EXHIBIT 10.4



                             AMENDMENT TO WARRANT A3

      This Amendment (this "Amendment") is dated as of September 26, 2005 and
amends the Warrant numbered A3, dated as of March 31, 2005 (the "Warrant"),
issued by Emisphere Technologies Inc., a Delaware corporation (the "Company"),
to MHR Capital Partners (100) LP, a Delaware limited partnership ("MHR").

                                   WITNESSETH

      WHEREAS, the Company previously issued to MHR the Warrant to purchase
114,114 shares of common stock of the Company, $0.01 par value per share (the
"Common Stock"); and

      WHEREAS, the Company and MHR hereby wish to amend the terms of the Warrant
pursuant to Section 13(a) of the Warrant on the terms set forth herein.

      NOW, THEREFORE, in consideration of the foregoing premises and for other
good and valuable consideration, the sufficiency of which is hereby
acknowledged, the parties hereby agree as follows:

SECTION I

                            AMENDMENT TO THE WARRANT

      (a) Section 7(e)(i)(A)(1) of the Warrant is hereby amended in the
following manner:

            (i) inserting the phrase "in effect on or prior to September 26,
      2005 and" immediately after the phrase "stock option or stock purchase
      plans or agreements"; and

            (ii) inserting the phrase "and granted, sold or awarded in the
      ordinary course of business and consistent with past practice" after the
      phrase "approved by the Company's Board of Directors" and immediately
      prior to the semicolon.

      (b) Section 7(e)(i)(A)(2) of the Warrant is hereby deleted in its entirety
and replaced with the following:

      for an aggregate consideration (determined pursuant to Section 7(e)(v)
      hereof) of not more than $10,000,000 during any 24-month period;

      (c) Section 7(e)(iv) is hereby amended in the following manner:

            (i) by deleting the word "In" and adding a "(a) Subject to the last
      sentence of subsection (b) below, in ..." at the beginning of the first
      sentence;

            (ii) by deleting the phrase "Exercise Price in effect on the date of
      and" in the fourth line of the first sentence and replacing it with
      "closing price per Share of Common Stock as reported on a publicly traded
      exchange ("MARKET PRICE") on the last full trading day";



            (iii) by deleting the phrase "Exercise Price" in the tenth line of
      the first sentence and replacing it with "Market Price";

            (iv) by adding the following new subsection after the second
      paragraph of Section 7(e)(iv):

      (b) In the event the Company, at any time while this Warrant is
      outstanding, shall issue Additional Shares of Common Stock (including
      Additional Shares of Common Stock deemed to be issued pursuant to Section
      7(e)(iii)) with a purchase price, conversion price or exercise price,
      respectively, that is less than the Exercise Price in effect immediately
      prior to the time of such issuance or sale, then and in each such case the
      then-existing Exercise Price shall be reduced, as of the close of business
      on the effective date of such issuance or sale, to the lowest purchase
      price, conversion price or exercise price at which any Additional Shares
      of Common Stock were issued or sold. In the event that both subsections
      (iv)(a) and (iv)(b) hereof may apply to any issuance, sale or deemed
      issuance or sale, then only this section (b) shall be deemed to apply to
      such transaction.

      (d) Section 7(j) is hereby amended and replaced in its entirety by the
      following:

                  Notwithstanding anything to the contrary in this Section 7, in
      no event will this Warrant be exercisable for a number of Warrant Shares
      that would cause the Holder's beneficial ownership of the outstanding
      Common Stock, Convertible Securities or Options, together with any
      affiliates of the Holder, to exceed 19.9% of the sum of (a) the number of
      Warrant Shares and (b) the issued and outstanding shares of Common Stock
      of the Company prior to any such exercise. In the event any exercise of
      this Warrant would contravene this provision, the number of shares of
      Common Stock for which this Warrant would otherwise be exercisable shall
      automatically be reduced accordingly.

                                   SECTION II

                                  MISCELLANEOUS

      (a) Ratification. Except as expressly amended hereby, all of the
provisions of the Warrant shall otherwise remain in full force and effect to the
same extent as if fully set forth herein.

      (b) Separate Counterparts. This Amendment may be executed by the parties
hereto in separate counterparts, each of which when so executed and delivered
shall be an original, but all such counterparts shall constitute but one and the
same instrument.


                                       2

      IN WITNESS WHEREOF, the parties hereto have executed this Amendment as of
the day and year first above written.


                                    EMISPHERE TECHNOLOGIES, INC.


                                    By: /s/ Elliot M. Maza
                                        ----------------------------------------
                                        Name: Elliot M. Maza
                                        Title: Chief Financial Officer


                                    MHR CAPITAL PARTNERS (100) LP
                                    By:   MHR Advisors LLC, its general partner


                                         By:/s/ Hal Goldstein
                                            ------------------------------------
                                            Name:  Hal Goldstein
                                            Title: Authorized Signatory