REGISTRATION
      RIGHTS AGREEMENT

     

    This
      REGISTRATION RIGHTS AGREEMENT (this “Agreement”)
      is
      made as of January __, 2008, by and among (i) MiddleBrook Pharmaceuticals,
      Inc.,
      a Delaware corporation (the “Company”),
      (ii)
      each person listed on Exhibit A
      attached
      hereto (collectively, the “Initial
      Investors”
and
      each individually, an “Initial
      Investor”),
      and
      (iii) each person or entity that subsequently becomes a party to this Agreement
      pursuant to, and in accordance with, the provisions of Section 12 hereof
      (collectively, the “Investor
      Permitted Transferees”
and
      each individually an “Investor
      Permitted Transferee”).

     

    WHEREAS,
      the Company has agreed to issue and sell to the Initial Investors, and the
      Initial Investors have agreed to purchase from the Company, an aggregate of
      approximately 8,750,000 shares (the “Purchased
      Shares”)
      of the
      Company’s common stock, $0.01 par value per share (the “Common
      Stock”),
      and
      warrants to purchase an aggregate of approximately 3,500,000 shares of Common
      Stock (each a “Warrant”
and
      together the “Warrants”),
      all
      upon the terms and conditions set forth in that certain Securities Purchase
      Agreement, dated of even date herewith, between the Company and the Initial
      Investors (the “Securities
      Purchase Agreement”);
      and

     

    WHEREAS,
      the terms of the Securities Purchase Agreement provide that it shall be a
      condition precedent to the closing of the transactions thereunder, for the
      Company and the Initial Investors to execute and deliver this
      Agreement.

     

    NOW,
      THEREFORE, in consideration of the premises and mutual covenants contained
      herein, the parties hereto hereby agree as follows:

     

    1. DEFINITIONS.
      The
      following terms shall have the meanings provided therefor below or elsewhere
      in
      this Agreement as described below:

     

    “Board”
shall
      mean the board of directors of the Company.

     

    “Closing”
and
      “Closing
      Dates”
shall
      have the meanings ascribed to such terms in the Securities Purchase
      Agreement.

     

    “Exchange
      Act”
shall
      mean the Securities Exchange Act of 1934, as amended, and all of the rules
      and
      regulations promulgated thereunder.

     

    “Effectiveness
      Date”
means,
      with respect to the Initial Registration Statement, as soon as practicable,
      but
      in no event later than one hundred twenty (120) calendar days after the First
      Closing (or one hundred fifty (150) calendar days if the Initial Registration
      Statement is reviewed by the SEC) and, with respect to any additional
      Registration Statements which may be required to be filed hereunder pursuant
      to
      Section 3(d) or otherwise, sixty (60) calendar days following the date on
      which the additional Registration Statement is required to be filed hereunder
      (or ninety (90) calendar days if such additional Registration Statement is
      reviewed by the SEC); provided,
      however,
      that in
      the event the Company is notified by the SEC that one of the above Registration
      Statements will not be reviewed or is no longer subject to further review and
      comments, the Effectiveness Date as to such Registration Statement shall be
      the
      fifth (5th)
      Trading
      Day following the date on which the Company is so notified if such date precedes
      the dates required above.

     

    
      
         

      

      
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    “Filing
      Date”
means,
      with respect to the Initial Registration Statement, within five (5) business
      days after the First Closing and, with respect to any additional Registration
      Statements required to be filed hereunder pursuant to Section 3(d) or
      otherwise, one hundred ninety (190) days after any preceding Registration
      Statement is declared effective by the SEC or the earliest practicable date
      thereafter on which the Company is permitted by SEC Guidance to file such
      additional Registration Statement related to the Registrable
      Securities.

     

    “Initial
      Registration Statement”
means
      the initial Registration Statement filed pursuant to this
      Agreement.

     

    “Investors”
shall
      mean, collectively, the Initial Investors and the Investor Permitted
      Transferees; provided,
      however,
      that
      the term “Investors”
shall
      not include any of the Initial Investors or any of the Investor Permitted
      Transferees that does not own or hold any Registrable Securities.

     

    “Majority
      Holders”
shall
      mean, at the relevant time of reference thereto, those Investors holding more
      than fifty percent (50%) of the Registrable Securities held by all of the
      Investors.

     

    “Registrable
      Securities”
shall
      mean the Purchased Shares and the Underlying Shares, provided,
      however,
      such
      term shall not, after the Mandatory Registration Termination Date, include
      any
      of the Purchased Shares or Underlying Shares that become or have become eligible
      for resale without restrictions or volume limitations pursuant to Rule 144
      or
      pursuant to Regulation S.

     

     

    “Registration
      Statement”
      means any one or more registration statements filed with the SEC by the Company
      on Form
      S-3,
or
      in the event the Company is not eligible to use Form S-3, on Form S-1,
for
      the
      purpose of registering under the Securities Act all of the Registrable
      Securities for resale by, and for the account of, the Investors, including
      the
      Initial Registration Statement and any additional registration statements
      required to be filed hereunder pursuant to Section 3(d) or otherwise,
      including (in each case) the Prospectus, amendments and supplements to such
      registration statement or Prospectus, including pre- and post-effective
      amendments, all exhibits thereto, and all material incorporated by reference
      or
      deemed to be incorporated by reference in such registration statement.


     

    “Rule
      144”
shall
      mean Rule 144 promulgated by the SEC pursuant to the Securities Act and any
      successor or substitute rule, law or provision.

     

    “Rule 415”
      means Rule 415 promulgated by the SEC pursuant to the Securities Act, as
      such Rule may be amended from time to time, or any similar rule or regulation
      hereafter adopted by the SEC having substantially the same purpose and effect
      as
      such Rule. 

     

    “Rule 424”
      means Rule 424 promulgated by the SEC pursuant to the Securities Act, as
      such Rule may be amended from time to time, or any similar rule or regulation
      hereafter adopted by the SEC having substantially the same purpose and effect
      as
      such Rule.

