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 .
Priority
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/GB2020/053371 (filed 12/24/2020). Acknowledgement is made of Applicants’ claim for priority to foreign applications GB2012192.7 (filed 08/05/2020) and GB1919269.9 (filed 12/24/2019).
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/21/2026 has been entered.
Response to Amendment
The amendment filed on 07/22/2026 has been received and entered into the application file.
Status of Prior Rejections/Response to Arguments
RE: Rejections of claims 50, 54, and 56-63 under 35 U.S.C. 102(a)(1) and (a)(2) over Vandendriessche:
The amendment filed on 07/22/2026 removes CRE0079 (i.e., SEQ ID NO: 329) from independent claim 50. This is effective to obviate the rejections of record for claims 50, 54, and 56-63.
Accordingly, the rejections are withdrawn.
RE: Rejections of claims 51-52 and 55 under 35 U.S.C. 103 over Vandendriessche in view of Schwartz:
The amendment removing CRE0079 (i.e., SEQ ID NO: 329) from independent claim 50 is effective to obviate the rejections of record for claims 51-52 and 55; accordingly, the rejections are withdrawn.
However, as Schwartz is relied upon for rejections set forth below, and in the interest of compact prosecution, the arguments pertaining thereto will now be addressed.
Applicants’ assert Schwartz does not teach two or more of CRE0071 (i.e., SEQ ID NO: 321). Respectfully, this argument is not found persuasive.
As per MPEP 2143(I)(A), a prima facie case for obviousness exists when there is a finding that the prior art included each elements claimed, with the only difference between the claimed invention and the prior art being the lack of actual combination of the elements; a finding that one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately; and a finding that one of ordinary skill in the art would have recognized that the results of the combination were predictable. Schwartz teaches synthetic myogenic promoter SPc5-12 having a sequence as set forth in SEQ ID NO: 6 (par. 0076), which shares 100% sequence identity with instant SEQ ID NOs: 321 and 314 (i.e., CRE0071 and CRE0051, respectively); please see Office Action Appendix I for sequence alignments and percent identity (pg. 4). Thus, Schwartz teaches the claimed elements, with the only difference being the lack of combination of said elements. Additionally, Schwartz itself evidences the skilled artisan could have combined the elements as claimed by known methods, as the disclosure teaches promoters may be operably linked to other cis-acting regulatory elements such as enhancers (pars. 0087-0090). Further, as evidenced by Arboleda-Velasquez (US 2023/0190959), the use of multiple promoters is a well-known, predictable technique in the art (par. 0012).
Applicants’ further assert Schwartz the synthetic promoter SPc5-12 is limited to skeletal muscle. Respectfully, this argument is not found persuasive. As evidenced by Le Guiner, et al. (Nat Commun. 2017), SPc5-12 is a synthetic muscle- and heart-specific promoter (pg. 2; col. 2, par. 1).
RE: Rejection of claims 50, 54, and 56-63 on the ground of nonstatutory double patenting over copending Application No. 18/572,668:
The amendment to copending Application No. 18/572,668 filed on 06/02/2026 is effective to obviate the rejections of record for instant claims 56-63; accordingly, these rejections are withdrawn.
Applicants’ have requested withdrawal of the instant rejections in a traversal thereof based on the earlier patent term filing date of the instant application. Respectfully, MPEP 804(I)(B)(1)(b)(i) is applicable when a provisional nonstatutory double patenting rejection is the only rejection remaining in an application.
As there are new grounds of prior art rejections set forth below, the remaining provisional nonstatutory double patenting rejections of record for claims 50 and 54 are maintained.
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claims 50-54: These claims recite limitations drawn to cis-regulatory elements (CREs) and/or cis-regulatory modules (CRMs). The term CRE is interpreted as a nucleic acid sequence such as an enhancer, promoter, insulator, or silencer, that can regulate or modulate the transcription of a neighboring gene; this interpretation is supported by the instant specification (pg. 137, lines 12-14). The term CRM is interpreted as a nucleic acid module, comprising two or more CREs; this interpretation is supported by the instant specification (pg. 138, lines 14-15).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 50, 54, and 56-63 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Arboleda-Velasquez (US 2023/0190959).
