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1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/8/2026 has been considered.
Claims 48, 49, 51, 52 and 53 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 9/8/2026 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Withdrawn Rejections
The 35 USC § 112a Written Description – New Matter rejection of claims 48-59 is withdrawn in light of applicants claim amendments which delete the word “constitutively” from claims 48, 49, 51, 52 and 53. Previously, the subgenus of “constitutive promoter” referred to a specific subgenus that was not supported by the generic disclosure and specific examples of the instant specification.
The 35 U.S.C. 112(b) rejection of claims 48-49 is withdrawn in light of applicants claim amendments which delete the word “constitutively” from claims 48, 49, 51, 52 and 53. The promoters listed in claims 51-53 drive selective expression in differentiated mammalian muscle cells.
Furthermore, the 35 U.S.C. 102 and 103 rejections have been withdrawn. The 103 rejection has been re-applied in modified form to address applicants claim amendments which delete the word “constitutively” from claims 48, 49, 51, 52 and 53. The claim interpretation statement has been updated accordingly.
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.
Applicants’ description of a promoter that drives expression in differentiated muscle cells in claims 48-49 is interpreted broadly and does not exclude expression in other cell types in addition to differentiated muscle cells. For example, para 62 of applicant’s specification lists the U6 promoter as a one that fulfills the specific functions claimed within the 112(f) definition. It is emphasized that the U6 promoter is not specific to injured differentiated muscle cells and is considered am ubiquitous promoter with expression in most cell types. Similarly, the muscle creatine kinase (MCK) promoter drives expression in both myoblasts (undifferentiated cells) and myotubes (differentiated cell).
Furthermore, although claim 49 describes “the means for constitutively expressing the exogenous AUF1”, any expression will be considered (constitute or not) given the 112b issues described below.
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 § 112b
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.
Claims 49-53 and 55-59 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 pre-AIA the applicant regards as the invention. This rejection is newly applied to address applicants claim amendments filed on 9/8/2026.
Claim 48 describes a composition comprising a means for expressing exogenous AUF1 in differentiated mammalian muscle cells. However, dependent claim 49 describes the composition of claim 48 in which “the means for constitutively expressing” the exogenous AUF1 in the differentiated mammalian muscle cells is operably coupled to a AUF1 transgene. There is a lack of antecedent basis for the means for “the means for constitutively expressing” the exogenous AUF1 in the differentiated mammalian muscle cells since claim 48 has been amended to recite that the composition comprises a means for expressing exogenous AUF1. As a result of this indefinite term, one of ordinary skill in the art would not understand what type of AUF1 transgene expression is achieved. Dependent claims 50-53 and 55-59 are rejected for their dependency on indefinite claim 49. Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
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 Childers et al. US 2017/0112905, published 4/27/2017 (hereinafter Childers, reference of record) in view of Schneider et al. US 2018/0163178, published 6/14/2018 (hereinafter Schneider, reference of record). This rejection is applied in modified form to address applicants claim amendments on 9/8/2026. A response to applicant’s traversal is found below.
Claims 48-49 and 51: 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 differentiated muscle cells (Childers, para 110, 111). It is noted that muscle creatine kinase is one of the listed promoters in para 62 of applicants specification. Childers does not specifically describe expressing exogenous AUF1.
Claims 52-53: 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 differentiated mammalian muscle cells (Childers, para 110, 111). It is noted that muscle creatine kinase is one of the listed promoters in para 62 of applicants specification.
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 differentiated mammalian muscle cells (Childers, para 99, 101, 186).
Claims 48-49: 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).
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.
PNG
media_image1.png
113
430
media_image1.png
Greyscale
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 differentiated mammalian muscle cells. Therefore, it would have been a matter of simply substituting the AUF1 transgene described by Schneider into the expression construct comprising a tMCK promoter and AAV8 vector serotype describe by Childers 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 differentiated mammalian skeletal muscle cells. Furthermore, the tMCK promoter is only active in skeletal muscle cells and would allow for targeted AUF1 expression with minimal side effects in other tissues as a therapy for muscle regeneration. One would have a reasonable expectation of success given that the exchange of one known transgene for another in an expression vector 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
Although the rejection is newly applied, some of applicant’s arguments are relevant and are addressed below.
Applicant traverses the rejection by arguing that the newly amended claims in invoke 112(f) and in view of the description in the specification of the structures that perform those functions (promoters and their nucleotide sequences at para 62 and table 1). Applicant states that the claims do not require but do not exclude constitutive promoters that perform the claimed function as properly construed under 112(f) and the claims are limited to the promoters disclosed in the specification and equivalents promoters thereof that perform the claimed function of expressing exogenous AUF1 in differentiated mammalian muscle cells. Applicant points to the previously submitted Schneider Declarations which argue that the promoters selected provided continuous expression of AUF1 and are compact enough to fit into an rAAV vector which has a 4.7 kb upper limit.
These arguments have been fully considered, and the 112a written description rejection has been withdrawn accordingly. As stated in the claim interpretation section, it is now 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. Since ubiquitous promoters like U6 are listed as promoters that fulfill the specific functions claimed within the 112(f) definition, 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.
Applicant traverses the 103 rejection by arguing that the genetic defect treated by the method of Childers treats affected muscle maintenance rather than myogenesis which is a regenerative process. Applicant argues that there is no motivation to combine Childers and Schneider since each reference targets different host cells in muscle, using unrelated transgenes, for a different purpose. Schneider targets AUF1 to satellite cells whereas Childers targets MTM1 to muscle fibers to restore structural maintenance. Applicant points to the disclosure of Childers and Schneider for support in arguing that skilled person looking to solve XLMTM disease would not have looked to Schneider who is focused on activating myogenesis for muscle repair for a solution and there would be no motivation to substitute Schneider’s AUF1 transgene for the MTM1 transgene in Childers.
These arguments have been fully considered but are not found persuasive since the motivation to combine can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose, see MPEP 2144. The rationale to modify or combine prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles or legal precedence established by case law, see MPEP 2144. Since 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), one of ordinary skill would find it prima facie obvious 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. It would have been a matter of simply substituting the AUF1 transgene described by Schneider into the expression construct comprising a tMCK promoter and AAV8 vector serotype describe by Childers 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 differentiated mammalian skeletal muscle cells.
Nonstatutory 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 Langi, 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 706.02(1)(1) - 706.02(1)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 48-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-17, 24-25, 31-33, 35 and 41 of co-pending Application No: 18/771,850. Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims would anticipate the instant claims if they were available as prior art. This rejection is newly applied to address applicants claim amendments filed on 9/8/2026.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 48-49: The co-pending claims describe a composition comprising an rAAV vector comprising a muscle cell-specific promoter and a nucleic acid molecule encoding a AUF1 protein (Claim 16).
The co-pending claims would fully anticipate the instantly claimed invention, which is drawn to a related composition for expressing exogenous AUF1 in differentiated mammalian muscle cells. The claim sets are patentable indistinct therefore.
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.
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, Maria Leavitt can be reached on (571)272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
Prosecution Insights