Document:

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                                                                   EXHIBIT 10.16

                               LICENSE AGREEMENT

     This Agreement is made as of February 23 , 1989, by and between
ZymoGenetics, Inc., a Washington corporation ("ZymoGenetics"), and the
University of Washington, a public institution of higher education
("University"), with respect to the following:

     A.  University and ZymoGenetics have collaborated and are continuing to
collaborate with respect to the cloning and expression of DNA sequences encoding
Factor XIII and portions thereof pursuant to that certain Research Agreement
dated August 1986, as amended and extended (the "Research Agreement").

     B.  Pursuant to the Research Agreement, title to all inventions and
discoveries arising out of the research undertaken pursuant thereto (the
"Inventions") vest in University, ZymoGenetics or jointly in University and
ZymoGenetics depending upon the good faith determination of the parties as to
the inventive contribution.

     C.  University and ZymoGenetics have filed joint United States and foreign
patent applications on certain Inventions (including U.S. Patent Application
Serial Nos. 909,512 and 174,287 and foreign equivalents pending in Australia,
Canada, Denmark, the European Patent Office and Japan) which disclose and claim
DNA sequences coding for Factor XIII and portions thereof, expression vectors,
plasmids comprising DNA sequences encoding Factor XIII and portions thereof,
mammalian cells transfected to produce Factor XIII and portions thereof, methods
of making Factor XIII and portions thereof, as well as the recombinant proteins
and pharmaceutical compositions containing the proteins, and which are included
herein as part of the Licensed Patent Rights (as defined below).

     D.  University desires to grant, and ZymoGenetics desires to obtain, the
exclusive license, with the right to sublicense, to all Inventions to which
ZymoGenetics does not, or will not, have sole title pursuant to the Research
Agreement.

     NOW, THEREFORE, in consideration of the mutual covenants and premises
herein contained, the parties hereby agree as follows:

     1.  Definitions.  As used herein, the following terms shall have the
         -----------
meanings set forth below:

[ * ] designates portions of this document that have been omitted pursuant to a
request for confidential treatment filed separately with the Commission.
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          1.1  "Improvements" shall mean any modifications, alterations,
enhancements or improvements to the Inventions, whether developed pursuant to
the Research Agreement or separately.

          1.2  "Licensed Patent Rights" shall mean University's rights in and to
the Inventions and Improvements covered at any time by United States or foreign
patents or patent applications and all divisions, continuations, continuations-
in-part, reissues, reexaminations or extensions thereof, and any letters patent
that issue thereon.

          1.3  "Licensed Products" shall mean materials (including organisms)
the manufacture, use or sale of which would, in the absence of this license,
infringe one or more claims of Licensed Patent Rights.

          1.4  "Net Royalties" shall mean royalty payments, advances on
royalties or license fees actually received by ZymoGenetics with respect to any
sublicense of any of its rights hereunder, less any taxes withheld at the source
and any third party royalties.

          1.5  "Net Sales" shall mean the gross proceeds actually received by
ZymoGenetics pursuant to sales of the Licensed Product by ZymoGenetics, less
sales and/or use taxes paid, import and/or export duties paid, outbound
transportation, insurance, wholesaler and cash discounts, returns and allowances
granted, and third party royalties.

     2.  Grant.  University hereby grants to ZymoGenetics a worldwide, exclusive
         -----
license (with the right to sublicense) to practice the Licensed Patent Rights
and to make, have made, use and sell Licensed Products under Licensed Patent
Rights.  However, University shall have the right to exercise the Licensed
Patent Rights solely for its own non-commercial research purposes.  The license
granted herein shall include any Improvements made by or on behalf of University
or made jointly by University and ZymoGenetics during the term of this
Agreement, and University agrees to promptly provide ZymoGenetics with access to
such Improvements and full disclosure thereof.  Title to any Improvements made
by or on behalf of ZymoGenetics shall be and remain in ZymoGenetics.

     3.  Royalties.
         ---------

          3.1  In consideration of the rights granted herein, ZymoGenetics shall
pay to University the following royalties:

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

                                      -2-
<PAGE>

               3.1.1  [ * ] Royalties received by ZymoGenetics from any
sublicensee.

               3.1.2  [ * ] of Net Sales of Licensed Products when sold in bulk
to third parties for incorporation into a finished product or when the Licensed
Product is not the primary active ingredient in the final product sold by
ZymoGenetics.

               3.1.3  [ * ] of Net Sales of Licensed Products in all other
cases.

          3.2  ZymoGenetics shall not pay more than one royalty to University
for each Licensed Product sold or sublicense granted, regardless of the number
of Inventions or Improvements included in the Licensed Product or sublicense.

          3.3  The royalties payable under this Agreement shall be due and
payable thirty (30) days after the end of each calendar quarter for all
royalties earned during the preceding calendar quarter.  A written statement
shall be submitted quarterly with each royalty payment showing the calculation
of royalties due and payable.

          3.4  All monies due to University hereunder shall be paid by
ZymoGenetics in United States dollars. Computation of the amount of currency
equivalent to United States dollars due to University shall be made at the rate
of exchange in effect at Chase Manhattan Bank on the last business day of the
quarter in which the royalty was earned.

          3.5  ZymoGenetics shall keep complete, true and accurate records for
the purpose of showing the derivation of all amounts payable to University under
this Agreement.  ZymoGenetics shall maintain such records for a period of at
least three (3) years following the end of the calendar year to which they
pertain, and University or its representatives shall have the right to inspect
such records no more often than annually, at University's expense during
ZymoGenetics' regular business hours, for the purpose of verifying ZymoGenetics'
royalty statement. ZymoGenetics shall have the right to specify that any such
representative be a Certified Public Accountant.

     4.  Term and Termination.
         --------------------

          4.1  The term of this Agreement shall extend from the date hereof
until expiration of the last to expire of the Licensed Patent Rights.  Royalty
obligations shall terminate with respect to any sales of Licensed Products or
any sublicense of Licensed Patent Rights in a particular jurisdiction upon the
expiration in such jurisdiction of the last Licensed Patent Right incorporated
into such Licensed Product or covered in such sublicense, or when such last
Licensed Patent Right is held to be

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

                                      -3-
<PAGE>

invalid or the application therefor is denied in such jurisdiction, and no
appeal can be, or has been, taken from such decision.

          4.2  Except as otherwise provided in Section 4.3, upon any material
breach of, or default under, this Agreement by ZymoGenetics, University may
terminate this Agreement by ninety (90) days' written notice to ZymoGenetics.
Said notice shall become effective at the end of such period unless during said
period ZymoGenetics shall cure such defect or default.

          4.3  University shall not have the right to terminate this Agreement
for any purported breach which is the subject of a bona fide good faith dispute
between the parties.

          4.4  ZymoGenetics shall have the right to terminate this Agreement at
any time upon ninety (90) days' written notice to University.