Arboleda-Velasquez teaches compositions, formulas, and methods for inhibiting, treating, and preventing small vessel disease (Abstract).
Regarding claims 50, 54: Arboleda-Velasquez teaches a promoter sequence for human transgelin (i.e., TAGLN, SM22α), comprising a nucleic acid sequence as set forth in SEQ ID NO: 15 (par. 0050); in an embodiment, two promoters are combined to achieve cell type specificity (par. 0012). SEQ ID NO: 15 shares 100% sequence identity with instant SEQ ID NO: 308; please see Office Action Appendix I for sequence alignments and percent identity (pgs. 2-3). Thus, Arboleda-Velasquez anticipates:
the synthetic cardiac muscle-specific CRM comprising two or more operably linked CRE0031s limitation recited in claim 50; and
the synthetic cardiac muscle-specific promoter comprising one CRM of claim 50 limitation recited in claim 54.
Regarding claims 56-60: Following the above discussion, Arboleda-Velasquez teaches a genetic construct comprising the promoter, wherein the promoter is operably linked to a NOTCH3 coding sequence; in an embodiment, an adeno-associated viral vector comprises said construct (par. 0009). This anticipates:
the expression cassette comprising a synthetic cardiac muscle-specific promoter of claim 54 operably linked to a sequence encoding an expression product limitation recited in claim 56;
the vector comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 57;
the vector comprising an expression cassette according to claim 56 limitation recited in claim 58; and
the AAV vector limitations recited in claims 59 and 60.
Regarding claims 61, 63: Following the above discussion, Arboleda-Velasquez teaches an embodiment wherein the viral nucleic acid molecule (e.g., in a viral particle) is transfected or transformed into a host cell (par. 0014). This anticipates:
the virion comprising a vector according to claim 57 limitation recited in claim 61; and
the cell comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 63.
Regarding claim 62: Following the above discussion, Arboleda-Velasquez teaches an embodiment wherein a pharmaceutical composition comprising the vector is administered to a subject (see e.g., pars. 0190, 0194, 0198-0199); this anticipates the pharmaceutical composition comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 62.
Claim Rejections - 35 USC § 103
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.
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 50, 54, and 56-63 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz, et al. (US 2003/0074679), as evidenced by Le Guiner, et al. (Nat Commun. 2017) and Arboleda-Velasquez (US 2023/0190959).
Schwartz, et al. (hereinafter Schwartz) teaches nucleic acids and vectors encoding growth hormone releasing hormone, and methods comprising use thereof (Abstract).
Regarding claims 50, 54: Schwartz teaches synthetic myogenic promoter SPc5-12, comprising a nucleic acid sequence as set forth in SEQ ID NO: 6 (par. 0076). SEQ ID NO: 6 shares 100% sequence identity with instant SEQ ID NOs: 321 and 314; please see Office Action Appendix I for sequence alignments and percent identity (pg. 4). As evidenced by Le Guiner, et al. (Nat Commun. 2017), SPc5-12 is a synthetic muscle- and heart-specific promoter (pg. 2; col. 2, par. 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the SPc5-12 promoter of Schwartz by operably linking it with a second SPc5-12 promoter. This conclusion of obviousness is based on the ‘combining known alternatives rationale’. Schwartz discloses the inclusion of an SPc5-12 promoter in an expression vector (pars. 0085-0086); additionally, the disclosure teaches molecular cloning techniques, e.g., ligation (par. 0097), for combining two nucleic acid molecules. Further, as evidenced by Arboleda-Velasquez, the use of multiple promoters is a well-known technique in the art (par. 0012). Both Schwartz and Arboleda-Velasquez illustrate the skilled artisan would have more than a reasonable expectation of success in combining two promoters. Thus, the combination of two SPc5-12 promoters using methods for molecular cloning known in the art is a predictable use of known alternatives for directing expression of a coding sequence to a cell, leading to the predictable result of expression of the coding sequence product in said cell. This rationale aligns with the principle of combining known prior art elements according to known methods to yield predictable results; see MPEP 2143(I)(A).