     

    “SEC”
shall
      mean the Securities and Exchange Commission.

     

    
      
         

      

      
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    “SEC
      Guidance”
      means (i) any publicly-available written guidance, or rule of general
      applicability of the SEC staff, or (ii) written comments, requirements or
      requests of the SEC staff to the Company in connection with the review of a
      Registration Statement. 

     

    “Securities”
      shall
      mean the Purchased Shares, the Warrants and the Underlying Shares.

     

    “Securities
      Act”
shall
      mean the Securities Act of 1933, as amended, and all of the rules and
      regulations promulgated thereunder.

     

    “Trading
      Day”
means
      (a) if the Common Stock is listed or quoted on the NASDAQ Global Market, then
      any day during which securities are generally eligible for trading on the NASDAQ
      Global Market, or (b) if the Common Stock is not then listed or quoted and
      traded on the NASDAQ Global Market, then any business day.

     

    “Underlying
      Shares”
shall
      mean the shares of Common Stock issuable upon exercise of the
      Warrants.

     

    2. EFFECTIVENESS;
      TERMINATION.
      This
      Agreement shall become effective and legally binding only if the First Closing
      occurs. This Agreement shall terminate and be of no further force or effect,
      automatically and without any action being required of any party hereto, upon
      the termination of the Securities Purchase Agreement pursuant to Section 7
      thereof.

     

    3. MANDATORY
      REGISTRATION.

     

    (a) The
      Company shall be required to file a Registration Statement on or prior to each
      Filing Date until all of the Registrable Securities are registered for resale
      by
      the Investors as selling stockholders thereunder. On or prior to each Filing
      Date, the Company shall prepare and file with the SEC a Registration Statement
      for the purpose of registering under the Securities Act the resale of all,
      or
      such portion as permitted by SEC Guidance (provided that, the Company shall
      use
      commercially reasonable efforts to advocate with the SEC for the registration
      of
      all or the maximum number of the Registrable Securities as permitted by SEC
      Guidance), of the Registrable Securities by, and for the account of, the
      Investors as selling stockholders thereunder, that are not then registered
      on an
      effective Registration Statement for an offering to be made on a continuous
      basis pursuant to Rule 415. Each Registration Statement shall contain
      (unless otherwise directed by the Majority Holders) substantially the “Plan of
      Distribution” in the Investor Questionnaire the form of which is attached to the
      Securities Purchase Agreement as Appendix I. Subject to the terms of this
      Agreement, the Company shall cause a Registration Statement to be declared
      effective under the Securities Act as promptly as possible after the filing
      thereof, but in any event on or prior to the applicable Effectiveness
      Date.

     

    (b) The
      Company shall be required to keep a Registration Statement effective until
      such
      date that is the earlier of (i) the date as of which all of the Investors as
      selling stockholders thereunder may sell all of the Registrable Securities
      registered for resale thereon without restriction pursuant to Rule 144 (or
      any
      successor rule thereto) promulgated under the Securities Act or (ii) the date
      when all of the Registrable Securities registered thereunder shall have been
      sold (such date is referred to herein as the “Mandatory
      Registration Termination Date”).
      Thereafter, the Company shall be entitled to withdraw such Registration
      Statement and the Investors shall have no further right to offer or sell any
      of
      the Registrable Securities registered for resale thereon pursuant to the
      respective Registration Statement (or any prospectus relating thereto).


     

    
      
         

      

      
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    (c) Notwithstanding
      any other provision of this Agreement and subject to the payment of liquidated
      damages in Section 4(a), if any SEC Guidance sets forth a limitation of the
      number of Registrable Securities to be registered on a particular Registration
      Statement (and notwithstanding that the Company used commercially reasonable
      efforts to advocate with the SEC for the registration of all or a greater number
      of Registrable Securities), unless otherwise directed in writing by an Investor
      as to its Registrable Securities, the number of Registrable Securities to be
      registered on such Registration Statement will first be reduced by Registrable
      Securities represented by Underlying Shares (applied, in the case that some
      Underlying Shares may be registered, to the Investors on a pro rata basis based
      on the total number of unregistered Underlying Shares held by such Investors
      on
      a fully diluted basis), and second by Registrable Securities represented by
      Purchased Shares (applied, in the case that some Purchased Shares may be
      registered, to the Investors on a pro rata basis based on the total number
      of
      unregistered Purchased Shares held by such Investors).

     

    (d) If
      during
      the Effectiveness Period, subject to Section 3(a), the number of
      Registrable Securities at any time exceeds 100% of the number of Purchased
      Shares then registered for resale in a Registration Statement, then the Company
      shall file as soon as reasonably practicable an additional Registration
      Statement covering the resale by the Investors of not less than the number
      of
      such Registrable Securities.

     

    (e) The
      offer
      and sale of the Registrable Securities pursuant to any Registration Statement
      shall not be underwritten.  

     

    4. PENALTIES/SUSPENSION
      OF A REGISTRATION STATEMENT

     

