Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant's amendments and remarks filed on June 17, 2026 are acknowledged. Claims 4-5, 7-11, and 14-29 have been canceled. Claims 1, 3, 6, 12, 13, and 30 were amended.
Claims 1-3, 6, 12, 13, and 30 are pending and are examined on the merits herein.
This action is NON-FINAL due to new grounds of rejection not necessitated by amendment.
Claim Objections
Claim 30 is objected to because of the following informalities:
Claim 30 recites in part “all comprise 2'-O-methoxyethyl ribose sugars”. The word “comprise” should recite “comprising”.
Claim 30 recites in part “U and C are are methylated”. There should only be one (1) instance of the word “are”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 6, 12, 13, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Aznarez et al. (US 11,096,956; reference previously cited by the Examiner) in view of van Deutekom et al. (US 2022/0025368; reference previously cited by the Examiner).
Regarding claims 1-3, 6, 12, 13, and 30, Aznarez et al. teaches compositions for increasing the expression of a protein [abstract]. Aznarez et al. discloses that in some embodiments the antisense oligomer comprises a nucleotide sequence selected from SEQ ID NOS: 12685-14026 [column 42-43]. SEQ ID NO: 13225 (designated as Db) is 18 nucleotides in length and matches to instant SEQ ID NO: 9 (designated as Qy) as shown in the alignment below. Aznarez et al. also teaches that in some embodiments the antisense oligomer consists of from 8 to 50 nucleobases [column 42].
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Aznarez et al. also discloses that compositions comprising an antisense oligomer are described for use in a method of treating a list of recited conditions including a condition associated with STXBP1, the method comprising the step of increasing expression of STXBP1 [column 40, second paragraph]. Aznarez et al. teaches that any of the ASOs or any component of an ASO (e.g., a nucleobase, sugar moiety, backbone) may be modified in order to achieve desired properties or activities of the ASO or reduce undesired properties or activities of the ASO [column 119, first full paragraph]. Further, Aznarez et al. teaches that ASOs comprised of 2’-O-(2-methoxyethyl) (MOE) phosphorothioate-modified nucleotides have significantly enhanced resistance to nuclease degradation and increased bioavailability [column 119, second full paragraph]. Aznarez et al. also teaches that in some examples each monomer of the ASO is modified in the same way, for example each linkage of the backbone of the ASO comprises a phosphorothioate linkage or each ribose sugar moiety comprises a 2′O-methyl modification [column 118, last paragraph]. In some embodiments, the antisense oligomer comprises a phosphorodiamidate morpholino, a locked nucleic acid, a peptide nucleic acid, a 2′-O-methyl, a 2′-Fluoro, or a 2′-O-methoxyethyl moiety. Further, in some embodiments, each sugar moiety is a modified sugar moiety [column 6, first paragraph].
However, Aznarez et al. does not explicitly teach at least 94% sequence similarity to SEQ ID NO: 9 or 100% sequence similarity to SEQ ID NO: 9. Aznarez et al. does not teach that at least 50% of instances of U and C are methylated at position 5. Aznarez et al. also does not explicitly teach that all of the bases in the nucleic acid comprise 2’-O-methoxyethyl ribose sugars.
van Deutekom et al. teaches splice-switching compounds with improved characteristics that enhance clinical applicability preferably for treating, ameliorating, preventing, and/or delaying neuromuscular disorders [abstract]. van Deutekom et al. also teaches that the first and/or second antisense oligonucleotide preferably comprises a base modification that increases binding affinity to target strands, increases melting temperature of the resulting duplex of said oligonucleotide with its target, and/or decreases immunostimulatory effects, and/or increases biostability, and/or improves biodistribution and/or intra-tissue distribution, and/or cellular uptake and trafficking [0129]. Further, preferably at least one 5-methylcytosine and/or 5-methyluracil is comprised in the first oligonucleotide and more preferably that all cytosine bases are 5-methylcytosine and/or all uracil bases are 5-methyluracil [0131] and [0135].
Although Aznarez et al. does not explicitly teach at least 94% sequence similarity to SEQ ID NO: 9 or 100% sequence similarity to SEQ ID NO: 9, Aznarez et al. taught that in some embodiments the antisense oligomer comprises a nucleotide sequence selected from SEQ ID NOS: 12685-14026 and SEQ ID NO: 13225 is 18 nucleotides in length and matches to instant SEQ ID NO: 9. It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the length of the oligonucleotide and arrive at the instantly claimed limitations because Aznarez et al. taught that in some embodiments the antisense oligomer consists of from 8 to 50 nucleobases and Aznarez et al. taught that increased expression of STXBP1 can benefit central nervous system diseases or conditions [column 2, last paragraph bridging to column 3]. Further, extending on either the 5’ end of the 3’ end provides a finite number of options and thus one of ordinary skill in the art would have been motivated to test the effect of the antisense oligonucleotide because Aznarez et al. taught compositions for increasing the expression of a protein capable of treating conditions associated with STXBP1.
Although Aznarez et al. does not explicitly teach that all of the bases in the nucleic acid comprise 2’-O-methoxyethyl ribose sugars, Aznarez et al. taught uniform modification of the antisense oligonucleotide and taught that an antisense oligomer may comprise a 2′-O-methoxyethyl moiety. It would have been obvious to try because there are a finite number of bases in the oligonucleotide and Aznarez et al. taught that ASOs comprised of 2’-O-(2-methoxyethyl) (MOE) phosphorothioate-modified nucleotides have significantly enhanced resistance to nuclease degradation and increased bioavailability.
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified at least 50% of instances of C and U in the composition of Aznarez et al. because van Deutekom et al. taught antisense oligonucleotides comprising base modifications such that all cytosine bases are 5-methylcytosine and all uracil bases are 5-methyluracil. One skilled in the art would have been motivated to do so in order to increase binding affinity to target strands.
Conclusion
No claims are allowed.
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/C.T./
Examiner, Art Unit 1637 /Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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