AMENDMENT NO. 1 TO LICENSE AGREEMENT FOR RECOMBINANT FACTOR XIII

“[ * ]” = omitted, confidential material, which material has been separately filed with the Securities and Exchange Commission pursuant to a request for confidential treatment.

Exhibit 10.46

AMENDMENT NO. 1 TO

LICENSE AGREEMENT FOR RECOMBINANT FACTOR XIII

THIS AMENDMENT NO. 1 TO LICENSE AGREEMENT FOR RECOMBINANT FACTOR XIII (“Amendment No. 1”) is entered into as of December 7, 2007 (“Effective Date”) by and among ZymoGenetics, Inc., a Washington corporation whose address is 1201 Eastlake Ave. East, Seattle, WA 98102 (“ZGEN”), Novo Nordisk A/S, a Danish corporation whose address is Novo Allé, DK-2880, Bagsvaerd, Denmark (“Novo”), and Novo Nordisk Health Care AG, a Swiss corporation and wholly-owned affiliate of Novo whose address is Andreasstrasse 15, 8050 Zürich, Switzerland (“NN”). ZGEN and NN are sometimes referred to herein individually as a “Party” and collectively as the “Parties”.

BACKGROUND

A. The Parties and Novo are parties to the License Agreement for Recombinant Factor XIII, effective as of October 4, 2004 (the “Agreement”).

B. Novo has expended significant effort and made significant progress toward improving the manufacturing process and developing a new formulation.

C. The Parties and Novo desire to amend the Agreement to, among other things, revise the time-based milestone schedule and incorporate additional milestones.

AGREEMENT

NOW, THEREFORE, the Parties and Novo agree as follows:

Terms used with initial capital letters and not otherwise defined in this Amendment No. 1 shall have the meanings given to them in the Agreement.

Certain milestone fees shall be amended as set forth in this Section 2.

(a) The first two rows below the headings in the table in Section 4.2(a) of the Agreement (i.e., rows relating to milestone fees of $[  *  ] and $[  *  ] respectively) shall be deleted in their entirety.

(b) The new table in Section 4.2(a) of the Agreement shall be as follows:

(a) The second row below the headings in the table in Section 4.2(b) of the Agreement (i.e., row relating to a milestone fee of $[  *  ]) shall be deleted in its entirety.

(b) The dates “[  *  ]” and “[  *  ]” in the fourth column (headed “Time Milestone (subject to Section 4.2(e)”) of the table in Section 4.2(b) of the Agreement shall be deleted in their entirety and replaced in each case with “[ * ]”.

(c) The milestone fee “$[  *  ]” in the first column (headed “Milestone Fee”) of the table in Section 4.2(b) of the Agreement shall be deleted in its entirety and replaced with “$[  *  ]”.

(d) The milestone fee “$[  *  ]” (for First Marketing Approval for a Factor XIII Product or Combination Product) in the second column (headed “Milestone Fee if Licensed Product for Congenital Factor XIII Deficiency Not Developed Due to Section 3.2(b)(*)”) of the table in Section 4.2(b) of the Agreement shall be deleted in its entirety and replaced with “$[  *  ]”.

(e) The new table in Section 4.2(b) of the Agreement shall be as follows:

(a) The first two rows below the headings in the table in Section 4.2(c) of the Agreement (i.e., rows relating to milestone fees of $[  *  ] and $[  *  ] respectively) shall be deleted in their entirety.

(b) The dates “[  *  ]” and “[  *  ]” in the fourth column (headed “Time Milestone (subject to Section 4.2(e)”) of the table in Section 4.2(c) of the Agreement shall be deleted in their entirety and replaced in each case with “[  *  ]”.

(c) The milestone fee “$[  *  ]” (for the First Marketing Approval for a Factor XIII Product or Combination Product) in the first column (headed “Milestone Fee”) of the table in Section 4.2(c) of the Agreement shall be deleted in its entirety and replaced with “$[  *  ]”.

(d) The milestone fee “$[  *  ]” (for First Marketing Approval for a Factor XIII Product or Combination Product) in the second column (headed “Milestone Fee if Licensed Product for Congenital Factor XIII Deficiency Not Developed Due to Section 3.2(b)(*)”) of the table in Section 4.2(b) of the Agreement shall be deleted in its entirety and replaced with “$[  *  ]”.

(e) The new table in Section 4.2(c) of the Agreement shall be as follows: