Document:

<PAGE>

                                                                   Exhibit 10.43
                                                                   -------------

                                AMENDMENT NO. 7

                                      To

                            SHAREHOLDERS' AGREEMENT
                            -----------------------
                                      OF
                              KIRIN-AMGEN, INC.,

          THIS AMENDMENT NO. 7 ("Amendment No. 7") TO THAT CERTAIN SHAREHOLDERS'
AGREEMENT OF KIRIN-AMGEN, INC., dated May 11, 1984, as previously amended
("Shareholders' Agreement"), is made and entered into this 17th day of July,
1987, and is made effective as of April 1, 1987, by and among KIRIN BREWERY,
CO., LTD., a Japanese corporation ("Kirin"), AMGEN INC., a Delaware corporation
("Amgen"), and KIRIN-AMGEN, INC., a California corporation ("Corporation").

                                 R E C I T A L

          The parties desire to memorialize their intent to make changes to
certain agreements and understandings previously entered into regarding the
payment of EPO and G-CSF clinical and non-clinical expenses.

          From and after April 1, 1987, Kirin and Amgen (and not Corporation)
shall each pay one-half (1/2) of the total clinical expenses incurred for EPO
and G-CSF for Japan and the United States.

2.        NON-CLINICAL EXPENSES

          Corporation has requested that Kirin arrange and guarantee a credit
facility with Mitsubishi Bank, Ltd. to pay for non-clinical expenses incurred by
Corporation for EPO and G-CSF. Corporation is hereby authorized and directed to
take such steps as are reasonable and necessary to assist in arranging the
credit facility, including but not limited to, the issuance of the letter to
Kirin attached hereto as Exhibit "A" requesting it to arrange the credit
facility for Corporation and to guarantee the same. Corporation shall also
present to the Board of Directors the credit facility loan documentation for
formal approval.

3.        Except to the extent as provided herein, the provisions of the
Shareholders' Agreement, as amended, are hereby ratified and confirmed in all
respects.
<PAGE>

          IN WITNESS WHEREOF, the undersigned have caused this Amendment No. 7
to be executed as of the first day written above.

                                        KIRIN BREWERY CO., LTD., a Japanese
                                        corporation

                                        By /s/ Y. Yamamoto
                                           Yashushi Yamamoto
                                          Senior Managing Director

                                                            "Kirin"

                                        AMGEN INC.,
                                        a Delaware corporation

                                        By /s/ George B. Rathman
                                        George B. Rathmann, President

                                                            "Amgen"

                                        KIRIN-AMGEN, INC., a
                                        California corporation

                                        By /s/ Y. Yamamoto
                                        Yashushi Yamamoto, Chairman

                                                            "Corporation"

                                      -2-<PAGE>

                                                                   Exhibit 10.44
                                                                   -------------

                                AMENDMENT NO. 8
                                       TO
                            SHAREHOLDERS' AGREEMENT
                                       OF
                               KIRIN-AMGEN, INC.

          THIS AMENDMENT NO. 8 TO SHAREHOLDERS' AGREEMENT OF KIRIN-AMGEN, INC.,
a Delaware corporation ("K-A") ("Amendment No. 8"), dated May 28, 1993, and made
effective as of November 13, 1990, is made and entered into by and among KIRIN
BREWERY, CO., LTD., a Japanese corporation ("Kirin"), AMGEN INC., a Delaware
corporation ("Amgen"), and K-A.

                                   RECITALS
                                   --------

          A.   The parties hereto are parties to that certain Shareholders'
Agreement of K-A dated May 11, 1984, as amended ("Shareholders' Agreement").

          B.   The parties hereto have entered into various agreements with each
other and third parties with respect to the glycoprotein molecule consisting of
the amino acid sequence of granulocyte-colony stimulating factor or "G-CSF," as
such agreements are more particularly described below.

          C.   The parties have benefitted from their relationship with respect
to G-CSF and desire to adopt this Amendment No. 8 to clarify their agreements
and understandings with respect to G-CSF and the payment of royalties on the
commercial sale of G-CSF products ("G-CSF Products") throughout the world.