     5.  Representations, Warranties and Indemnities.
         -------------------------------------------

          5.1  University represents and warrants that:

               5.1.1  To the best of its knowledge (which for the purposes of
this Agreement shall mean to the best knowledge of any of University's faculty
or research personnel directly involved in the research relating to any of the
Inventions or Improvements or of any of University's administrative staff or
counsel), the Inventions and Improvements covered by the Licensed Patent Rights
were made and developed without the use of, or infringement upon, the secrets,
patents or other proprietary rights or interests of any third party and without
the use of any equipment, supplies or facilities of any third party and that it
has the full right and authority to lawfully grant the license granted herein.

               5.1.2  The obligations of University under this Agreement are not
subject to prior commitments and obligations to any third party.

               5.1.3  It has not entered into any contract, agreement,
partnership, joint venture or other arrangement, whether oral or written, with
any third party relating to the Inventions, Licensed Products or Licensed
Patents.

          5.2  Nothing in this Agreement shall be construed as:

               5.2.1  A warranty or representation by University as to the
validity or scope of any Licensed Patents.

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

                                      -4-
<PAGE>

               5.2.2  An obligation to bring or prosecute actions or suits
against third parties for infringement.

               5.2.3  A warranty, representation or undertaking with respect to
utility, efficacy, nontoxicity, safety or appropriateness of using the
Inventions or the Licensed Products, except that University represents and
warrants that it has fully disclosed, and will fully disclose, to ZymoGenetics
all data and information in its possession, knowledge or control relating to the
utility, efficacy, nontoxicity, safety and appropriateness of the Inventions or
the Licensed Products.

          5.3  ZymoGenetics agrees to indemnify and hold University harmless
from any and all liability arising out of ZymoGenetics' development,
manufacture, use or sale of the Licensed Product unless such liability results
from information not disclosed in breach of Section 5.2.3. and except for
liability covered by the University's indemnification pursuant to Section 5.4

          5.4  University agrees to indemnify and hold ZymoGenetics harmless
from and against any and all liability arising out of any breach by University
of its representations and warranties under this Agreement and, to the extent of
the total royalties payable by ZymoGenetics to University under this Agreement,
against any loss, damage, liability and expense arising out of or related to any
claim that any portion of the Inventions, Improvements or Licensed Products
attributable to University's contribution thereto infringes upon or makes
improper use of any patent, copyright, trade secret or other proprietary right
or interest of any third party.

          5.5  ZymoGenetics shall be entitled to a set off against royalties for
any loss, damage, liability and expense that it incurs with respect to any claim
covered by the University's indemnification pursuant to Section 5.4.

          5.6  ZymoGenetics understands that the Inventions and Improvements may
be, or have been, developed under funding agreements with the Government of the
United States of America (the "U.S."), and, if so, that the U.S. may have
certain rights relative thereto.  This Agreement is explicitly made subject to
the U.S.'s rights under any such agreement and any applicable law or regulation.

     6.   Infringement by Others.
          ----------------------

          6.1  ZymoGenetics and University shall promptly inform each other of
any suspected infringement of any Licensed Patent Rights by a third party, and
University and ZymoGenetics each shall have the right to institute an action for
infringement of the Licensed Patent Rights against such third party in
accordance with the following:

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

                                      -5-
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               6.1.1  If, within sixty (60) days after written request therefor
by either party hereto, University and ZymoGenetics both give written notice to
the other party of their intention to institute suit, the suit shall be brought
jointly in both their names and all costs thereof shall be borne equally.
ZymoGenetics shall exercise control over such action, provided, however, that
University may, if it so desires, be represented by counsel of its own
selection, the fees for which counsel shall be paid by University. Recoveries,
if any, whether by judgment, award, decree or settlement, shall, after the
reimbursement of each of University and ZymoGenetics for its costs in such
action, be shared as follows:

          (i)  Any portion of such net recoveries which constitutes the
          equivalent of, or damages or payments in lieu of, Net Royalties which
          would have been received by ZymoGenetics had the infringing party been
          operating under a sublicense shall be shared between ZymoGenetics and
          University in accordance with Section 3.1.1 as if it were Net
          Royalties received by ZymoGenetics for the sublicensing of Licensed
          Patent Rights; and

          (ii) Any remaining portion of such net recoveries shall be shared
          between ZymoGenetics and University equally.

               6.1.2  If, within the sixty (60) day period described above, only
one (1) of the parties has given written notice of its intention to institute
suit, it may at any time within one (1) year from the last day of such sixty
(60) day period institute suit in its own name, and may join the other party as
a plaintiff. All costs of the suit shall be borne by the party who has
instituted such suit, and recoveries, if any, whether by judgment, award, decree
or settlement, shall belong solely to such party. If no suit is brought within
such one (1) year period, then the right to institute suit reverts to both of
the parties and the procedure described in Section 6.1.1 shall apply thereto.

               6.1.3  If, within the sixty (60) day period described above,
neither party has given written notice of an intention to institute suit, then
the right to institute suit reverts to both of the parties and the procedure
described in Section 6.1.1 shall apply thereto.

          6.2  Should either University or ZymoGenetics commence a suit under
the provisions of this Section and thereafter elect to abandon the same, it
shall give timely notice to the other party, who may, if it so desires, continue
prosecution of such suit, provided, however, that the sharing of expenses and
any recovery in such suit shall be as agreed upon between University and
ZymoGenetics.

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

                                      -6-
<PAGE>

     7.   Obligations of ZymoGenetics.
          ---------------------------

          7.1  ZymoGenetics shall have the sole right to prosecute any patent
applications covered by the Licensed Patent Rights and to maintain the Licensed
Patent Rights.  ZymoGenetics shall have the right to apply for patents (in its
name, in the University's name, or in both names, in accordance with the terms
of the Research Agreement) to Inventions and Improvements not already covered by
the Licensed Patent Rights, and the University's rights, if any, in and to such
applications, and to any patents that issue thereon, shall then be included in
the Licensed Patent Rights.  ZymoGenetics will promptly provide University with
copies of all patent applications and any amendments or correspondence with the
United States Patent Office and foreign patent offices relating thereto.
ZymoGenetics has to date borne, and shall continue to bear, all expenses of the
patent filing, prosecution and maintenance activities undertaken by it.
ZymoGenetics shall, at University's request and at University's expense, permit
University to participate in any proceedings to which ZymoGenetics may be a
party relating to any Licensed Patent Rights.

          7.2  If at any time during the term of this Agreement ZymoGenetics
elects to abandon any issued patent or pending patent application included
within the Licensed Patent Rights, it shall notify University of that decision
at least sixty (60) days prior to any deadline for the filing of any response or
the taking of any other action necessary to maintain such patent or patent
application in existence.  Thereafter, University shall have the right to take
over the sole and exclusive responsibility for the maintenance of such patent or
the prosecution of such patent application, at University's sole expense.

