AMENDMENT NUMBER 4 TO THE DEVELOPMENT AND SUPPLY AGREEMENT DATED DECEMBER 28, 2001 BETWEEN

Exhibit 10.16.4

[*] = CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.

AMENDMENT NUMBER 4 TO THE

DEVELOPMENT AND SUPPLY AGREEMENT DATED DECEMBER 28, 2001

BETWEEN

ABBOTT LABORATORIES AND INTERMUNE, INC. (TARGANTA

THERAPEUTICS)

This Fourth Amendment, to the Development and Supply Agreement dated as of December 28, 2001, as amended by Amendment Number 1 dated April 26, 2002, Amendment Number 2 dated October 15, 2002, and Amendment Number 3 dated December 22, 2005 (the “Agreement”), is effective as of December 15, 2006 (“Amendment Effective Date”), between Abbott Laboratories, an Illinois corporation (“Abbott”), and Targanta Therapeutics Corporation, an Indianapolis, Indiana corporation (“Targanta”) as purchaser of all rights title and interest related to Oritavancin from InterMune, Inc., a Delaware corporation (“InterMune”). Any capitalized term used and not otherwise defined herein shall have the meaning set forth in the Agreement.

WHEREAS, the parties desire to amend the Agreement to revise certain provisions relating to the forecasts for the Product and/or Bulk Drug Substance;

WHEREAS, InterMune sold to Targanta and Targanta purchased from InterMune all rights, title and interest in Oritavancin, including, without limitation, the contractual rights and obligations contained in the Agreement and this Agreement was automatically assigned to Targanta in accordance with Section 15 of the Agreement.

NOW, THEREFORE, in consideration of the premises and the mutual covenants and agreements contained herein, the parties hereto, intending to be legally bound, hereby agree as follows:

Research and Development Fee. The parties acknowledge and agree that Abbott has been paid in full for its participation in the Project for Stages 1 – 3 of the Project. The parties further agree that to reimburse Abbott for its participation in the Stage 4 Project, Targanta shall pay Abbott a [*] research and development fee [*] (the “Fee”). The Fee shall be paid on a [*] basis as broken down in the Payment Schedule Forecast set forth in Exhibit C and is mutually exclusive and in addition to the research and development fee already paid by InterMune for the completion of Stages 1, 2, and 3. Invoices shall be sent to Targanta on a [*] basis and payment for the applicable Fee for that period shall be made within [*] of receipt of each applicable invoice. If milestones in the Stage 4 Project are reached earlier than forecasted, the Stage 4 Project will move to the next area of focus with a commensurate reduction in the forecasted fees, if applicable, and any such adjusted fee shall be set forth in writing.

Validation Supplies. Abbott has provided to InterMune validation supplies consisting of [*] of Bulk Drug Substance. As a component of the development activities described in the Stage 4 Project set forth in Exhibit C, Abbott shall supply to Targanta [*] of Bulk Drug Substance for clinical, regulatory, and/or commercial use. The [*] shall target [*] of Bulk Drug Substance and incorporate [*] defined in the Stage 4 Project.

Quality Assurance. Within [*] following the signing of this amendment, representatives of the parties’ Quality Assurance departments shall meet to develop and approve a quality agreement (“Quality Agreement”) outlining the responsibilities and key contacts for quality and compliance related issues. Items to be included in the Quality Agreement include, but are not limited to, recalls, annual product reviews, returned goods, regulatory audits, compliance with cGMP, and compliance with such other quality related concerns deemed appropriate.

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The parties acknowledge and agree that equipment modifications are necessary for the Stage 4 Project and for continued commercial production of Bulk Drug Substance thereafter. The parties acknowledge that equipment modifications are estimated to be approximately [*], but are subject to change, and shall be billed by Abbott to Targanta at Abbott’s cost, as the aforementioned equipment modifications occur. Notwithstanding the foregoing, in the event the equipment modifications are anticipated to [*] (the “Maximum Equipment Fee”), Abbott shall obtain Targanta’s prior written approval of the costs in excess of the Maximum Equipment Fee before commencing such equipment modifications.

Upon expiration or termination of this Agreement for any reason by Targanta, upon Targanta’s request, Abbott will reasonably assist Targanta with the technology transfer of the manufacturing process associated with Bulk Drug Substance to Targanta or its designee, and Targanta [*].

Upon termination of this Agreement for any reason by Abbott (excluding for Targanta’s uncured breach), upon Targanta’s request, Abbott will reasonably assist Targanta with the technology transfer of the manufacturing process associated with Bulk Drug Substance to Targanta or its designee, and Abbott [*].

Upon expiration or termination of this Agreement by Abbott for Targanta’s uncured breach of this Agreement, upon Targanta’s request and upon Targanta’s payment of (i) any payments due to Abbott for services rendered or Bulk Drug Substance provided under the Agreement prior to termination and (ii) Abbott’s reasonable costs and expenses for Abbott’s assistance of Targanta with the technology transfer of the manufacturing process associated with Bulk Drug Substance to Targanta or its designee, Abbott will reasonably assist Targanta with such technology transfer.

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IN WITNESS WHEREOF, the parties, through their authorized officers, have executed this Amendment as of the Amendment Effective Date.

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Attachment 1

Exhibit C - Stage 4

STAGE 4 ORITAVANCIN [*]

ASM FREE, PROCESS DEMONSTRATION &

COMMERCIAL MANUFACTURING

CONFIDENTIAL

No use or disclosure outside Abbott is permitted without prior written authorization from Abbott.

Stage 4 Project

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Exhibit C - Stage 4

TARGANTA DEVELOPMENT PROPOSAL

[*]

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