          D.   Pursuant to that certain Agreement by and between Sloan-Kettering
Institute for Cancer Research ("SKI") and Amgen dated February 12, 1986, as
amended ("SKI Agreement"), K-A is defined as an affiliate of Amgen thereunder.

          NOW, THEREFORE, in consideration of the mutual covenants set forth
herein and for other good and valuable consideration, the receipt of which is
hereby acknowledged, the parties hereby agree as follows:

1.   Royalties for G-CSF Product Sales in the United States.
     ------------------------------------------------------

          a.   Acknowledgements. The parties hereto acknowledge the
               ----------------
following:
<PAGE>

               (1)  Pursuant to that certain G-CSF United States License
Agreement dated June 1, 1987, by and between K-A and Amgen, as amended ("G-CSF
United States License Agreement"), Amgen is obligated to pay to K-A royalties on
the Sales Value (as defined therein) of G-CSF Products in the United States
equal to between zero percent (0%) and five percent (5%).

               (2)  Pursuant to that certain Agreement dated February 12, 1986,
by and between Sloan-Kettering Institute for Cancer Research, a not-for-profit
corporation of the State of New York ("SKI"), and Amgen, as amended ("SKI
Agreement"), as further amended by that certain Amendment No. 2 to the SKI
Agreement dated November 13, 1990, by and between SKI and Amgen (together with
the SKI Agreement, collectively, "Amended SKI Agreement"), Amgen is obligated to
pay to SKI royalties on the Net Sales (as defined therein) of G-CSF Products in
the United States each year equal to three percent (3%) of such Net Sales in
excess of three hundred and fifty million dollars ($350,000,000) (which
royalties may be reduced as provided in the Amended SKI Agreement in the event
that Amgen pays royalties with respect to the sale of such G-CSF Products in
such territory to a third party or parties based upon the patent rights of such
third party or parties.

               (3)  Pursuant to the G-CSF United States License Agreement, (a)
 K-A is obligated to bear responsibility for royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement for sales of G-CSF Products in the United
States, up to five percent (5%), and (b) Amgen is obligated to bear
responsibility for all such royalties in excess of five percent (5%).

               (4)  In addition to the royalties described above, the Amended
SKI Agreement requires Amgen to pay to SKI two milestone payments of ten million
dollars ($10,000,000) and fifteen million dollars ($15,000,000), respectively,
upon the occurrence of the events described in the Amended SKI Agreement,
subject to the terms set forth therein.

          b.   Understandings and Agreements. It is understood and hereby
               -----------------------------
        agreed to by the parties that Amgen shall have satisfied its obligations
        under the G-CSF United States License Agreement with respect to the
        royalties payable by Amgen to K-A on sales of G-CSF Products in the
        United States, and K-A shall have satisfied its obligations under the G-
        CSF United States License Agreement with respect to the royalties
        payable by K-A to SKI on sales of G-CSF Products in the United states,
        if Amgen shall pay directly to SKI the royalties required to be paid by
        Amgen to SKI under the Amended SKI Agreement with respect to sales of G-
        CSF Products in the United States.

2.   Royalties for G-CSF Product Sales in Japan.
     ------------------------------------------

                                       2
<PAGE>

               a.   Acknowledgements. The parties hereto acknowledge the
                    ----------------
following:

                    (1)  Pursuant to the G-CSF Japanese License Agreement dated
June 1, 1987, by and between K-A and Kirin, as amended (the "G-CSF Japanese
License Agreement"), Kirin is obligated to pay to K-A royalties on the Sales
Value (as defined therein) of G-CSF Products in Japan equal to between zero
percent (0%) and five percent (5%).

                    (2)  Pursuant to the Amended SKI Agreement, Amgen is
obligated to pay to SKI royalties equal to five percent (5%) of Net Sales (as
defined therein) of G-CSF Products in Japan (which royalties may be reduced as
provided in the Amended SKI Agreement in the event that Amgen pays to a third
party or parties based upon the patent rights of such third party or parties).