    (a) If:
      (i) the Initial Registration Statement and any other Registration Statement
      is not filed on or prior to its Filing Date or if the Company files the Initial
      Registration Statement or any other Registration Statement without affording
      the
      Investors the opportunity to review and comment on the same, or (ii) the
      Company fails to file with the SEC a request for acceleration in accordance
      with
      Rule 461 promulgated under the Securities Act, within five (5) Trading Days
      of the date that the Company is notified (orally or in writing, whichever is
      earlier) by the SEC that the Initial Registration Statement or any other
      Registration Statement will not be “reviewed” or not be subject to further
      review, or (iii) prior to the Effectiveness Date of the Initial
      Registration Statement or any other Registration Statement, the Company fails
      to
      file a pre-effective amendment and otherwise respond in writing to comments
      made
      by the SEC in respect of such Initial Registration Statement or any other
      Registration Statement within ten (10) calendar days after the receipt of
      comments by or notice from the SEC that such amendment is required in order
      for
      such Initial Registration Statement or any other Registration Statement to
      be
      declared effective, or (iv) subject to the tolling provisions contained
      herein, as to, in the aggregate among all Investors on a pro-rata basis based
      on
      their purchase of the Securities pursuant to the Securities Purchase Agreement,
      the lesser of (A) all of the Registrable Securities constituting the
      Securities and (B) the maximum number of Securities permitted by SEC
      Guidance (collectively, the “Initial
      Shares”),
      a Registration Statement registering for resale all of the Initial Shares is
      not
      declared effective by the SEC by the Effectiveness Date of the Initial
      Registration Statement, or (v) subject to the tolling provisions contained
      herein, all of the Registrable Securities constituting the Securities other
      than
      the Initial Shares are not registered for resale pursuant to one or more
      effective Registration Statements on or before October 31, 2008, or
      (vi) after the Effectiveness Date of the Initial Registration Statement or
      any other Registration Statement, such Initial Registration Statement or other
      Registration Statement ceases for any reason to remain continuously effective
      as
      to all Registrable Securities included in such Initial Registration Statement
      or
      other Registration Statement, as applicable, or the Investors are otherwise
      not
      permitted to utilize the Prospectus therein to resell such Registrable
      Securities, for more than ten (10) consecutive calendar days or more than an
      aggregate of fifteen (15) calendar days during any twelve (12) month period
      (which need not be consecutive calendar days), provided however that no such
      payments shall be required in connection with a Suspension Period (as
      hereinafter defined) (any such failure or breach being referred to as an
“Event”, and for purposes of clause (i), (iv) or (v) the date on which
      such Event occurs, or for purposes of clause (ii) the date on which such
      five (5) Trading Day period is exceeded, or for purposes of clause
      (iii) the date which such ten (10) calendar day period is exceeded, or for
      purposes of clause (vi) the date on which such ten (10) or fifteen (15)
      calendar day period, as applicable, is exceeded being referred to as
“Event
      Date”),
      then, in addition to any other rights the Investors may have hereunder or under
      applicable law, on each such Event Date and on each monthly anniversary of
      each
      such Event Date (if the applicable Event shall not have been cured by such
      date)
      until the applicable Event is cured, the Company shall pay to each Investor
      on a
      monthly basis within three (3) business days of the end of the month an amount
      in cash, as partial liquidated damages and not as a penalty, equal to 1% of
      the
      aggregate purchase price paid by such Investor pursuant to the Securities
      Purchase Agreement for any Registrable Securities then held by such Investor
      (as
      applicable under clauses (iv) and (v)). The parties agree that the maximum
      aggregate liquidated damages payable to a Investor under this Agreement shall
      be
      20% of the aggregate amount paid by such Investor for its respective Securities
      pursuant to the Securities Purchase Agreement. If the Company fails to pay
      any
      partial liquidated damages pursuant to this Section in full within seven (7)
      calendar days after the date payable, the Company will pay interest thereon
      at a
      rate of 18% per annum (or such lesser maximum amount that is required to be
      paid
      by applicable law) to the Investor, accruing daily from the date such partial
      liquidated damages are due until such amounts, plus all such interest thereon,
      are paid in full. The partial liquidated damages pursuant to the terms hereof
      shall apply on a daily pro-rata basis for any portion of a month prior to the
      cure of an Event. 

     

    
      
         

      

      
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    (b) The
      Company shall notify the Investors by facsimile or e-mail as promptly as
      practicable, and in any event, within two (2) Trading Days, after a Registration
      Statement is declared effective and shall simultaneously provide the Investors
      with copies of any related prospectus to be used in connection with the sale
      or
      other disposition of the Securities covered thereby. Failure to notify the
      Investors in accordance with this Section 4(b) shall be deemed an Event under
      Section 4(a). 

     

    (c) No
      Investor shall be entitled to a payment pursuant to this Section 4 if
      effectiveness of a registration statement has been delayed or a prospectus
      has
      been unavailable as a result of (i) a failure by such Investor to promptly
      provide on request by the Company the information required under the Securities
      Purchase Agreement or this Agreement or requested by the SEC as a condition
      to
      effectiveness of a Registration Statement; (ii) the provision of inaccurate
      or
      incomplete information by such Investor; or (iii) a statement or determination
      of the SEC that any provision of the rights of the Investor under this Agreement
      are contrary to the provisions of the Securities Act. 

     

    
      
         

      

      
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    5. OBLIGATIONS
      OF THE COMPANY.
      In
      connection with the Company’s obligation under Section 3 hereof to file a
      Registration Statement with the SEC and to use its commercially reasonable
      efforts to cause a Registration Statement to become effective, the Company
      shall, as expeditiously as reasonably possible:

     

    (a) Prepare
      and file with the SEC such amendments and supplements to a Registration
      Statement and the prospectus used in connection therewith as may be necessary
      to
      comply with the provisions of the Securities Act with respect to the disposition
      of all Registrable Securities covered by a Registration Statement;

     

    (b) Furnish
      to the selling Investors such number of copies of a prospectus, including a
      preliminary prospectus, in conformity with the requirements of the Securities
      Act, and such other documents (including, without limitation, prospectus
      amendments and supplements as are prepared by the Company in accordance with
      Section 5(a) above) as the selling Investors may reasonably request in order
      to
      facilitate the disposition of such selling Investors’ Registrable
      Securities;

     