          7.3  ZymoGenetics shall report to University in writing at least once
per year, during the month of January, with respect to the progress made toward
the development and promotion of the manufacture and sale of the Licensed
Products.  ZymoGenetics shall provide one additional such report on an interim
basis during any such year, if University requests that it do so in a written
request given at least thirty (30) days prior to the requested date of such
interim report.

          7.4  ZymoGenetics shall at all times during the term of this Agreement
use commercially reasonable efforts to develop and to promote the manufacture
and sale of the Licensed Products.  If at any time the University believes that
ZymoGenetics is not using such efforts, University may notify ZymoGenetics
thereof in writing, which notice must specify in reasonable detail the reasons
why University believes ZymoGenetics is not in compliance with this Section.  If
ZymoGenetics and University are, after good faith discussions over a period of
at least ninety (90) days, unable to resolve any material disagreement over the
level of effort

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

                                      -7-
<PAGE>

required to be made, or actually being made, by ZymoGenetics hereunder, either
party may demand that the disagreement be settled by binding arbitration as
provided herein for disputes between the parties; provided, however, that
University's SOLE REMEDY for any failure by ZymoGenetics to comply with this
Section (if and as determined in such arbitration) shall be to convert the
license herein to a non-exclusive license, whereupon the royalties payable
hereunder shall be the amounts set forth in Section 3 [ * ].

     8.  Use of Names, Trade Names and Trademarks.  Except as provided herein,
         ----------------------------------------
nothing contained in this Agreement shall be construed as conferring any right
on either party to use in advertising, publicity or other promotional activities
any name, trade name, trademark or other designation of the other party hereto,
including any contraction, abbreviation or simulation of any of the foregoing,
unless the express written permission of such other party has been obtained.

     9.  Disputes.  Any dispute between the parties hereunder which cannot be
         --------
resolved by good faith negotiation between the parties over a period of at least
ninety (90) days shall be resolved by arbitration under the then current rules
and procedures of the American Arbitration Association (the "AAA"), or other
rules and procedures as the parties may agree.  Each party shall bear its own
costs incurred in connection with such arbitration, and the fees, expenses and
costs of the AAA, the arbitrator(s) and the arbitration proceeding not incurred
solely by one party shall be divided equally between the parties.  The arbitral
award shall be binding and conclusive on both parties and may be enforced in any
court of competent jurisdiction.

     10. Miscellaneous.
         -------------

          10.1  Headings are included for convenience of reference only and
shall not limit or affect the parties' agreement or constitute terms hereof.
The use herein of pronouns of any gender shall include all other genders, as
appropriate.

          10.2  Neither party shall be in default by reason of failure in its
performance under this Agreement if such failure is due to causes beyond such
party's reasonable control and is without the fault or negligence of such party.

          10.3  This Agreement shall be governed by the laws of the State of
Washington.

          10.4  This Agreement is the complete and exclusive statement of the
agreement between the parties and supersedes any or all prior or contemporaneous
oral or written communications with respect to the subject matter hereof.  Each
party has read and reviewed this Agreement and intends to be bound by its terms,
which

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

                                      -8-
<PAGE>

shall be construed without regard to which of the parties may have drafted any
such terms.

          10.5  No modification, waiver, or amendment hereof shall be binding
unless stated in a writing signed by the parties thereto, and no waiver of a
right hereunder in any instance shall constitute a waiver of the same or any
other right in any other instance.

          10.6  If any provision of this Agreement shall be held to be invalid,
illegal or unenforceable, such provision shall be enforced to the maximum extent
permitted by law and the parties' fundamental intentions hereunder, and the
remaining provisions shall not be affected.

          10.7  Notices and payments under this Agreement shall be sufficiently
given if delivered in person or sent by telecopier, first class prepaid mail, or
reputable courier service to the respective addresses stated on the signature
page of this Agreement (or to such other address as a party may by notice
specify for notices to it), and shall be effective upon the earlier of actual
delivery or the third day after mailing.

          10.8  Neither party may assign or transfer this Agreement or its
rights or responsibilities hereunder without the prior written consent of the
other party, provided, however, that ZymoGenetics and its permitted assigns may
without such consent assign all of ZymoGenetics' rights and responsibilities
hereunder to any successor to or acquirer of all or substantially all of the
assets and business operations of ZymoGenetics.  Subject to the foregoing
limitation, this Agreement shall be binding upon and inure to the benefit of the
parties hereto and their successors and assigns.

          10.9  No employment, agency, trust, partnership or joint venture is
created by, or shall be founded upon, this Agreement.

     IN WITNESS WHEREOF, the parties have caused this Agreement to be executed
by their duly authorized officers as of the date first written above.

UNIVERSITY OF WASHINGTON                   ZYMOGENETICS, INC.

Address:  Graduate School, AG-10           Address:  4225 Roosevelt Way N.E.
          -----------------------------              --------------------------
          Seattle, WA  98195                         Seattle, WA  98105
          -----------------------------              --------------------------
Attn:     Donald R. Baldwin                Attn:     Dr. Bruce L.A. Carter
          -----------------------------              --------------------------
Telecopier:  (206) 633-2981                Telecopier: (206) 548-2329
             --------------------------                ------------------------

BY: /s/ D R Baldwin                        BY: /s/ Bruce L.A. Carter
   ------------------------------------       ---------------------------------
TITLE:  Director of Technology Transfer       TITLE:  President
        -------------------------------               -------------------------

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

                                      -9-<PAGE>

                                                                   EXHIBIT 10.17

                               LICENSE AGREEMENT

This Agreement is made and entered into on this 18th day of January, 1994,
between

          NOVO NORDISK A/S, with its place of business at Novo Alle, DK-2880
          Bagsvaerd, Denmark, and

          ZYMOGENETICS INC., with its place of business at 4225 Roosevelt Way
          NE, Seattle, Washington 98105, USA

          (hereinafter collectively called NOVO NORDISK)

and       JOHNSON & JOHNSON, with its place of business at One Johnson & Johnson
          Plaza, New Brunswick, N.J. 08933, USA, (hereinafter called JOHNSON &
          JOHNSON),

and       CHIRON CORPORATION, with its place of business at 4560 Horton Street,
          Emeryville, California 94608, USA, (hereinafter call CHIRON)

                                  WITNESSETH:

WHEREAS,  NOVO NORDISK is the owner of certain Patent Rights concerning platelet
          derived growth factor ("PDGF"), its manufacture and use as a wound
          healing agent, and

WHEREAS,  JOHNSON & JOHNSON and CHIRON desire to obtain a license under such
          Patent Rights,

NOW THEREFORE, the parties agree as follows:

1    DEFINITIONS

     1.1  The term "Patent Rights", shall mean all the patents and the patent
          applications owned, controlled or licensed to NOVO NORDISK concerning
          PDGF, a partial listing of which is identified in Exhibit I attached
                                                            ---------
          hereto, any patents maturing from the said applications and their
          parents, and any divisions, continuations, continuation in parts,
          reissues, reexaminations, renewals, or extensions thereof.

