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EXHIBIT 5.1
OPINION OF GRANTLAND E. BRYCE
June 7, 2000
Isis Pharmaceuticals, Inc.
2292 Faraday Avenue
Carlsbad, CA 92008
Ladies and Gentlemen:
You have requested my opinion with respect to certain matters in connection
with the filing by Isis Pharmaceuticals, Inc. (the "Company") of a Registration
Statement on Form S-3 (the "Registration Statement") with the Securities and
Exchange Commission (the "Commission") covering the offering of 4,000,000 shares
of the Company's Common Stock, as described in the Registration Statement (the
"Common Stock").
In connection with this opinion, I have examined and relied upon the
Registration Statement, the Company's Amended and Restated Certificate of
Incorporation and Bylaws and the originals or copies certified to my
satisfaction, of such records, documents, certificates, memoranda and other
instruments as in my judgment are necessary or appropriate to enable me to
render the opinion expressed below.
On the basis of the foregoing, and in reliance thereon, I am of the opinion that
the Common Stock, when sold in accordance with the Registration Statement, will
be validly issued, fully paid and nonassessable.
I consent to the reference to me under the caption "Legal Matters" in the
Prospectus included in the Registration Statement and to the filing of this
opinion as an exhibit to the Registration Statement.
Very truly yours,
/s/ Grantland E. Bryce
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Grantland E. Bryce
Vice President, General Counsel