    (c) Use
      commercially reasonable efforts to comply with all applicable rules and
      regulations of the SEC under the Securities Act and the Exchange Act, including,
      without limitation, Rule 172 under the Securities Act, file any final
      prospectus, including any supplement or amendment thereof, with the SEC pursuant
      to Rule 424 under the Securities Act, promptly inform the Investors in writing
      if, at any time during the Effectiveness Period, the Company does not satisfy
      the conditions specified in Rule 172 and, as a result thereof, the Investors
      are
      required to deliver a prospectus in connection with any disposition of
      Registrable Securities; notify the selling Investors of the happening of any
      event as a result of which the prospectus included in or relating to a
      Registration Statement contains an untrue statement of a material fact or omits
      any fact necessary to make the statements therein not misleading; and,
      thereafter, subject to Section 11 hereof, the Company will promptly prepare
      (and, when completed, give notice and provide a copy thereof to each selling
      Investor) a supplement or amendment to such prospectus so that such prospectus
      will not contain an untrue statement of a material fact or omit to state any
      fact necessary to make the statements therein not misleading; provided
      that
      upon such notification by the Company (which shall be a Suspension pursuant
      to
      Section 11), the selling Investors will not offer or sell Registrable Securities
      until the Company has notified the selling Investors that it has prepared a
      supplement or amendment to such prospectus and filed it with the SEC or, if
      the
      Company does not then meet the conditions for the use of Rule 172, delivered
      copies of such supplement or amendment to the selling Investors (it being
      understood and agreed by the Company that the foregoing proviso shall in no
      way
      diminish or otherwise impair the Company’s obligation to promptly prepare a
      prospectus amendment or supplement as above provided in this Section 5(c) and
      deliver copies of same as above provided in Section 5(b) hereof);
      and

     

    (d) Use
      commercially reasonable efforts to register and qualify the Registrable
      Securities covered by a Registration Statement under such other securities
      or
      Blue Sky laws of such states as shall be reasonably appropriate in the opinion
      of the Company, provided
      that the
      Company shall not be required in connection therewith or as a condition thereto
      to qualify to do business or to file a general consent to service of process
      in
      any such states or jurisdictions, and provided
      further
      that
      (notwithstanding anything in this Agreement to the contrary with respect to
      the
      bearing of expenses) if any jurisdiction in which any of such Registrable
      Securities shall be qualified shall require that expenses incurred in connection
      with the qualification therein of any such Registrable Securities be borne
      by
      the selling Investors, then the selling Investors shall, to the extent required
      by such jurisdiction, pay their pro rata share of such qualification
      expenses.

     

    
      
         

      

      
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    (e) Subject
      to the terms and conditions of this Agreement, including Section 3 hereof,
      the
      Company shall use its commercially reasonable efforts to (i) prevent the
      issuance of any stop order or other suspension of effectiveness of a
      Registration Statement, or the suspension of the qualification of any of the
      Registrable Securities for sale in any jurisdiction in the United States, and
      (ii) if such an order or suspension is issued, obtain the withdrawal of such
      order or suspension at the earliest practicable moment and notify each holder
      of
      Registrable Securities of the issuance of such order and the resolution thereof
      or its receipt of notice of the initiation or threat of any proceeding such
      purpose.

     

    (f) The
      Company shall (i) comply with all requirements of the National Association
      of
      Securities Dealers, Inc. with regard to the issuance of the Purchased Shares
      and
      the listing thereof on the NASDAQ Global Market and such other securities
      exchange or automated quotation system, as applicable, and (ii) engage a
      transfer agent and registrar to maintain the Company’s stock ledger for all
      Registrable Securities covered by a Registration Statement not later than the
      effective date of a Registration Statement.

     

    (g) The
      Company will notify the Investors of any pending proceeding against the Company
      under Section 8A of the Securities Act in connection with the offering of the
      Registrable Securities.

     

    (h) The
      Company will file a Registration Statement and all amendments and supplements
      thereto electronically on EDGAR.

     

    6. FURNISH
      INFORMATION.
      It
      shall be a condition precedent to the obligations of the Company to take any
      action pursuant to this Agreement that the selling Investors shall furnish
      to
      the Company such information regarding them and the securities held by them
      as
      the Company shall reasonably request and as shall be required in order to effect
      any registration by the Company pursuant to this Agreement. Each Investor shall
      promptly notify the Company of any changes in the information furnished to
      the
      Company. 

     

    7. EXPENSES
      OF REGISTRATION.
      Except
      as set forth in Section 5(d), all expenses incurred in connection with the
      registration of the Registrable Securities pursuant to this Agreement (excluding
      underwriting, brokerage and other selling commissions and discounts), including
      without limitation all registration and qualification and filing fees, printing,
      and fees and disbursements of counsel for the Company, shall be borne by the
      Company; provided however that the Investors shall be required to pay the
      expenses of counsel and any other advisors for the Investors and any brokerage
      or other selling discounts or commissions and any other expenses incurred by
      the
      Investors for their own account.

     

    
      
         

      

      
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    8. DELAY
      OF REGISTRATION.
      The
      Investors shall not take any action to restrain, enjoin or otherwise delay
      any
      registration as the result of any controversy which might arise with respect
      to
      the interpretation or implementation of this Agreement.

     

    9. INDEMNIFICATION.

     

