CTFR 17/921,336 CTFR 99556 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. This action is in response to the amendment filed 03/23/2026, in which claims 1, 19, 20, 23 and 44 were amended, claims 8-10, 13, 14 and 24 were previously presented, and claims 25, 28, 30, 31, 36, 38, 40 and 43 were withdrawn due to a restriction election mailed in a previous office action. Claims 1, 8-10, 13, 14, 19, 20, 23, 24 and 44 are currently pending. Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the reasons that follow. Any rejection and objections not reiterated in this action have been withdrawn. This action is FINAL. Information Disclosure Statement Receipt of acknowledgment of the information disclosure statements filed on 02/23/2026 and 04/15/2026 have been received and all references have been considered. Claim Rejections - 35 USC § 112 07-36 AIA 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. 07-36-01 AIA Claim 8 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. Independent claim 1 requires “A vector composition comprising:(a) a polynucleotide sequence encoding at least one guide RNA (gRNA);(b) a polynucleotide sequence encoding a Cas9 protein or a fusion protein comprising the Cas9 protein; and(c) one or more muscle specific promoters, each promoter operably linked to the polynucleotide sequence encoding the at least one gRNA and/or the polynucleotide sequence encoding the Cas9 protein or fusion protein, wherein the one or more muscle specific promoters are selected from a SPc5-12 promoter or a MHCK7 promoter or a combination thereof”. Claim 8 does not further limit claim 1 in that claim recites “The composition of claim 1, wherein the composition comprises a single vector that comprises (a) the polynucleotide sequence encoding at least one gRNA, (b) the polynucleotide sequence encoding a Cas9 protein or a fusion protein comprising the Cas9 protein, and (c) the one or more promoters”, therefore, containing all the limitations of independent claim 1 but not any additional limitations that would further limit claim 1 . 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. Response to Amendments - Claim Rejections - 35 USC § 112 The previous rejection of claim 19 under 35 U.S.C. 112(b), second paragraph, has been withdrawn in view of Applicant’s amendments to the claims filed on 03/23/2026. Claim Rejections - 35 USC § 101 The previous rejection of claim 23 under 35 U.S.C. 101, has been withdrawn in view of Applicant’s amendments to the claims filed on 03/23/2026. Claim Rejections - 35 USC § 102 The previous rejection of claims 1, 3, 8-10, 13, 14, 19, 20, 23, 24 and 44 under 35 U.S.C. 102(a)(1)/(a)(2), has been withdrawn in view of Applicant’s amendments to the claims filed on 03/23/2026. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-21-aia AIA Claim s 1, 8-10, 13, 14, 19, 23 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Chamberlain et al (US 2017/0362635 A1; Cited in a Prior Office Action) in view of Rodino-Klapac et al (WO 2019/078916 A1). This is a NEW Rejection necessitated by the amendment filed on 03/23/2026 . Regarding claims 1, 8 and 19, Chamberlain teaches a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs (Page 2, Figure 1 and [0006]). Chamberlain does not teach the use of the muscle specific MHCK7 promoter. Rodino-Klapac teaches a recombinant AAV vector comprising the human micro-dystrophin nucleotide sequence and the MHCK7 promoter sequence (SEQ ID NO: 2) for treatment of muscular dystrophy, wherein the sequence of SEQ ID NO: 2 is 100% identical to instant SEQ ID NO: 53 (See Appendix I; [0043]; Page 49, Figure 1 and Page 58, Figure 10). 