<PAGE>

                                                                   EXHIBIT 10.20

 Amended and Restated Human Glucagon, Analogues of Human Glucagon, Analogs of
                        Human Insulin Letter Agreement

WHEREAS, ZGI, formerly an indirectly wholly owned subsidiary of NN, is engaged
generally in the research and development of biopharmaceutical products;

WHEREAS, NN and ZGI have settled NN's ongoing royalty obligation under this
Agreement for product known as NovoRapid(R), a human insulin analogue, pursuant
to a License Agreement having an effective date of September 28, 2000; and

WHEREAS, NN and ZGI wish to clarify the scope of this Agreement by deleting
analogues of human insulin therefrom;

NOW, THEREFORE, AS OF SEPTEMBER 28, 2000, THE PARTIES AGREE TO RESTATE THEIR
AGREEMENT AS FOLLOWS:

Pursuant to Section 6 of the Agreement dated August 6, 1982, between
ZymoGenetics, Inc. (formerly Zymos Corporation) and Novo Industri A/S (the
"Agreement") and with reference to our discussions at Novo on January 22, 1987,
we write to confirm the Agreement of ZymoGenetics, Inc. to the following terms
and conditions:

     1.  ZymoGenetics, Inc. ("ZYMO") hereby grants to Novo Industri A/S ("NOVO")
     a perpetual, exclusive, irrevocable, worldwide license (with the right to
     sublicense) to manufacture, have manufactured, use and sell Human Glucagon
     and Analogues of Human Glucagon through the use of Insulin Organisms,
     Technical Information and/or any Patents, the terms "Insulin Organisms",
     "Technical Information" and "Patents", having in this document the same
     meanings as in the Agreement.

     2.  In consideration of receiving the aforesaid license, NOVO shall make
     payments to ZYMO as set forth below:

         (a)  Definitions:

              (i)   "Participation Year" shall mean each successive twelve (12)
                    month period commencing on the date of the First Commercial
                    Sale;

              (ii)  "Net Sales" shall gross revenues to the NOVO Group from the
                    sale of Glucagon and/or Analogues of Glucagon produced
                    through the use of Insulin Organisms, Technical Information
                    and/or Patents under this license realized in each
                    participation Year less:

                       -  insurance and delivery charges paid or allowed by the
                       NOVO Group;

                       -  trade and cash discounts and commissions;

[ * ] designates portions of this document that have been omitted pursuant to a
request for confidential treatment filed separately with the Commission.
<PAGE>

                       -  returns, credits or allowances; and

                       -  sales and excise taxes, duties or other governmental
                       charges (other than taxes on the NOVO Group's profits).
                       Net sales shall not include sales between members of the
                       NOVO Group.

              (iii) "First Commercial Sale" shall mean with respect to Glucagon
                    or Analogues of Glucagon the first sale of each produced
                    through use of Insulin Organisms, Technical Information
                    and/or Patents under this license by a member of the NOVO
                    Group to any company not a member of the NOVO Group for
                    consideration in an arms-length transaction.

         (b)  Payments:

              An amount with respect to each Participation Year equal to [ * ]
              in aggregate Net Sales of Glucagon and Analogues of Glucagon,
              [ * ] Net Sales.

         (c)  Term:

              The obligation of NOVO to make such payments shall commence with
              respect to each country where Glucagon or Analogues of Glucagon
              are sold under this license on the date of the First Commercial
              Sales of such product and shall continue until December 31, 2000,
              or, subject to the terms of Section 7(b) of the Agreement, for the
              normal life of any Patents licensed in respect of each country,
              whether such normal life is shorter or longer.

         (d)  If NOVO enters into any sublicense, other than a sublicense to a
              member of the NOVO Group, pursuant to the provisions hereof, it
              shall pay to ZYMO [ * ] of the aggregate amount of any royalties
              received by NOVO in connection with such sublicense.

     3.  The provisions of Sections 1(a), (b), (d), (g), (h), (i) and (j), 7
     (except 7(d) and (g)), 10, 11, 12, 13, 14, 15, 16 and 17 of the Agreement
     are incorporated herein by reference and made a part hereof as if fully set
     out herein.  The provisions of Sections 7(m), (n) and (o) shall apply with
     equal force to Human Glucagon and Analogues of Human Glucagon.

[ * ] designates portions of this document that have been omitted pursuant to a
request for confidential treatment filed separately with the Commission.
<PAGE>

          IN WITNESS WHEREOF, NOVO and ZYMO have caused this amended and
restated Agreement to be executed in their names by their properly and duly
authorized officers or representatives.



Novo Nordisk A/S


/s/ Lars K. Sorensen                   /s/ ILLEGIBLE
----------------------------------     --------------------------------------
Lars Rebien Sorensen                   Mads Krogsgaard Thomsen
Corporate Executive Vice President     Corporate Vice President, Health Care
                                       Discovery and Pre-Clinical Development


ZymoGenetics, Inc.


/s/ Bruce L.A. Carter
---------------------
Bruce L.A. Carter
President & CEO

[ * ] designates portions of this document that have been omitted pursuant to a
request for confidential treatment filed separately with the Commission.