    (a) To
      the
      extent permitted by law, the Company will indemnify and hold harmless each
      selling Investor, and each officer and director of such selling Investor and
      each person, if any, who controls such selling Investor, within the meaning
      of
      the Securities Act, against any losses, claims, damages or liabilities, joint
      or
      several, to which they may become subject under the Securities Act or otherwise,
      insofar as such losses, claims, damages or liabilities (or actions in respect
      thereof) arise out of or are based upon (i) any untrue or alleged untrue
      statement of any material fact contained in a Registration Statement, in any
      preliminary prospectus or final prospectus relating thereto or in any amendments
      or supplements to a Registration Statement or any such preliminary prospectus
      or
      final prospectus, or arise out of or are based upon the omission or alleged
      omission to state therein a material fact required to be stated therein, or
      necessary to make the statements therein not misleading and (ii) (ii) any blue
      sky application or other document executed by the Company specifically for
      that
      purpose or based upon written information furnished by the Company filed in
      any
      state or other jurisdiction in order to qualify any or all of the Registrable
      Securities under the securities laws thereof (any such application, document
      or
      information herein called a “Blue Sky Application”); (iii) the omission or
      alleged omission to state in a Blue Sky Application a material fact required
      to
      be stated therein or necessary to make the statements therein not misleading;
      (iv) any violation by the Company or its agents of any rule or regulation
      promulgated under the Securities Act applicable to the Company or its agents
      and
      relating to action or inaction required of the Company in connection with such
      registration; or (v) any failure to register or qualify the Registrable
      Securities included in any such Registration Statement in any state where the
      Company or its agents has affirmatively undertaken or agreed in writing that
      the
      Company will undertake such registration or qualification on an Investor’s
      behalf; and will reimburse such selling Investor, or such officer, director
      or
      controlling person for any legal or other expenses reasonably incurred by them
      in connection with investigating or defending any such loss, claim, damage,
      liability or action; provided,
      however,
      that
      the indemnity agreement contained in this Section 9(a) shall not apply to
      amounts paid in settlement of any such loss, claim, damage, liability or action
      if such settlement is effected without the consent of the Company (which consent
      shall not be unreasonably withheld), nor shall the Company be liable in any
      such
      case for any such loss, damage, liability or action to the extent that it arises
      out of or is based upon (i) an untrue statement or alleged untrue statement
      or
      omission made in connection with a Registration Statement, any preliminary
      prospectus or final prospectus relating thereto or any amendments or supplements
      to a Registration Statement or any such preliminary prospectus or final
      prospectus, in reliance upon and in conformity with written information
      furnished expressly for use in connection with a Registration Statement or
      any
      such preliminary prospectus or final prospectus by the selling Investors or
      (ii)
      at any time when the Company has advised the Investor in writing that the
      Company does not meet the conditions for use of Rule 172 and as a result that
      the Investor is required to deliver a current prospectus in connection with
      any
      disposition of Registrable Securities, an untrue statement or alleged untrue
      statement or omission in a prospectus that is (whether preliminary or final)
      corrected in any subsequent amendment or supplement to such prospectus that
      was
      delivered to the selling Investor before the pertinent sale or sales by the
      selling Investor.

     

    
      
         

      

      
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    (b) To
      the
      extent permitted by law, each selling Investor will severally and not jointly
      indemnify and hold harmless the Company, each of its directors, each of its
      officers who have signed a Registration Statement, each person, if any, who
      controls the Company within the meaning of the Securities Act, against any
      losses, claims, damages or liabilities to which the Company or any such
      director, officer, controlling person, may become subject to, under the
      Securities Act or otherwise, insofar as such losses, claims, damages or
      liabilities (or actions in respect thereto) arise out of or are based upon
      any
      untrue or alleged untrue statement of any material fact contained in a
      Registration Statement or any preliminary prospectus or final prospectus,
      relating thereto or in any amendments or supplements to a Registration Statement
      or any such preliminary prospectus or final prospectus, or arise out of or
      are
      based upon the omission or alleged omission to state therein a material fact
      required to be stated therein or necessary to make the statements therein not
      misleading, in each case to the extent and only to the extent that such untrue
      statement or alleged untrue statement or omission or alleged omission (i) was
      made in a Registration Statement, in any preliminary prospectus or final
      prospectus relating thereto or in any amendments or supplements to a
      Registration Statement or any such preliminary prospectus or final prospectus,
      in reliance upon and in conformity with written information furnished by the
      selling Investor expressly for use in connection with a Registration Statement,
      or any preliminary prospectus or final prospectus or (ii) at any time when
      the
      Company has advised the Investor in writing that the Company does not meet
      the
      conditions for use of Rule 172 and as a result that the Investor is required
      to
      deliver a current prospectus in connection with any disposition of Registrable
      Securities, was corrected in any subsequent amendment or supplement to such
      prospectus that was delivered to the selling Investor before the pertinent
      sale
      or sales by the selling Investor; and such selling Investor will reimburse
      any
      legal or other expenses reasonably incurred by the Company or any such director,
      officer, controlling person, or other selling Investor in connection with
      investigating or defending any such loss, claim, damage, liability or action,
      provided,
      however,
      that
      the liability of each selling Investor hereunder shall be limited to the net
      proceeds (net of underwriting discounts and commissions, if any) received by
      such selling Investor from the sale of Registrable Securities giving rise to
      such liability, and provided,
      further,
      however,
      that
      the indemnity agreement contained in this Section 9(b) shall not apply to
      amounts paid in settlement of any such loss, claim, damage, liability or action
      if such settlement is effected without the consent of those selling Investor(s)
      against which the request for indemnity is being made (which consent shall
      not
      be unreasonably withheld).

     

