby by Generex and its
      representatives.

     

    
      
         

      

      
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    (h)  Compliance
      with Existing Agreements.
      Generex
      is in compliance with the respective terms and conditions of the Purchase
      Agreement and “Transaction Documents” (as therein defined) entered into in
      connection therewith (including those pertaining to Amendment No. 1, Amendment
      No. 2, Amendment No. 3 and Amendment No. 4). No “Event of Default” (as defined
      under the Debentures and the AIR Debentures) has occurred, and no event has
      occurred that with notice or lapse of time or both would become an Event of
      Default under the Debentures or AIR Debentures.

     

    (i)  Certain
      Fees.
      Except
      for fees payable to the Shemano Group, described in the Disclosure Schedules
      to
      the Purchase Agreement, no brokerage or finder’s fees or commissions are or will
      be payable by Generex to any broker, financial advisor or consultant, finder,
      placement agent, investment banker, bank or other Person with respect to the
      transactions contemplated by this Amendment. The Purchasers shall have no
      obligation with respect to any fees or with respect to any claims made by or
      on
      behalf of other Persons for fees of a type contemplated in this Section that
      may
      be due in connection with the transactions contemplated by this
      Amendment.

     

    (j)  
      Listing and Maintenance Requirements.
      The
      Common Stock is registered pursuant to Section 12(g) of the Exchange Act, and
      Generex has taken no action designed to, or which to its knowledge is likely
      to
      have the effect of, terminating the registration of the Common Stock under
      the
      Exchange Act, nor has Generex received any notification that the Commission
      is
      contemplating terminating such registration. Except as disclosed in Generex’s
      publicly available periodic reports and Form 8-K’s under the Exchange Act,
      Generex has not, in the 12 months preceding the date hereof, received notice
      from any Trading Market on which the Common Stock is or has been listed or
      quoted to the effect that Generex is not in compliance with the listing or
      maintenance requirements of such Trading Market. Other than as to minimum stock
      price requirements, Generex is, and has no reason to believe that it will not
      in
      the foreseeable future continue to be, in compliance with all such listing
      and
      maintenance requirements.

     

    (k)  Bring
      Down of Certain Representations and Warranties.
      Generex
      hereby restates, as if first made as of and on the date of this Amendment,
      the
      representations and warranties set forth in the Purchase Agreement (as modified
      by the Disclosure Schedules to the extent they apply thereto) in Sections
      3.1(a), (b), (g), (h), (i), (j), (k), (l), (m), (n), (o), (p), (q), (r), (u),
      (v), (x), (aa), (cc), (ee), and (hh); provided that (1) the term “Transaction
      Documents” therein shall refer not only to such term as defined in the Purchase
      Agreement but also to the Transaction Documents defined in this Amendment,
      and
      (2) the term the “Company” defined in such Purchase Agreement shall also refer
      to “Generex” as used herein.

     

    (l)  Disclosure.
      Generex
      confirms that neither it nor any other Person acting on its behalf has provided
      any of the Purchasers or their agents or counsel with any information that
      constitutes or might constitute material, nonpublic information (except to
      the
      extent that the existence of this Amendment may be material). Generex
      understands and confirms that the Purchasers will rely on the foregoing
      representations in effecting transactions in securities of Generex. All
      disclosure provided to the Purchasers regarding Generex, its business and the
      transactions contemplated hereby, including any disclosure schedules to this
      Amendment, furnished by or on behalf of Generex with respect to the
      representations and warranties made herein are true and correct in all material
      respects with respect to such representations and warranties and do not contain
      any untrue statement of a material fact or omit to state any material fact
      necessary in order to make the statements made therein, in light of the
      circumstances under which they were made, not misleading. Generex acknowledges
      and agrees that each Purchaser does not make or has not made any representations
      or warranties with respect to the transactions contemplated hereby other than
      those specifically set forth in this Section 4.2. 

