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).
Response to Amendment
The amendment filed on 02/02/2026 has been received and entered into the application file.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 02/12/2026 lists a disclosure with the Publication No. 20180034467 under U.S. Patent Application Publications, listed as corresponding to Korean Publication No. 20180034467. There is no U.S. Patent Application Publication with the aforementioned document identification number. This reference has been lined through. Korean Publication No. 20180034467 is listed on the 02/12/2026 IDS under Foreign Patent Documents.
However, this is presumed to be an editing error. The IDS filed on 04/30/2026 lists Korean Publication No. 20180034467 under Foreign Patent Documents, and additionally lists Publication No. 20190032079 under U.S. Patent Application Publications; the latter shares the same Applicant and Publication Date as the erroneous document from the 02/12/2026 IDS.
Accordingly, and as indicated in the annotated copy of the 04/30/2026 IDS, both Korean Publication No. 20180034467 and U.S. Publication No. 20190032079 have been considered by the Examiner.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 50-63 under the written description requirement of 35 U.S.C. 112(a):
The amendment to claims 50-51 and 53-55 removing the functional variant thereof claim language is sufficient to obviate the rejections of record; accordingly, the rejections are withdrawn.
RE: Rejection of claims 50-63 under 35 U.S.C. 112(b) for indefiniteness:
The amendment to claims 50-51 and 53-55 removes the functional variant thereof claim language; similarly, the amendment to claim 52 removes the preferably claim language.
These amendments are sufficient to obviate the rejections of record; therefore, the rejections are withdrawn.
RE: Rejection of claims 50-63 under 35 U.S.C. 102(a)(1) and (a)(2) over Ding:
The amendment to claims 50-51 and 53-55 removes the functional variant thereof claim language. This changes the scope of the instant claims, as the instant claims are now directed to CREs/CRMs comprising the sequences recited therein; i.e., a sequence recited in the prior art must now share 100% sequence identity to a corresponding sequence recited in an instant claim in order to be within the scope of said claim.
Applicants assert Ding, et al. does not teach each and every element required by the claims; i.e., SEQ ID NO: 1 of Ding, et al. does not share 100% sequence identity to SEQ ID NO: 310 of claims 50-63. This argument is found persuasive.
Therefore, the rejections of record are withdrawn.
RE: Rejection of claims 50, 54, and 56-63 on the ground of nonstatutory double patenting over copending Application No. 18/572,668:
Applicants have requested the rejections of record be held in abeyance until allowable subject matter is identified.
Respectfully, Applicants are reminded 37 CFR 1.111 requires that replies by applicant or patent owner must reply to every ground of objection and rejection in the prior Office action. Only objections or requirements as to form not necessary to further consideration of the claims may be requested to be held in abeyance until allowable subject matter is indicated. Nonstatutory double patenting rejections may not be held in abeyance; see MPEP 714.02.
Applicants did not traverse the instant rejections of record; accordingly, the rejections 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)(1) and (a)(2) as being anticipated by Vandendriessche, et al. (US 2016/0340693).
Vandendriessche, et al. (assigned to Vrije Universiteit Brussel; hereinafter VUB) teaches nucleic acid regulatory elements which enhance muscle-specific expression of genes, in particular expression in cardiac muscle and/or skeletal muscle (Abstract).
Regarding claims 50, 54: VUB teaches a nucleic acid regulatory element for enhancing muscle specific gene expression comprising a sequence as set forth in SEQ ID NO: 10 (par. 0011). SEQ ID NO: 10 shares 100% sequence identity to SEQ ID NO: 329, i.e. CRE0079; please see end of Office action for all sequence alignments.
VUB further teaches an embodiment wherein two identical, operably linked regulatory elements are provided as tandem repeats; i.e., two regulatory elements which each comprise SEQ ID NO: 10 (pars. 0117-0119). This anticipates the synthetic cardiac muscle-specific CRM comprising two or more operably linked CREs (CRE0079) limitation recited in claim 50, as well as the synthetic cardiac muscle-specific promoter comprising at least one CRM of claim 50 limitation recited in claim 54.
Regarding claims 56-61: Following the above discussion, VUB teaches an embodiment wherein the nucleic acid regulatory elements are operably linked to a transgene (par. 0027) and contained within an expression cassette (par. 0025). Further disclosed is an embodiment wherein the expression cassette is contained with an adeno-associated viral (AAV) vector (pars. 0033-0034). 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;
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, VUB teaches an embodiment wherein the expression cassette is contained in a pharmaceutical composition (par. 0034); this anticipates 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, VUB teaches an embodiment wherein the vector is used to transport the nucleic acid molecule into a host cell (par. 0146); this anticipates the cell comprising a synthetic cardiac muscle-specific promoter of claim 54 limitation recited in claim 63.