                    (3)  Pursuant to the G-CSF Japanese License Agreement, K-A
is obligated to bear responsibility for all royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement on sales of G-CSF Products in Japan.

                  b.  Understandings and Agreements. It is understood and hereby
                      -----------------------------
agreed to by the parties that Kirin shall have satisfied its obligations under
the G-CSF Japanese License Agreement with respect to the royalties payable by
Kirin to K-A on sales of G-CSF Products in Japan if Kirin shall pay to K-A
royalties equal to the royalties required to be paid by Amgen to SKI under the
Amended SKI Agreement with respect to sales of G-CSF Products in Japan. The
parties hereto confirm that in accordance with the terms of the G-CSF Japanese
License Agreement, K-A shall pay to SKI all royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement for sales of G-CSF Products in Japan.

                  To the extent that K-A realizes a tax benefit from the use of
any withholding tax originating from the royalty payments made by Kirin to K-A,
after first using all tax withholdings that originated from K-A's business
operations, K-A shall pay to SKI the amount of any such benefit realized. Kirin
shall provide to K-A, on a timely basis, copies of tax receipts issued by the
government of Japan relating to the required payments.

3.   Royalties for G-CSF Product Sales in Europe
-------------------------------------------

                  a.  Acknowledgements. The parties hereto acknowledge the
                      ----------------
following:

                      (1)     Pursuant to that certain G-CSF European License
Agreement dated December 30, 1986, by and between K-A and Amgen, as amended ("G-
CSF European License Agreement"), Amgen is obligated to pay to K-A royalties on
the Sales Value (as defined

                                       3
<PAGE>

therein) of G-CSF Products in Europe (including European Community and non-
European Community countries) equal to ten percent (10%). Pursuant to the G-CSF
European License Agreement, Amgen also is required to pay to K-A certain
milestone payments as set forth therein, upon the occurrence of the events
described in the G-CSF European License Agreement and subject to the terms set
forth therein.

                      (2)     Pursuant to the Amended SKI Agreement, Amgen is
obligated to pay to SKI royalties equal to five percent (5%) of Net Sales (as
defined therein) of G-CSF Products in Europe (which royalties shall be reduced
as provided in the Amended SKI Agreement in the event that Amgen pays royalties
on sales of such G-CSF Products in such territory to a third party or parties
based upon the patent rights of such third party or parties). The parties
hereby acknowledge that such royalties currently paid by Amgen with respect to
sales of G-CSF Products in Europe include (a) royalties to the Board of Trustees
of Leland Stanford Junior University equal to one-half of one percent (.5%) of
net sales of G-CSF Products, and (b) royalties paid to Nycomed Pharma AS equal
to between one and one-half percent (1.5%) and five-hundredths of one percent
(.05), with the applicable percentage to depend on the worldwide net sales of G-
CSF Products in a given royalty period. The parties acknowledge and agree that
Amgen may be obligated to pay such additional royalties in the future.

                      (3)     Pursuant to the G-CSF European License Agreement,
K-A and Amgen each are obligated to bear the responsibility for one-half (1/2)
of all royalties payable by Amgen to SKI pursuant to the Amended SKI Agreement
on sales of G-CSF Products in Europe.

                      (4)     Pursuant to that certain Agreement on G-CSF in the
EC dated September 26, 1988, by and between Amgen and F. Hoffman LaRoche & Co.,
Limited Company, a Switzerland corporation ("Roche"), as amended ("Roche EC
Agreement"), Amgen and Roche have agreed to share on a 60/40 basis (with the
higher proportion to Amgen) the Operating Profit or Operating Loss (each as
defined in the Roche EC Agreement), as the case may be, relating to the sale of
G-CSF Products in the countries comprisingthe European Community, subject to the
terms set forth therein. Pursuant to the Roche EC Agreement, Roche also is
obligated to pay to Amgen certain milestone payments, as set forth therein, upon
the occurrence of the events set forth in the Roche EC Agreement and subject to
the terms set forth therein.

