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1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/8/2025 has been considered.
Claims 7 and 8 are amended. Claims 7 and 8 are pending and are the subject of the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/162,796, 63/166,915 and PCT/US2022/020990 filed on 3/18/2021, 3/26/2021 and 3/18/2022, 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 3/18/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/8/2025 was received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Withdrawn Rejections
The 35 U.S.C. 112(a) rejection of claims 7 and 8 has been withdrawn in light of applicants claim amendments which reduce the genus of “Ig2 modulator that increases the altered splicing of MuSK transcripts or modulates MuSK Ig2” to using a MuSK Ig2 blocking antibody agent.
The 35 U.S.C. 103 rejection of claims 7 and 8 has been withdrawn and reapplied in modified form in light of applicants claim amendments which describe using a MuSK Ig2 blocking antibody agent.
The nonstatutory double patenting rejections of claims 7 and 8 over co-pending Application No: 17/604,279 and co-pending Application No: 17/769,165 have been withdrawn and reapplied in modified form, respectively, in light of applicants claim amendments which describe using a MuSK Ig2 blocking antibody agent.
Claim Interpretation
Claims 7 and 8 describe administering a MuSK Ig2 blocking antibody agent. Taking the broadest reasonable interpretation, this reads on any antibody which binds to a MuSK Ig2 target and consequently prevents other antibodies or molecules from binding to it, thereby interfering with its function.
Furthermore, claims 7 and 8 describe that the MuSK Ig2 blocking antibody agent (a) increases the level or activity of a MuSK polypeptide lacking a functional Ig2 domain “OR” (b) reduces the level of a BMP receptor (ALK)-MuSK polypeptide complex followed by a number of wherein statements. Since options (a) and (b) are described in the alternative using the “OR” conjunction, all of the “wherein” statements are considered exclusively part of option (b).
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 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Fallon et al. WO 2020/214987, published 10/22/2020 (hereinafter Fallon, reference of record) in view of Yilmaz et al. "MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells." Science signaling 9.444 (2016): ra87-ra87 (hereinafter Yilmaz). This rejection is newly applied to address applicants claim amendments on 9/8/2025.
Claims 7 and 8: Fallon describes a method of treating a subject afflicted with neurodegeneration or increasing neurogenesis by increasing the level or activity of a MuSK polypeptide lacking a functional Ig3 domain and/or reducing the level or activity of a BMP-MuSK polypeptide complex (Fallon, para 8). Fallon describes how MuSK acts as a BMP co-receptor in muscle cells (Fallon, para 89). Fallon provides embodiments wherein the MuSK comprises a functional Ig3 domain and lacking a functional Ig3 domain (Fallon, para 8). Fallon describes embodiments wherein a further pharmaceutical composition is administered that increases the altered splicing of MuSK transcripts (Fallon, para 6 and 8). Fallon describes alterations wherein one or more exons are skipped (Fallon, para 8 step 19). Fallon describes the administration of pharmaceutical compositions that modulate MuSK Ig3 including antibodies, oligonucleotides and polypeptides (Fallon, para 8). In particular, Fallon states that the MuSK NG agonizing agent may be an antibody that binds to a MuSK polypeptide (e.g. an antibody that blocks MuSK Ig3) so that it fails to effectively participate in interaction(s) with BMP resulting in an increase in activity (Fallon, para 7, 100 and 106-109). Although Fallon describes specific embodiments wherein the antibody targets the Ig3 domain of a MuSK protein (i.e. MuSK Ig3 blocking antibody agent) which increase the activity of a MuSK polypeptide that lacks a functional Ig3 domain, Fallon does not disclose a MuSK Ig2 targeting antibody which increases the activity of a MuSK polypeptide lacking a functional Ig2 domain.
