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/Amendments/Claims/RCE 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1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicants’ submission filed on 8/26/2025 has been considered.
The declaration submitted by Bradley Owen on 8/26/2025 was received and fully considered. Briefly, Dr. Owens made an assessment of whether the functions of the Pax7, MyoD and MyoG promoters are equivalent to the function of the mature muscle cell promoters and synthetic promoters described in the ‘463 application. Dr. Owens describes literature references which were considered. Dr. Owens states that Pax7, MyoD and MyoG promoters are “downregulated” in mature muscle cells where expression is minimal and are therefore not functional equivalents.
Claims 49 and 51 have been amended. Claims 48-59 are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 62/962,712 and PRO 63/128,047 filed on 1/17/2020 and 12/19/2020, 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 1/17/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 8/26/2025 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.
Withdrawn Rejections
The 35 U.S.C. 102(a)(1) and 102(a)(2) rejections of claims 48-50 has been withdrawn and reapplied in modified form to provide further evidentiary references showing that the promoters described by Schneider (MyoD and myogenin promoters in particular) drive expression in differentiated muscle cells.
Similarly, the 35 U.S.C. 103 rejection of Claims 51-59 has been withdrawn and reapplied in modified form.
Claim Interpretation
It is acknowledged that applicant intends to invoke 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function and equivalents thereof. It is emphasized that although applicant has invoked 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function, equivalents thereof must also be considered. Furthermore, applicants’ description of a promoter that drives expression in differentiated muscle cells in claim 49 is interpreted broadly and does not exclude expression in other cell types in addition to differentiated muscle cells. For example, the myosine heavy chain (MHC) promoter, muscle creatine kinase (MCK) promoter, MyoD promoter and myogenin promoters drive expression in both myoblasts (undifferentiated cells) and myotubes (differentiated cell). In fact, even ubiquitous promoters like CAG promoters or CMV promoters read on the limitations of claim 48 since they still provide a means for expression in differentiated muscle cells (among other cell types).
It is noted that AUF1 consists of four related protein isoforms identified by their molecular weight (p37, p40, p42 and p45) derived by differential splicing of a single pre-mRNA. SEQ IDs 10, 14, 18 and 22 relate to specific splice variants.
New 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 48-50 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) in modified form as being anticipated by Schneider et al. US 2018/0163178, published 6/14/2018 (hereinafter Schneider, reference of record) as evidenced by Ohkawa et al. "Myogenin and the SWI/SNF ATPase Brg1 maintain myogenic gene expression at different stages of skeletal myogenesis." Journal of Biological Chemistry 282.9 (2007): 6564-6570 (hereinafter Ohkawa), Chargé et al. "MyoD-and nerve-dependent maintenance of MyoD expression in mature muscle fibres acts through the DRR/PRR element." BMC Developmental Biology 8.1 (2008): 5 (hereinafter Charge) and Weeratna et al. "Designing gene therapy vectors: avoiding immune responses by using tissue-specific promoters." Gene therapy 8.24 (2001): 1872-1878 (hereinafter Weeratna, reference of record). This rejection is applied in modified form to address applicants claim amendments on 8/26/2025. A response to applicant’s traversal is found below.
Claim 48: Schneider describes compositions and methods for the skeletal muscle-specific gene transfer of AU-rich mRNA binding factor 1 (AUF1) to restore muscle mass, increase exercise endurance and provide a therapeutic strategy for treating age-related muscle loss (Schneider, para 4-8, 19, 37 and claims 1, 14 and 32). Schneider states that AUF1 plays a critical role in the control of muscle satellite cell fate and muscle regeneration, through programmed rapid degradation of muscle-differentiation checkpoint mRNAs (Schneider, para 4, 6). Schneider describes gene transfer approaches using recombinant adeno-associated viruses (rAAV) viruses for delivering an AUF1 expression vector to the site of muscle injury (Schneider, para 57, 58, 62, 63 and examples 2-3). Schneider describes the use of additional expression construct elements including enhancers, leader sequences, 3’ regulatory elements and reporter genes which can be cloned into the expression vector (Schneider, para 54). Schneider describes the use of “targeting elements” comprising MyoD and myogenin promoters (Schneider, para 51, 55, 58). As stated in the claim interpretation section, it is acknowledged that applicant intends to invoke 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function and equivalents thereof. It is emphasized that although applicant has invoked 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function, equivalents thereof must also be considered.