                      (5)     Pursuant to that certain Agreement on G-CSF on
Certain European Countries dated January 1, 1989, by and between Amgen and Roche
("Roche Non-EC Agreement"), Roche is obligated to pay to Amgen royalties on Net
Sales (as defined therein) of G-CSF Products in certain European countries,
other than the countries comprising the European Community, equal to twenty five
percent (25%) of Net Sales (as defined therein) of G-CSF Products in each
country where relevant patents exist until

                                       4
<PAGE>

August 22, 2006 (subject to reduction to sixteen percent (16%) of such Net Sales
of G-CSF Products in applicable countries in the event of significant unlicensed
competition by third parties in such countries, as described in the Roche Non-EC
Agreement), and sixteen percent (16%) of such Net Sales of G-CSF Products in
each country where such patents have expired, or where no patent otherwise
exists, until August 22, 2006.

                  b.  Understandings and Agreements. It is understood
                      -----------------------------
and hereby agreed by the parties that Amgen shall have satisfied its obligations
under the G-CSF European License Agreement with respect to the royalties payable
by Amgen to K-A on sales of G-CSF Products in Europe, and K-A shall have
satisfied its obligations under the G-CSF European License Agreement with
respect to the royalties payable by K-A to SKI on sales of G-CSF Products in
Europe, if (i) Amgen shall pay to K-A the royalties payable to K-A under the G-
CSF European License Agreement, reduced by one-half (1/2) of all of the
royalties payable by K-A to SKI pursuant to the G-CSF European License
Agreement, and (ii) Amgen shall further pay to SKI all of the royalties payable
by Amgen to SKI under the Amended SKI Agreement on sales of G-CSF Products in
Europe.

4.   Royalties for G-CSF Product Sales in Australia, Canada and New
     --------------------------------------------------------------
     Zealand.
     -------

                  a.  Acknowledgements. The parties hereto acknowledge the
                      ----------------
following:

                      (1)     Pursuant to that certain G-CSF Australia, Canada
and New Zealand License Agreement dated October 20, 1988, by and between K-A and
Amgen, as amended ("G-CSF Australian License Agreement"), Amgen is obligated to
pay to K-A royalties on the Sales Value (as defined therein) of G-CSF Products
in Australia, Canada and New Zealand equal to ten percent (10%).

                      (2)     Pursuant to the Amended SKI Agreement, Amgen is
obligated to pay to SKI royalties equal to five percent (5%) of Net Sales (as
defined therein) of G-CSF Products in Australia, Canada and New Zealand (which
royalties may be reduced as provided in the Amended SKI Agreement in the event
that Amgen pays royalties on sales of such G-CSF Products in such territory to a
third party or parties based upon the patent rights of such third party or
parties).

                      (3)     Pursuant to the G-CSF Australian License
Agreement, K-A is obligated to bear responsibility for all royalties payable by
Amgen to SKI pursuant to the Amended SKI Agreement on sales of G-CSF Products in
Australia, Canada and New Zealand.

                  b.  Understandings and Agreements. It is understood and hereby
                      -----------------------------
agreed by the parties that Amgen shall have satisfied

                                       5
<PAGE>

its obligations under the G-CSF Australian License Agreement with respect to
royalties payable by Amgen to K-A on sales of G-CSF Products in Australia,
Canada and New Zealand, and K-A shall have satisfied its obligations under the G
CSF Australian License Agreement with respect to the royalties payable by K-A to
SKI on sales of G-CSF Products in Australia, Canada and New Zealand, if (i)
Amgen shall pay to K-A the royalties payable to K-A under the G-CSF Australian
License Agreement, reduced by the royalties payable by K-A to SKI pursuant to
the G-CSF Australian License Agreement, and (ii) Amgen shall further pay to SKI
all of the royalties payable by Amgen to SKI under the Amended SKI Agreement on
sales of G-CSF Products in Australia, Canada and New Zealand.

5.    Royalties for G-CSF Product Sales in the Republic of China (Taiwan) and
      -----------------------------------------------------------------------
      the Republic of Korea
      ---------------------

          a.   Acknowledgements. The parties hereto acknowledge the following:
               ----------------
following:

               (1)  Pursuant to that certain G-CSF Republic of China
and Republic of Korea License Agreement dated October 20, 1988, by and between K
A and Kirin, as amended ("G-CSF ROC/ROK License Agreement"), Kirin is obligated
to pay to K-A royalties on the Sales Value (as defined therein) of G-CSF
Products in the Republic of China (Taiwan) and the Republic of Korea equal to
ten percent (10%).

