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AMENDED AND RESTATED MANUFACTURING AGREEMENT

Manufacturing Agreement

AMENDED AND RESTATED MANUFACTURING AGREEMENT | Document Parties: CELLADON CORPORATION | TARGETED GENETICS CORPORATION You are currently viewing:
This Manufacturing Agreement involves

CELLADON CORPORATION | TARGETED GENETICS CORPORATION

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Title: AMENDED AND RESTATED MANUFACTURING AGREEMENT
Governing Law: California     Date: 5/7/2009
Industry: Biotechnology and Drugs     Sector: Healthcare

AMENDED AND RESTATED MANUFACTURING AGREEMENT, Parties: celladon corporation , targeted genetics corporation
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Exhibit 10.3

 

 

*Confidential Treatment has been requested for the marked portions of this exhibit pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as amended.

AMENDED AND RESTATED MANUFACTURING AGREEMENT

T HIS A MENDED AND R ESTATED M ANUFACTURING A GREEMENT (the “Agreement” ) is made effective as of February 25, 2009 (the “Amendment Date” ) by and between C ELLADON C ORPORATION , a California corporation, with its principal place of business at 2223 Avenida de la Playa, Suite 300, c/o Enterprise Partners Venture Capital, La Jolla, CA 92037 ( “Celladon” ), and T ARGETED G ENETICS C ORPORATION , a Washington corporation with its principal offices at 1100 Olive Way, Suite 100, Seattle, Washington 98101 ( “TGC” ).

R ECITALS

W HEREAS , Celladon and TGC are parties to that certain Manufacturing Agreement dated December 31, 2004 (the “2004 Agreement” ), as amended by that certain First Amendment to Manufacturing Agreement dated March 19, 2008 (the “First Amendment” and, collectively with the 2004 Agreement, the “Original Agreement” ), pursuant to which TGC is responsible for the manufacture and supply of certain gene therapy products, subject to the terms and conditions set forth therein;

W HEREAS , Celladon and TGC now wish to amend and restate the Original Agreement as set forth herein;

W HEREAS , concurrently herewith, Celladon and TGC are entering into a License Agreement (the “License Agreement” ), which supersedes and replaces the Collaboration Agreement between the parties dated December 31, 2004, as amended to date (the “Collaboration Agreement” ), and pursuant to which TGC is granting Celladon an exclusive license to develop and commercialize certain gene therapy products; and

W HEREAS , this Agreement and the Collaboration Agreement will supersede and replace the letter agreement between the parties dated January 16, 2009 (the “2009 Letter” )

A GREEMENT

N OW , T HEREFORE , in consideration of the foregoing and the mutual promises and covenants hereinafter set forth, Celladon and TGC, intending to be legally bound, hereby agree as follows:

 

1.

D EFINITIONS .

1.1 “Affiliates” shall mean any company or entity controlled by, controlling, or under common control with a party hereto and shall include any company more than 50% of whose voting stock or participating profit interest is owned or controlled, directly or indirectly, by a party, and any company which owns or controls, directly or indirectly, more than 50% of the voting stock of a party.


1.2 “Applicable Laws” means all laws, statutes, ordinances, codes, rules and regulations which have been enacted by a Government Authority and are in force as of the Amendment Date or come into force during the Term, in each case to the extent that the same are applicable to the performance by the parties of their respective obligations under this Agreement. For purposes of this Agreement, cGMP shall be deemed to be within the term “Applicable Laws.”

1.3 “Celladon Designee” shall have the meaning provided in Section 3.1.

1.4 “Celladon Product” shall have the meaning provided in the License Agreement.

1.5 “cGMP” shall mean current good manufacturing practices for medicinal products established by U.S. laws, rules and regulations (including 21 CFR Parts 210 and 211, as amended, and any successor regulations thereto, each as in effect from time to time).

1.6 “cGMP3” shall have the meaning provided in Section 2.1(a).

1.7 “CMC” shall mean chemistry, manufacture and control.

1.8 “Commercially Reasonable Efforts” shall mean, with respect to the efforts to be expended by any entity with respect to any objective, the level of reasonable, diligent, good faith efforts and resources devoted to accomplish such objective as a typical biotechnology company would normally use to accomplish a similar objective under similar circumstances.

1.9 “Development Plan” shall mean the cGMP3 Development Plan attached to this Agreement as Exhibit A .

1.10 “FFDCA” means the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 321 et seq. , as amended from time to time.

