Document:

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                                                               Exhibit 10.43.1

         FIRST AMENDMENT TO PARADIGM GENETICS INC. WARRANT TO PURCHASE
         -------------------------------------------------------------
                            SHARES OF COMMMON STOCK
                            -----------------------

                            Void After July 27, 2009

     This FIRST AMENDMENT (the "First Amendment") to the Warrant to Purchase
Shares of Common Stock issued by PARADIGM GENETICS, INC., a DELAWARE corporation
(the "Company"), to ARE-104 ALEXANDER ROAD, LLC ("ARE"), (the "WARRANT"), is
dated April __, 2000.

                                  WITNESSETH:

     WHEREAS, the Company issued to ARE the WARRANT to purchase One Hundred
Fifty Thousand (150,000) shares of Common Stock on July 27, 1999;

     WHEREAS, the Company and ARE agree to amend the WARRANT in order to revise
certain provisions therein; and

     WHEREAS, the provisions of the WARRANT may be modified by the party against
which enforcement is sought and the signatory hereto constitute the requisite
party to approve the amendments contained herein.

     NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
set forth herein, and for other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties hereto, intending to
be legally bound, hereby amend the WARRANT and agree as follows:

     1.   The "Term" set forth specifically in Section 1.1 is hereby deleted and
               ----
replaced with the following:

     "1.1  Term.  The purchase right represented by this Warrant may be
           ----
exercised in whole or in part at any time and from time to time from and after
the date hereof and on or before the earlier of (i) July 27, 2009 (the tenth
anniversary of the date hereof) or (ii) the fifth anniversary of the date of the
consummation of a bona fide, underwritten initial public offering of Common
Stock, at a public offering price equal to or exceeding $6.00 per share (as
adjusted for any stock dividends, combinations, splits or the like with respect
to such shares) and an aggregate offering price to the public of not less than
$20,000,000; provided that, if the last day on which this Warrant may be
             --------
exercised is a Sunday or a legal holiday or a day on which banking institutions
doing business in the State of North Carolina are authorized by law to close,
this Warrant may be exercised
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prior to 5:00 p.m. local time) on the next succeeding full business day with the
same force and effect as if exercised on such last day specified herein."

     2.   The conditions of termination of rights to request registration as set
forth specifically in clause (iv) of subsection (h) of Section 15 is hereby
deleted and replaced with the following:

     "(iv) three years after the closing of a firm commitment underwritten
public offering pursuant to an effective registration statement under the
Securities Act covering the offer and sale of the Company's Common Stock at a
price per share of not less than $6.00 (as adjusted for stock splits, dividends,
combinations and the like) and an aggregate offering price to the public of not
less than $20,000,000.  Such three-year period shall not include any period of
time during which adequate current public information, as defined in Rule 144(c)
promulgated under the Securities Act, is not available with respect to the
Company."

     3.   This First Amendment shall be governed by and construed in accordance
with the laws of the State of Delaware, without giving effect to its conflicts
of law provisions.

     This First Amendment may be executed in multiple counterparts and shall be
and constitute the valid agreement of the parties executing the same with
respect to any one or more of the provisions of this First Amendment set forth
above at such time as this First Amendment has been executed by those parties
whose execution of this First Amendment is required to under the terms of the
WARRANT to make such provisions effective.

     Executed as of the date above written.

               [Remainder of this page intentionally left blank]
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COMPANY:
--------

PARADIGM GENETICS, INC.

By:
   -----------------------------

Name:
     ---------------------------

Title:
      --------------------------

WARRANTHOLDER:
--------------

ARE-104 ALEXANDER ROAD, LLC,
a Delaware limited liability company

By:  Alexander Real Estate Equities, L.P.,
     a Delaware limited partnership
     Its Managing Member

By:  ARE-QRS Corp.,
     a Maryland Corporation
     Its General Partner

By:
   -----------------------------

Name:
     ---------------------------

Title:
      --------------------------<PAGE>

                                                                 EXHIBIT 10.45.1

                   FIRST AMENDMENT TO PARADIGM GENETICS INC.
                   WARRANT TO PURCHASE SHARES OF COMMON STOCK

                           VOID AFTER JANUARY 19, 2010

     This FIRST AMENDMENT (the "First Amendment") to the Warrant to Purchase
Shares of Common Stock issued by PARADIGM GENETICS, INC., a DELAWARE corporation
(the "Company"), to ARE-104 ALEXANDER ROAD, LLC ("ARE") subject to the Escrow
Agreement entered into by the Company and ARE on January 19, 2000, (the
"WARRANT") is dated April __, 2000.

                                  WITNESSETH:

     WHEREAS, the Company issued to ARE the WARRANT to purchase Sixty Thousand
(60,000) shares of Common Stock subject to the Escrow Agreement entered into by
the Company and ARE on January 19, 2000;

     WHEREAS, the Company and ARE agree to amend the WARRANT in order to revise
certain provisions therein; and

     WHEREAS, the provisions of the WARRANT may be modified by the party against
which enforcement is sought and the signatory hereto constitute the requisite
party to approve the amendments contained herein.

     NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
set forth herein, and for other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties hereto, intending to
be legally bound, hereby amend the WARRANT and agree as follows:

          1. The "Term" set forth specifically in Section 1.1 is hereby deleted
     and replaced with the following:

               "1.1 Term. The purchase right represented by this Warrant may be
          exercised in whole or in part at any time and from time to time from
          and after the date hereof and on or before the earlier of (i) January
          19, 2010 (the tenth anniversary of the date hereof) or (ii) the fifth
          anniversary of the date of the consummation of a bona fide,
          underwritten initial public offering of Common Stock, at a public
          offering price equal to or exceeding $6.00 per share (as adjusted for
          any stock dividends, combinations, splits or the like with respect to
          such shares) and an aggregate offering price to the public of not less
          than $20,000,000; provided that, if the last day on which this Warrant
          may be exercised is a Sunday or a legal holiday or a day on which
          banking institutions doing business in the State of North Carolina are
          authorized by law to close, this Warrant may be exercised

<PAGE>

          prior to 5:00 p.m. local time) on the next succeeding full business
          day with the same force and effect as if exercised on such last day
          specified herein.

          2. The conditions of termination of rights to request registration as
     set forth specifically in clause (iv) of subsection (h) of Section 15 is
     hereby deleted and replaced with the following:

               "(iv) three years after the closing of a firm commitment
          underwritten public offering pursuant to an effective registration
          statement under the Securities Act covering the offer and sale of the
          Company's Common Stock at a price per share of not less than $6.00 (as
          adjusted for stock splits, dividends, combinations and the like) and
          an aggregate offering price to the public of not less than
          $20,000,000. Such three-year period shall not include any period of
          time during which adequate current public information, as defined in
          Rule 144(c) promulgated under the Securities Act, is not available
          with respect to the Company."

          3. This First Amendment shall be governed by and construed in
     accordance with the laws of the State of Delaware, without giving effect to
     its conflicts of law provisions.

     This First Amendment may be executed in multiple counterparts and shall be
and constitute the valid agreement of the parties executing the same with
respect to any one or more of the provisions of this First Amendment set forth
above at such time as this First Amendment has been executed by those parties
whose execution of this First Amendment is required to under the terms of the
WARRANT to make such provisions effective.

     Executed as of the date above written.

               [Remainder of this page intentionally left blank]

                                       2
<PAGE>

COMPANY:
--------

PARADIGM GENETICS, INC.

By: _____________________________
Name: __________________________
Title: ___________________________

WARRANTHOLDER:
--------------

ARE-104 ALEXANDER ROAD, LLC,
a Delaware limited liability company

By:  Alexander Real Estate Equities, L.P.,
     a Delaware limited partnership
     Its Managing Member

     By:  ARE-QRS Corp.,
          a Maryland Corporation
          Its General Partner

By: _____________________________
Name: __________________________
Title: ___________________________

                                       3<PAGE>

                                                                EXHIBIT 10.46.1

         FIRST AMENDMENT TO PARADIGM GENETICS INC. WARRANT TO PURCHASE
         -------------------------------------------------------------
                 SHARES OF SERIES A CONVERTIBLE PREFERRED STOCK
                 ----------------------------------------------

                           EXPIRES FEBRUARY 12, 2008

     This FIRST AMENDMENT (the "First Amendment") to the Warrant to Purchase
Shares of Series A Convertible Preferred Stock issued by PARADIGM GENETICS,
INC., a DELAWARE corporation (the "Company"), to INTERSOUTH PARTNERS III, L.P.
("Intersouth") on February 12, 1998, (the "WARRANT"), is dated April __, 2000.

                                  WITNESSETH:

     WHEREAS, the Company issued to Intersouth the WARRANT to purchase Thirty
One Thousand Two Hundred Fifty (31,250) shares of Series A Preferred Stock on
February 12, 1998;

     WHEREAS, the Company and Intersouth agree to amend the WARRANT in order to
revise certain provisions therein; and

     WHEREAS, the provisions of the WARRANT may be modified by the party against
which enforcement is sought and the signatory hereto constitute the requisite
party to approve the amendments contained herein.

     NOW, THEREFORE, in consideration of the foregoing and the mutual covenants
set forth herein, and for other good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties hereto, intending to
be legally bound, hereby amend the WARRANT and agree as follows:

     1.  The "Term" set forth specifically in Section 1 is hereby deleted and
               ----
replaced with the following:

"1.  Term.  The purchase right represented by this Warrant is exercisable, in
     ----
whole or in part, at any time and from time to time from and after the Grant
Date and prior to the earlier of the tenth annual anniversary date of the Grant
Date or the fifth annual anniversary of the consummation of the Company's
initial public of its Common Stock, at a public offering price equal to or
exceeding $6.00 per share (as adjusted for any stock dividends, combinations,
splits or the like with respect to such shares) and the aggregate gross proceeds
to the Company and/or any selling stockholders of which equal or exceed
$20,000,000."

     2.   This First Amendment shall be governed by and construed in accordance
with the laws of the State of Delaware, without giving effect to its conflicts
of law provisions.
<PAGE>

     This First Amendment may be executed in multiple counterparts and shall be
and constitute the valid agreement of the parties executing the same with
respect to any one or more of the provisions of this First Amendment set forth
above at such time as this First Amendment has been executed by those parties
whose execution of this First Amendment is required to under the terms of the
WARRANT to make such provisions effective.

     Executed as of the date above written.

               [Remainder of this page intentionally left blank]
<PAGE>

COMPANY:
--------

PARADIGM GENETICS, INC.

By:
   -----------------------------

Name:
     ---------------------------

Title:
      --------------------------

WARRANTHOLDER:
--------------

INTERSOUTH PARTNERS III, L.P.

By:
   -----------------------------

Name:
     ---------------------------

Title:
      --------------------------

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