Isis Pharmaceuticals Earns $3 Million Milestone Payment from Eyetech for FDA Marketing Clearance of Macugen(TM)

Isis Pharmaceuticals Earns $3 Million Milestone Payment from
Eyetech for FDA Marketing Clearance of Macugen(TM)
Isis to Receive Future Royalty Stream from Product Sales 


CARLSBAD, Calif., Dec. 20  /PRNewswire-FirstCall/ -- Isis Pharmaceuticals, Inc.
(NASDAQ:ISIS) announced today that it has earned a $3 million milestone from
Eyetech Pharmaceuticals, Inc. (NASDAQ:EYET) associated with the marketing
clearance of Macugen(TM) (pegaptanib sodium injection) by the U.S. Food and
Drug Administration (FDA).  Macugen, a non-antisense drug, is a treatment for
patients with wet age-related macular degeneration (AMD).  The drug is also in
clinical trials for the treatment of diabetic macular edema. In 2002, Eyetech
licensed from Isis specific patents necessary to develop, manufacture and
commercialize Macugen.  In June 2004, Isis earned a $1 million milestone
payment from Eyetech associated with its submission of a New Drug Application
(NDA) for Macugen to the FDA. Under the terms of the agreement, Isis may earn
additional milestone payments from Eyetech, and will earn royalties on
commercial sales of the drug.

"The $6 million we have earned thus far from our agreement with Eyetech, and
our potential to earn significant revenue from future product sales, validates
the near and long-term value of our large patent estate," said B. Lynne
Parshall, Isis' Executive Vice President and Chief Financial Officer. "To date,
we have earned more than $45 million from licensing our intellectual property. 
By successfully commercializing our inventions and innovation, we are
generating revenue for the continued advancement of our RNA-based drug
pipeline, while supporting other companies in bringing valuable new products to
market for the benefit of patients."

Isis' chemistry suite of patents represents a subset of Isis' overall
intellectual property estate of more than 1,400 issued patents that the company
owns or exclusively licenses covering RNA-based drug discovery and development.
More specifically, the estate covers fundamental oligonucleotide chemistries;
antisense-based gene functionalization and identification of validated target
regions of relevant genes; multiple antisense mechanisms; antisense
therapeutics; manufacturing; formulations, and delivery of oligonucleotide
therapeutics.  Additionally, Isis' patents cover Ibis' RNA technology for the
identification of infectious biological agents (TIGER).

Isis has taken advantage of its work in RNA-based drug discovery and
development to build the industry's leading intellectual property position in
this field.  While Isis continues to patent its inventions, the company
actively leverages its intellectual property rights and seeks licensing
partners.

About Wet AMD and Macugen

AMD is the leading cause of severe vision loss in Americans age 65 years and
over. The "wet" form of macular degeneration accounts for about 10% of all AMD
cases. Macugen is a pegylated anti-vascular endothelial growth factor (VEGF)
aptamer (an oligonucleotide) which binds to and thus inhibits the activity of
VEGF. VEGF is a protein that plays a critical role in angiogenesis (the
formation of new blood vessels) and increased permeability (leakage from blood
vessels), two of the primary pathological processes responsible for the vision
loss associated with wet AMD.

About Isis Pharmaceuticals, Inc.

Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and
develop novel human therapeutic drugs for its pipeline and for its partners.
The company has successfully commercialized the world's first antisense drug
and has 10 antisense products in development to treat metabolic,
cardiovascular, inflammatory and viral diseases, and cancer. Through its Ibis
Therapeutics(R) program, Isis is developing a biosensor to identify infectious
organisms, and discovering small molecule drugs that bind to RNA. As an
innovator in RNA-based drug discovery and development, Isis is the owner or
exclusive licensee of more than 1,400 issued patents worldwide. Additional
information about Isis is available at http://www.isispharm.com/

This press release contains forward-looking statements concerning Isis
Pharmaceuticals, its business relationship with Eyetech Pharmaceuticals and the
potential of the company's intellectual property position and potential for
future payments to the company related to the success of Macugen. Any statement
describing our goals, expectations, intentions or beliefs is a forward-looking
statement and should be considered an at-risk statement, including those
statements that are described as Isis' clinical goals.  Such statements are
subject to certain risks and uncertainties, particularly those inherent in the
process of developing technology and in discovering and commercializing drugs
that are safe and effective for use as human therapeutics and in the endeavor
of building a business around such products. Actual results could differ
materially from those discussed in this press release.  As a result, you are
cautioned not to rely on these forward-looking statements.  These and other
risks concerning Isis' research and development programs are described in
additional detail in Isis' Annual Report on Form 10- K for the year ended
December 31, 2003, and quarterly report on Form 10-Q for the quarter ended
September 30, 2004, which are on file with the U.S. Securities and Exchange
Commission. Copies of these and other documents are available from the company.

Macugen(R) is a trademark of Eyetech Pharmaceuticals, Inc.

Ibis Therapeutics(R) is a registered trademark of Isis Pharmaceuticals, Inc. 

DATASOURCE: Isis Pharmaceuticals, Inc.



CONTACT:  Kristina Peterson, Corporate Communications of Isis

Pharmaceuticals, Inc., [phone] 



Web site:  http://www.isispharm.com/ 

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