Therefore, the modified tandem SPc5-12 promoter of Schwartz renders obvious the:
the synthetic cardiac muscle-specific CRM comprising two or more operably linked CREs selected from the group consisting of CRE0071 and CRE0051 limitation recited in claim 50; and
the synthetic cardiac muscle-specific promoter comprising one CRM of claim 50 limitation recited in claim 54.
Regarding claims 56-61: Following the above discussion, Schwartz teaches an expression vector comprising the promoter operably linked to a nucleotide sequence encoding a growth hormone releasing hormone, wherein the vector is an adeno-associated virus vector (pars. 0085-0086); this renders obvious:
the expression cassette comprising a synthetic cardiac muscle-specific promoter of claim 54 operably linked to a sequence encoding an expression product limitation recited in claim 56;
the vector comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 57;
the vector comprising an expression cassette according to claim 56 limitation recited in claim 58;
the AAV vector limitations recited in claims 59 and 60; and
the virion comprising a vector according to claim 57 limitation recited in claim 61.
Regarding claim 62: Following the above discussion, Schwartz teaches a pharmaceutical composition comprising the vector (par. 0127); this renders obvious the pharmaceutical composition comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 62.
Regarding claim 63: Following the above discussion, Schwartz teaches a host cell comprising the vector (par. 0315); this renders obvious the cell comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 63.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 50 and 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 8, 12-16, and 18 of copending Application No. 18/572,668 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 50, 54: Copending claim 6 recites a muscle-specific cis-regulatory element (CRE) comprising a sequence according to any one of SEQ ID NOs: 48-61 or 67. Copending SEQ ID NO: 61 is identical to instant SEQ ID NO: 320; both sequences teach CRE0069. Copending SEQ ID NO: 67 is identical to instant SEQ ID NO: 308; both sequences teach CRE0031. Please see Office Action Appendix I for sequence alignments and percent identity (pg. 5). Additionally, copending claim 8 recites a synthetic muscle-specific promoter comprising a CRE according to claim 6.
Copending Application No. 18/572,668 does not teach a cis-regulatory module (CRM) comprising two or more operably linked CREs.
However, copending Application No. 18/572,668 does teach each of CRE0069 and CRE0031; further, methods of DNA recombination are well known in the art (e.g., sequence and ligation independent cloning, restriction enzyme mediated integration). Thus, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the muscle-specific CRE of copending Application No. 18/572,668 by combining it with a second muscle-specific CRE, using methods for the generation of recombination known in the art; such a modification would result in a synthetic muscle-specific CRE comprising CRE0031 and CRE0069, which reads on the limitations recited in instant claims 50 and 54.
This conclusion of obviousness is based on the ‘combining known alternatives rationale’; the combination of two muscle-specific CREs is a predictable use of known alternatives of non-coding DNA involved in transcription regulation, leading to the predictable result of enhancing gene transcription. This rationale aligns with the principle of combining known prior art elements according to known methods to yield predictable results; see MPEP 2143(I)(A). This renders obvious the limitations recited in claims 50 and 54 over copending Application No. 18/572,668.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Objections
Claims 51-52 and 55 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Allowable Subject Matter - Claims
Claim 53 is allowed.
Allowable Subject Matter - Sequences
SEQ ID NOs: 145, 161, 169, 171-176, 184-188, 198, 200-202, 211, 216-217, 221, 226, 232-233, 236-237, 249, 251, 253, 303, 307, 310-311, 320, 417, 514, 519-520, 523-525, 527-528, 530, 549 are free from the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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