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 muscle specific CK8 promoter of Chamberlain for the muscle specific MHCK7 promoter as taught by Rodino-Klapac because Chamberlain teaches it is within the ordinary skill in the art to use a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs and Rodino-Klapac teaches a recombinant AAV vector comprising the human micro-dystrophin nucleotide sequence and the MHCK7 promoter sequence (SEQ ID NO: 2) for treatment of muscular dystrophy, wherein the sequence of SEQ ID NO: 2 is 100% identical to instant SEQ ID NO: 53. One would have been motivated to make such a modification in order to receive the expected benefit of muscle specific expression using the MHCK7 promoter as taught by Rodino-Klapac. Regarding claims 9 and 10, Chamberlain teaches two vectors wherein one vector comprises sgRNAs operably linked to U6 promoters and a second vector comprising a SpCas9 protein operably linked to the muscle specific CK8 promoter (Page 2, Figure 1 and [0006]). Regarding claims 13 and 14, Chamberlain teaches the vector of strategy one comprising a CK8 promoter operably linked to the SpCas9 protein along with a gRNA operably linked to the U6 promoter, co-transduced with a second vector of strategy one comprising a CK8 promoter operably linked to an SaCas9 protein along with a gRNA operably linked to the U6 promoter [0010 and 0048]. Chamberlain teaches that both single- and dual- vector approaches yielded widespread dystrophin expression in the heart [0048]. Regarding claim 23, Chamberlain teaches administration of the vector comprising a gRNA and CK8 operably linked to a SpCas9 to a HEK293 cell [0071]. Regarding claim 24, “A kit” is interpreted as a collection of items. Therefore, prior art teaching the collection of items, in the instant case the composition, also teaches the kit comprising the composition. Chamberlain teaches a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs (Page 2, Figure 1 and [0006]) . 07-22-aia AIA Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Chamberlain et al (US 2017/0362635 A1; Cited in a Prior Office Action) in view of Rodino-Klapac et al (WO 2019/078916 A1) as applied to claim s 1, 8-10, 13, 14, 19, 23 and 24 above, and further in view of Gersbach et al (WO 2014/197748 A2) and Wilson et al (US 2019/0078119 A1). This is a NEW Rejection necessitated by the amendment filed on 03/23/2026 . The teachings of Chamberlain and Rodino-Klapac are described above and applied as before. Regarding claim 20, Chamberlain teaches a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs (Page 2, Figure 1 and [0006]). Chamberlain teaches AAV vectors derived from serotypes 6, 8, and 9 have shown considerable promise in animal models for DMD by enabling systemic delivery of genetic cassettes that can partially compensate for the absence of dystrophin [0004]. Chamberlain teaches spCas9 nuclease expression cassette was generated by PCR cloning of NLS-SpCas9-NLS from LentiCRISPRvl and insertion into pAAV (STRATAGENE™) containing the muscle-specific creatine kinase 8 (CK8) [0071]. Chamberlain and Rodino-Klapac do not teach the specific use of pAAV2/8 delivery vector for the delivery of the composition. Gersbach teaches schematic diagrams of a "Single vector, multiplex CRISPR system," Dual vector, multiplex CRISPR system," and "Single vector, single gRNA system” wherein each vector comprises, at least, a Cas9 protein, at least one guide RNA and a promoter ([0073] and Page 180, Fig. 39). Gersbach teaches the modified AAV vector based on AAV2 pseudotype with alternative muscle-tropic AAV capsids, such as AAV2/8 vectors that efficiently transduce skeletal muscle or cardiac muscle by systemic and local delivery [00208]. Gersbach does not teach the specific sequence of SEQ ID NO: 56 for the pAAV2/8. Wilson teaches vectors employing the AAV8 mutant capsid show increased transduction in a selected tissue as compared to AAV8 (Page 1, Abstract). Wilson teaches the delivery vector of pAAV2/8 plasmid as SEQ ID NO: 43 which is 100% identical to instant SEQ ID NO: 56 (See Appendix II; [0144]). 