     

    
      
         

      

      
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    4.2.  Representations
      and Warranties of the Purchasers.
      Each
      Purchaser hereby, for itself and for no other Purchaser, represents and warrants
      as of the date hereof to Generex as follows:

     

    (a)  Organization;
      Authority.
      Such
      Purchaser is an entity duly organized, validly existing and in good standing
      under the laws of the jurisdiction of its organization with the requisite right,
      corporate or partnership power and authority to enter into and to consummate
      the
      transactions contemplated by this Amendment and to carry out its obligations
      hereunder. The execution, delivery and performance by such Purchaser of the
      transactions contemplated by this Amendment have been duly authorized by all
      necessary corporate or similar action on the part of such Purchaser. This
      Amendment has been duly executed by such Purchaser, and when delivered by such
      Purchaser in accordance with the terms hereof, will constitute the valid and
      legally binding obligation of such Purchaser, enforceable against it in
      accordance with its terms, except (i) as limited by general equitable principles
      and applicable bankruptcy, insolvency, reorganization, moratorium and other
      laws
      of general application affecting enforcement of creditors’ rights generally,
      (ii) as limited by laws relating to the availability of specific performance,
      injunctive relief or other equitable remedies and (iii) insofar as
      indemnification and contribution provisions may be limited by applicable
      law.

     

    (b)  Investment
      Intent.
      Such
      Purchaser understands that the Securities are “restricted securities” and have
      not been registered under the Securities Act or any applicable state securities
      law and is acquiring the Securities as principal for its own account and not
      with a view to or for distributing or reselling such Securities or any part
      thereof (this representation and warranty not limiting such Purchaser’s right to
      sell the Securities pursuant to the Registration Statement or otherwise in
      compliance with applicable federal and state securities laws). Nothing contained
      herein shall be deemed a representation or warranty by such Purchaser to hold
      Securities for any period of time. Such Purchaser is acquiring the Securities
      hereunder in the ordinary course of its business. Such Purchaser does not have
      any agreement or understanding, directly or indirectly, with any Person to
      distribute any of the Securities.

     

    (c)  Purchaser
      Status.
      Such
      Purchaser is either (i) an “accredited investor” as defined in Rule 501(a) under
      the Securities Act or (ii) a “qualified institutional buyer” as defined in Rule
      144A(a) under the Securities Act. Such Purchaser is not registered as a
      broker-dealer under Section 15 of the Exchange Act.

     

    
      
         

      

      
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    (d)  Experience
      of Such Purchaser.
      Such
      Purchaser, either alone or together with its representatives, has such
      knowledge, sophistication and experience in business and financial matters
      so as
      to be capable of evaluating the merits and risks of the prospective investment
      in the Securities, and has so evaluated the merits and risks of such investment.
      Such Purchaser is able to bear the economic risk of an investment in the
      Securities and, at the present time, is able to afford a complete loss of such
      investment.

     

    (e)  General
      Solicitation.
      Such
      Purchaser is not purchasing the Securities as a result of any advertisement,
      article, notice or other communication regarding the Securities published in
      any
      newspaper, magazine or similar media or broadcast over television or radio
      or
      presented at any seminar or any other general solicitation or general
      advertisement.

     

    (f)  Access
      to Information.
      Such
      Purchaser acknowledges that it has reviewed such materials it deems necessary
      to
      make an informed investment decision and has been afforded (i) the opportunity
      to ask such questions as it has deemed necessary of, and to receive answers
      from, representatives of Generex concerning the terms and conditions of the
      offering of the Securities and the merits and risks of investing therein; (ii)
      access to information about Generex and the Subsidiaries and their respective
      financial condition, results of operations, business, properties, management
      and
      prospects sufficient to enable it to evaluate its investment; and (iii) the
      opportunity to obtain such additional information that Generex possesses or
      can
      acquire without unreasonable effort or expense that is necessary to make an
      informed investment decision with respect to the investment. Neither such
      inquiries nor any other investigation conducted by or on behalf of such
      Purchaser or its representatives or counsel shall modify, amend or affect such
      Purchaser’s right to rely on the truth, accuracy and completeness of such
      materials it has reviewed and Generex’s representations and warranties contained
      in this Amendment.

