DETAILED ACTION
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 .
Application Status
This action is written in response to applicant’s correspondence received 4 February 2026. Claims 1, 4-22, 25-35 are currently pending. Claims 12-22 and 25-31 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1, 4-11, and 32-35 and are examined herein. The restriction requirement between the Groups I-II, mailed 12 May 2025, is still deemed proper. Applicant's elected Group I with traverse in the reply filed 14 July 2025. The species election between the claimed SEQ ID NOs: 7, 11, and 19, mailed 12 May 2025, has been withdrawn.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant' s amendments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Regarding claim 5, the claim recites the nucleic acid molecule of claim 1 comprising of the nucleotide sequence of SEQ ID NO: 11. However, claim 1 recites that the target sequence of the nucleic acid molecule consists of the claimed SEQ ID NO: 7. Accordingly, claim 5 encompasses oligonucleotides that are longer than SEQ ID NO 11, and include bases that would bind to nucleotides beyond SEQ ID NO: 7, and fails to further limit the subject matter of claim 1 because the target sequence would not be limited to SEQ ID NO: 7 only.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sazani (PG Pub No. US 2010/0130591 A1).
Regarding claim 1, it is noted that the claimed SEQ ID NO: 11 is the antisense sequence of the claimed SEQ ID NO: 7 (Remarks filed 4 February 2026; pg. 12).
Sazani is directed towards an invention concerned with antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping, and methods of use thereof to treat muscular dystrophy (Abstract). Sazani teaches the use of an antisense oligomer sequence that is 25 base pairs in length, comprises a sequence that is 100% identical to the claimed SEQ ID NO: 11 and is complementary to the claimed SEQ ID NOs: 7 and SEQ ID NO: 35 that can induce skipping of exon 44 in the processing of human dystrophin pre-processed mRNA (i.e., the antisense oligonucleotide of Sazani is complementary to a target mRNA sequence of exon 44 of a human dystrophin gene that comprises a sequence that has 100% identity to the claimed SEQ ID NO: 35) ([0026]-[0027]; see SEQ ID NO: 16 in attached sequence alignment).
Sazani does not teach or suggest that the target DNA sequence encoding exon 44 of the human dystrophin gene is shortened by 4 base pairs such that it consisted the claimed SEQ ID NO: 7 (Claim 1). Sazani does not teach or suggest that the target mRNA nucleotide sequence that is targeted via the antisense oligonucleotide is shortened by 4 base pairs such that it consisted the claimed SEQ ID NO: 35 (Claim 1). Sazani does not teach or suggest that the nucleic acid molecule of claim 1 is shorted by 4 base pairs such that it consisted the claimed SEQ ID NO: 11 (Claim 5).
However, Sazani further teaches that oligomers for use in antisense applications can range in length from 15-25 bases, including those having 21 bases ([0176]). Sazani further teaches that a series of antisense oligonucleotides could be designed in order to target exon 44 of the human dystrophin gene and their effectiveness of skipping the exon tested ([0294]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antisense oligonucleotide of Sazani such that it was shortened by 4 base pairs such that the target sequence consisted of the claimed SEQ ID NO: 7, and the antisense sequence consisted of the claimed SEQ ID NO: 11, and the target mRNA sequence consisted of the claimed SEQ ID NO: 35. A person of ordinary skill in the art would have recognized that Sazani taught that there was a need in the art to design antisense oligonucleotides that could bind to, and induce skipping of, exon 44 via the use of an antisense oligonucleotide that comprises a sequence that has 100% identity to the claimed SEQ ID NO: 7 and 11 in the processing of a human dystrophin pre-processed mRNA that comprises the claimed SEQ ID NO: 35. A person of ordinary skill in the art would have recognized that there had been a finite number of identifiable, predictable solutions because Sazani teaches that oligomers for use in antisense applications can range in length from 15-25 bases, including those having specifically 21 bases. A person of ordinary skill in the art would have recognized that Sazani taught that series of antisense oligonucleotides that could target exon 44 of a human dystrophin gene could be designed and their effectiveness of skipping the exon tested.
Accordingly, a person of ordinary skill in the art would have recognized that the claimed SEQ ID NO: 11 antisense molecule that targets a sequence consisting of the claimed SEQ ID NO: 7 or mRNA sequence consisting of the claimed SEQ ID NO: 35 is a simple combination of applying known lengths for antisense oligonucleotides to a known sequence via a routine optimization of the length of the siRNA within prior art conditions.
