EXHIBIT 4.1
                                                                     -----------

                                 AMENDMENT NO. 1
                             DATED NOVEMBER 14, 2000
                                     TO THE
                      AMENDED AND RESTATED RIGHTS AGREEMENT
                                     BETWEEN
                            NEOSE TECHNOLOGIES, INC.
                                       AND
                    AMERICAN STOCK TRANSFER AND TRUST COMPANY

         THIS AMENDMENT NO. 1, dated November 14, 2000, to the AMENDED AND
RESTATED RIGHTS AGREEMENT between NEOSE TECHNOLOGIES, INC. and AMERICAN STOCK
TRANSFER AND TRUST COMPANY dated as of DECEMBER 3, 1998.

         WHEREAS, Neose Technologies, Inc. ("Neose") and American Stock Transfer
and Trust Company ("ASTT") entered into a Rights Agreement, dated as of December
3, 1998 (the "Agreement") dealing with, among other things, certain rights of
the holders of Neose Common Stock; and

         WHEREAS, Neose has entered into an agreement with LeRoy C. Kopp, Kopp
Investment Advisors, Inc. and Kopp Holding Company (collectively, "Kopp") dated
November 14, 2000 (the "Letter Agreement") under which the Company, in exchange
for other consideration, has agreed to permit Kopp not to become an "Acquiring
Person", as defined under the Agreement, subject to the terms and conditions of
the Agreement and the Letter Agreement; and

         WHEREAS, to implement the requirements of the Letter Agreement, Neose
and ASTT, pursuant to Section 26 of the Agreement, have agreed to amend the
Agreement as set forth herein.

         NOW THEREFORE, the parties intending to be legally bound, agree as
follows:

         1. Representations and Warranties. The Company represents and warrants
to the Rights Agent that:


             (a)  to the best knowledge of the Company, a Distribution Date has
                  not occurred prior to the effective date hereof, and

             (b)  this Amendment is authorized pursuant to the requirements of
                  Section 26 of the Agreement, having been approved by the
                  Company's Directors.




         2. Amendment of Section 1(a). The definition of "Acquiring Person" set
forth in Section 1, paragraph (a) of the Rights Agreement, is amended by adding
a new clause at the end of the definition reading as follows:

                  ; and provided, however, that Kopp Investment Advisors, Inc.,
                  a Minnesota corporation, on its own behalf and on behalf of
                  LeRoy C. Kopp, Kopp Emerging Growth Fund, and Kopp Holding
                  Company, joint filers of a Schedule 13G (and collectively
                  referred to herein as "Kopp") shall not be an Acquiring Person
                  unless and until Kopp (i) is the Beneficial Owner of 20% or
                  more of the shares of Common Stock then outstanding, or (ii)
                  is the Beneficial Owner of 15% or more of the shares of Common
                  Stock then outstanding and is not permitted to file a Schedule
                  13G, in lieu of Schedule 13D, pursuant to the Securities
                  Exchange Act of 1934 and the rules and regulations promulgated
                  thereunder.

         3. No Other Changes. Except as specifically amended by this Amendment,
all other provisions of the Agreement remain in full force and effect. This
Amendment shall not constitute or operate as a waiver of, or estoppel with
respect to, any provisions of the Agreement by any party hereto. Capitalized
terms used and not otherwise defined herein will have the meanings ascribed
thereto in the Agreement.

         4. Counterparts. This Amendment may be executed in one or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same agreement.

         IN WITNESS WHEREOF, the parties have caused this Amendment No. 1 to be
duly executed, all as of the date first written above.

                                 NEOSE TECHNOLOGIES INC.



                                 By: /s/ P. Sherrill Neff
                                     -------------------------
                                       P. Sherrill Neff
                                       President and Chief Operating Officer

                                 AMERICAN STOCK TRANSFER AND
                                 TRUST COMPANY



                                 By: /s/ Herbert J. Lemmer
                                     ------------------------
                                       Herbert J. Lemmer
                                       Vice President


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