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

     1.2  The term "Licensed Product" shall mean any PDGF (including A chain or
          B chain polypeptide, monomers or dimers thereof, or fragments,
          modifications or derivatives thereof) containing agent for human use
          to accelerate healing of soft tissue wounds, excluding ophthalmic
          wounds, but including surgical incision healing unless used as a
          component in a tissue glue, biologically derived for use in
          controlling intense bleeding in surgery, the manufacture, use or sale
          of which is covered by at least one valid and granted claim of Patent
          Rights.

     1.3  The term "Affiliate" shall mean a legal entity which owns or controls,
          is owned or controlled by or is under common ownership or control with
          a party to this Agreement. Ownership for purposes of this paragraph
          shall mean ownership of at least 50% of the equity ownership to direct
          or cause the direction of the management and policies of such legal
          entity.

     1.4  The term "Net Proceeds of Sales" shall mean JOHNSON & JOHNSON's and
          CHIRON's and/or their Affiliates' gross proceeds of sales to
          independent third parties of Licensed Product less

          a)   Trade, cash and/or quantity discounts allowed, if any;

          b)   Commission and discounts which are in the nature of refunds,
               rebates or allowances, which effectively reduce the selling
               price;

          c)   Actual returns and allowances;

          d)   Credits, if any, to customers on account of retroactive price
               reductions;

          e)   Value added taxes and sales taxes;

          f)   Duties; and

          g)   Freight charges paid for delivery.

          Sales of Licensed Product between JOHNSON & JOHNSON or CHIRON and an
          Affiliate of JOHNSON & JOHNSON or CHIRON, and between Affiliates of
          JOHNSON & JOHNSON or CHIRON are not to be included within the Net
          Proceeds of Sales.

          In the event of commercial use of Licensed Product by JOHNSON &
          JOHNSON or CHIRON and/or an Affiliate of JOHNSON & JOHNSON or CHIRON,
          the Net Proceeds of Sales

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

                                      -2-
<PAGE>

          thereof shall be the comparable selling price of JOHNSON & JOHNSON or
          CHIRON and/or Affiliate of JOHNSON & JOHNSON or CHIRON to independent
          third parties for such Licensed Product so used.

          If, in a market, JOHNSON & JOHNSON or CHIRON (or its Affiliates) sells
          all or part of its sales to the trade through a marketing/business
          partner, the royalty to be paid on such sales shall be calculated on
          the basis of the price invoiced by such marketing/business partner
          when selling to independent third parties. Should such invoice price
          not be identifiable, the royalty shall instead be based on JOHNSON &
          JOHNSON's or CHIRON's average selling price in the same market or, if
          JOHNSON & JOHNSON or CHIRON is not present in the relevant market, by
          the average selling price obtainable in that market.

          In the event that Licensed Product is sold in the form of a
          combination product containing one or more growth factors, other than
          the Licensed Product, Net Proceeds of Sales for such combination
          product will be calculated by multiplying actual net Proceeds of Sales
          of such combination product by the fraction A/(A+B) where A is the
          invoice price of the Licensed Product if sold separately, and B is the
          total invoice price of any other growth factor in the combination, if
          sold separately by JOHNSON & JOHNSON or CHIRON or an Affiliate.

          In no event will the royalty to be paid on a combination product be
          less than [ * ] of the running royalty payments payable to NOVO
          NORDISK on the Net Proceeds of Sales, if calculated for the entire
          combination product.

     1.5  The term "First Commercial Sale" shall mean the first sale or disposal
          of a Licensed Product for a value in an arm's length transaction
          following approval by the appropriate regulatory agency for the sale
          of Licensed Product to the public.

2    LICENSING OF PATENT RIGHTS

     2.1  NOVO NORDISK grants to JOHNSON & JOHNSON and CHIRON a worldwide
          exclusive right and license under Patent Rights to make, have made,
          use or sell Licensed Product during the term of this Agreement.

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

                                      -3-
<PAGE>

     2.2  Subject to such agreement as may exist between JOHNSON & JOHNSON and
          CHIRON from time to time, each of JOHNSON & JOHNSON and CHIRON has the
          right to sublicense their Affiliates to make, use or sell Licensed
          Product -or a marketing/business partner as mentioned in Clause 1.4 to
          sell Licensed Product - provided JOHNSON & JOHNSON and CHIRON will
          separately guarantee payment to NOVO NORDISK of royalties under this
          Agreement for their own sublicenses.

     2.3  It is presently contemplated that CHIRON will manufacture PDGF for
          JOHNSON & JOHNSON for use in Licensed Product under this Agreement. If
          CHIRON products PDGF, CHIRON will supply NOVO NORDISK with PDGF for
          NOVO NORDISK's requirements for development and manufacture of PDGF
          products outside Licensed Product on reasonable terms to be agreed
          upon between CHIRON and NOVO NORDISK. Failure of CHIRON and NOVO
          NORDISK to agree on such reasonable terms will not constitute a breach
          of this Agreement or in any way jeopardize JOHNSON & JOHNSON's rights
          under this Agreement.

          JOHNSON & JOHNSON and CHIRON can have the Licensed Product made or
          manufactured for it by another third party contract manufacturer,
          provided that prior to contracting for such third party manufacture,
          JOHNSON & JOHNSON and CHIRON will notify NOVO NORDISK in advance of
          the chosen contract manufacturer for the purpose of approval by NOVO
          NORDISK, which may only be withheld for reasonable cause.

     2.4  In the event that JOHNSON & JOHNSON and CHIRON determine that the
          commercialization of Licensed Product for the treatment of diabetic
          ulcers is best achieved through a co-promotion arrangement with NOVO
          NORDISK, JOHNSON & JOHNSON, CHIRON and NOVO NORDISK will consider the
          utilization of the NOVO NORDISK sales and marketing organization via
          separately negotiated co-promotion agreements on the basis of fair
          compensation to each party.

3    ROYALTIES AND PAYMENT

     3.1  In consideration of all the rights and licenses granted hereunder,
          JOHNSON & JOHNSON and CHIRON shall jointly pay to NOVO NORDISK

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

                                      -4-
<PAGE>

     3.1.1.  a license fee of [ * ] payable within 30 (thirty) days after
             signature of this Agreement, which amount shall be non-refundable
             and non-creditable.

     3.1.2.  a further license fee of [ * ], payable at the earliest of (i)
             within 30 (thirty) days after the filing of a Product License
             Application ("PLA") for Licensed Product with the U.S. Food and
             Drug Administration, the filing of a similar application with the
             CPMP in Europe, or the filing of a similar application in either of
             the countries France, Germany, UK, Japan, or (ii) December 31,
             1996. [ * ] shall be creditable against any future running
             royalties.

