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                                                                    EXHIBIT-99.1


FRIDAY MAY 25, 2001

PRESS RELEASE

ISIS PHARMACEUTICALS AND HYBRIDON COMPLETE INTELLECTUAL PROPERTY LICENSING
AGREEMENTS

ISIS PHARMACEUTICALS TAKES AN EXCLUSIVE LICENSE TO HYBRIDON'S ANTISENSE
CHEMISTRY AND DELIVERY TECHNOLOGY PATENTS

HYBRIDON TAKES A LICENSE TO ISIS' RNASE H SUITE OF PATENTS

CAMBRIDGE, Mass. and CARLSBAD, Calif., May 25 /PRNewswire/ -- Hybridon (OTC
Bulletin Board: HYBN - news) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIP -
NEWS), the two pioneers of antisense technology, announced today patent
licensing activities that would eliminate any potential patent conflict between
them, fortify Isis' dominant position in antisense technology and enhance
Hybridon's ability to exploit the advances it has made in antisense technology.
These transactions support the application of each company's technologies. Isis
has taken an exclusive license to all of Hybridon's antisense chemistry and
delivery patents and technology. Hybridon retains the right to practice its
licensed antisense patent technologies and to sublicense it to collaborators.
Hybridon has taken a license to Isis' suite of RNase H patents that covers the
mechanism of action of many antisense drugs to support Hybridon's activities in
antisense therapeutics.

In exchange for the license to Hybridon's antisense intellectual property, Isis
will pay Hybridon $15 million in cash and will pay $19.5 million in Isis stock
over two years. Under the agreement Isis has also acquired the exclusive right
to sub-license the licensed Hybridon technology to third parties. In return for
access to Isis' RNase H suite of patents, Hybridon will pay Isis $6 million in
Hybridon stock over three years. The license of Isis' RNase H patents to
Hybridon is not sublicenseable, except in connection with Hybridon antisense
drugs. Under the terms of the non-exclusive license from Isis, Hybridon cannot
use those licenses to practice commercial functional genomics and target
validation as a service for third parties.

"We are extremely pleased to complete this transaction with Isis," stated Sudhir
Agrawal D.Phil., Hybridon's President and Chief Scientific Officer. "We believe
antisense is maturing into a broad technology platform. The licensing
arrangements we established today allow each company to move forward to exploit
the opportunity without encumbering the other, and the success of either party
will benefit the other. This transaction also solidifies Hybridon's financial
position, and allows us to create value through the commercialization of our
three DNA chemistry technology platforms which include immunomodulatory Oligos,
Cyclicon(TM) DNA and antisense therapeutics."

"The license of Hybridon's intellectual property is part of our continuing
strategy to dominate antisense for drug discovery and functional genomics," said
B. Lynne Parshall, Isis' Executive Vice President. "Hybridon has performed
high-quality science, and these patents round out our


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antisense patent portfolio. Control of these patents also boosts our strategic
position as the licensor of antisense technology to partners for antisense
functional genomics and target validation activities, as well as antisense
therapeutics. Additionally, it will decrease Isis' potential for conflict and
associated expenses."

Isis' intellectual property position in RNA-based drug discovery is the product
of 12 years of focused research and is comprised of over 700 issued and allowed
patents. Isis began consolidation of non-Isis antisense intellectual property
two years ago with the acquisition of Gilead's antisense patent estate. The
licensing of Hybridon's patent portfolio augments Isis' estate and further
solidifies Isis' control of patented technology in the field of antisense.

"This agreement is an important milestone for the clinical and commercial
application of antisense," said James B. Wyngaarden, M.D., Chairman of the Board
of Directors of Hybridon. "Hybridon is proud to join with Isis in achieving this
significant milestone. We look forward to combining Hybridon's technological and
financial resources to create further value for our shareholders."

"We believe the strength of our intellectual property position in antisense will
be a tremendous source of value to our shareholders," said Stanley T. Crooke,
M.D., Ph.D., Isis' Chairman and CEO. "The licensing of our RNase H suite of
patents to Hybridon is the latest example of how Isis is generating value from
its existing patent estate. Last year Isis generated over $12 million in revenue
from sales and licensing of patents that were non-essential to our antisense
focus. The exclusive license of Hybridon's intellectual property has further
fortified our position in antisense."

Isis Pharmaceuticals, Inc. is exploiting its expertise in RNA to discover and
develop novel human therapeutic drugs. The company has commercialized its first
product, Vitravene(TM) (fomivirsen), to treat CMV-induced retinitis in AIDS
patients. In addition, Isis has 11 products in its development pipeline, with
two in late-stage development and four in Phase II human clinical trials. ISIS
3521, an inhibitor of PKC-alpha, is in Phase III trials for non-small cell lung
cancer. Isis is preparing to initiate a Phase III program for ISIS 2302
(alicaforsen) an ICAM-1 inhibitor, in Crohn's disease. Isis has a broad and
proprietary patent estate of more than 700 issued and allowed patents worldwide.
Isis' GeneTrove(TM) division uses antisense to assist pharmaceutical industry
partners in validating and prioritizing potential gene targets through
customized services and access to an extensive gene function database. Ibis
Therapeutics(TM) is a division focused on the discovery of small molecule drugs
that bind to RNA.

Hybridon is a leader in the development of oligonucleotide chemistries for
therapeutics and diagnostics. Its three primary technology platforms are:
immunomodulatory oligonucleotides (Hybridon's IMOs) for use alone or in
conjunction with a wide variety of other compounds where stimulation of the
immune system would have a beneficial effect; Cyclicon(TM) oligonucleotides, a
unique fluorescent tool for use in drug discovery, PCR applications, and DNA
microarray chips and diagnostics; and antisense oligonucleotides for
therapeutics and diagnostics. These platforms allow Hybridon to create value
through a combination of in-house development of products, collaborations with
partners and the licensing of broadly applicable technology. For more detailed
information about Hybridon, please visit the website at http://www.hybridon.com.


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This press release contains forward-looking statements concerning the
intellectual property positions of both Isis Pharmaceuticals, Inc. and Hybridon,
Inc. Such statements are subject to certain risks and uncertainties,
particularly those inherent in the process of discovering, developing and
commercializing drugs that are safe and effective for use as human therapeutics
and financing such activities. Actual results could differ materially from those
projected in this release. As a result, the reader is cautioned not to rely on
these forward-looking statements. These and other risks concerning Isis' and
Hybridon's research and development programs are described in additional detail
in Isis' Annual Report on Form 10K-A for the year ended December 31, 2000, and
Hybridon's Annual Report on Form 10K-A for the year ended December 31, 2000,
which are on file with the U.S. Securities and Exchange Commission. Copies are
available from the respective companies.

Vitravene(TM) is a trademark of Novartis AG.

GeneTrove(TM) and Ibis Therapeutics(TM) are trademarks of Isis Pharmaceuticals,
Inc.