               (2)  Pursuant to the Amended SKI Agreement, Amgen is obligated to
pay to SKI royalties equal to five percent (5%) of Net Sales (as defined
therein) of G-CSF Products in the Republic of China and the Republic of Korea
(which royalties may be reduced as provided in the Amended SKI Agreement in the
event that Amgen pays any royalties on sales of such G-CSF Products in such
territory to a third party or parties based upon the patent rights of such third
party or parties).

               (3)  Pursuant to the G-CSF ROC/ROK License Agreement, K-A is
obligated to bear responsibility for all royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement on sales of G-CSF Products in the Republic
of China and the Republic of Korea.

          b.   Understandings and Agreements. The parties hereto confirm that,
               -----------------------------
in accordance with the terms of the G-CSF ROC/ROK License Agreement, (i) Kirin
shall pay to K-A the royalties payable to K-A under the G-CSF ROC/ROK License
Agreement, and (ii) K-A shall pay to SKI all royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement on sales of G-CSF Products in the Republic
of China and the Republic of Korea.

          To the extent that K-A realizes a tax benefit from the use of any
withholding tax originating from the royalty payments made by Kirin to K-A,
after first using all tax withholdings that

                                       6
<PAGE>

originated from K-A's business operations, K-A shall pay to SKI the amount of
any such benefit realized. Kirin shall provide to K-A, on a timely basis, copies
of tax receipts issued by the government of Japan, Republic of China or Republic
of Korea relating to the required payments.

6.   Royalties for G-CSF Product Sales in the People's Republic of China.
     -------------------------------------------------------------------

          a.   Acknowledgements. The parties hereto acknowledge the
               ----------------
following:

               (1) Pursuant to that certain License Agreement for the People's
Republic of China dated May 29, 1992, by and among K-A, Kirin and Amgen ("PRC
License Agreement"), each of Kirin and Amgen is obligated to pay to K-A
royalties on Net Sales (as defined therein) of G-CSF Products by each such party
in the People's Republic of China equal to five percent (5%).

               (2) Pursuant to the Amended SKI Agreement, Amgen is obligated to
pay to SKI royalties equal to five percent (5%) of Net Sales (as defined
therein) of G-CSF Products in the People's Republic of China (which royalties
may be reduced as provided in the Amended SKI Agreement in the event that Amgen
pays to third party or parties based upon the patent rights of such third party
or parties royalties on sales of such G-CSF Products in such territory).

               (3) Pursuant to the PRC License Agreement, each of Kirin and
Amgen is obligated to bear responsibility for all third party royalties (as
described in Section 3.4 of the PRC License Agreement) payable by such party on
sales in the People's Republic of China.

          b.   Understandings and Agreements. (i) It is understood and hereby
               -----------------------------
agreed to by the parties that Kirin shall have satisfied its obligations under
the PRC License Agreement with respect to the royalties payable by Kirin to K-A
on sales of G-CSF Products in the People's Republic of China if Kirin shall pay
to K-A royalties equal to the royalties required to be paid by Amgen to SKI
under the Amended SKI Agreement with respect to Kirin's sales of G-CSF Products
in the People's Republic of China, and (ii) Kirin and Amgen each shall pay all
third party royalties, payable by such party on sales of G-CSF Products in the
People's Republic of China (as described in Section 3.4 of the PRC License
Agreement). K-A hereby agrees that it shall have satisfied its obligations to
SKI by virtue of all royalties paid by Amgen to SKI on sales of G-CSF Products
in the People's Republic of China.

7.   Royalties for G-CSF Product Sales in the Rest of the World.
     ----------------------------------------------------------

                                       7
<PAGE>

          a.  Acknowledgements. The parties hereto acknowledge the following:
              ----------------

              (1)   Pursuant to that certain G-CSF Rest of the World License
Agreement dated January 1, 1989 ("ROW Agreement"), by and between K-A and Roche,
Roche shall pay royalties to K-A equal to twenty-five percent (25%) of Net Sales
(as defined therein) of G-CSF Products in each country where relevant patents
exist until August 22, 2006 (subject to reduction to sixteen percent (16%) of
such Net Sales of G-CSF Products in applicable countries in the event of
significant unlicensed competition by third parties in such countries, as
described in the ROW Agreement), and sixteen percent (16%) of such Net Sales of
G-CSF Products in each country where such patents have expired, or where no
patent otherwise exists, until August 22, 2006.