     3.1.3.  a running royalty payable on a country by country basis on all
             Licensed Products sold by JOHNSON & JOHNSON and CHIRON, its
             Affiliates - or a marketing/business partner as mentioned in Clause
             1.4 - at a rate of [ * ]% of Net Proceeds of Sales of Licensed
             Product. JOHNSON & JOHNSON and CHIRON shall jointly pay this
             running royalty quarterly within sixty (60) days after the end of
             each calendar quarter.

             JOHNSON & JOHNSON and CHIRON shall diligently pursue the
             development, registration and product introduction into the market
             and minimum royalties shall be payable after the earliest of (i)
             the first twelve (12) months of sales of Licensed Product after the
             First Commercial Sale or (ii) January 1st 1998 according to the
             following schedule:

              Year 1                          [ * ]
              Year 2                          [ * ]
              Year 3-6                        [ * ]

             In any year in which running royalties are less than the applicable
             minimum royalty under this paragraph, then JOHNSON & JOHNSON and
             CHIRON shall, within sixty (60) days after such year, pay to NOVO
             NORDISK a sum equal to [ * ].

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

                                      -5-
<PAGE>

     3.2  JOHNSON & JOHNSON and CHIRON shall make all payments hereunder after
          deducting or withholding all taxes as required by the laws of Denmark
          or laws of any other country in which an Affiliate of JOHNSON &
          JOHNSON or CHIRON is selling Licensed Product; and shall furnish NOVO
          NORDISK as soon as practicable with proper evidence as to the payment
          of such taxes.

     3.3  JOHNSON & JOHNSON and CHIRON shall make all payments to NOVO NORDISK
          under this Agreement in USD calculated on the rate of exchange quoted
          by Reuter's at the end of the quarter for which payment is due and
          such payment is made and shall make all payments by telegraphic
          transfer to a bank account designated by NOVO NORDISK. If the transfer
          or the conversion into USD equivalents in any country is not lawful or
          possible, the payment as is necessary shall be made by the deposit
          thereof, in the currency of the country where the sales were made on
          which the royalty was based to the credit and account of NOVO NORDISK
          or its nominees in any commercial bank or trust company of its choice
          located in that country, notice of which shall be given to NOVO
          NORDISK by JOHNSON & JOHNSON and CHIRON.

     3.4  JOHNSON & JOHNSON and CHIRON shall pay only one royalty under this
          Agreement for Net Proceeds of Sale of each Licensed Product,
          regardless of the number of claims, patents or patent applications
          applicable hereto.

4    LICENSES, PERMITS ETC.

     4.1  JOHNSON & JOHNSON and CHIRON shall obtain and maintain at its sole
          expense all clearances, permits, licenses, authorizations, and
          registrations required by any nation, country, sovereignty,
          commonwealth, possession, territory, state, county, parish,
          municipality, local or similar government entity which are necessary
          to manufacture, use and/or sell Licensed Product.

5    RECORD KEEPING, PAYMENT AND REPORTS

     5.1  JOHNSON & JOHNSON and CHIRON shall keep, and cause its Affiliates and
          as far as possible its marketing/business partners as mentioned in
          Clause 1.4 to keep, complete and correct records concerning Net
          Proceeds of Sales of Licensed Product. JOHNSON &

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

                                      -6-
<PAGE>

          JOHNSON and CHIRON shall be obliged to keep such records for three (3)
          years after the making of a royalty payment as provided in Article 3.

     5.2  JOHNSON & JOHNSON and CHIRON shall within sixty (60) days after the
          end of each calendar quarter after the First Commercial Sale send to
          NOVO NORDISK a written statement, certified by a responsible
          representative of JOHNSON & JOHNSON and CHIRON, showing Net Proceeds
          of Sales. Such statements shall be accompanied by a payment of the
          total amount of royalty then due. After the First Commercial Sale,
          JOHNSON & JOHNSON and CHIRON shall render a statement even if no
          royalty is due.

     5.3  Upon NOVO NORDISK's request, JOHNSON & JOHNSON and CHIRON shall
          provide to NOVO NORDISK a statement from JOHNSON & JOHNSON's and
          CHIRON's outside auditors certifying the correctness of JOHNSON &
          JOHNSON's and CHIRON's royalty payments. The statement shall be
          provided at NOVO NORDISK's request and expense, no more than once in a
          calendar year.

     5.4  JOHNSON & JOHNSON and CHIRON shall grant NOVO NORDISK the right to
          have an independent certified public accountant to whom JOHNSON &
          JOHNSON and CHIRON has no reasonable objection with access, during
          ordinary business hours to such records of JOHNSON & JOHNSON, CHIRON
          and their Affiliates as provided for in Section 5.1 in order to verify
          the accuracy of royalty payments made or payable hereunder. Such
          access shall be granted at NOVO NORDISK's request and expense, but no
          more than once in a calendar year. Such accountant shall be under
          confidentiality obligations to JOHNSON & JOHNSON and CHIRON to
          disclose to NOVO NORDISK only the amount of royalties payable and the
          accuracy of the royalty payments made hereunder.

6    TERM

     6.1  Unless terminated according to Section 7 below, this Agreement shall
          become effective on the day and year first written above and shall
          continue to be in full force and effect on a country-by-country basis
          until the expiration date of the last of Patent Rights to expire in
          each such country.

     6.2  Upon expiry of the Patent Rights in a country JOHNSON & JOHNSON and
          CHIRON shall have the fully paid up license regarding such Patent

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

                                      -7-
<PAGE>

          Rights, provided JOHNSON & JOHNSON and CHIRON pays all royalties
          accrued in relation to Licensed Products manufactured and/or sold in
          that country before expiry of the Patent Rights.

7    TERMINATION

     7.1  JOHNSON & JOHNSON and CHIRON may terminate this Agreement at any time
          by providing NOVO NORDISK with sixty (60) days' advance notice. In
          such case no refund of payments made according Article 3 shall take
          place.

     7.2  If JOHNSON & JOHNSON and CHIRON or NOVO NORDISK at any time materially
          defaults i) in rendering any of the reports required under, ii) or
          making the payment of any money due hereunder, iii) or in fulfilling
          any of the other obligations or conditions hereunder, the other party
          may in its sole discretion waive the default; if not electing to waive
          the default, the other party shall notify the defaulting party in
          writing of the default and allow the defaulting party sixty (60) days
          from such notification to correct the default. If at the end of said
          sixty (60) days the default remains uncorrected, the aggrieved party
          may terminate this Agreement and also any licenses granted thereunder
          by giving written notice of termination to the defaulting party.