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 50-52 and 54-63 are rejected under 35 U.S.C. 103 as being unpatentable over Vandendriessche, et al. (US 2016/0340693) in view of Schwartz, et al. (US 2003/0074679).
The teachings of VUB are set forth above; claims 50, 54, and 56-63 are anticipated by the same.
Schwartz, et al. teaches methods of administering a nucleic acid sequence (Abstract).
Regarding claims 51-52: It is set forth above VUB teaches a nucleic acid molecule comprising tandem repeats of a regulatory element comprising SEQ ID NO: 10 (pars. 0011, 0117-0119), which anticipates a CRM comprising CRE0079 adjacent a second CRE0079. VUB does not teach the remaining limitations of the instant claims.
However, Schwartz, et al. teaches synthetic promoter SPc5-12 comprising a sequence as set forth in SEQ ID NO: 6 (par. 0076). SEQ ID NO: 6 shares 100% sequence identity to SEQ ID NO: 321, or CRE0071; please see end of Office action for all sequence alignments.
Given that both SEQ ID NO: 10 of VUB (pars. 0077, 0084, 0091) and SEQ ID NO: 6 of Schwartz, et al. (par. 0076) are regulatory elements (e.g., enhancer, promoter) capable of increasing and/or driving gene expression in muscle cells, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the nucleic acid molecule of VUB by substituting the second regulatory element comprising SEQ ID NO: 10 with the synthetic promoter SPc5-12 comprising SEQ ID NO: 6 of Schwartz, et al. This conclusion of obviousness is based on the ‘substitution rationale’. The use of the SPc5-12 molecule of Schwartz, et al. in place of the nucleic acid regulatory element of VUB is a predictable use of prior art elements according to their established functions as gene expression regulatory elements, leading to the predictable result of a nucleic acid molecule capable of driving gene expression in muscle cells. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
Thus, the modified nucleic acid molecule set forth above reads on the synthetic cardiac muscle-specific CRM comprising a combination of CRE0079 and CRE0071 limitation recited in claim 51, as well as the wherein the CREs are present in the recited order and adjacent to one another limitation recited in claim 52.
Regarding claim 55: Following the above discussion, Table D of the instant Specification evidences SP0366 comprises CRE0079 adjacent CRE0071 (pg. 26). Thus, the modified nucleic acid molecule of VUB reads on the synthetic cardiac muscle-specific promoter of claim 54, wherein the promoter is SP0366 limitation recited in claim 55.
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, 54, and 56-63 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 as 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. 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 claim 50 over copending Application No. 18/572,668.
Regarding claim 56: Following the above discussion, copending claim 12 recites an expression cassette comprising a synthetic muscle specific promoter operably linked to a sequence encoding an expression product; this reads on the limitations of claim 56.
Regarding claims 57-61: Copending claims 13-15 of copending Application No. 18/572,668 recite a vector comprising the synthetic muscle specific promoter or expression cassette (copending claim 13), which reads on the limitations of instant claims 57-58; wherein the vector is an AAV vector, an adenoviral vector, a retroviral vector, or a lentiviral vector (copending claim 14), which reads on the limitations of instant claims 59-60; a virion comprising the vector (copending claim 15), which reads on the limitations of instant claim 61.
Regarding claim 62: Copending claim 16 recites a pharmaceutical composition comprising the synthetic muscle specific promoter, expression cassette, vector, or virion; this reads on the limitations recited in instant claim 62.
Regarding claim 63: Copending claim 18 recites a cell comprising the synthetic muscle-specific promoter, expression cassette, vector, or virion; this reads on the limitations recited in instant claim 63.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Objections
Claim 53 is 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. 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, 514, 519-520, 523-525, 527-528, 530, 549 are free from the prior art.
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 GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
SEQUENCE ALIGNMENTS
Query, ‘Qy’ (SEQ ID NO: 329) vs. Database, ‘Db’ (‘VUB’ US 2016/0340693; SEQ ID NO: 10)
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330
695
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Greyscale
Query, ‘Qy’ (SEQ ID NO: 321) vs. Database, ‘Db’ (Schwartz, et al. US 2003/0074679; SEQ ID NO: 6)
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544
762
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Greyscale
Prosecution Insights