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                                                             EXHIBIT 10.9

Optionee:                                                   Date:
         --------------------------------------------------      ---------------

                           ISIS PHARMACEUTICALS, INC.
                       SUPPLEMENTAL STOCK OPTION AGREEMENT

Isis Pharmaceuticals, Inc. (the "Company"), pursuant to its 1989 Stock Option
Plan (the "Plan") has this day granted to the undersigned optionee, an option to
purchase shares of the common stock of the Company ("Common Stock") as described
herein. This option is not intended to qualify and will not be treated as an
"incentive stock option" within the meaning of Section 422 of the Internal
Revenue Code of 1986, as amended from time to time (the "Code"). This option is
subject to all of the terms and conditions as set forth herein and on Attachment
I hereto, which is incorporated herein in its entirety.

                   Number of Shares Subject to Option:________

VESTING SCHEDULE:

<TABLE>
<S>                                               <C>
           Number of Shares (installment)         Date of Earliest Exercise (vesting)(1)

           ---------------------                  ---------------------

           ---------------------                  ---------------------

Exercise Price Per Share:  (2)                    Expiration Date:                           (3)
                          -----                                   ---------------------------
                                                  Percentage of Full-Time Work:  100%
                                                                                ------
Isis Pharmaceuticals, Inc.


By:                                               Optionee:
   --------------------------------------                  ----------------------------------
Duly authorized on behalf of                      Address:
  the Board of Directors
</TABLE>

OPTIONEE:

Acknowledges receipt of the option as described herein and the attachments
referenced therein and understands that all rights and liabilities with respect
to this option are set forth in the option and the Plan; and acknowledges that
as of the date of grant of this option, it sets forth the entire understanding
between the optionee and the Company regarding the acquisition of stock in the
Company and supersedes all prior oral and written agreements on that subject.

(1) The option will vest monthly with 4.167% of the total grant vesting each
month; provided, however, that during any period in which the undersigned
provides service at less than the Percentage of Full-Time Work set forth above,
a reduced number of shares will vest as follows: the percentage of shares which
will vest during such period of reduced service will equal (a) the percentage of
shares that would vest as set forth on this schedule, multiplied by (b) the
percentage of full-time work furnished during the period of reduced service
divided by the Percentage of Full Time Work as set forth above. Increases of
work percentage up to but not in excess of the Percentage of Full Time Work
specified above will result in a corresponding increase in the percentage of
shares vesting. This reduction in vesting will not apply during any period of
paid leave or the first 20 weeks of a period of unpaid leave. No shares will
vest during unpaid leave after the first 20 weeks of such leave. Shares which do
not vest because of reductions in work percentage or unpaid leave will be
canceled and no longer subject to this option.

(2) Not less than 85% of the fair market value of the Common Stock on the date
of grant of this option.

(3) Less than 10 years from the date of grant of this option.