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 AAV delivery vectors of Chamberlain and Rodino-Klapac for the pAAV2/8 delivery vector as taught by Wilson and Gersbach because Chamberlain teaches it is within the ordinary skill in the art to use teaches spCas9 nuclease expression cassette was generated by PCR cloning of NLS-SpCas9-NLS from LentiCRISPRvl and insertion into pAAV (STRATAGENE™) containing the muscle-specific creatine kinase 8 (CK8), Rodino-Klapac teaches a recombinant AAV vector comprising the human micro-dystrophin nucleotide sequence and the MHCK7 promoter sequence (SEQ ID NO: 2) for treatment of muscular dystrophy, wherein the sequence of SEQ ID NO: 2 is 100% identical to instant SEQ ID NO: 53, Gersbach teaches the modified AAV vector based on AAV2 pseudotype with alternative muscle-tropic AAV capsids, such as AAV2/8 vectors that efficiently transduce skeletal muscle or cardiac muscle by systemic and local delivery and Wilson teaches the delivery vector of pAAV2/8 plasmid as SEQ ID NO: 43 which is 100% identical to instant SEQ ID NO: 56. One would have been motivated to make such a modification in order to receive the expected benefit of AAV2/8 vectors that efficiently transduce skeletal muscle or cardiac muscle by systemic and local delivery with the specific sequence of SEQ ID NO: 43 as taught by Gersbach and Wilson . 07-22-aia AIA Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Chamberlain et al (US 2017/0362635 A1; Cited in a prior Office Action) in view of Rodino-Klapac et al (WO 2019/078916 A1) as applied to claim s 1, 8-10, 13, 14, 19, 23 and 24 above, and further in view of Gersbach et al (WO 2014/197748 A2). This is a NEW Rejection necessitated by the amendment filed on 03/23/2026 . The teachings of Chamberlain and Rodino-Klapac are described above and applied as before. Regarding claim 44, Chamberlain teaches a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs (Page 2, Figure 1 and [0006]). Chamberlain and Rodino-Klapac do not teach the specific gRNA sequence of SEQ ID NOs: 49, 50, 60 and/or 61. Gersbach teaches schematic diagrams of a "Single vector, multiplex CRISPR system," Dual vector, multiplex CRISPR system," and "Single vector, single gRNA system” wherein each vector comprises, at least, a Cas9 protein, at least one guide RNA and a promoter ([0073] and Page 180, Fig. 39). Gersbach teaches the gRNA comprises a nucleotide sequence of SEQ ID NO: 120 which is 100% identical to instant SEQ ID NO: 49 for the targeting of the DMD gene at intron 22 (See Appendix III; Page 93, Table 6). 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 gRNA sequence of Chamberlain for the gRNA sequence of SEQ ID NO: 49 as taught by Gersbach because Chamberlain teaches it is within the ordinary skill in the art to use a single vector comprising an SpCas9 operably linked to a muscle specific promoter, CK8, and two gRNAs, Rodino-Klapac teaches a recombinant AAV vector comprising the human micro-dystrophin nucleotide sequence and the MHCK7 promoter sequence (SEQ ID NO: 2) for treatment of muscular dystrophy, wherein the sequence of SEQ ID NO: 2 is 100% identical to instant SEQ ID NO: 53 and Gersbach teaches a vector construct wherein each vector comprises, at least, a Cas9 protein, at least one guide RNA and a promoter and the gRNA nucleotide sequence of SEQ ID NO: 120 which is 100% identical to instant SEQ ID NO: 49 for the targeting of the DMD gene at intron 22. One would have been motivated to make such a modification in order to receive the expected benefit of targeting of the DMD gene at intron 22 using the specific gRNA as taught by Gersbach. Conclusion 07-40 AIA 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 ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm 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, JENNIFER A DUNSTON can be reached at (571) 272-2916. 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. /ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637 /CELINE X QIAN/Primary Examiner, Art Unit 1637 Application/Control Number: 17/921,336 Page 2 Art Unit: 1637 Application/Control Number: 17/921,336 Page 3 Art Unit: 1637 Application/Control Number: 17/921,336 Page 4 Art Unit: 1637 Application/Control Number: 17/921,336 Page 5 Art Unit: 1637 Application/Control Number: 17/921,336 Page 6 Art Unit: 1637 Application/Control Number: 17/921,336 Page 7 Art Unit: 1637 Application/Control Number: 17/921,336 Page 8 Art Unit: 1637 Application/Control Number: 17/921,336 Page 9 Art Unit: 1637 Application/Control Number: 17/921,336 Page 10 Art Unit: 1637
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