     

    (g)  Limited
      Ownership.
      The
      purchase by such Purchaser of the Securities issuable to it upon the closing
      under this Amendment (including the Amendment No. 4 Underlying Shares then
      immediately issuable in respect of such Securities) will not result in such
      Purchaser (individually or together with any other Person with whom such
      Purchaser has identified, or will have identified, itself as part of a “group”
in a public filing made with the Commission involving Generex’s securities)
      acquiring, or obtaining the right to acquire, in excess of 19.999% of the Common
      Stock or the voting power of Generex on a post transaction basis that assumes
      that the closing shall have occurred. Such Purchaser does not presently intend
      to, alone or together with others, make a public filing with the Commission
      to
      disclose that it has (or that it together with such other Persons have)
      acquired, or obtained the right to acquire, as a result of the closing (when
      added to any other securities of Generex that it or they then own or have the
      right to acquire), in excess of 19.999% of the Common Stock or the voting power
      of Generex on a post transaction basis that assumes that the closing shall
      have
      occurred.

     

    
      
         

      

      
        9

        
          

        

      

      
         

      

    

    (h)  Principal
      Amount of AIR Debentures.
      The
      principal amount of AIR Debentures which such Purchaser’s Additional Investment
      Right permits it to acquire immediately prior to its execution of this Amendment
      is set forth on such Purchaser’s signature page to this Amendment.

     

    (i)  Independent
      Investment Decision.
      Such
      Purchaser has independently evaluated the merits of its decision to purchase
      Securities pursuant to this Agreement, such decision has been independently
      made
      by such Purchaser and such Purchaser confirms that it has only relied on the
      advice of its own business and/or legal counsel and not on the advice of any
      other Purchaser’s business and/or legal counsel in making such decision. Such
      Purchaser understands that its investment in the Securities involves a high
      degree of risk. Such Purchaser has sought such accounting, legal and tax advice
      as it has considered necessary to make an informed investment decision with
      respect to its acquisition of the securities.

     

    (j)  Reliance
      on Exemptions.
      Such
      Purchaser understands that the Securities are being offered and sold to it
      in
      reliance on Regulation D and that Generex is relying upon the truth and accuracy
      of, and such Purchaser’s compliance with, the representations, warranties,
      agreements, acknowledgments and understandings of such Purchaser set forth
      herein in order to determine the availability of Regulation D and the
      eligibility of such Purchaser to acquire such Securities.

     

    (k)  No
      Governmental Review.
      Such
      Purchaser understands that no United States federal or state agency or any
      other
      government or governmental agency has passed on or made any recommendation
      or
      endorsement of the Securities or the fairness or suitability of the investment
      in the Securities nor have such authorities passed upon or endorsed the merits
      of the offering of the Securities. 

     

    (l)  Residency.
      Such
      Purchaser certifies that it resides or has a bona fide place of business at
      the
      address set forth below such Purchaser’s name on its signature page to this
      Amendment. 

     

     

    	5.  	
            Continued
              Validity of Transaction Documents under Purchase Agreement.
              The parties hereto agree that the Purchase Agreement and the Transaction
              Documents entered into in connection therewith (as amended by Amendment
              No. 1), remain in full force and effect, modified to the extent and
              only
              to the extent necessary to give effect to this Amendment and the
              transactions herein contemplated. Article IV of the Purchase Agreement
              is
              hereby incorporated by reference in its entirety, except for Sections
              4.6
              and 4.15 therein, into this Amendment with the understanding that if
              any
              term is identified in each of Article IV of the Purchase Agreement
              and in
              this Amendment, the term shall have the meaning set forth in this
              Amendment and references in such Article IV to “the Company” shall mean
              Generex.

          


     

     

    	6.  	
            Closing.

          


     

     

    
      
         

      

      
        10

        
          

        

      

      
         

      

    

     

    	6.1.  	
            Closing.
              On the Trading Day following the date on which the conditions set forth
              in
              Section 6.3 are satisfied, or on such other date as the parties may
              agree
              (the “Closing Date”), the closing of the transactions contemplated by this
              Amendment shall occur (the “Closing”).