1.11 “Government Authority” means any supranational, national, regional, state or local government, court, governmental agency, authority, board, bureau, instrumentality or regulatory body.

1.12 “Information” shall have the meaning provided in the License Agreement.

1.13 “Manufacturing Process” shall mean the manufacturing process for the cGMP3 manufacturing campaign for Mydicar developed by TGC pursuant to the First Amendment.

1.14 “Mydicar” shall mean the Celladon Product known as MYDICAR ® (AAV1/SERCA2a).

1.15 “Quality Agreement” shall mean that certain Quality Agreement for cGMP Manufacturing of Phase II/III and III AAV1/SERCA2a Purified Bulk Drug Substance and Testing of Bulk Drug Substance and Drug Product entered into by the parties prior to the Amendment Date.

1.16 “Term” shall have the meaning provided in Article 10.

 

  

2.

  

*Confidential Treatment Requested.


1.17 “Third Party” means any entity or individual other than TGC or Celladon or their respective Affiliates.

 

2.

C LINICAL M ANUFACTURING S ERVICES

2.1 cGMP3 Pre-Bulk Drug Substance.

(a) Manufacture. Subject to the terms and conditions of this Agreement, TGC shall use Commercially Reasonable Efforts to manufacture Mydicar pre-bulk drug substance using the Manufacturing Process under a manufacturing campaign designated by the parties as cGMP3, as more fully described in the Development Plan ( “cGMP3” ). TGC shall manufacture such Mydicar pre-bulk drug substance in accordance with this Section 2.1(a), the Development Plan, all applicable batch records and test procedures for cGMP3 approved by Celladon and communicated to TGC in writing prior to the Amendment Date, and all Applicable Laws (including, without limitation, cGMP, to the extent applicable to TGC’s manufacturing activities hereunder, as demonstrated by the batch records and test procedures described above as well as those steps and procedures which are (i) specified in the Development Plan, (ii) previously agreed to by the parties with respect to validation of equipment and facilities used by TGC to manufacture Mydicar, or (iii) otherwise agreed to by the parties in writing), provided that TGC shall not be obligated to perform, and shall not perform, analytical or other testing, nor any quality assurance or control, except, in each case, as expressly set forth for TGC to perform in the Development Plan (or as otherwise mutually agreed in writing).

(b) Permitted Use of cGMP3 Pre-Bulk Drug Substance. Mydicar pre-bulk drug substance manufactured pursuant to Section 2.1(a) shall be used solely for preclinical or clinical development and regulatory approval purposes.

2.2 Transfer of Analytical Methods. TGC shall provide its existing analytical methods for Mydicar in accordance with Section 3.1 hereof.

2.3 Mydicar Production Records. TGC shall maintain, and allow Celladon to access or provide to Celladon (as specified in the Development Plan), all records required to be prepared by TGC under the Development Plan in connection with TGC’s manufacture of Mydicar pre-bulk drug substance pursuant to this Agreement. All such records shall be maintained by TGC for such period as may be required by Applicable Laws; provided, however, that any such records provided to Celladon shall be maintained by Celladon for such period as may be required by Applicable Law (and TGC shall have no such obligation with respect thereto).

2.4 Product Delivery. TGC shall ship Mydicar pre-bulk drug substance manufactured pursuant to Section 2.1(a), under quarantine and stored frozen in accordance with cGMP, to such Celladon Designee as Celladon specifies in writing to TGC (and Celladon shall specify such Celladon Designee and corresponding shipping destination prior to March 31, 2009). TGC shall package all items in suitable containers to permit safe transportation and handling. Each shipped container will be labeled and marked to identify its contents without having to be opened, and all boxes and packages must contain packing sheets listing the contents. Celladon shall bear all transportation, insurance, taxes, duties, and other costs and risks

 

  

3.

  

*Confidential Treatment Requested.


of loss, spoilage and damage associated with the shipping and delivery of Mydicar pre-bulk drug substance to such Celladon Designee.

2.5 Limited Obligations. TGC provides no warranties or guarantees hereunder that its manufacture of Mydicar pre-bulk drug substance will be successful or result in drug substance suitable for use in clinical trials. Except to the extent TGC does not comply with its obligations set forth in Sections 2.1 through 2.4, TGC shall have no liability hereunder for any failures to manufacture or supply Mydicar pre-bulk drug substance hereunder.

 

3.

M ANUFACTURING T ECHNOLOGY T RANSFER .