Claim(s) 4, 6, 7-11, and 32-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sazani (PG Pub No. US 2010/0130591 A1) as applied to claims 1 and 5 above, and further in view of Flanigan (PG Pub No. US 2017/0218366 A1).
Regarding claim 5, it is noted that the claimed SEQ ID NO: 11 is the reverse complement of the claimed SEQ ID NO: 7 (Remarks filed 4 February 2026; pg. 8). Further, it is noted that the claimed SEQ ID NO: 19 is directed towards a U7 sequence that comprises the claimed SEQ ID NO: 11 (Remarks filed 4 February 2026; pg. 9).
Regarding claims 4 and 7-11, Sazani renders obvious claim 1 as described above. Sazani further teaches that vectors can be utilized to deliver the antisense oligomers ([0119]).
Sazani does not teach or suggest that the nucleic acid molecule comprises a nucleotide sequence having at least 90%, 95%, 96%, 98%, or 99% identity to the claimed SEQ ID NO: 19 (Claims 4, 6 and 32-35). Sazani does not teach or suggest the use of an rAAV comprising the genome comprising at least one of the nucleic acid molecules of claim 1 (Claim 7). Sazani does not teach or suggest that the genome is a self-complementary genome (Claim 8). Sazani does not teach or suggest that the rAAV is rAAV-1 (Claim 9). Sazani does not teach or suggest that the genome lacks AAV rep and cap DNA (Claim 10). Sazani does not teach or suggest that the rAAV of claim 10 further comprises an AAV-9 capsid (Claim 11).
However, one of ordinary skill in the art would have considered the teachings of Flanigan as both references are common fields of endeavor pertaining to the use of oligonucleotides to treat patients with mutations in a DMD gene.
Flanigan is drawn towards an invention concerned with the delivery of oligomers for treating patients with mutations in a DMD gene (Abstract). Flanigan teaches the use of an rAAV comprising a DMD exon 5 IRES-activating oligomer construct ([0022]). Flannigan teaches the use of a reverse complement of an rAAV genome insert that comprises a sequence that has 100% identity to the claimed SEQ ID NO: 19 other than an antisense oligonucleotide sequence, termed “C”, located at positions 888-900 of the AAV genome insert ([0038]; see FIG. 15B and SEQ ID NO: 26 in previously attached sequence alignment). Flanigan teaches the use of an AAV that comprises a self-complementary genome consisting of a DMD IRES-activating U7 snRNA polynucleotide construct ([0022]; see FIG. 15A-B). Flanigan teaches that the rAAV can be an rAAV-1 virus and can lack both AAV rep and cap DNA ([0022]). Flanigan teaches that the rAAV can further comprise an rAAV9 capsid ([0059]). Flanigan teaches that AAVs possess unique features that make it attractive as a vector for delivering foreign DNA to cells, for example, in gene therapy ([0009]). Flanigan teaches that AAVs infect many mammalian cells allowing the possibility of targeting many different tissues in vivo and that the AAV proviral genome is infectious as cloned DNA in plasmids which makes construction of recombinant genomes feasible ([0009]).
It is noted that Flannigan teaches the use of a reverse complement of an rAAV genome insert that comprises a sequence that has 100% identity to the claimed SEQ ID NO: 19 other than an antisense oligonucleotide sequence, termed “C”, located at positions 888-900 of the AAV genome insert. It is noted that if the antisense oligomer consisting of the claimed SEQ ID NO: 11 were instead present in the “C” position of Flannigan, the rAAV genome insert would comprise 100% identity to the claimed SEQ ID NO: 19 (see previously attached sequence alignment).
Therefore, regarding the delivery vector of the antisense molecule, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the delivery vector of Sazani for the rAAV-1 vector that is self-complementary, AAV rep and cap DNA, and comprises an rAAV9 capsid as described by Flanigan. A person of ordinary skill in the art would have had a reasonable expectation of success because both Sazani and Flanigan teach the use of functional delivery vectors that can deliver antisense oligonucleotides to DMD exons in order to treat patients with mutations in the DMD exons.