              (2)   Pursuant to that certain Supply Agreement between Amgen and
K-A, dated January 1, 1989 ("Supply Agreement"), (a) Amgen has agreed to supply
K-A with Roche's requirements of G-CSF Products pursuant to the ROW Agreement,
and (b) K-A has agreed to pay to Amgen two (2) times Amgen's cost of G-CSF
Products supplied by Amgen to K-A pursuant to the Supply Agreement (manufactured
at standard cost), as determined by Amgen (collectively, the "K-A Product
Payments").

              (3)   Pursuant to the Amended SKI Agreement, Amgen is obligated to
pay to SKI royalties equal to five percent (5%) of net sales of G-CSF Products
in the world other than the United States (which royalties may be reduced as
provided in the Amended SKI Agreement in the event that Amgen pays any royalties
on sales of such G-CSF Products in such territory to a third party or parties
based upon the patent rights of such third party or parties).

          b.  Understandings and Agreements. It is understood and hereby agreed
              -----------------------------
by the parties that K-A shall have satisfied its obligations under the Supply
Agreement to pay the K-A Product Payments to Amgen in accordance with the ROW
Agreement if (i) K-A shall pay to SKI all royalties payable by Amgen to SKI
pursuant to the Amended SKI Agreement on sales of G-CSF Products in the world
other than the territories covered by the G-CSF United States License Agreement,
the G-CSF Japanese License Agreement, the G-CSF European License Agreement, the
G-CSF Australian License Agreement; the G-CSF ROC/ROK License Agreement and the
PRC License Agreement (together with the ROW Agreement and as amended through
the date hereof, collectively "License Agreements"), and (ii) other than as
herein provided (e.g., the People's Republic of China), K-A shall pay all
royalties to third parties in every territory throughout the world.

8.   Further Instruments.
     -------------------

                                       8
<PAGE>

          Each party hereto agrees to perform any and all further acts and to
execute and deliver any and all further documents and instruments which may be
reasonable or necessary to carry out the purposes of this Amendment and the
Shareholder Agreement, as amended.

9.   Ratification and Integration.
     ----------------------------

          Except to the extent provided herein, the provisions of the
Shareholders' Agreement and the License Agreements, as amended through the date
hereof, are hereby ratified and confirmed in all respects. Without limiting the
foregoing, the Shareholder's Agreement (as amended through the date hereof and
including this Amendment), together with the License Agreements (as amended
through the date hereof, including the amendments effected by this Amendment),
constitutes the entire agreement among the parties hereto with respect to the
subject matter hereof, and supersedes all other agreements, whether oral or
written, express or implied, with respect to the subject matter hereof. This
Amendment may not be amended or modified except by a written instrument signed
by the parties hereto.

10.  Governing Law and Severability.
     ------------------------------

          This Amendment shall be construed under and in accordance with, and
governed in all respects by, the laws of the State of California (without giving
effect to principles of conflicts of law). If any provision of this Amendment is
deemed invalid or unenforceable by a court of competent jurisdiction, such
invalidity or enforceability shall not affect or limit the validity or
enforceability of any other provision hereof.

11.  Counterparts.
     ------------

          This Amendment may be executed in two or more counterparts, each of
which shall be deemed an original and all of which together shall constitute one
instrument.

                                       9
<PAGE>

          IN WITNESS WHEREOF, the undersigned have caused this Amendment No. 8
to be duly executed as of May 28, 1993.

                               KIRIN BREWERY CO., LTD., a Japanese corporation

                              By /s/ T. Sasahara
                                 ---------------
                                    Toru Sasahara,
                                    President, Pharmaceuticals
                                    Division

                               AMGEN INC.,
                               a Delaware corporation

                               By /s/ Lowell E. Sears
                                  -------------------
                                    Lowell E. Sears, Sr. Vice
                                    President

                               KIRIN-AMGEN, INC.,
                               a Delaware corporation

                               By /s/ Lowell E. Sears
                                  -------------------
                                    Lowell E. Sears, President

                                       10

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