Claim 49: Schneider describes the use of “targeting elements” comprising MyoD and myogenin promoters (Schneider, para 51, 55, 58). Given the claim interpretation section above, these promoters directly read on promoters that drives expression in differentiated muscle cells which are operably coupled to an AUF1 transgene. This interpretation is supported by Ohkawa with respect to myogenin promoters which drive expression in differentiated muscle cells, specifically mature myotubes and adult myofibers where it plays a role in maintaining muscle phenotype and responding to physiological changes like denervation or growth stimuli (Ohkawa, pg 1). This interpretation is further supported by Charge with respect to MyoD promoters which drives expression in differentiated muscle cells, specifically mature myotubes and adult myofibers (Charge, pg 1). Applicants’ description of a promoter that drives expression in differentiated muscle cells in claim 49 is interpreted broadly and does not necessarily exclude expression in other cell types in addition to differentiated muscle cells. For example, applicant lists muscle creatine kinase (MCK) promoter as one that drives expression in differentiated muscle cells (i.e. claim 51). However, MCK promoters drive strong expression in both myoblasts (undifferentiated cells) and myotubes (differentiated cell) as evidenced by Weeratna (Weeratna, Results para 1). It is emphasized that although applicant has invoked 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function, equivalents thereof must also be considered. Thus, although MyoD and myogenin may drive expression in undifferentiated muscle satellite cells, they also drive expression in differentiated mature myotubes and adult myofibers as evidenced by Ohkawa and Charge, thus meeting the claim limitations.
Claim 50: It is emphasized that the “OR” conjugation used when listing the AUF1 polypeptides in claim 50. Schneider states that the AUF1 protein may include one or more of the AUF1 isoforms including p37, p40, p42 and p45 (Schneider, para 43). Schneider provides the GenBank accession numbers for all related isoforms in Table 1. Schneider discloses SEQ ID NO: 26 which shares a 100% match to instant SEQ ID NO: 22 (sequence search results shown below.
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Response to Traversal
Applicant traverses the rejection by arguing that the application of a prior art reference to a means-plus-function limitation requires that the prior element perform the identical function specified in the claim. Applicant argues that the means-plus-function definition narrowly limits the definintion to the promoters disclosed at para 62 and table 1 that drive expression in differentiated muscle cells as well as equivalents. Applicant cites the declaration submitted by Bradley Owen on 8/26/2025 for support. Briefly, Dr. Owens made an assessment of whether the functions of the Pax7, MyoD and MyoG promoters are equivalent to the function of the mature muscle cell promoters and synthetic promoters described in the ‘463 application. Dr. Owens describes literature references which were considered. Dr. Owens states that Pax7, MyoD and MyoG promoters are “downregulated” in mature muscle cells where expression is minimal and are therefore not functional equivalents.
These arguments have been fully considered, but are not found persuasive since Applicants’ description of a promoter that drives expression in differentiated muscle cells in claim 49 is interpreted broadly and does not necessarily exclude expression in other cell types in addition to differentiated muscle cells. For example, applicant lists muscle creatine kinase (MCK) promoter as one that drives expression in differentiated muscle cells (i.e. claim 51). However, MCK promoters drive strong expression in both myoblasts (undifferentiated cells) and myotubes (differentiated cell) as evidenced by Weeratna (Weeratna, Results para 1). It is emphasized that although applicant has invoked 35 U.S.C 112(f) such that the claims are construed to cover the corresponding structures disclosed in the application that accomplish the specified function, equivalents thereof must also be considered. Thus, although MyoD and myogenin may drive expression in undifferentiated muscle satellite cells, they also drive expression in differentiated mature myotubes and adult myofibers as evidenced by Ohkawa and Charge, thus meeting the claim limitations. In fact, even ubiquitous promoters like CAG promoters or CMV promoters read on the limitations of claim 48 since they still provide a means for expression in differentiated muscle cells (among other cell types).
With respect to the declaration, it is emphasized that Dr. Owens admits that MyoD shows expression (although minimal) in mature muscle cells. The claims do not specify the extent to which the “means for expressing” is achieved. However, Dr. Owens admission along with the disclosure of Chargé clearly show that MyoD fits applicants means-plus-function definition for expressing exogenous AUF1 in differentiation muscle cells.
New 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 48-59 are rejected under 35 U.S.C. 103 in modified form as being unpatentable over Schneider (supra) as evidenced by Ohkawa (supra), Chargé (supra) and Weeratna (supra) as applied to claims 48-50 above in further view of Childers et al. US 2017/0112905, published 4/27/2017 (hereinafter Childers, reference of record). This rejection is applied in modified form to address applicants claim amendments on 8/26/2025. A response to applicant’s traversal is found below.
A description of Schneider, Ohkawa, Chargé and Weeratna can be found above. Schneider does not describe the use of an AAV8 vector. Schneider does not describe the use of the promoters listed in claims 51 or 52.
Claims 51-53: Childers describes gene therapy approaches for treating X-linked myotubular myopathy (XLMTM) comprising administering AAV vectors that increase the expression of myotubularin in muscle cells (Childers, para 3, 7 and 87). Childers describes the use of expression constructs comprising muscle creatine kinase (tMCK and MCK) promoters with high specificity and efficiency towards driving gene expression in muscle cells, corresponding to the limitations described in claim 51-53 (Childers, para 110, 111).
Claims 54-59: Childers describes the systematic delivery of AAV vectors comprising the MTM1 gene which drastically improved regional and global muscle function (Childers, para 87). Childers describes preferred embodiments toward the use of AAV8 serotype capsids given their preferential expression in muscle cells (Childers, para 99, 101, 186).
It would have been prima facie obvious to one of ordinary skill in the art to use the AAV8 expression construct employing a tMCK promoter as described by Childers to express AUF1 in muscle cells as described by Schneider as a therapeutic strategy for muscle regeneration. Schneider identifies AUF1 as a key regulator of muscle regeneration and describes a skeletal muscle-specific gene transfer therapy to drive AUF1 expression (Schneider, para 57, 58, 62, 63). Childers describes a similar gene therapy approach using AAV8 and tMCK promoters which showed high specificity and efficiency towards driving gene expression in muscle cells. Therefore, it would have been a matter of simply substituting the tMCK promoter and AAV8 serotype describe by Childers into the expression construct and therapeutic methods described by Schneider to meet the claim limitations. One of ordinary skill in the art would have been motivated to make this substitution given that the tMCK promoter and AAV8 serotype show high specificity and efficiency towards driving gene expression in skeletal muscle cells. Furthermore, the tMCK promoter is only active in skeletal muscle cells and is unlikely to cause unwanted side effects in other tissues. One would have a reasonable expectation of success given that the exchange of one known expression vector element for another is considered routine in the art. 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.
Response to Traversal
Applicant traverses the rejection by arguing that Childers is focused on monogenetic gene therapy and unlike AUF1 is normally expressed in mature muscle cells which is why tMCK was selected to supply mature muscle cells with a correct version of the defective gene in those cells. Applicant argues that there would have been no motivation to make the substitution of promoters since AUF1 had no functional effect in mature muscle cells.
These arguments have been fully considered, but are not found persuasive since the tMCK promoter and AAV8 serotype show high specificity and efficiency towards driving gene expression in skeletal muscle cells as shown by Childers. Schneider identifies AUF1 as a key regulator of muscle regeneration and describes a skeletal muscle-specific gene transfer therapy to drive AUF1 expression (Schneider, para 57, 58, 62, 63). Thus, it would have been prima facie obvious to one of ordinary skill in the art to use the AAV8 expression construct employing a tMCK promoter as described by Childers to express AUF1 in muscle cells as described by Schneider as a therapeutic strategy for muscle regeneration. One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references, see MPEP 2145.
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