AMENDMENT TO MORTGAGE, SECURITY AGREEMENT AND FIXTURE FILING

Exhibit 10.4

When recorded return to:

Christopher J. Lhulier, Esq.

Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

One Financial Center

Boston, MA 02111

AMENDMENT TO MORTGAGE, SECURITY AGREEMENT

AND FIXTURE FILING

THIS AMENDMENT TO MORTGAGE, SECURITY AGREEMENT AND FIXTURE FILING (this “ Amendment ”) is made as of the 18th day of June, 2009, by and between GTC BIOTHERAPEUTICS, INC. , a Massachusetts corporation, formerly known as GENZYME TRANSGENICS CORPORATION , having an address of 175 Crossing Boulevard, Suite 410, Framingham, Massachusetts 01702 (the “ Grantor ”), and LFB BIOTECHNOLOGIES S.A.S. , having as address 3, avenue des Tropiques, LES ULIS, 91940 Courtaboeuf - FRANCE (the “ Grantee ”).

W I T N E S S E T H      T H A T:

WHEREAS, the Grantor granted the Grantee a certain Second Mortgage, Security Agreement and Fixture Filing dated as of December 22, 2008 and recorded with the Registry of Deeds for Worcester County, Massachusetts on December 22, 2008 in Book 43614, Page 182 with respect to certain real property of Grantor located in the Towns of Charlton and Spencer, County of Worcester, Commonwealth of Massachusetts and more particularly described therein (the “ Existing Mortgage ”), to secure, inter alia , certain indebtedness, obligations and liabilities of the Grantor to the Grantee; and

WHEREAS, the parties hereto desire to amend the Existing Mortgage in the manner as hereinafter set forth.

NOW, THEREFORE, for good and valuable consideration, the receipt and adequacy of which are hereby acknowledged, the parties hereto hereby agree as follows:

1. Recitals . There foregoing recitals are hereby incorporated by reference herein.

2. Priority of Existing Mortgage . The parties hereto acknowledge that certain mortgage from the Grantee to General Electric Capital Corporation (“ GECC ”) dated May 26, 2004 and recorded with the Worcester County Registry of Deeds on May 26, 2004 in Book 33705, Page 97, as affected by that certain Amended and Restated Mortgage, Security Agreement and Fixture Filing by the Grantor in favor of GECC dated December 29, 2006 and recorded in Book 40438, Page 257, as amended, is as of

the date hereof being paid in full and discharged and the Grantor accordingly acknowledges and agrees that the Existing Mortgage, as amended hereby, shall be a first lien on the Property from and after the date hereof.

3. Amendments to the Existing Mortgage . The Existing Mortgage is hereby further amended as follows:

(a) The Existing Mortgage is hereby amended by deleting in its entirety the “legend” provision contained in first full paragraph of the Existing Mortgage located immediately above the title thereof.

(b) The Existing Mortgage is hereby amended by deleting the word “Second” from the title thereof and in each place where the title is used and from the introductory paragraph immediately following the title thereof.

(c) The recitals beginning on page 1 of the Existing Mortgage are hereby deleted in their entirety and the following recitals are hereby substituted in their stead:

“WHEREAS, Grantor is the holder of (i) the 2006 Convertible Note (as defined below), (ii) the 2008 Convertible Note (as defined below) issued pursuant to that certain Note and Warrant Purchase Agreement, executed on October 31, 2008, by and between the Grantor and the Grantee (the “NPA”), (iii) the 2009 Convertible Note (as defined below) issued in connection with that certain Securities Purchase Agreement executed on June 18, 2009, by and between the Grantor and the Grantee (the “SPA” and together with the NPA, collectively, the “Purchase Agreements”), and (iv) the Secured Note (as defined below) issued pursuant to that certain Loan Agreement dated as of June 18, 2009 by and between the Grantor and the Grantee (as amended, the “Loan Agreement”); and

WHEREAS, Grantor and Grantee have agreed that this Mortgage, among other things, shall secure the Grantor’s obligations to the Grantee, including without limitation, those obligations memorialized by the Purchase Agreements, the Loan Agreement and the Notes (as defined below); and

NOW, THEREFORE, in consideration of the Purchase Agreements, the Loan Agreement, the Notes and other obligations of Grantor to Grantee, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, and intending to be legally bound, Grantor hereby agrees as follows:”

(d) Section 1.1(a) of the Existing Mortgage is hereby amended as follows:

““ Notes ” means collectively, (a) the 2006 Convertible Note, (b) the 2008 Convertible Note, (c) the 2009 Convertible Note, and (d) the Secured Note.”

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““ Secured Note ” means the Promissory Note dated June 18, 2009 executed by Grantor, payable to the order of Grantee, in the stated principal amount of Three Million Five Hundred Thousand and 00/100 Dollars ($3,500,000.00), which is scheduled to mature on January 1, 2012.”

““ 2006 Convertible Note ” means the Subordinated Convertible Note dated December 14, 2006, executed by Grantor, payable to the order of Grantee, in the stated principal amount of Two Million Five Hundred Fifty Eight Thousand Six Hundred Fifty and 00/100 Dollars ($2,558,650.00), which is scheduled to mature on December 14, 2011.”

““ 2008 Convertible Note ” means the Convertible Promissory Note dated on or about December 22, 2008, executed by Grantor, payable to the order of Grantee, in the stated principal amount of Fifteen Million and 00/100 Dollars ($15,000,000.00), which is scheduled to mature on June 1, 2012.”

““ 2009 Convertible Note ” means the Secured Convertible Note dated on or about June 18, 2009, executed by Grantor, payable to the order of Grantee, in the stated principal amount of Four Million Five Hundred Twelve Thousand Two Hundred Sixty-Eight and 00/100 Dollars ($4,512,268.00), which is scheduled to mature on January 1, 2012.”

““ Loan ” means collectively, (a) the loan in the aggregate principal amount of Two Million Five Hundred Fifty Eight Thousand Six Hundred Fifty and 00/100 Dollars ($2,558,650.00) made by Grantee to Grantor, evidenced by the 2006 Convertible Note, (b) the loan in the aggregate principal amount of Fifteen Million and 00/100 Dollars ($15,000,000.00) made by Grantee to Grantor pursuant to the NPA, evidenced by the 2008 Convertible Note, (c) the loan in the aggregate principal amount of Four Million Five Hundred Twelve Thousand Two Hundred Sixty-Eight and 00/100 Dollars ($4,512,268.00) made by Grantee to Grantor as described in the SPA, evidenced by the 2009 Convertible Note, and (d) the term loan to be made by Grantee to Grantor pursuant to the Loan Agreement in the aggregate principal amount of Three Million Five Hundred Thousand and 00/100 Dollars ($3,500,000.00) to be evidenced by the Secured Note; all of which are to be secured by the Loan Documents.”

““ Loan Documents ” means, collectively: (a) the Purchase Agreements; (b) the Notes; (c) this Mortgage; (d) the Amended and Restated Security Agreement dated as of June 18, 2009 executed by

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Grantor and Grantee (as amended, the “Security Agreement”); (e) the Loan Agreement, and (f) all other documents now or hereafter executed by Grantor or any other Person to evidence, secure or otherwise related to the payment or the performance of the Obligations or otherwise executed in connection with the documents described in the foregoing items (a) through (e); and (g) all amendments, modifications, renewals, restatements, extensions, substitutions and replacements of any of the foregoing items.”

““ Obligations ” means, collectively: (a) the Loan; (b) all other principal and all interest, fees, expenses, charges, reimbursements, and other amounts due under or secured by the Loan Documents, including without limitation, any interest arising or accruing after the filing of a bankruptcy petition, whether allowed or disallowed, and all prepayment premiums, if any; (c) all principal, interest and other amounts which may hereafter be loaned by Grantee, its successors or assigns, to or for the benefit of Grantor, when evidenced by .a promissory note or other instrument which, by its terms, is governed or secured by any of the Loan Documents; (d) all other indebtedness, obligations, covenants, and liabilities now or hereafter existing of any kind of Grantor to Grantee, including without limitation, all indebtedness, obligations, covenants, and liabilities under any of the Loan Documents; and (e) all other indebtedness, obligations, covenants, and liabilities now or hereafter existing of any kind of Grantor to Grantee.”

““ Permitted Encumbrances ” means the outstanding liens, easements, restrictions, security interests, mechanics’ or materialmans’ liens and other exceptions to title set forth in that certain Loan Policy for title insurance issued by Old Republic National Title Insurance Company dated December 22, 2008 and identified as policy number LX 350856, and the endorsement thereto dated on or about June 18, 2009, none of which, Grantee hereby acknowledges, individually or in the aggregate, materially interferes with the benefits o