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 .
1. Claims 1, 2, 4, 6, 8, 9, 11 – 16, 18, and 20 – 23 are pending.
Election/Restrictions
2. Applicant's election with traverse of Group I (claims 1, 2, and 4) in the reply filed on 06/02/2026 is acknowledged. The traversal is on the ground(s) that Groups 4 – 8 (claims 12 – 16 and 18) necessarily contain the subject matter of Group I and thus should be included in the search of Group I because it would not create an undue search burden on the Examiner. This is found persuasive and the restriction requirement between Group I and Groups 4 – 8 is withdrawn. Therefore, claims 1, 2, 4, 12 – 16 and 18 are under consideration.
3. Claims 6, 8, 9, 11, and 20 – 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/02/2026.
4. Applicant’s election of a cis-regulatory module (CRM) comprising a sequence that is at least 95% identical to SEQ ID NO: 47 in the reply filed on 06/02/2026 is acknowledged. Applicant’s election is interpreted as election of “b) a cis-regulatory module (CRM) comprising a sequence according to SEQ ID NO: 47 or a functional variant thereof” of claim 1. Applicant’s election is interpreted as election of “wherein the CRM of b) comprises a sequence which is at least 95% identical to SEQ ID NO: 47” of claim 2.
Priority
5. This application is a 35 U.S.C. § 371 National Phase Entry Application of International Application No. PCT/GB2022/051611 filed June 23, 2022, which claims benefit of GB Application Nos. 2108997.4 filed June 23, 2021, and 2111317.0 filed August 5, 2021.
Information Disclosure Statement
6. The information disclosure statement (IDS) submitted on 12/20/2023 and 05/14/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
7. The information disclosure statement filed 05/14/2026 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. A copy of Non-Patent Literature Cite No. 4 has not been provided.
Drawings
8. The drawings filed on 12/03/2020 are acknowledged.
Specification
9. The disclosure is objected to because it contains an embedded hyperlink (at page 29) and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
10. The use of the term Glutamax, Milli-Q, Dual Luciferase, FLUOstar Omega, ONE-Glo, Taqman, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
11. Claim 12 is objected to because of the following informalities: in line 1, “a synthetic muscle-“ should read “the synthetic muscle-“ to clarify that it is the same synthetic muscle-specific promoter recited in claim 1. Appropriate correction is required.
12. Claim 13 is objected to because of the following informalities: in line 1, “a synthetic muscle-specific“ should read “the synthetic muscle-specific“ to clarify that it is the same synthetic muscle-specific promoter recited in claim 1. Appropriate correction is required.
13. Claim 15 is objected to because of the following informalities: “a vector“ should read “the vector“ to clarify that it is the vector recited in claim 13. Appropriate correction is required.
14. Claim 16 is objected to because of the following informalities: in line 1, “a synthetic “ should read “the synthetic “ to clarify that it is the same synthetic muscle-specific promoter recited in claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
15. Claim 1, 4, 12 – 16, and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims encompass a sequence according to any one of SEQ ID NOs: 1 – 29, 66 or a functional variant thereof or a sequence according to any one of SEQ ID NOs: 30 – 47 or a functional variant thereof. Thus, the claims encompass a genus of nucleic acids. However, the instant specification fails to describe the entire genus of functional variants of the recited SEQ ID NOs. Thus, the genus of nucleic acids, which, when comprised in a synthetic muscle-specific promoter as claimed, lacks a written description, and as such, there is no indication that Applicants had possession of the claimed invention.
From the specification, it is clear that Applicants have possession of the recited SEQ ID NOs 1 -29, 66, and 30 – 47 (listed in Tables 1 and 2). However, the claims are not limited to a nucleic acid with the specific structure and sequence of these SEQ IDs. The claims only require a functional variant be a variant of a reference sequence that retains the ability to function in the same way as the reference sequence as defined in the specification at page 55, lines 9 – 15. The specification fails to teach or describe any other nucleic acid which is a variant of the recited SEQ IDs of claim 1 and functions in the same way.
The claimed invention as a whole is not adequately described if the claims require essential or critical elements which are not adequately described in the specification, and are not conventional in the art as of Applicant’s effective filing date. Possession may be shown by actual reduction to practice, clear depiction of the claimed invention in a detailed drawing, or by describing the invention with sufficient, relevant, identifying characteristics (as it relates to the claimed invention as a whole), such that one of skill in the art would recognize that the inventor had possession of the claimed invention. Pfaff v. Wells Electronics, Inc., 48 USPQ2d 1641, 1646 (1998). In the instant case, the breadth of the genus of functional variants of the recited SEQ ID NOs of claim 1, lacks a written description. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the specification is that a functional variant of a CRM can comprise substitutions, deletions and/or insertions compared to a reference CRM, provided they do not render the CRM substantially non-functional (page 29, lines 20 – 26); and functional variants of a synthetic muscle-specific promoter often retain a significant level of sequence similarity to a reference synthetic muscle-specific promoter (page 32, lines 30 – 35). However, this guidance lacks essential instruction; what substitutions, deletions, and/or insertions may be made to any of the recited SEQ ID NOs of claim 1 while substantially retaining its activity? Is there some core structure within the recited sequence required for functionality? That is, which nucleotides are critical in order for the recited SEQ ID NOs of claim 1 to retain its activity? Which nucleotides are critical for any of the promoter SEQ ID NOs and CRM SEQ ID NOs to substantially retain activity? What are the requisite transcription factors sites? How many transcription factors must the CRM be capable of binding for expression? The specification lacks any clear guidance or teaching regarding which portions are required; thus, there is no correlation of the function of these regulatory elements and any particular structure. Applicant’s specification is limited to the specific nucleic acid sequences in Tables 1 – 3, which is not considered to be representative of the full breadth of the genus claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus.
Therefore, Applicants' disclosure has support for a synthetic muscle-specific promoter comprising the recited SEQ ID NOs of claim 1, but not functional variants thereof.
Thus, a person having ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as claimed, at the time the invention was made. Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 U.S.C. § l 12(a).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
16. Claims 1, 2, 4, 12 – 16, and 18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
17. Regarding claim 1, it is unclear if “comprising a sequence according to any one of” means “as set forth in SEQ ID NOs: 1 – 29, 66” or “as set forth in SEQ ID NOs: 30 – 47”, or means the muscle-specific promoter can comprise fragments or portions (“a sequence”) of a sequence of any of the recited SEQ ID NOs. Claims 2, 4, 12 – 16, and 18 are also rejected as they depend from claim 1 and do not clarify the grounds of rejection.
18. Regarding claim 2, it is unclear if “comprises a sequence” and “to any one of” means “as set forth in SEQ ID NOs: 1 – 29, 66” or “as set forth in SEQ ID NOs: 30 – 47”, or means the muscle-specific promoter can comprise fragments or portions (“a sequence”) of a sequence that is at least 70% (for a)) or at least 95% identical (for b)) to any sequence (fragments or portions) of any of the recited SEQ ID NOs .
19. Regarding claim 4, it is unclear what is meant by “is as set out above”. It is unclear if “is as set out above” refers to the SEQ ID NOs and functional variants or something else.
Claim Interpretation
20. For the purpose of applying prior art, claim 1 is interpreted as a CRM comprising any sequence of any length of SEQ ID NO: 47 (fragments or portions of SEQ ID NO: 47) or a functional variant of SEQ ID NO: 47 having any sequence of any length that retains the ability to function as a muscle-specific CRM that enhances the transcription of a gene based on Applicant’s specification at page 29, lines 20 – 26, page 53, lines 16 – 29 and page 55, lines 9 – 15.
21. For the purpose of applying prior art, claim 2 is interpreted as the CRM comprising any sequence of any length (fragments or portions of SEQ ID NO: 47) that has at least 95% sequence identity to a sequence of SEQ ID NO: 47.
22. For the purpose of applying prior art, “promoter element” of claim 4 is interpreted to include minimal promoters or muscle-specific proximal promoters based on Applicant’s specification at page 31, lines 15 – 17.
23. For the purpose of applying prior art, “a sequence encoding an expression product” is interpreted to include any gene based on Applicant’s specification at page 11, lines 30 – 35.
Claim Rejections - 35 USC § 102
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 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.
24. Claim(s) 1, 2, 4, 12 – 16, and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Piekarowicz (Piekarowicz, Katarzyna, et al. Molecular Therapy Methods & Clinical Development 15 (2019): 157-169.), hereinafter Piekarowicz.