    (c) Promptly
      after receipt by an indemnified party under this Section 9 of notice of the
      commencement of any action, such indemnified party will, if a claim in respect
      thereof is to be made against any indemnifying party under this Section 9,
      notify the indemnifying party in writing of the commencement thereof and the
      indemnifying party shall have the right to participate in and, to the extent
      the
      indemnifying party desires, jointly with any other indemnifying party similarly
      noticed, to assume at its expense the defense thereof with counsel satisfactory
      to the indemnifying party or indemnifying parties,
      but the omission so to notify the indemnifying party will not relieve it from
      any liability which it may have to any indemnified party for contribution or
      otherwise under the indemnity agreement contained in this Section 9 (except
      to
      the extent that such omission materially and adversely affects the indemnifying
      person’s ability to defend such action).
      In the
      event that the indemnifying party assumes any such defense, the indemnified
      party may participate in such defense with its own counsel and at its own
      expense,
      provided, however, if the defendants in any such action include both the
      indemnified party and the indemnifying party and the indemnified party shall
      have reasonably concluded, based on an opinion of counsel reasonably
      satisfactory to the indemnifying party, that there may be a conflict of interest
      between the positions of the indemnifying party and the indemnified party in
      conducting the defense of any such action or that there may be legal defenses
      available to it and/or other indemnified parties which are different from or
      additional to those available to the indemnifying party, the indemnified party
      or parties shall have the right to select separate counsel to assume such legal
      defenses and to otherwise participate in the defense of such action on behalf
      of
      such indemnified party or parties. Upon receipt of notice from the indemnifying
      party to such indemnified party of its election to assume the defense of such
      action and approval by the indemnified party of counsel, the indemnifying party
      will not be liable to such indemnified party under this Section 9 for any legal
      or other expenses subsequently incurred by such indemnified party in connection
      with the defense thereof unless the indemnified party shall have employed such
      counsel in connection with the assumption of legal defenses in accordance with
      the proviso to the preceding sentence (it being understood, however, that the
      indemnifying party shall not be liable for the expenses of more than one
      separate counsel and one local counsel, reasonably satisfactory to such
      indemnifying party, representing all of the indemnified parties who are parties
      to such action in which case the reasonable fees and expenses of counsel shall
      be at the expense of the indemnifying party.

     

    
      
         

      

      
        -9-

        
          

        

      

      
         

      

    

    (d) Notwithstanding
      anything to the contrary herein, the indemnifying party shall not be entitled
      to
      settle any claim, suit or proceeding unless in connection with such settlement
      the indemnified party receives an unconditional release with respect to the
      subject matter of such claim, suit or proceeding and such settlement does not
      contain any admission of fault by the indemnified party.

     

    (e) If
      the
      indemnification provided for in this Section 9 is unavailable to or insufficient
      to hold harmless an indemnified party under subsection (a) or (b) above in
      respect of any losses, claims, damages or liabilities (or actions or proceedings
      in respect thereof) referred to therein, then each indemnifying party shall
      contribute to the amount paid or payable by such indemnified party as a result
      of such losses, claims, damages or liabilities (or actions in respect thereof)
      in such proportion as is appropriate to reflect the relative fault of the
      Company on the one hand and the Investors on the other in connection with the
      statements or omissions or other matters which resulted in such losses, claims,
      damages or liabilities (or actions in respect thereof), as well as any other
      relevant equitable considerations. The relative fault shall be determined by
      reference to, among other things, in the case of an untrue statement, whether
      the untrue statement relates to information supplied by the Company on the
      one
      hand or an Investor on the other and the parties’ relative intent, knowledge,
      access to information and opportunity to correct or prevent such untrue
      statement. The Company and the Investors agree that it would not be just and
      equitable if contribution pursuant to this subsection (e) were determined by
      pro
      rata allocation (even if the Investors were treated as one entity for such
      purpose) or by any other method of allocation which does not take into account
      the equitable considerations referred to above in this subsection (e). The
      amount paid or payable by an indemnified party as a result of the losses,
      claims, damages or liabilities (or actions in respect thereof) referred to
      above
      in this subsection (e) shall be deemed to include any legal or other expenses
      reasonably incurred by such indemnified party in connection with investigating
      or defending any such action or claim. No person guilty of fraudulent
      misrepresentation (within the meaning of Section 11(f) of the Securities Act)
      shall be entitled to contribution from any person who was not guilty of such
      fraudulent misrepresentation. The Investors’ obligations in this subsection to
      contribute are several in proportion to their sales of Registrable Securities
      to
      which such loss relates and not joint. In no event shall the contribution
      obligation of an Investor be greater in amount than the dollar amount of the
      net
      proceeds (net of all expenses paid by such Investor in connection with any
      claim
      relating to this Section 9 and the amount of any damages such Investor has
      otherwise been required to pay by reason of such untrue or alleged untrue
      statement or omission or alleged omission) received by it upon the sale of
      the
      Registrable Securities giving rise to such contribution obligation.

     

    
      
         

      

      
        -10-

        
          

        

      

      
         

      

    

    (f) The
      parties to this Agreement hereby acknowledge that they are sophisticated
      business persons who were represented by counsel during the negotiations
      regarding the provisions hereof including, without limitation, the provisions
      of
      this Section 9, and are fully informed regarding said provisions. They further
      acknowledge that the provisions of this Section 9 fairly allocate the risks
      in
      light of the ability of the parties to investigate the Company and its business
      in order to assure that adequate disclosure is made in a Registration Statement
      as required by the Securities Act and the Exchange Act. 

     

    10. REPORTS
      UNDER THE EXCHANGE ACT.
      With a
      view to making available to the Investors the benefits of Rule 144 and any
      other
      rule or regulation of the SEC that may at any time permit the Investors to
      sell
      the Purchased Shares to the public without registration, the Company agrees
      to
      use commercially reasonable efforts: (i) to make and keep public information
      available as those terms are understood in Rule 144, (ii) to file with the
      SEC
      in a timely manner all reports and other documents required to be filed by
      an
      issuer of securities registered under the Securities Act or the Exchange Act
      pursuant to Rule 144, (iii) as long as any Investor owns any Purchased Shares,
      to furnish in writing upon such Investor’s request a written statement by the
      Company that it has complied with the reporting requirements of Rule 144 and
      of
      the Securities Act and the Exchange Act, and to furnish to such Investor a
      copy
      of the most recent annual or quarterly report of the Company, and such other
      reports and documents so filed by the Company as may be reasonably requested
      in
      availing such Investor of any rule or regulation of the SEC permitting the
      selling of any such Purchased Shares without registration and (iv) undertake
      any
      additional actions reasonably necessary to maintain the availability of a
      Registration Statement or the use of Rule 144.