3.1 Technology Transfer. Subject to the terms and conditions of this Agreement (including, without limitation, Article 5 hereof), commencing promptly after the Amendment Date and throughout the Term, TGC shall provide to a Third Party contract manufacturing organization or contract research organization (as applicable) designated by Celladon (each, a “Celladon Designee” ) all manufacturing and other technology and know-how in TGC’s possession (and, if not owned by TGC, that TGC has a right to disclose), that is necessary to practice the Manufacturing Process and to manufacture and test the Mydicar pre-bulk drug substance manufactured hereunder (the “Technology Transfer” ), as more fully described below and in the Development Plan. It is contemplated that the Celladon Designee [*] ; provided, however, that TGC shall not be responsible for any delays or failures to complete the Technology Transfer prior to the end of the Term to the extent caused by [*] . It is the intention of the parties that the Technology Transfer will enable the Celladon Designee(s) to replicate the Manufacturing Process to manufacture and test Mydicar in the same manner as TGC manufactures Mydicar pursuant to this Agreement and in the same manner as TGC tests or has tested Mydicar as of the Amendment Date or during the Term. The Technology Transfer shall include at least the following activities during the Term:

(a) TGC shall provide to Celladon or a Celladon Designee the existing analytical methods for conformance testing of Mydicar, including [*]

(b) TGC shall provide to Celladon or a Celladon Designee [*] in all such cases (i) as are necessary to manufacture Mydicar as manufactured hereunder, to test Mydicar or to support regulatory filings for Mydicar, and (ii) to the extent in the possession and control of TGC;

(c) TGC shall provide [*] in order to enable such Celladon Designee to manufacture Mydicar as manufactured hereunder and to test Mydicar [*]

(d) TGC shall provide Celladon or a Celladon Designee [*] ; and

(e) TGC shall [*]

3.2 Limitations on Obligations In Light of Available Personnel. The parties acknowledge that, in accordance with the Development Plan and payment schedule attached hereto as Exhibit B , TGC has a limited number of personnel to perform its obligations hereunder [*] . Accordingly, TGC’s obligations under Section 3.1 shall be limited to the extent of what can reasonably be accomplished by the anticipated personnel and staffing (working solely on the

 

  

4.

  

*Confidential Treatment Requested.


obligations under this Agreement) during the Term. Celladon shall designate the Celladon Designees who will receive the Technology Transfer reasonably promptly after the Amendment Date, and in any event within such time so that TGC, using Commercially Reasonable Efforts and in accordance with the Development Plan, can reasonably be expected to complete the Technology Transfer as contemplated in the Development Plan [*] . TGC is not responsible or liable for any delays or failure to complete the Technology Transfer due to (a) Celladon’s failure to provide timely designation of the Celladon Designees as described above, or (b) the inexperience of, or excessive need for consultation by, any Celladon Designee.

3.3 Disclosure and Use of Technology Transfer. All Information provided or disclosed to Celladon under the Technology Transfer (or otherwise under Section 3.1) shall be subject to the terms and conditions of Section 2.2(d) of the License Agreement (“Disclosure and Use of Released Materials”) and shall be deemed part of the “TGC Manufacturing Information” thereunder with respect to the application of such Section 2.2(d). All such Information shall be used for the sole purpose of exercising and fully exploiting the license granted to Celladon under Section 2.1 of the License Agreement, subject to the terms and conditions of the License Agreement (and Celladon and its Affiliates and Licensees, as defined in the License Agreement, shall not use such Information for any other purpose).

3.4 Retained Rights; TGC Use of Celladon Designees. TGC and, if applicable, its licensors retain ownership of, and all rights, title and interest in, to and under, the Information provided or disclosed to Celladon under the Technology Transfer or otherwise under this Agreement (except for the equipment on Exhibit C hereto, which is being sold to Celladon), subject only to Celladon’s rights therein as expressly provided for in the License Agreement, including, without limitation, Sections 2.1, 2.2 and 2.8 of the License Agreement. Any use of the term “transfer” or similar terms herein (including in any exhibit hereto) shall be construed accordingly and not as an assignment or sale. For the avoidance of doubt, TGC is entitled to retain and use copies and/or originals of such Information (subject to the exclusive license granted to Celladon under the License Agreement), and nothing herein restricts TGC (or its Affiliates or licensees) from utilizing any Celladon Designee and/or such Information to manufacture or test products (subject to the exclusive license granted to Celladon under the License Agreement). Furthermore, Celladon shall not restrict, and shall otherwise


 
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