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. Election/Restrictions Applicant’s election of Group 1 in the reply filed on 12/10/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse . See MPEP § 818.01(a). Claims 55-59 and 64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 1-2, 27, 29-30, 32-33, 35-36, 47, 49-50, 52, 61 , and 63 have been examined on the merits. Power of Attorney There is no Power of Attorney on file and it is recommended that applicant submits one to facilitate prosecution. Priority The instant application is a national stage entry of PCT/US2021/064332 filed on 12/20/2021, which claim s priority benefit of U.S. Provisional A pplication No. 63 / 128758 filed on 12/21/2020 under 35 U.S.C. 119(e). Claim Objections Claims 1 and 35 objected to because of the following informalities: (i) the term “ Clostridial ” is not a formal taxonomic name and should therefore not be italicized; and (ii) “botulinum” is not a proper noun and should not be capitalized nor italicized . To resolve these issues, it is recommended that both “ Clostridial Botulinum neurotoxin” (line 1) and “ Clostridial Botulinum serotype A1 ” (line 2) be amended to “Clostridial botulinum neurotoxin” and “ Clostridial b otulinum neurotoxin serotype A1”, respectively . 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. (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, 27, 29-30 , 61, and 63 are rejected under 35 U.S.C. 102(a)(1)/ 102(a)(2) as being anticipated by Jacky et al . (Pub. No. US 2019/0185837 A1). Jacky et al . discloses a polypeptide containing the binding domain sequence of a Clostridial toxin like botulinum toxin (BoNT) produced by Clostridium botulinum (par. [0104] ), as well as a pharmaceutical composition comprising said polypeptide and a kit (par. [0032]-[0034], [0063]) . The polypeptide can comprise an amino acid sequence substantially identical to an amino acid sequence of a full-length botulinum toxin or a fragment thereof (par. [0017], [0026]) such as an amino acid sequence in the heavy chain , the C-terminal segment of the heavy chain, or the binding domain of the botulinum toxin (par. [0017], [0145]) . Moreover, the toxin can be a mosaic botulinum toxin or a chimera (par. [014 7 ], [0149]- [0150]). O ne embodiment of the disclosed invention is a homolog of a Clostridial toxin like artificially-created variants of BoNT/A 1 or a fragment thereof (par. [0151]) . In some embodiment s , the variant is a mutant comprising at least 1 mutation up to 10 mutations in a core Clostridial toxin polypeptide sequence or a fragment thereof. Examples of mutant Clostridial toxins include a BoNT/A mutant comprising T1145A and T11 4 6A or a fragment thereof ( H C fragment of BoNT/A mutant; SEQ ID NO: 25) , and a BoNT/A mutant comprising G1292R or a fragment thereof ( H C fragment of BoNT/A mutant; SEQ ID NO: 27) (par. [0157]). Jacky et al . reads on the instant application as follows: Regarding claim 1: the binding domain-containing polypeptide or a fragment thereof being a mutant of a Clostridial toxin like BoNT/A1 , which includes the toxin deposited under UNIPROT accession # P0DPI1 (par. [0154]) , is identical to “ A modified Clostridial Botulinum neurotoxin (BoNT) polypeptide comprising a modified receptor binding domain of Clostridial Botulinum serotype Al (BoNT/A1) ”. The mutant comprising 1-10 mutations such as T1145A and T1146A, or G1292R reads on “ one or more amino acid substitutions at positions corresponding to 917, 953, 954, 955, 957, 968, 1025, 1026, 1052, 1062, 1063, 1064, 1065, 1066, 1145, 1156, 1232, 1272, 1278, 1288, 1289, 1292, 1294, and 1295 in SEQ ID NO: 1 ” . Regarding claim 27 : sequence-to-sequence alignment of the disclosed mutant’s Hc fragment comprising G1292R mutation is 99.4% identical to applicant’s SEQ ID NO: 80 (H C of BoNT/A1 with G1292R mutation) , thereby meeting “ wherein the modified receptor binding domain comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 51-85 ”. Regarding claim 29: a suitable botulinum toxin includes the toxin deposited under UNIPROT accession # P0DPI1 (par. [0154]), which harbors a peptidase domain and a translocation domain (see screenshot of NCBI graphics for UNIPROT accession # P0DPI1) and thus satisfies “ further comprising a protease domain and a translocation domain from BoNT/A1 ”. Regarding claim 30: sequence-to-sequence alignment of the toxin deposited under UNIPROT accession # P0DPI1 with G1292R mutation shows 100% identity with applicant’s SEQ ID NO: 32 (BoNT/A1 with G1292R mutation) , which fulfills “ wherein the modified BoNT polypeptide comprises an amino acid sequence that is at least 80% identical to the amino acid sequence of SEQ ID NO: 3-37 ”. Alignment result GenCore version 6.5.2 Copyright (c) 1993 - 2026 Biocceleration Ltd. OM protein - protein search, using sw model Run on: March 21, 2026, 22:13:46 ; Search time 1 Seconds (without alignments) 1.680 Million cell updates/sec Title: US-18-268-477-32 Perfect score: 6773 Sequence: 1 MPFVNKQFNYKDPVNGVDIA..........TLGCSWEFIPVDDGWRERPL 1296 Scoring table: BLOSUM62 Gapop 10.0 , Gapext 0.5 Searched: 1 seqs, 1296 residues Total number of hits satisfying chosen parameters: 1 Minimum DB seq length: 0 Maximum DB seq length: inf Post-processing: Minimum Match 0% Maximum Match 100% Listing first 1 summaries Database : AASEQ2_03212026_221344.pep:* SUMMARIES % Result Query No. Score Match Length DB ID Description ---------------------------------------------------------------------------- 1 6773 100.0 1296 1 AASEQ2_03212026_221344 ALIGNMENTS RESULT 1 AASEQ2_03212026_221344 Query Match 100.0%; Score 6773; DB 1; Length 1296; Best Local Similarity 100.0%; Matches 1296; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Regarding claim 61: the pharmaceutical composition comprising the disclosed polypeptide which can be a mutant of BoNT/A1 (par. [0032]-[0033]) corresponds to “ A pharmaceutical composition comprising the modified BoNT polypeptide of claim 1” . Regarding claim 63: the kit comprising the disclosed polypeptide and instructions for administration is equivalent to “ A kit comprising a pharmaceutical composition of claim 61 or claim62 and directions for therapeutic administration of the pharmaceutical composition ”. 