     

    11. SUSPENSION.
      Notwithstanding anything in this Agreement to the contrary, in the event (i)
      of
      any request by the SEC or any other federal or state governmental authority
      during the period of effectiveness of a Registration Statement for amendments
      or
      supplements to a Registration Statement or related prospectus or for additional
      information; (ii) of the issuance by the SEC or any other federal or state
      governmental authority of any stop order suspending the effectiveness of a
      Registration Statement or the initiation of any proceedings for that purpose;
      (iii) of the receipt by the Company of any notification with respect to the
      suspension of the qualification or exemption from qualification of any of the
      Registrable Securities for sale in any jurisdiction or the initiation of any
      proceeding for such purpose; (iv) of any event or circumstance which
      necessitates the making of any changes in a Registration Statement or related
      prospectus, or any document incorporated or deemed to be incorporated therein
      by
      reference, so that, in the case of a Registration Statement, it will not contain
      any untrue statement of a material fact or any omission to state a material
      fact
      required to be stated therein or necessary to make the statements therein not
      misleading, and that in the case of the prospectus, it will not contain any
      untrue statement of a material fact or any omission to state a material fact
      required to be stated therein or necessary to make the statements therein,
      in
      the light of the circumstances under which they were made, not misleading;
      or
      (v) that the Board has made the good faith determination (A) that continued
      use
      by the selling Investors of a Registration Statement for purposes of effecting
      offers or sales of Registrable Securities pursuant thereto would require, under
      the Securities Act, premature disclosure in a Registration Statement (or the
      prospectus relating thereto) of material, nonpublic information concerning
      the
      Company, its business or prospects or any proposed material transaction
      involving the Company, (B) that such premature disclosure would be materially
      adverse to the Company, its business or prospects or any such proposed material
      transaction or would make the successful consummation by the Company of any
      such
      material transaction significantly less likely and (C) that it is therefore
      essential to suspend the use by the Investors of such Registration Statement
      (and the prospectus relating thereto) for purposes of effecting offers or sales
      of Registrable Securities pursuant thereto, then the Company shall furnish
      to
      the selling Investors a certificate signed by the President or Chief Executive
      Officer of the Company setting forth one or more of the above described
      circumstances, and the right of the selling Investors to use a Registration
      Statement (and the prospectus relating thereto) shall be suspended for a period
      (the “Suspension
      Period”)
      of not
      more than forty-five (45) days after delivery by the Company of the certificate
      referred to above in this Section 11; provided that
      the
      Company shall be entitled to no more than two such Suspension Periods during
      the
      twelve (12) month period commencing on the First Closing and during each
      subsequent twelve (12) month period until the Mandatory Registration Termination
      Date (including any extension thereto). During the Suspension Period, none
      of
      the Investors shall offer or sell any Registrable Securities pursuant to or
      in
      reliance upon a Registration Statement (or the prospectus relating thereto)
      and
      each of the Investors shall keep the fact of the above described certificate
      and
      its contents confidential. The Company shall use commercially reasonable efforts
      to terminate any Suspension Period as promptly as practicable. 

     

    
      
         

      

      
        -11-

        
          

        

      

      
         

      

    

    12. TRANSFER
      OF REGISTRATION RIGHTS.
      An
      Investor may transfer or assign, in whole or from time to time in part, to
      one
      or more persons its rights hereunder in connection with the transfer of
      Registrable Securities by such Investor to such person, provided that such
      Investor complies with all laws applicable thereto and provides written notice
      of assignment to the Company promptly after such assignment is effected and,
      provided, further that such person agrees to become a party to, and bound by,
      all of the terms and conditions of, this Agreement by duly executing and
      delivering to the Company an Instrument of Adherence in the form attached as
      Exhibit B
      hereto.

     

    13. ENTIRE
      AGREEMENT.
      This
      Agreement, the Warrant and the Securities Purchase Agreement constitute and
      contain the entire agreement and understanding of the parties with respect
      to
      the subject matter hereof, and supersede any and all prior negotiations,
      correspondence, agreements or understandings with respect to the subject matter
      hereof.

     

    
      
         

      

      
        -12-

        
          

        

      

      
         

      

    

    14. MISCELLANEOUS.

     

    (a) This
      Agreement may not be amended, modified or terminated, and no rights or
      provisions may be waived, except with the written consent of the Majority
      Holders and the Company.

     

    (b) This
      Agreement shall be governed by and construed and enforced in accordance with
      the
      laws of the State of New York and without regard to any conflicts of laws
      concepts which would apply the substantive law of some other jurisdiction,
      and
      shall be binding upon and inure to the benefit of the parties hereto and their
      respective heirs, personal representatives, successors or assigns, provided
      that, to
      the extent applicable, the terms and conditions of Section 12 hereof are
      satisfied. This Agreement shall also be binding upon and inure to the benefit
      of
      any transferee of any of the Purchased Shares provided
      that the
      terms and conditions of Section 12 hereof are satisfied. Notwithstanding
      anything in this Agreement to the contrary, if at any time any Investor shall
      cease to own any Registrable Securities, all of such Investor’s rights under
      this Agreement shall immediately terminate.

     

    (c) Each
      of
      the parties hereto irrevocably submits to the exclusive jurisdiction of the
      courts of the State of New York located in New York County and the United States
      District Court for the Southern District of New York for the purpose of any
      suit, action, proceeding or judgment relating to or arising out of this
      Agreement and the transactions contemplated hereby. Service of process in
      connection with any such suit, action or proceeding may be served on each party
      hereto anywhere in the world by the same methods as are specified for the giving
      of notices under this Agreement. Each of the parties hereto irrevocably consents
      to the jurisdiction of any such court in any such suit, action or proceeding
      and
      to the laying of venue in such court. Each party hereto irrevocably waives
      any
      objection to the laying of venue of any such suit, action or proceeding brought
      in such courts and irrevocably waives any claim that any such suit, action
      or
      proceeding brought in any such court has been brought in an inconvenient forum.
      EACH
      OF THE PARTIES HERETO WAIVES ANY RIGHT TO REQUEST A TRIAL BY JURY IN ANY
      LITIGATION WITH RESPECT TO THIS AGREEMENT AND REPRESENTS THAT COUNSEL HAS BEEN
      CONSULTED SPECIFICALLY AS TO THIS WAIVER.