     7.3  JOHNSON & JOHNSON and CHIRON or NOVO NORDISK, in addition to any other
          remedies available to it in law or equity, may terminate this
          Agreement by written notice to the other party in the event the other
          party shall:

          a)   become insolvent or bankrupt;

          b)   make an assignment for the benefit of its creditors;

          c)   appoint a trustee or receiver for itself for all or a substantial
               part of its property;

          d)   have any case of proceeding commenced or other action taken by or
               against itself in bankruptcy;

          e)   seek reorganization, liquidation, dissolution, a winding-up
               arrangement, composition or readjustment of its debts;

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

                                      -8-
<PAGE>

          f)   seek any other relief under any bankruptcy, insolvency,
               reorganization or other similar act or law of any jurisdiction,
               now or hereafter in effect; or

          g)   have issued against itself a warrant of attachment, execution,
               distraint or similar process against any substantial part of its
               property of the other party.

     7.4  Upon termination of this Agreement for any reason, except for the
          expiration of the term of this Agreement, all rights and licenses
          granted to JOHNSON & JOHNSON, CHIRON and their Affiliates hereunder
          shall automatically terminate and revert to NOVO NORDISK. JOHNSON &
          JOHNSON and CHIRON shall immediately discontinue and cause their
          Affiliates to immediately discontinue any further use of Patent
          Rights; and shall forthwith cease and desist from manufacturing,
          having manufactured, using or selling Licensed Product under the
          Patent Rights, except that each - for a period of 1 year after the
          effective date of the termination - shall have the right to sell off
          any existing inventory, subject to the royalty provisions herein.

8    LITIGATION

     8.1  NOVO NORDISK agrees to notify JOHNSON & JOHNSON and CHIRON in writing
          if the validity, infringement, or priority of invention of any Patent
          Rights is made an issue by any person not a party hereto. JOHNSON &
          JOHNSON and CHIRON agree to notify NOVO NORDISK in writing if any
          dispute with a third party or parties arises out of or in relation to
          or in connection with the manufacture, use and/or sale of Licensed
          Product by JOHNSON & JOHNSON, CHIRON and/or their Affiliates.

     8.2  In the event that there is infringement on a substantial commercial
          scale by a third party of any patent licensed to JOHNSON & JOHNSON and
          CHIRON hereunder, JOHNSON & JOHNSON and/or CHIRON shall notify NOVO
          NORDISK in writing to that effect, including with said written notice
          evidence establishing a prima facie case of infringement by such third
          party. If, prior to the expiration of 120 days from the date of said
          notice, NOVO NORDISK obtains a discontinuance of such infringement or
          brings suit against the third party infringer, then the obligation of
          JOHNSON & JOHNSON and CHIRON to pay royalties under such licensed
          patent shall continue unabated. NOVO NORDISK

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

                                      -9-
<PAGE>

          shall bear all the expenses of any suit brought by it and shall retain
          all damages or other monies awarded or received in settlement of such
          suit. JOHNSON & JOHNSON and CHIRON will cooperate with NOVO NORDISK in
          any such suit and shall have the right to be represented by their own
          counsel at their own expense.

          If, after the expiration of said 120 days from the date of said
          notice, NOVO NORDISK has not overcome the prima facie case of
          infringement, obtained a discontinuance of such infringement, or
          brought suit against the third party infringer, then JOHNSON & JOHNSON
          and CHIRON shall be relieved of all obligation to make payment of
          further royalties hereunder until such time as either the third party
          infringement has ceased or suit for infringement has been filed by
          NOVO NORDISK. In addition, JOHNSON & JOHNSON and/or CHIRON shall have
          the right after such 120 day notice period, but not the obligation, to
          bring suit against such infringer and join NOVO NORDISK as a party
          plaintiff, provided that JOHNSON & JOHNSON and/or CHIRON shall bear
          all the expenses of such suit. NOVO NORDISK will cooperate with
          JOHNSON & JOHNSON and/or CHIRON in any suit for infringement of a
          licensed patent brought by JOHNSON & JOHNSON and/or CHIRON against a
          third party, and shall have the right to consult with JOHNSON &
          JOHNSON and/or CHIRON and to participate in and be represented by
          independent counsel in such litigation at its own expense. JOHNSON &
          JOHNSON and/or CHIRON shall incur no liability to NOVO NORDISK as a
          consequence of such litigation or any unfavorable decision resulting
          therefrom, including any decision holding NOVO NORDISK's patent
          invalid or unenforceable.

          Royalties which are based solely on the infringed licensed patent
          which accrue during the pendency of any suit for infringement brought
          by JOHNSON & JOHNSON and/or CHIRON shall be held in escrow by JOHNSON
          & JOHNSON and/or CHIRON until a final decision is rendered by a court
          of competent jurisdiction from which appeal can be or is taken. In the
          event the patent under which such royalties are payable is held to be
          invalid, the accrued royalty shall be retained by JOHNSON & JOHNSON
          and/or CHIRON. In the event the validity of the patent is upheld, the
          accrued royalty shall be paid to NOVO

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

                                     -10-
<PAGE>

               NORDISK, and any damages or other monies awarded or received in
               settlement of such suit shall be retained by JOHNSON & JOHNSON
               and/or CHIRON in satisfaction of its litigation expenses. If the
               amount awarded exceeds such litigation expenses, the remaining
               amount shall firstly be used for reimbursing NOVO NORDISK its
               litigation expenses, if any. If the amount awarded further
               exceeds NOVO NORDISK's litigation expenses, the remainder shall
               be made payable to JOHNSON & JOHNSON and/or CHIRON.

9     PATENT RIGHTS

      9.1      NOVO NORDISK shall, at its expense, make its best efforts to
               obtain and maintain the Patent Rights.

      9.2      In the event that any patent or any claim thereof included in the
               Patent Rights shall be held invalid or unenforceable in any
               country by a court of competent jurisdiction and last resort, or
               by an inferior tribunal from which no appeal has or can be taken,
               such invalid or unenforceable patent or claim in such country
               shall be excluded from the definition of the Patent Rights.

10    INDEMNIFICATION

      10.1     JOHNSON & JOHNSON and CHIRON shall indemnify and hold NOVO
               NORDISK harmless from and against any and all claims, judgments,
               costs, awards, expenses (including, but not limited to, any
               attorney's fees) or liability of any kind arising out of injury
               to a third party caused or alleged to be caused by the Licensed
               Product. In addition, JOHNSON & JOHNSON and CHIRON hereby assume
               all obligations for warranties that accompany the sale Licensed
               Product; and indemnifies and holds NOVO NORDISK harmless from and
               against any and all claims, judgments, costs, awards, expenses
               (including, but not limited to, any attorney's fees) or liability
               of any kind arising from such customers, relating to such
               warranty obligations.

11    CONFIDENTIALITY

      11.1     Subject to applicable law, the existence and contents of this
               Agreement and the activities hereunder shall be kept strictly
               secret by the parties unless otherwise agreed in writing by the
               parties, except that each party

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

                                      -11-
<PAGE>

               may disclose the contents of this Agreement to its Affiliates and
               sublicensees.