Further, regarding the claimed SEQ ID NO: 19, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the “C” antisense molecule sequence of Flanigan for the claimed antisense oligomer consisting of the claimed SEQ ID NO: 11 which targets a sequence consisting of the claimed SEQ ID NO: 7 and an mRNA sequence consisting of the claimed SEQ ID NO: 35, as rendered obvious by Sazani, in order to arrive at a nucleic acid comprising 100% identity to the claimed SEQ ID NO: 19. A person of ordinary skill in the art would have had a reasonable expectation of success because both Sazani and Flanigan teach the use of vectors that can deliver antisense oligonucleotides to DMD exons.
Response to Arguments
Applicant's arguments filed 4 February 2026 have been fully considered but they are not persuasive.
Applicant alleges that Sazani discloses an antisense oligonucleotide that is 25 base pairs in length and consists of four base pairs not found in the claimed SEQ ID NO: 7 or 11 of the pending claims (Remarks; pg. 11-12). Applicant alleges that Sazani’s disclosure of an antisense oligonucleotide comprising the claimed SEQ ID NO: 11 (i.e., an antisense oligonucleotide that targets a sequence that comprises the claimed SEQ ID NO: 7) does not render obvious the use of an antisense oligonucleotide that targets a nucleotide sequence that consists of the claimed SEQ ID NO: 7.
These arguments are not found persuasive because, as described above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the antisense oligonucleotide of Sazani such that the oligonucleotide sequence consisted of the claimed SEQ ID NO: 11 and the target sequence consisted of the claimed SEQ ID NO: 11 while the target mRNA sequence consisted of the claimed SEQ ID NO: 35.
A person of ordinary skill in the art would have recognized that Sazani taught that there was a need in the art to design antisense oligonucleotides that could bind to, and induce skipping of, exon 44 via the use of an antisense oligonucleotide that comprises a sequence that has 100% identity to the claimed SEQ ID NO: 7 in the processing of a human dystrophin pre-processed mRNA that comprises the claimed SEQ ID NO: 35. A person of ordinary skill in the art would have recognized that there had been a finite number of identifiable, predictable solutions because Sazani teaches that oligomers for use in antisense applications can range in length from 15-25 bases, including those having specifically 21 bases. A person of ordinary skill in the art would have recognized that Sazani taught that series of antisense oligonucleotides that could target exon 44 of a human dystrophin gene could be designed and their effectiveness of skipping the exon tested.
Accordingly, a person of ordinary skill in the art would have recognized that the claimed SEQ ID NO: 11 antisense molecule that targets a sequence consisting of the claimed SEQ ID NO: 7 or mRNA sequence consisting of the claimed SEQ ID NO: 35 is a simple combination of applying known lengths for antisense oligonucleotides to a known sequence via a routine optimization of the length of the siRNA within prior art conditions
Applicant alleges that Flanigan's products and methods work by targeting and activating an internal ribosome entry site in exon 5 of the DMD gene resulting in a functional truncated isoform of dystrophin (Remarks; pg. 15). Applicant alleges that Flanigan does not provide products and methods for targeting exon 44 of a DMD gene and does not teach or suggest target sequences on exon 44 of a DMD gene (Remarks; pg. 15)..
These arguments are not found persuasive because both Sazani and Flanigan teach the use of vectors that can deliver antisense oligonucleotides in order to skip exons of a DMD gene. Accordingly, one of ordinary skill in the art would have had a reasonable expectation of success in substituting the delivery vector of Sazani for the rAAV vector of Flanigan, alongside the substitution of the “C” antisense molecule sequence of Flanigan for the claimed SEQ ID NO: 11, as described above. Further, it is noted that Applicant admits that “[…] nucleotides 630 to 1059 of SEQ ID NO: 26 [(i.e., the AAV genome insert of Flanigan)] comprises a U7C sequence comprising mostly the U7 promoter sequence, which is the same promoter present in SEQ ID NO: 19 of the claimed subject matter. This shared promoter apparently accounts for most of the shared sequence identity over a part of SEQ ID NO: 26.” Thus, Applicant teaches that the AAV genome insert of Flanigan is identical to the claimed SEQ ID NO: 19 other than the “C’ antisense sequence of Flanigan present within the genome insert. Thus, as described above, one of ordinary skill in the art would have had a reasonable expectation of success in substituting the “C” antisense sequence of Flanigan for an antisense sequence consisting of the claimed SEQ ID NO: 11 in order to arrive at a vector comprising a sequence that has 100% identity to the claimed SEQ ID NO: 19.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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