Exhibit 10.29.1

OMNIBUS AMENDMENT REGARDING

NOTE AND WARRANT PURCHASE AGREEMENT

This OMNIBUS AMENDMENT (this “Amendment”) dated December 21, 2009 is entered
into by and between LFB Biotechnologies S.A.S. (the “Purchaser”) and GTC
Biotherapeutics, Inc. (the “Company”).

WHEREAS, in connection with the execution and delivery of that certain Note and
Warrant Purchase Agreement dated as of October 31, 2008 by and between the
Purchaser and the Company (the “Purchase Agreement”), the Company issued and
sold to the Purchaser a Secured Convertible Promissory Note dated December 22,
2008 in the original principal amount of Fifteen Million Dollars ($15,000,000)
(the “Note”);

WHEREAS, on the date hereof, the Company has issued an Amended and Restated
Secured Convertible Note, (as further amended or otherwise modified from time to
time, the “Amended Note”) that amends, restates, replaces and supersedes the
Note in its entirety; and

WHEREAS, for the avoidance of doubt, the Company and the Purchaser desire to
amend (i) the Purchase Agreement, (ii) that certain Amended and Restated
Security Agreement by and between the Purchaser and the Company dated June 18,
2009 and effective as of December 22, 2008 with respect to certain matters,
(iii) that certain Common Stock Purchase Warrant executed by the Company dated
December 22, 2008, (iv) that certain Patent and License Security Agreement by
and between the Purchaser and the Company dated December 22, 2008, (v) that
certain Trademark and License Security Agreement by and between the Purchaser
and the Company dated December 22, 2008, (vi) that certain Second Mortgage,
Security Agreement and Fixture Filing executed by the Company dated December 22,
2008, as amended by that certain Amendment to Mortgage, Security Agreement and
Fixture Filing dated as of June 18, 2009 and (vii) any other documents and
agreements related to the Purchase Agreement, each as amended or otherwise
modified from time to time (collectively the “Transaction Documents”) such that
each reference to the Note contained in each of the Transaction Documents is
deemed to refer to the Amended Note; and

NOW, THEREFORE, in consideration for the mutual covenants contained herein and
for other good and valuable consideration, the receipt and sufficiency of which
are hereby acknowledged, the parties hereto agree as follows:

1. Amendment. Every reference contained in each of the Transaction Documents to
the “Note”, the “Promissory Note”, the “Convertible Note” or the “2008
Convertible Note”, as applicable and as the context shall so require, shall be
deemed to be a reference to the Amended Note.

2. Counterparts. This Amendment may be executed in any number of counterparts by
original or facsimile signature, each such counterpart shall be an original
instrument, and all such counterparts together shall constitute one and the same
agreement.

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IN WITNESS WHEREOF, the undersigned hereby executes this Omnibus Amendment as of
the date first set forth above.

 

COMPANY: GTC BIOTHERAPEUTICS, INC. By:   /s/ John B. Green Title: John B. Green,
Senior Vice President, Treasurer and Chief Financial Officer PURCHASER: LFB
BIOTECHNOLOGIES S.A.S. By:   /s/ Christian Béchon Christian Béchon President

Signature Page to Omnibus Amendment

(Note and Warrant Purchase Agreement)