12    NOTICES

      12.1     All notices required or provided for use in this Agreement shall
               be in writing and shall be given by certified mail prepaid,
               facsimile transmission or telex and properly addressed to the
               address of the party to be served as shown below. Unless
               otherwise provided for in this Agreement, notice shall be
               effective seven (7) days after mailing or transmission. When a
               facsimile transmission or telex is used, a confirmation letter
               shall be dispatched thereafter. Reports under Secti on 5.2 shall
               not be considered notices.

               If to NOVO NORDISK:         NOVO NORDISK A/S
                                           Novo Alle
                                           DK-2880 Bagsvaerd
                                           Denmark
                                           Att.: President, Health Care
                                                   Group

               with a copy to:             Legal Department
                                           NOVO NORDISK A/S
                                           Novo Alle
                                           DK-2880 Bagsvaerd
                                           Denmark

               If to JOHNSON & JOHNSON:    JOHNSON & JOHNSON
                                           One Johnson & Johnson Plaza,
                                           New Brunswick,
                                           N.J. 08933,  USA
                                           Att.: Peter T. Tattle

               with a copy to:             Chief Patent Counsel
                                           JOHNSON & JOHNSON
                                           One Johnson & Johnson Plaza,
                                           New Brunswick,
                                           N.J.  08933,  USA

               If to CHIRON:               CHIRON CORPORATION
                                           4560 Horton Street
                                           Emeryville
                                           California 94608,  USA
                                           Att.: General Counsel

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

                                      -12-
<PAGE>

13    FORCE MAJEURE

      13.1  Each of the parties hereto shall be excused from the performance of
            its obligations and shall not be liable for damages to the other in
            the event that such performance is prevented by circumstances beyond
            its effective control. Such excuse from performance shall continue
            so long as the condition responsible for such excuse continues and
            for a thirty (30) day period thereafter.

            For the purposes of this Agreement, circumstances beyond the control
            of the party which excuse that party from performance shall include,
            but shall not be limited to, acts of God, acts, regulations or laws
            of war, civil commotion, destruction of facility or materials by
            fire, earthquake, storm or other casualty, labour disturbances,
            epidemic and failure of public utilities or common carrier.

14    WARRANTIES AND REPRESENTATIONS

      14.1  NOVO NORDISK expressly warrants and represents that it owns all of
            the rights, title and interest in and to the Patent Rights and that
            it has the full right and authority to grant the rights granted to
            JOHNSON & JOHNSON and CHIRON hereunder.

      14.2  NOVO NORDISK expressly warrants and represents that it has no
            outstanding encumbrances or agreements, either written, oral or
            implied, in connection with the Licensed Product, and that it has
            not granted and will not grant during the term of this Agreement or
            any renewal thereof, any similar rights, license, consent or
            privilege with respect to the rights granted herein.

      14.3  NOVO NORDISK expressly warrants and represents that during the term
            of this Agreement it will not commercialize any Licensed Product.

15    MISCELLANEOUS

      15.1  This Agreement shall be construed in accordance with English law. In
            the event of any controversy or claim arising out of or in relation
            to or in connection with any provision of this Agreement, including
            breach

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

                                      -13-
<PAGE>

            hereof, the parties hereto shall try to settle the problem amicably
            between themselves. Should the parties hereto fail to agree, the
            matter in dispute may be finally settled by arbitration in London,
            in accordance with the arbitration rules of the International
            Chamber of Commerce, unless otherwise can be agreed to by the
            parties. In the event that the parties hereto cannot agree to final
            settlement by arbitration, the dispute shall be referred to the
            court of London, England.

      15.2  Each party hereto agrees that it does not intend to violate any
            public policy, statutory or common laws:

            However, if any sentence, paragraph, clause or combination of the
            same is in violation of any state or federal law or is found to be
            otherwise unenforceable by a court from which there is no appeal, or
            no appeal is taken, such sentences, paragraphs, clauses or
            combinations of the same shall be deleted and the remainder of this
            Agreement shall remain binding.

            Furthermore, in lieu of each such illegal, invalid or unenforceable
            sentences, paragraphs, clauses or combinations of the same there
            shall be added after consultation between the parties hereto as part
            of this Agreement sentences, paragraphs, clauses, or combinations
            which are as similar in terms to such illegal, invalid, or
            unenforceable sentences, paragraphs, clauses, or combinations of the
            same as may be possible and be legal, valid, and enforceable.

      15.3  This Agreement and the covenants herein contained shall be binding
            and inure to the benefit of the parties hereto and their heirs,
            assigns, successors and legal representatives. This Agreement shall
            not be assignable by either party without the other party's prior
            written consent.

      15.4  This Agreement constitutes the entire understanding between the
            parties with respect to the subject matter hereof and shall
            supersede all previous communications, representations,
            understandings and agreements, either oral or written, between the
            parties with respect to the subject matter of this Agreement;
            amendments or modifications of this Agreement may be made only by a
            written instrument executed by all of the parties hereto.

      15.5  The paragraph headings contained herein are for reference only; they
            are not a part of this Agreement nor shall they in any way affect
            the interpretation thereof.

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

                                      -14-
<PAGE>

      15.6  The express or implied waiver by a party of a breach of any
            provision of this Agreement shall not constitute a continuing waiver
            of other breaches of the same or other provisions of this Agreement.

IN WITNESS WHEREOF, the parties hereto have affixed their authorized signatures
as of the date first above written.

New Jersey, 1994 - 2/19 -                    Bagsvaerd, 1994 - 01-19
JOHNSON & JOHNSON                            NOVO NORDISK A/S

/s/ PETER S. TATTLE                          /s/ ERIK SORENSEN
--------------------------------------       -----------------------------------
By: Peter T. Tattle                          By:  Erik Sorensen

Emeryville, CA 1994-    -                    Seattle, 1994- 01-19
CHIRON CORPORATION                           ZYMOGENETICS INC.

/s/ ILLEGIBLE                                /s/ BRUCE CARTER
--------------------------------------       -----------------------------------
By:                                          By: Bruce Carter

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

                                      -15-
<PAGE>

                                   EXHIBIT I

                          Existing Patent List - PDGF
                            As of January 11, 1994

ISSUED PATENTS:
--------------

Country                        Patent Number                 Date of Issue

[*]

PENDING APPLICATIONS:
--------------------

Country                        Serial Number                 Filing Date

[*]

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

               First Amendment to the License Agreement between
               ------------------------------------------------
            NOVO NORDISK A/S, ZYMOGENETICS INC., JONSON & JOHNSON,
            ------------------------------------------------------
                    and CHIRON CORP. dated 18 January 1994
                    --------------------------------------

     THIS FIRST AMENDMENT is made this    1st    day of January, 1997, by and
                                       ---------
between:

NOVO NORDISK A/S with its place of business at Novo Alle, DK-2880 Bagsvaerd,
Denmark, and ZYMOGENETICS INC., with its place of business at 4225 Roosevelt Way
NE, Seattle, Washington 98105 U.S.A. (hereinafter collectively referred to as
"NOVO NORDISK"); and

JOHNSON & JOHNSON with its place of business at One Johnson & Johnson Plaza, New
Brunswick, New Jersey 08933 U.S.A. (hereinafter referred to as "JOHNSON &
JOHNSON"); and

CHIRON CORPORATION, with its place of business at 4560 Horton Street,
Emeryville, California 94608 U.S.A. (hereinafter referred to as "CHIRON").