          


     

    	6.2.  	
            Deliveries

          


     

    .

     

    	a)  	
            On
              the Closing Date, Generex shall deliver or cause to be delivered to
              each
              Purchaser the following:

          


     

    	(1)  	
            this
              Amendment, duly executed by Generex;

          


     

    	(2)  	
            an
              Amendment No. 4 AIR Debenture, registered in the name of such Purchaser
              in
              the correct principal amount;

          


     

    	(3)  	
            an
              Amendment No. 4 AIR Warrant, registered in the name of such
              Purchaser;

          


     

    	(4)  	
            an
              Amendment No. 4 Additional AIR, registered in the name of such Purchaser;
              and

          


     

    (5) a
      legal
      opinion issued by Company counsel.

     

    	b)  	
            On
              the Closing Date, each Purchaser shall deliver or cause to be delivered
              to
              Generex the following: 

          


     

    	(1)  	
            this
              Amendment, duly executed by such Purchaser;
              and

          


     

    	(2)  	
            100%
              of the principal amount of AIR Debentures issuable upon exercise in
              full
              of such Purchaser’s Additional Investment Right by wire transfer to the
              account as specified in writing by the Company.


          


     

    	6.3.  	
            Closing
              Conditions. 

          


     

    	a)  	
            The
              obligations of Generex hereunder in connection with the Closing are
              subject to the following conditions being
              met:

          


     

    	(1)  	
            the
              accuracy in all material respects when made and on the Closing Date
              of the
              representations and warranties of the Purchasers contained
              herein;

          


     

    	(2)  	
            all
              obligations, covenants and agreements of the Purchasers required to
              be
              performed at or prior to the Closing Date shall have been performed;
              and

          


     

    	(3)  	
            the
              delivery by the Purchasers of the items set forth in Section 6.2(b)
              of
              this Amendment.

          


     

     

    
      
         

      

      
        11

        
          

        

      

      
         

      

    

     

    	b)  	
            The
              respective obligations of the Purchasers hereunder in connection with
              the
              Closing are subject to the following conditions being
              met:

          


     

    	(4)  	
            the
              accuracy in all material respects on the Closing Date of the
              representations and warranties of Generex
              contained herein;

          


     

    	(5)  	
            all
              obligations, covenants and agreements of Generex required to be performed
              at or prior to the Closing Date shall have been performed;
              

          


     

    	(6)  	
            the
              delivery by Generex
              of
              the items set forth in Section 6.2(a) of this Amendment;
              

          


     

    	(7)  	
            there
              shall have been no Material Adverse Effect with respect to Generex
              since the date hereof; and

          


     

    	(8)  	
            From
              the date hereof to the Closing Date, trading in the Common Stock shall
              not
              have been suspended by the Commission (except for any suspension of
              trading of limited duration agreed to by Generex, which suspension
              shall
              be terminated prior to the Closing), and, at any time prior to the
              Closing
              Date, trading in securities generally as reported by Bloomberg Financial
              Markets shall not have been suspended or limited, or minimum prices
              shall
              not have been established on securities whose trades are reported by
              such
              service, or on any Trading Market, nor shall a banking moratorium have
              been declared either by the United States or New York State authorities
              nor shall there have occurred any material outbreak or escalation of
              hostilities or other national or international calamity of such magnitude
              in its effect on, or any material adverse change in, any financial
              market
              which, in each case, in the reasonable judgment of each Purchaser,
              makes
              it impracticable or inadvisable to exercise its Additional Investment
              Right at the Closing.

          


     

     

    	7.  	
            Miscellaneous.

          


     

    	7.1.  	
            Fees
              and Expenses.
              Generex has agreed to reimburse Cranshire Capital, L.P. (“Cranshire”)
              $15,000 for its legal fees and expenses in connection with this Amendment.
              Accordingly, the amount Cranshire must pay to Generex to exercise its
              Additional Investment Right under Section 1 shall be reduced by $15,000.
              Except for the foregoing, each party hereto will bear the fees and
              expenses of its own counsel and advisors in connection with the
              negotiation and entering into of this Amendment. Generex shall pay
              all
              transfer agent fees, stamp taxes and other taxes and duties levied
              in
              connection with the issuance of any
              Securities.

          


     

    	7.2.  	
            Entire
              Agreement.
              This Amendment and the Transaction Documents, together with the exhibits
              and schedules thereto, contain the entire understanding of the parties
              with respect to the subject matter hereof and supersede all prior
              agreements and understandings, oral or written, with respect to such
              matters, which the parties acknowledge have been merged into such
              documents, exhibits and schedules.

          


     

     

    
      
         

      

      
        12

        
          

        

      

      
         

      

    

     

    	7.3.  	
            Equal
              Treatment of Purchasers.
              No consideration shall be offered or paid to any person to amend or
              consent to a waiver or modification of any provision of any of the
              Transaction Documents unless the same consideration is also offered
              to all
              of the parties to the Transaction Documents. Further, Generex shall
              not
              make any payment of principal or interest on the Debentures, AIR
              Debentures or Amendment
              No. 4 AIR Debentures
              in
              amounts which are disproportionate to the respective principal amounts
              outstanding on the Debentures, AIR Debentures or Amendment No. 4 AIR
              Debentures at any applicable time. For clarification purposes, this
              provision constitutes a separate right granted to each Purchaser by
              Generex and negotiated separately by each Purchaser, and is intended
              to
              treat for Generex the Debenture, AIR Debenture and Amendment No. 4
              AIR
              Debenture holders as a class and shall not in any way be construed
              as the
              Purchasers acting in concert or as a group with respect to the purchase,
              disposition or voting of Securities or
              otherwise.

          


     

    	7.4.  	
            Public
              Announcement.
              Generex shall, by 4:30 p.m. Eastern time on the Trading Day following
              the
              date hereof, file a Current Report on Form 8-K, attaching the Transaction
              Documents thereto, each reasonably acceptable to each Purchaser. Generex
              and each Purchaser shall consult with each other in issuing any other
              press releases with respect to the transactions contemplated hereby,
              and
              neither Generex nor any Purchaser shall issue any such press release
              or
              otherwise make any such public statement without the prior consent
              of
              Generex, with respect to any press release of any Purchaser, or without
              the prior consent of each Purchaser, with respect to any press release
              of
              Generex, which consent shall not unreasonably be withheld, except if
              such
              disclosure is required by law, in which case the disclosing party shall
              promptly provide the other party with prior notice of such public
              statement or communication. Notwithstanding the foregoing, Generex
              shall
              not publicly disclose the name of any Purchaser, or include the name
              of
              any Purchaser in any filing with the Commission or any regulatory agency
              or Trading Market, without the prior written consent of such Purchaser,
              except (i) as required by federal securities law in connection with
              the
              registration statement contemplated by the Registration Rights Agreement
              and (ii) to the extent such disclosure is required by law or Trading
              Market regulations, in which case Generex shall provide the Purchasers
              with prior notice of such disclosure permitted under subclause (i)
              or
              (ii).

          


     

    	7.5.  	
            Notices.
              Any and all notices or other communications or deliveries required
              or
              permitted to be provided hereunder shall be in writing and shall be
              deemed
              given and effective as specified in the Purchase Agreement. The address
              for such notices and communications shall be as set forth on the signature
              pages attached to the Purchase Agreement.

          


     

     

    
      
         

      

      
        13

        
          

        

      

      
         

      

    

     

    	7.6.  	
            Amendments;
              Waivers.
              No provision of this Amendment may be waived or amended except in a
              written instrument signed, in the case of an amendment, by Generex
              and
              each Purchaser or, in the case of a waiver, by the party against whom
              enforcement of any such waiver is sought. No waiver of any default
              with
              respect to any provision, condition or requirement of this Amendment
              shall
              be deemed to be a continuing waiver in the future or a waiver of any
              subsequent default or a waiver of any other provision, condition or
              requirement hereof, nor shall any delay or omission of either party
              to
              exercise any right hereunder in any manner impair the exercise of any
              such
              right.

          


     

    	7.7.  	
            Amendment
              Controls.
              If any topic is addressed both in the Purchase Agreement (or any document
              related thereto) and in this Amendment, this Amendment shall
              control.

          


     

    	7.8.  	
            Construction.
              The headings herein are for convenience only, do not constitute a part
              of
              this Amendment and shall not be deemed to limit or affect any of the
              provisions hereof. The language used in this Amendment will be deemed
              to
              be the language chosen by the parties to express their mutual intent,
              and
              no rules of strict construction will be applied against any
              party.

          


     

    	7.9.  	
            Governing
              Law.
              All questions concerning the construction, validity, enforcement and
              interpretation of this Amendment shall be governed by and construed
              and
              enforced in accordance with the internal laws of the State of New York,
              without regard to the principles of conflicts of law thereof. The parties
              agree that Section 5.9 of the Purchase Agreement shall apply to this
              Amendment as if set forth in its entirety
              herein.

          


     

    	7.10.  	
            Survival.
              The representations and warranties contained herein shall survive the
              delivery, exercise and/or conversion of the Securities, as applicable
              for
              the applicable statue of limitations.

          


     

    	7.11.  	
            Execution.
              This Amendment may be executed in two or more counterparts, all of
              which
              when taken together shall be considered one and the same document and
              shall become effective when counterparts have been signed by each party
              and delivered to the other party, it being understood that both parties
              need not sign the same counterpart. 

          


     

    	7.12.  	
            Severability.
              If any provision of this Amendment is held to be invalid or unenforceable
              in any respect, the validity and enforceability of the remaining terms
              and
              provisions of this Amendment shall not in any way be affected or impaired
              thereby and the parties will attempt to agree upon a valid and enforceable
              provision that is a reasonable substitute therefor, and upon so agreeing,
              shall incorporate such substitute provision in this
              Amendment.

          


     

    	7.13.  	
            Independent
              Nature of Purchasers’ Obligations and Rights.
              The obligations of each Purchaser hereunder are several and not joint
              with
              the obligations of any other Purchaser, and no Purchaser shall be
              responsible in any way for the performance of the obligations of any
              other
              Purchaser. Nothing contained herein, and no action taken by any Purchaser
              pursuant hereto, shall be deemed to constitute the Purchasers as a
              partnership, an association, a joint venture or any other kind of entity,
              or create a presumption that the Purchasers are in any way acting in
              concert or as a group with respect to such obligations or the transactions
              contemplated hereby. Each Purchaser shall be entitled to independently
              protect and enforce its rights, including, without limitation, the
              rights
              arising out of this Amendment and it shall not be necessary for any
              other
              Purchaser to be joined as an additional party in any proceeding for
              such
              purpose. The Purchasers have not relied upon the same legal counsel
              in
              their review and negotiation of this Amendment. Generex has elected
              to
              provide all Purchasers with the same terms and form of Amendment for
              the
              convenience of Generex and not because it was required or requested
              to do
              so by the Purchasers. Each Purchaser represents that it has been
              represented by its own separate legal counsel in its review and
              negotiations of this Amendment and each party represents and confirms
              that
              Proskauer Rose LLP represents only Cranshire Capital, L.P. in connection
              with this Amendment.

          


     

    	7.14.  	
            Exempt
              Issuances.
              The term “Exempt Issuance” as defined in the Purchase Agreement is hereby
              amended to include Common Stock and Common Stock Equivalents to employees,
              officers, directors and consultants, if issued pursuant to a resolution
              adopted by the majority of the non-employee members of the Board of
              Directors.

          


     

    (Signature
      Pages Follow)

     


    
      
         

      

      
        14

        
          

        

      

      
         

      

    


    IN
      WITNESS WHEREOF, the parties hereto have caused this Amendment to be duly
      executed by their respective authorized signatories as of the date first
      indicated above.