     

    (d) Any
      notices, reports or other correspondence (hereinafter collectively referred
      to
      as “correspondence”) required or permitted to be given hereunder shall be in
      writing and shall be sent by postage prepaid first class mail, courier or
      telecopy or delivered by hand to the party to whom such correspondence is
      required or permitted to be given hereunder, and shall be deemed sufficient
      upon
      receipt when delivered personally or by courier, overnight delivery service
      or
      confirmed facsimile, or three (3) business days after being deposited in the
      regular mail as certified or registered mail (airmail if sent internationally)
      with postage prepaid, if such notice is addressed to the party to be notified
      at
      such party’s address or facsimile number as set forth below:

     

    
      
         

      

      
        -13-

        
          

        

      

      
         

      

    

    (i)
      All
      correspondence to the Company shall be addressed as follows:

     

    20425
      Seneca Meadows Parkway

    Germantown,
      Maryland 20878

    
      	
            	Attention:	
              Edward
                M. Rudnic, Ph.D.

            


      	 	 	President and Chief Executive
              Officer


      	 	Facsimile:	(301)
              944-6700


    

     

    with
      a
      copy to:

     

    Dewey
      Ballantine LLP

    1301
      Avenue of the Americas

    New
      York,
      New York 10019

    
      	
            	Attention:	
              Frederick
                W. Kanner, Esq.

            


      	 	Facsimile: 	(212)
              259-6333


    

     

    (ii)
      All
      correspondence to any Investor shall be sent to such Investor at the address
      set
      forth in Exhibit A.

     

    (iii)
      Any
      entity may change the address to which correspondence to it is to be addressed
      by written notification as provided for herein.

     

    (e) The
      parties acknowledge and agree that in the event of any breach of this Agreement,
      remedies at law may be inadequate, and each of the parties hereto shall be
      entitled to seek specific performance of the obligations of the other parties
      hereto and such appropriate injunctive relief as may be granted by a court
      of
      competent jurisdiction.

     

    (f) Should
      any part or provision of this Agreement be held unenforceable or in conflict
      with the applicable laws or regulations of any jurisdiction, the invalid or
      unenforceable part or provisions shall be replaced with a provision which
      accomplishes, to the extent possible, the original business purpose of such
      part
      or provision in a valid and enforceable manner, and the remainder of this
      Agreement shall remain binding upon the parties hereto.

     

    (g) This
      Agreement may be executed in a number of counterparts, any of which together
      shall for all purposes constitute one Agreement, binding on all the parties
      hereto notwithstanding that all such parties have not signed the same
      counterpart.

     

    [Signature
      Page to Follow]

     

    
      
         

      

      
        -14-

        
          

        

      

      
         

      

    

    IN
      WITNESS WHEREOF, the parties hereto have executed this Registration Rights
      Agreement as of the date and year first above written.

     

    
      	 	 	 
	 	MIDDLEBROOK
              PHARMACEUTICALS, INC.
	 
 	 
 	 
 
	 	By:  	/s/ Edward
              M.
              Rudnic, Ph.D.
	 	Name:	
              
Edward
              M. Rudnic, Ph.D.
	 	Title:	President and Chief
              Executive
              Officer


    

     

    THE
      INITIAL INVESTOR’S SIGNATURE TO THE INVESTOR QUESTIONNAIRE DATED OF EVEN DATE
      HEREWITH SHALL CONSTITUTE THE INITIAL INVESTOR’S SIGNATURE TO THIS REGISTRATION
      RIGHTS AGREEMENT.

     

    
      
         

      

      
        
          Signature
            Page to Registration Rights Agreement

        

        
          

        

      

      
         

      

    

    EXHIBIT
      A

     

    Investor
      Name and Address

     

     

     

    
      
         

      

      
        
          A-1

        

        
          

        

      

      
         

      

    

    EXHIBIT
      B

     

    Instrument
      of Adherence

     

    Reference
      is hereby made to that certain Registration Rights Agreement, dated as of
      April __, 2007, among MiddleBrook Pharmaceuticals, Inc., a Delaware
      corporation (the “Company”),
      the
      Initial Investors and the Investor Permitted Transferees, as amended and in
      effect from time to time (the “Registration
      Rights Agreement”).
      Capitalized terms used herein without definition shall have the respective
      meanings ascribed thereto in the Registration Rights Agreement.

     

    The
      undersigned, in order to become the owner or holder of [___________] shares
      of
      common stock, par value $0.01 per share (the “Common
      Stock”),
      of
      the Company, or a Warrant or Warrants to purchase [_______] Underlying Shares,
      hereby agrees that, from and after the date hereof, the undersigned has become
      a
      party to the Registration Rights Agreement in the capacity of an Investor
      Permitted Transferee, and is entitled to all of the benefits under, and is
      subject to all of the obligations, restrictions and limitations set forth in,
      the Registration Rights Agreement that are applicable to Investor Permitted
      Transferees. This Instrument of Adherence shall take effect and shall become
      a
      part of the Registration Rights Agreement immediately upon
      execution.

     

    Executed
      as of the date set forth below under the laws of the State of New
      York.

     

    
      	 	 	 
	 
 	 
 	 
 
	 	Signature:	 
	 	
              
Name:
	 	Title:


    

     

    
      	Accepted:	 	 	 
	[___________________]	 	 	 
	 	 	 	 	 
	 	 	 	 	 
	By:	 	 	 	 
	 	
              
Name:	 	 	
            
	 	Title:	 	 	 


    

     

    Date:
      _________, 200__

     

    
      
         

      

        B-1