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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 17 August 2026 has been entered.
Application Status
This action is written in response to applicant’s correspondence received 17 August 2026. Claims 1, 6-22, and 25-37 are currently pending. Claims 12-22 and 25-31 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1, 6-11, and 32-37 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 The species election between the claimed SEQ ID NOs: 7, 11, and 19, mailed 12 May 2025, was previously withdrawn.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant's arguments 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 § 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, 6-11, and 32-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sazani (PG Pub No. US 2010/0130591 A1) in view of Flanigan (PG Pub No. US 2017/0218366 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). 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).
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 further teaches that vectors can be utilized to deliver the antisense oligomers ([0119]).
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 comprises a nucleotide sequence having at least 90%, 95%, 96%, 98%, or 99% identity to the claimed SEQ ID NO: 19 (Claims 1, 6 and 32-36).
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]).
Additionally, 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, 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
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 in utilizing the rAAV genome insert of Flanigan to deliver the antisense molecule of Sazani because both Sazani and Flanigan teach the use of delivery vectors that can successfully deliver antisense oligonucleotides to DMD exons.
Regarding claims 7-11, 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). Sazani does not teach or suggest the use of an rAAV comprising a genome comprising the nucleic acid molecule of claim 36 (Claim 37).
However, the Applicable teachings of Flanigan are discussed above.
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 in utilizing the rAAV genome insert of Flanigan to deliver the antisense molecule of Sazani 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.
Response to Arguments
Applicant's arguments filed 30 June 2026 have been fully considered but they are not persuasive.
Applicant alleges that the examiner's combination requires both (a) shortening Sazani's 25-mer antisense oligonucleotide to the specific 21-mer of SEQ ID NO: 11 and (b) substituting that shortened sequence into Flanigan's exon 5-targeting construct in place of the "C" antisense sequence at positions 888-900 of the AAV genome insert (remarks; pg. 8). Applicant submits that this combination requires impermissible hindsight reconstruction (Remarks; pg. 8).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ209 (CCPA 1971).
Applicant alleges that Sazani's SEQ ID NO: 16 was not among the five sequences that Sazani identified as effective for exon 44 skipping (Remarks; pg. 8). Applicant alleges that this further undermines the motivation to select and shorten this particular sequence from among Sazani's twenty exon 44-targeting oligonucleotides (Remarks; pg. 8).
This argument is not found persuasive because Sazani explicitly teaches that SEQ ID NOs: 1-20 can be used as an antisense molecule that can target and skip exon 44 of a human dystrophin pre-processed mRNA ([0026]-[0027]). Additionally, Sazani teaches that SEQ ID NO: 16 is an oligonucleotide that can target exon 44 of a splice site of a human DMD gene (pg. 26 and 46). Therefore, one of ordinary skill in the art would have recognized that the SEQ ID NO: 16 of Sazani could be utilized to target exon 44 of a human dystrophin gene in order to induce exon skipping. Because Sazani further teaches that inducing skipping of exon 44 is a therapeutic strategy for the treatment of muscular dystrophy through the binding of the antisense molecules to selected target sites in the human dystrophin gene (Abstract), one would have recognized that Sazani identified a need in the art to target exon 44 with at least the twenty exon 44- targeting oligonucleotides disclosed.
Applicant alleges that the shared promoter sequence of Flanigan's construct and the claimed SEQ ID NO: 19 is coincidental and does not provide motivation to substitute the antisense sequences (Remarks; pg. 8- 9). Applicant alleges that one of ordinary skill in the art would not have been motivated to look to Flanigan's IRES-activating construct, which targets exon 5, as a scaffold for an exon 44 skipping sequence because the two references are directed to entirely different exons and mechanisms (Remarks; pg. 8-9).
These arguments are not found persuasive because MPEP 2144 teaches that the references do not have to explicitly suggest to combine the teachings. Rather, establishing a prima facie case of obviousness requires a clear articulation of a rationale for combining the teachings of the references, and such rationale has been provided in the previously recited 35 USC 103 rejection of record. Because both Sazani and Flanigan teach the use of delivery vector scaffolds that can deliver antisense molecules to a target exon of interest within a DMD gene, as discussed in the currently outstanding 35 USC 103 rejection of record, one would have expected substituting the delivery vector of Sazani for the rAAV genome insert of Flanigan to have similarly been able to successfully deliver the antisense molecule of Sazani to a DMD exon of interest within a cell of interest. Accordingly, claims 1, 6-11, and 32-35 remain rejected under the previously recited 35 USC 103 rejection that combined the disclosures of Sazani and Flanigan.
With regard to the newly added claim 36-37, it is noted that claim 36 is limited to part b) of claim 1 which was previously rejected under 35 USC 103 and addressed in the arguments above. It is also noted that claim 37 recites identical limitations to claim 7 which was previously rejected under 35 USC 103 as applied to claim 7. Accordingly, claims 36-37 remain rejected under the previously recited 35 USC 103 rejection that combined the disclosures of Sazani and Flanigan.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 Mon-Fri, 9AM-5PM (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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights