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 .
Status of Application/Election/Restrictions
Applicant's election with traverse of Group I (Claims 1-11 and 17-20) and species (Calpain 3) in the reply filed on 9/24/2025 is acknowledged. The traversal is on the ground(s) that the technical feature of a promoter comprising SEQ ID NO: 2 is a special technical feature since Brennan discloses SEQ ID NO: 1 which shares only 79.63% sequence identity to SEQ ID NO: 2. This is not found persuasive because the claim reads on the full length ACTA1 promoter since “comprising” language is used in the preamble of claim 1. Furthermore, the search and examination of methods is not coextensive with the search for compositions, since methods have manipulative steps that compositions don't have, and are evaluated differently under certain statutes (i.e. 35 U.S.C. §§ 101 and 112 in particular). Accordingly, there is a search and examination burden to search these inventions in the same application. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-11 and 14-20 are pending. Claims 14-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. It is noted that claim 17 is directed to the withdrawn species dystrophin. Claims 1-11 and 18-20 are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application EP202305796.3 and 371 of PCT/EP2021/069133 filed on 7/10/2020 and 7/9/2021, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 7/10/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 1/5/2023 and 9/24/2025 were received. The submissions were in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements were considered by the examiner.
Claim Interpretation
It is emphasized that since claim 1 describes a promoter “comprising” SEQ ID NO: 2 or greater than 90% sequence identity thereof, claim 1 may read on the full length ACTA1 promoter.
Sequence for transcript stabilization as recited in claim 8 reads on any intron since they can modulate mRNA decay.
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 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.
(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 1-6, 8, 10-11 and 18-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ronzitti et al. US 2022/0162640, published 5/26/2022, priority date 4/8/2019 (hereinafter Ronzitti).
Claims 1, 4 and 5: Ronzitti describes hybrid promoters to drive gene expression in muscle cells (Ronzitti, abstract). Ronzitti describes design constraints including providing strong expression of a transgene into a cell of interest but at a low vector dose to prevent both potential toxicity and immune response against the vector (Ronzitti, para 3). Ronzitti discloses a truncated alpha actin (ACTA1) promoter SEQ ID NO: 8 with 100% sequence similarity to instant SEQ ID NO: 2 (sequence search results shown below).
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Seq ID NO: 8 alignment with instant SEQ ID NO: 2
Claim 2: The ACTA1 promoter disclosed by Ronzitti is 324 nucleotides (see sequence search results above).
Claim 3: Ronzitti examined expression patterns in heart and skeletal muscle tissue and found higher expression in skeletal muscle tissue (Ronzitti, Fig 2, 6, 5)
Claim 6: Ronzitti provides alternative embodiments wherein the transgene for expression is Calpain 3 (CAPN3) as a gene therapy treatment for muscular dystrophies (Ronzitti, para 85).
Claim 8: Ronzitti describes expression constructs consisting of a sequence for transcript stabilization, polyadenylation signal, enhancer sequence and a target sequence for a microRNA (Ronzitti, para 65, 73, 78, 83).
Claims 10-11 and 19-20: Ronzitti describes pharmaceutical compositions comprising an expression system using the promoter to treat muscular dystrophies (Ronzitti, para 87, 99). Ronzitti provides alternative embodiments to the use of AAV8 capsids (Ronzitti, para 99).
Claim 18: Ronzitti describes the use of polyadenylation signals from SV40 (Ronzitti, para 78-83).
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 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.
Claims 1-8, 10-11 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ronzitti (supra) in view of Sahenk et al. US 2021/0277362, published 9/9/2021, priority date 6/21/2019 (hereinafter Sahenk).
A description of Ronzitti can be found above. Ronzitti does not disclose the calpain 3 sequence SEQ ID NO: 8.
Claim 7: However, calpain 3 is a known protein used for treating muscular dystrophy via AAV based gene therapy vectors. v discloses SEQ ID NO: 1 which shares 100% sequence similarity to instant SEQ ID NO: 8 (sequence search results shown below).
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Seq ID NO: 1 alignment with instant SEQ ID NO: 8
It would have been prima facie obvious to one of ordinary skill in the art to deliver the calpain 3 sequence disclosed by Sahenk using the vector construct and ACTA1 promoter described by Ronzitti. It would have been a matter of combining prior art elements according to known method to yield predictable results since the sequence of calpain 3 is known in the art as shown by Sahenk. One would have been motivated to make this combination since the ACTA1 promoter provides selective expression in skeletal muscle cells and can restore CAPN3 expression while minimizing cardiotoxicity (Sahenk, para 46). One would have a reasonable expectation of success given that Ronzitti provides alternative embodiments wherein the transgene for expression is Calpain 3 and is used as a gene therapy treatment for muscular dystrophies (Ronzitti, para 85). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 1-8, 10-11 and 18-20 to have been prima facie obvious to at the time the invention was made.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Ronzitti (supra) and Sahenk (supra) as applied to claims 1-8, 10-11 and 18-20 above in further view of Buj Bello et al. US 2016/0058890, published 3/3/2016 (hereinafter Bij Bello).
A description of Ronzitti and Sahenk can be found above. Although Ronzitti describes the inclusion of microRNA target sequences as a means for further controlling expression of the therapeutic transgene, neither Ronzitti nor Sahenk describe the specific target sequence of miR208a.
Claim 9: However, miR208a is a known heart specific microRNA as shown by Buj Bello. For example, Buj Bello describes a viral vector expression system which contains a miR208a target sequence such that expression of the construct is preferably expressed in skeletal muscle cells and minimized in non-target heart tissue (Buj Bello, para 92-95 and claim 6). Buj Bello states that the inclusion of a single target sequence of miR208a is sufficient to reduce cardiac toxicity (Buj Bello, para 214).
It would have been prima facie obvious to one of ordinary skill in the art to include a target sequence of miR208a as described by Buj Bello in the expression construct of Ronzitti in view of Sahenk to minimize cardiotoxicity. It would have been a matter of combining prior art elements according to known method to yield predictable results since Buj Bello demonstrates that the inclusion of a single target sequence of miR208a is sufficient to reduce cardiac toxicity. One would have been motivated to make this combination to limit CAPN3 expression to skeletal muscles through the use of both the claimed tissue specific ACTA1 promoter and microRNA target sequence, thereby providing a dual strategy to minimize cardiotoxicity. One would have a reasonable expectation of success given that Ronzitti alludes to this same strategy via the inclusion of microRNA target sequences as a means for further controlling expression of the therapeutic transgene (Ronzitti, para 65, 73, 78, 83). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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Alexander Nicol
Patent Examiner
Art Unit 1633
/ALEXANDER W NICOL/Examiner, Art Unit 1634