Claims 7 and 8: However, Ig2 is a known part of the ectodomain of MuSK. As shown by Yilmaz in Fig 7 (reproduced below), MuSK is a transmembrane tyrosine kinase whose ectodomain comprises three immunoglobulin-like (Ig1, Ig2, Ig3) domains. Yilmaz demonstrates the importance of the Ig3 domain by generating a ΔIg3 MuSK protein and compares the affinity interaction with BMP against the full-length protein (Yilmaz, Fig 1). Yilmaz found that Ig3 was critical for the high affinity interaction of MuSK and BMP. However, Fig 1 and 7 also shows that both Ig2 and Ig1 play an important role in this interaction given their integral part in the MuSK ectodomain.
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It would have been prima facie obvious to one of ordinary skill in the art to administer a MuSK Ig2 blocking antibody that increases the activity of a MuSK polypeptide that lacks a functional Ig2 domain as a method for treating neurodegeneration or increasing neurogenesis. It would have been a matter of combining prior art elements according to known methods to yield predictable results given that Fallon describes a MuSK Ig3 blocking antibody agent which increase the activity of a MuSK polypeptide that lacks a functional Ig3 domain so that it fails to effectively participate in interaction(s) with BMP resulting in an increase in activity (Fallon, para 7, 100 and 106-109). One of ordinary skill in the art would be motivated to administer a MuSK Ig2 blocking antibody rather than a Ig3 blocking antibody given that Fallon expressly considers the interaction of Ig3 relative to the Ig2 and that both immunoglobulins comprise the ectodomain of MuSK and play important roles in the BMP-MuSK binding complex. One would have reasonable expectation of success since there are reliable methods for performing alternative splicing to generate ΔIg2 MuSK proteins and blocking antibodies thereof. 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.
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 7 and 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-85, 17-19 and 22-31 of co-pending Application No: 17/769,165 (US Patent Application Publication Number US 2023/0304012) in view of Yilmaz (supra). 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 is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. This rejection is newly applied to address applicants claim amendments on 9/8/2025.
Claims 7 and 8: The co-pending claims describes a method of treating a subject afflicted with neurodegeneration or increasing neurogenesis by increasing the level or activity of a MuSK polypeptide lacking a functional Ig3 domain and/or reducing the level or activity of a BMP-MuSK polypeptide complex wherein the MuSK comprises a functional Ig3 domain (Claims 1-3). The co-pending claims describes embodiments wherein a further pharmaceutical composition is administered that increases the altered splicing of MuSK transcripts (Claims 19-27). The co-pending claims describes describe wherein the agent is an antibody or polyclonal antibody (Claims 12-14). The co-pending claims describes alterations wherein one or more exons are skipped (Claims 24-29). Although the co-pending claims describes a MuSK polypeptide lacking a functional Ig3 domain and a BMP-MuSK polypeptide complex wherein the MuSK comprises a functional Ig3 domain, the co-pending claims do not disclose a MuSK polypeptide lacking a functional Ig2 domain, BMP-MuSK polypeptide complex comprising a functional Ig2 domain or agents that act on MuSK Ig2.
However, it would have been prima facie obvious to one of ordinary skill in the art to administer a MuSK Ig2 blocking antibody that increases the activity of a MuSK polypeptide that lacks a functional Ig3 domain as a method for treating neurodegeneration or increasing neurogenesis. It would have been a matter of combining prior art elements according to known methods to yield predictable results given that the co-pending claims describes a MuSK Ig3 blocking antibody agent which increase the activity of a MuSK polypeptide that lacks a functional Ig3 domain. One of ordinary skill in the art would be motivated to administer a MuSK Ig2 blocking antibody rather than a Ig3 blocking antibody given that Fallon expressly considers the interaction of Ig3 relative to the Ig2 and that both immunoglobulins comprise the ectodomain of MuSK and play important roles in the BMP-MuSK binding complex. One would have reasonable expectation of success since there are reliable methods for performing alternative splicing to generate ΔIg2 MuSK proteins and blocking antibodies thereof as described by Yilmaz. 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.
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Alexander Nicol
Patent Examiner
Art Unit 1633
/ALEXANDER W NICOL/Examiner, Art Unit 1634