patenting antisense oligonucleotides and methods robert a. schwartzman, ph.d. acting supervisory...
TRANSCRIPT
Patenting Antisense Patenting Antisense Oligonucleotides and MethodsOligonucleotides and Methods
Robert A. Schwartzman, Ph.D.Acting Supervisory Patent Examiner
Art Unit 1636
Antisense Art UnitAntisense Art Unit
• Art Unit 1635• John LeGuyader,
SPE• Created October
1996
• Art Unit 1636• George Elliott,
Ph.D. SPE• On fellowship at
the National Academy of Sciences
Mechanism of AntisenseMechanism of Antisense
Antisense TechnologiesAntisense Technologies
• Antisense Oligonucleotides (Oligos)• Catalytic Nucleic Acids: Ribozymes and
Dnazymes• Triplex• Pnas and Other Nonstandard Nucleic Acids• Aptamers• Decoys• Nucleic Acid Modifications• Oligo-based Gene Regulation and Gene Therapy
Issued U.S. Patents Classified in Issued U.S. Patents Classified in 536/24.5 – Nucleic Acid Expression Inhibitors 536/24.5 – Nucleic Acid Expression Inhibitors
(as of July 17, 2001)(as of July 17, 2001)
2 4 8 11 11 1754
150176
255 239
99
0
100
200
300
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Year
Case LawCase Law
• Antisense-Specific:
– Enzo Biochem Inc. v. Calgene Inc., 52 USPQ2d 1129 (Fed. Cir. 1999)
– Enablement - antisense highly unpredictable
– Decision is based on patents with effective filing dates of at least 1989 and the technology at that time
– Decision does not necessarily determine the outcome for examination of antisense patent applications recently filed because current knowledge and level of skill in the art is high (antisense has progressed as a technology since 1989)
Gene WalkGene Walk
0
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Antisense Oligo - 5' to 3'
% I
nhib
ition
Antisense Oligonucleotide Antisense Oligonucleotide ClaimsClaims
• Consider a Broad Claim To:
An antisense oligonucleotide that inhibits expression of a nucleic
acid encoding protein X.
Utility RequirementUtility Requirement
• Utility generally not an issue for antisense.
• If no function for target nucleic acid (protein or regulatory) is shown or was known:– antisense would likely lack utility– also raises enablement (how to use) and possibly written
description issues– probe function alone for target not sufficient to provide
utility for antisense, but may be for purposes other than claiming antisense.
Written Description Written Description RequirementRequirement
• Written description generally not an issue for broad claims to antisense oligos inhibiting expression of a nucleic acid encoding a protein.
• May lack written description if the claim reads on targeting many different nucleic acids.
• Analysis turns on what is shown in the specification and what was known about the various versions of the gene at the time of filing.
• Provide evidence that antisense targets identified in one gene correlate with targets in other versions of the gene.
Enablement RequirementEnablement Requirement
• Probability of finding functional antisense oligonucleotide to a target gene is high.
• Predictability of any single antisense oligonucleotide being effective is low
– Claim to specific antisense oligonucleotide may require evidence of function
• The current state of predictability for antisense may support a broad claim to antisense oligonucleotides
– But this may also raise prior art issues depending on what was known at the time of filing
Pharmaceutical and Method ClaimsPharmaceutical and Method Claims
• Consider Broad Claims To:
A pharmaceutical composition comprising an antisense oligonucleotide that inhibits expression of a nucleic acid encoding protein X.
A method of treating a disease comprising administering an antisense oligonucleotide that inhibits expression of a nucleic acid encoding protein X.
Enablement Analysis for In Enablement Analysis for In Vivo Method ClaimsVivo Method Claims
– Describe scope of the claimed invention– Cite known unpredictability in the art
via journal articles– Indicate amount of guidance in the
specification– Indicate presence or absence of working
examples– Identify additional experimentation that
would be required
Enablement RequirementEnablement Requirement
• Commonly Cited Unpredictable Factors for Antisense:– Predicting target accessibility
• Target folding/structure• Antisense/target protein interactions• Lack of correlation between in vitro and in
vivo– Efficient delivery to cells and cell targeting for
specific disorders– Oligo affinity/stability in vivo
Enablement RequirementEnablement Requirement
– Modulation of target
• In vitro (cell culture) results generally in vivo success
– Animal model shown may not be art recognized
– Human data is not ordinarily required by the examiner for in vivo claims
• But may be the only evidence to enable treatment claims
• Disorder dependent issue
ObviousnessObviousness• Expect an obviousness rejection against broad antisense claims to
known genes if the prior art suggested inhibiting the gene by antisense or other means and the gene sequence was known.
• The current knowledge and level of skill in the art is high such that one of ordinary skill in the art would expect at least one effective antisense against every known gene (e.g. a full-length antisense), absent evidence to the contrary.
• Narrow claims to specific antisense oligos may be free of the art, since there may be no motivation to modify the prior art to achieve the specific antisense sequence claimed.
RecommendationsRecommendations
• Claim functional antisense oligos by specific sequence if you have evidence of activity.
• List Results of “Gene Walk”
– Showing activity of each oligo
– “Gene walk” data may provide representative number of species for broad breadth/scope for a generic claim, but there is no magic number
RecommendationsRecommendations
• Provide claims commensurate in scope with the disclosure of the specification
– Consider the scope of the target nucleic acid.
– Consider the scope of disease/disorder being treated.
– Consider the scope of route of administration.
– Consider the scope of vector delivery system.
RecommendationsRecommendations• Provide objective evidence that in vitro results are
representative of in vivo applicability.• Respond to examiner-cited unpredictable factors
with objective evidence to the contrary.• Expert opinions are more favorably viewed when
supported using objective evidence.• Provide objective evidence that a particular
animal model is generally accepted as representative of disease or methods of treating, particularly for humans.
RecommendationsRecommendations
• Objective Evidence
– Case law– Journal articles– Experimental data – Comparisons commensurate with the
disclosure as filed.
QUESTIONS?QUESTIONS?
• Robert Schwartzman
• Acting SPE - Art Unit 1636
• (703) 308-7307
• John LeGuyader
• SPE - Art Unit 1635
• (703) 308-0447
Patenting Antisense Patenting Antisense Oligonucleotides and MethodsOligonucleotides and Methods
Robert A. Schwartzman, Ph.D.Acting Supervisory Patent Examiner
Art Unit 1636