NOVO NORDISK, JOHNSON & JOHNSON, AND CHIRON are collectively referred to below
as "THE PARTIES".

                                  WITNESSETH:

     WHEREAS, THE PARTIES wish to amend in certain respects the License
Agreement between them dated as of the 18th day of January 1994, a copy of which
is attached hereto (hereinafter referred to as "THE AGREEMENT").

     NOW, THEREFORE, in consideration of the mutual covenants and provisions set
forth herein, THE PARTIES agree as follows:

     1.)   In Article 3.1.3 of THE AGREEMENT the first paragraph of Article
3.1.3 is deleted in its entirety, and is replaced by the following new
paragraph:

     "a running royalty payable on a country by country basis on all Licensed
Products sold by JOHNSON & JOHNSON and CHIRON, its Affiliates - or a
marketing/business partner as mentioned in Clause 1.4 - at the following rate
schedule:

     i)    a [*] royalty on the annual Net Proceeds of Sales up to and including
[*];

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

                                      -2-
<PAGE>

     ii)   a [*] royalty on the annual Net Proceeds of Sales over [*] up to
and including [*]; and
     iii) an [*] royalty on the annual Net Proceeds of Sales over [*].

     For example, if the annual Net Proceeds of Sales is [*] then the royalty
would be[*]; [*]; and [*]. JOHNSON & JOHNSON and CHIRON shall jointly pay this
running royalty on annual Net Proceeds of Sales quarterly within sixty (60) days
after the end of each calendar quarter."

     IN WITNESS WHEREOF, THE PARTIES have executed this First Amendment to be
effective as of the date written above.

NOVO NORDISK A/S                            JOHNSON & JOHNSON

By: /s/ Bruce Carter                        By: /s/ Peter T. Tattle
    -----------------------------------         --------------------------------

Name: Bruce Carter                          Name: Peter T. Tattle
      ---------------------------------           ------------------------------

Title: Chief Scientific Officer             Title: Company Group Chairman
       --------------------------------            -----------------------------

Date: 1 May 97                              Date:
      ---------------------------------           ------------------------------

ZYMOGENETICS INC.                           CHIRON CORPORATION

By: /s/ Claus Kuhl                          By: /s/ Edward E. Penhoet
    -----------------------------------         --------------------------------

Name: Claus Kuhl                            Name: Edward E. Penhoet
      ---------------------------------           -----------------------------

Title: President                            Title: CEO
       --------------------------------            -----------------------------

Date: 5/1/97                                Date: 5/9/97
      ---------------------------------           -----------------------------

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

                                      -3-
<PAGE>

               Second Amendment to the License Agreement between
               -------------------------------------------------
            NOVO NORDISK A/S, ZYMOGENETICS, INC., JOHNSON & JOHNSON
            -------------------------------------------------------
                     and CHIRON CORP. dated 18 January 1994
                     --------------------------------------

     THIS SECOND AMENDMENT is made this 5th day of June, 2000, by and between:

NOVO NORDISK A/S, with its place of business at Novo Alle, DK-2880, Bagsvaerd,
Denmark (hereinafter referred to as "NOVO NORDISK"); and

ZYMOGENETICS, INC., with its place of business at 1201 Eastlake Avenue East,
Seattle, Washington 98102 U.S.A (hereinafter referred to as "ZYMOGENETICS); and

JOHNSON & JOHNSON, with its place of business at One Johnson & Johnson Plaza,
New Brunswick, New Jersey 08933 U.S.A. (hereinafter referred to as "JOHNSON &
JOHNSON"); and

CHIRON CORPORATION, with its place of business at 4560 Horton Street,
Emeryville, California 94608 U.S.A. (hereinafter referred to as "CHIRON").

NOVO NORDISK, ZYMOGENETICS JOHNSON & JOHNSON and CHIRON are collectively
referred to below as "THE PARTIES".

                                  WITNESSETH:

     WHEREAS, ZYMOGENETICS has been presented with an opportunity to pursue
commercialization of platelet-derived growth factor (PDGF) in the fields of
periodontal disease and cranio-maxillofacial osseous defects; and

     WHEREAS, THE PARTIES wish to amend in certain respects THE AGREEMENT.

     NOW, THEREFORE, in consideration of the mutual covenants and provisions set
forth herein, THE PARTIES agree as follows:

     In Article 1.2 of THE AGREEMENT the paragraph is deleted in its entirety,
and is replaced by the following new paragraph:

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

     "The term "Licensed Product" shall mean any PDGF (including A chain or B
chain polypeptide, monomers or dimers thereof, or fragments, modifications or
derivatives thereof) containing agent for human use to accelerate healing of
soft tissue wounds, excluding ophthalmic wounds and the treatment or diagnosis
of periodontal disease and/or the repair, restoration and reconstruction of
cranio-maxillofacial osseous defects, but including surgical incision healing
unless used as a component in a tissue glue, biologically derived for use in
controlling intense bleeding in surgery, in the manufacture, use or sale of
which is covered by at least one valid and granted claim of Patent Rights."

     The remainder of THE AGREEMENT remains unchanged.

     IN WITNESS WHEREOF, THE PARTIES have executed this SECOND AMENDMENT to be
effective as of the date written above.

NOVO NORDISK A/S                              JOHNSON & JOHNSON

By: /s/ BRUCE CARTER                          By: /s/ PETER T. TATTLE
    ---------------------------------             ------------------------------

Name: Bruce Carter                            Name: Peter T. Tattle
      -------------------------------               ----------------------------

Title: CSO                                    Title: C.G.C.
       ------------------------------                ---------------------------

Date: 7 June 00                               Date: 6/20/00
      -------------------------------               ----------------------------

ZYMOGENETICS                                  CHIRON CORPORATION

By: /s/ BRUCE CARTER                          By: /s/ PHILLIP MOODY
    ---------------------------------             -----------------------------

Name: Bruce Carter                            Name: Philip Moody
      -------------------------------               ----------------------------

Title: CEO                                    Title: Vice President, Finance &
       ------------------------------                ---------------------------
                                                     Operations
                                                     ---------------------------
Date: 7 June 00                                      Chiron BioPharmaceuticals
      -------------------------------                ---------------------------
                                              Date: 7/11/00
                                                    ----------------------------

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

                                      -2-

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