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 ( 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 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. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim s 1, 27, 29-30 , 32 -33 , 61, and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Jacky et al . (Pub. No. US 2019/0185837 A1) in view of Johnson et al . (Pub. No. US 2018/0193435 A1) . The teachings of Jacky et al . are set forth above and applied herein. Jacky et al . is found to anticipate claims 1, 27, 29-30, 61, and 63 . Jacky et al . ’s polypeptide is comparable to the claims below: Regarding claim 32: the polypeptide of claim is further required to compris e “ a protease domain and a translocation domain from a second BoNT, optionally wherein the second BoNT is of serotype B, C, D, E, F, G, H, X, or En ” . T he prior art teaches that the polypeptide can be a fusion protein , mosaic, or chimeric botulinum neurotoxin derived from various subtypes, indicating that it can comprise not only BoNT/A but also BoNT of serotypes B, C, D, E, F, G (par. [0031], [0149]-[0150]). Although Jacky et al . does not teach which specific domains of the botulinum toxin comprise a serotype other than BoNT/A , chimeric botulinum neurotoxins are known in the art. Johnson et al . provides chimeric botulinum neurotoxins with altered properties (par. [0007]). In one embodiment, the chimera is a hybrid comprising the same subtype for the light chain polypeptide (contains the protease domain) and the heavy chain polypeptide (contains the translocation domain and the receptor binding domain) with a portion of the latter from a second subtype such as the receptor binding domain (par. [0008]). For example, the light chain can be serotype B and the heavy chain can be serotype A (par. [0048]). A person with ordinary skill in the art before the effective filing date of the claimed invention would have applied the teachings of Johnson et al . to Jacky et al . with reasonable expectation that a chimera comprising a receptor binding domain of BoNT/A1, as well as a protease domain and a translocation domain from another serotype of BoNT , would be produced. Obviousness is based on the rationale that all claimed elements were known in the prior art and their combination would have yielded nothing more than predictable results. See MPEP § 2143 and KSR , 550 U.S. 398 , 82 USPQ2d at 1395. Hence, claim 32 is obvious over Jacky et al . in view of Johnson et al . . Regarding claim 33: Jacky et al . discloses amino acid sequences of botulinum neurotoxins of other various serotypes with respect to their light chain, translocation domain (HN), and receptor binding domain (HC) (Table 1, page 14). One of the disclosed serotype example s is BoNT/B (accession # P10844) , which is found to share 100% identity with applicant’s SEQ ID NO: 97. Alignment result GenCore version 6.5.2 Copyright (c) 1993 - 2026 Biocceleration Ltd. OM protein - protein search, using sw model Run on: March 21, 2026, 23:34:24 ; Search time 1 Seconds (without alignments) 1.106 Million cell updates/sec Title: US-18-268-477-97 Perfect score: 4448 Sequence: 1 MPVTINNFNYNDPIDNNNII..........FDLSIYTNDTILIEMFNKYN 857 Scoring table: BLOSUM62 Gapop 10.0 , Gapext 0.5 Searched: 1 seqs, 1291 residues Total number of hits satisfying chosen parameters: 1 Minimum DB seq length: 0 Maximum DB seq length: inf Post-processing: Minimum Match 0% Maximum Match 100% Listing first 1 summaries Database : AASEQ2_03212026_233421.pep:* SUMMARIES % Result Query No. Score Match Length DB ID Description ---------------------------------------------------------------------------- 1 4448 100.0 1291 1 AASEQ2_03212026_233421 ALIGNMENTS RESULT 1 AASEQ2_03212026_233421 Query Match 100.0%; Score 4448; DB 1; Length 1291; Best Local Similarity 100.0%; Matches 857; Conservative 0; Mismatches 0; Indels 0; Gaps 0; In light of the teachings of Johnson et al . as discussed above, it would have been obvious to combine the protease domain and a translocation domain of BoNT/B with Jacky et al . ’s BoNT/A1 receptor binding domain and predict that a chimera would be successfully formed. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT MICHELLE F PAGUIO FRISING whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-6224 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday, 8:00 a.m. - 4:00 p.m. . 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, FILLIN "SPE Name?" \* MERGEFORMAT Melenie L. Gordon can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571) 272-8037 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /Michelle F. Paguio Frising/ Primary Examiner, Art Unit 1651