Claim 1 is drawn to a synthetic muscle-specific promoter comprising: a) a sequence according to any one of SEQ ID NOs: 1-29, 66 or a functional variant thereof; or b) a cis-regulatory module (CRM) comprising a sequence according to any one of SEQ ID NOs: 30-47 or a functional variant thereof.
Regarding claims 1, 2, and 4, Piekarowicz teaches a synthetic muscle-specific promoter (MH promoter) (“synthetic muscle-specific promoter” and “functional variant thereof” of a) of claim 1) comprising the murine Des gene enhancer and the murine Ckm gene enhancer (enh2) (“CRM” of b) of claim 1), operably linked to a proximal promoter (pp) (claim 4) where the sequence of the Ckm gene enhancer comprises a sequence that is at least 95% identical to a sequence of SEQ ID NO: 47 (claim 2) as shown in the sequence alignment below (Figure 1 and 3A; page 158, left col. para. 5 – 7 and right col. para. 1 – 4). Piekarowicz teaches the MH promoter is highly active in muscle cells (Figure 2; page 158, right col. para. 5 – 6). Piekarowicz teaches in Figure 4A that the MH promoter comprising the Des and Ckm gene enhancers function as muscle-specific (C2C12 and myotubes) enhancers of luciferase transcription (page 160, left col. last para. and right col. para. 1).
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Regarding claim 12, Piekarowicz teaches the MH promoter is operably linked to EGFP (page 160, right col. para. 4; page 166, left col. para. 3).
Regarding claims 13, 14, and 15, Piekarowicz teaches AAV2/9 (claim 13 and “AAV vector” of claim 14) vectors comprising the MH promoter and viruses (claim 15) comprising the vector (page 160, right col. para. 4; page 166, left col. para. 3).
Regarding claim 16, Piekarowicz teaches the AAV2/9 vectors comprising the MH promoter in PBS was injected into mice (page 160, right col. para. 4; page 165, right col. para. 5; page 166, left col. para. 3).
Regarding claim 18, Piekarowicz teaches C2C12 cells comprise the MH promoter (page 160, left col. last para. and right col. para. 1; Figure 4A).
Therefore, Piekarowicz anticipates claims 1, 2, 4, 12 – 16, and 18.
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.
25. Claims 1, 2, 4, 12 – 16, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50 – 63 of copending Application No. 17788679 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims and reference claims are drawn to muscle-specific CRMs.
Instant claim 1 maps to reference claim 50 because the instant specification defines “CRM” as a plurality of CREs (page 53, lines 15 – 30) and reference claim 50 recites “a synthetic cardiac muscle-specific CRM comprising two or more operably linked CREs”. SEQ ID NO: 321 and 308 (CRE0069 and CRE0031, respectively) of reference claims 50 and 51 are taught in the instant specification as CREs (Table 3), and the instant specification teaches in Table 5 that the muscle-specific synthetic promoter SP0321 comprises CRE0031 and the muscle-specific synthetic promoter SP0511 (SEQ ID NO: 15) comprises CRE0069. Therefore, instant claims 1, 2, and 4 are not patentably distinct from reference claims 50 – 55 because instant claim 1 broadly recites “functional variant thereof” that encompasses the SEQ ID NOs recited in reference claims 50 – 55. Further, SEQ ID NO: 47 of the instant claims shares 99% identity with CRE0035 (SEQ ID NO: 310) recited in reference claims 50 – 54. Additionally, methods of DNA recombination are well known in the art and thus it would have been obvious to a person having ordinary skill in the art to have modified the CREs recited in reference claims 50 – 54 and the muscle-specific promoters of reference claim 55 using methods for the generation of recombination known in the art resulting in a synthetic cardiac muscle-specific CRMs comprising two or more CREs that reads on claims 50 – 54 and resulting in a synthetic cardiac muscle specific promoter that reads on claim 55. Further, as instant claim 1 is broader than the reference claims because instant claim 1 recites “functional variants thereof”, instant claim 1 is anticipated by the reference claims.
Instant claim 12 maps to reference claim 56.
Instant claim 13 maps to reference claim 57 and 58.
Instant claim 14 maps to reference claim 59 and 60.
Instant claim 15 maps to reference claim 61.
Instant claim 16 maps to reference claim 62.
Instant claim 18 maps to reference claim 63.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/ZANNA MARIA BEHARRY/Examiner, Art Unit 1632
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