     

    
      	
              GENEREX
                BIOTECHNOLOGY CORPORATION

               

            
	
              By:/s/
                Mark A. Fletche 

              Name:
                Mark A. Fletcher

              Title:
                Executive Vice-President, General
                Counsel

            


    

    


    [REMAINDER
      OF PAGE INTENTIONALLY LEFT BLANK

    SIGNATURE
      PAGE FOR PURCHASERS FOLLOWS]

     


    
      
         

      

      
        15

        
          

        

      

      
         

      

    


    


    IN
      WITNESS WHEREOF, the undersigned have caused this Amendment to be duly executed
      by their respective authorized signatories as of the date first indicated
      above.

     

    Name
      of
      Investing Entity: __________Smithfield
      Fiduciary LLC____________________________

    Signature
      of Authorized Signatory of Investing Entity:
      __/s/
      Scott M. Wallace_______________

    Name
      of
      Authorized Signatory: _______Scott
      M. Wallace________________________________

    Title
      of
      Authorized Signatory: ________Authorized
      Signatory______________________________

    Email
      Address of Authorized Entity:__________________________________________________

    


    


    The
      principal amount of AIR Debentures which such 

    Purchaser’s
      Additional Investment Right permits it to acquire: $___1,000,000___________

    


    


    Residency
      of Investing Entity: ______Cayman
      Islands________________________


    
      
         

      

      
        16

        
          

        

      

      
         

      

    


    


     

    IN
      WITNESS WHEREOF, the undersigned have caused this Amendment to be duly executed
      by their respective authorized signatories as of the date first indicated
      above.

     

    Name
      of
      Investing Entity: _____Cranshire
      Capital LP_________________________________

    Signature
      of Authorized Signatory of Investing Entity:
      __/s/
      Lawrence A. Prosser_________

    Name
      of
      Authorized Signatory: __Lawrence
      A. Prosser_______________________________

    Title
      of
      Authorized Signatory: ____CFO
      -
      Downsview Capital Inc. - The General Partner_____

    Email
      Address of Authorized Entity:______________________________________________

    


    


    The
      principal amount of AIR Debentures which such 

    Purchaser’s
      Additional Investment Right permits it to acquire: $_____1,000,000_______

    


    


    Residency
      of Investing Entity: _____Illinois_________________________

    


     


    
      
         

      

      
        17

        
          

        

      

      
         

      

    


    


    IN
      WITNESS WHEREOF, the undersigned have caused this Amendment to be duly executed
      by their respective authorized signatories as of the date first indicated
      above.

     

    Name
      of
      Investing Entity: ______Omicron
      Master Trust___________________________________

    Signature
      of Authorized Signatory of Investing Entity:
      ___/s/
      Bruce Bernstein________________

    Name
      of
      Authorized Signatory: _______Bruce
      Bernstein__________________________________

    Title
      of
      Authorized Signatory: ________Managing
      Partner_________________________________

    Email
      Address of Authorized
      Entity:__________________________________________________

    


    


    The
      principal amount of AIR Debentures which such 

    Purchaser’s
      Additional Investment Right permits it to acquire: $_____1,000,000__________

    


    


    Residency
      of Investing Entity: ______________________________

    


     


    
      
         

      

      
        18

        
          

        

      

      
         

      

    


    


    IN
      WITNESS WHEREOF, the undersigned have caused this Amendment to be duly executed
      by their respective authorized signatories as of the date first indicated
      above.

     

    Name
      of
      Investing Entity: ___________Iroquois
      Capital, L.P._______________________________

    Signature
      of Authorized Signatory of Investing Entity:
      __/s/
      Joshua Silverman_________________

    Name
      of
      Authorized Signatory: _______Joshua
      Silverman__________________________________

    Title
      of
      Authorized Signatory: ________Partner__________________________________________

    Email
      Address of Authorized
      Entity:___________________________________________________

    


    


    The
      principal amount of AIR Debentures which such 

    Purchaser’s
      Additional Investment Right permits it to acquire: $______1,000,000____________

    


    


    Residency
      of Investing Entity: ______________________________

    


     

    


    
      
         

      

      
        19