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 Claims
The preliminary amendment to the claims filed 6-29-2026 has been entered. Claims 24-27 are pending. Claims 1-23 have been canceled.
Sequence Requirements
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § § 1.821-1.825 for the reason(s) set forth below. Figure 1, recites sequences that are not followed by a proper sequence identifier either in the Figure per se or in the Description of the Figure. Correction is required. Full compliance with the sequence rules is required in response to this office action.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/094,254, filed on 10-17-2018.
Information Disclosure Statement
The information disclosure statement filed 8-25-2025 has been considered. An intialed copy is enclosed.
Specification
The disclosure is objected to because of the following informalities:
The use of the terms UNIPROT®, NEUPAGETM, BENZONASE®, BOTEST®, which are trade names or a marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Applicant should review the specification for any other trademarks/names that are not in compliance and provide the appropriate generic terminology as applicable.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
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 Longi, 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(l)(1) - 706.02(l)(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.
Claim 24 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of U.S. Patent No. 12,421,284. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 24 recites a nucleic acid encoding a chimeric neurotoxin comprising an amino acid sequence having at least 95% sequence identity with SEQ ID NO:12 as an alternative. The claim encompasses at least 95% identity to fully identical (100%). As such, claim 24 is anticipated or obvious over claim 6 of the ‘284 patent.
Claims 25-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3 and 6 of U.S. Patent No. 12,421,284.
The claims differ by not reciting a vector comprising the nucleic acid of patented claim 6, host cell comprising the nucleic acid of claim 6 as reciting SEQ ID NO:12 and a cell comprising the vector. However, claim 6 depends on the nucleic acid sequence of claim 1 and claims 25-27 are obvious over the combination of the nucleic acid of claim 6 encoding SEQ ID NO:12 as reading on claim 1 in view of the vector and host cells of claims 2 and 3 of the ‘284 patent. It is prima facie obvious to place the nucleic acid encoding the amino acid set forth in SEQ ID NO:12 in a vector in a host cell for the manufacture of the recombinant chimeric neurotoxin.
Claim Rejections - 35 USC § 102
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.
Claim 24-27 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Rummel et al (FEBS Journal 278:4506-4515, 2011).
Rummel et al teach recombinantly expressed hybrid (i.e. chimeric) neurotoxins (see 4510, Figure 4 (AABB in particular). Rummel et al teach presence and construction of the hybrid neurotoxins from plasmids encoding wild-type Hc fragments and expression plasmids encoding full length BoNT/A; BoNT/B and BoNT/C (see pages 4510, column 2 to page 4511, column 1 and Figure 4; and 4512, column 2). The expression vectors were used to express the hybrid neurotoxins in E. coli strain M15 according to manufacturers instructions (see page 4513, column 1). Chimeric neutotoxin AABB and AAAB are particular identified and recombinantly made. Figure 4 identifies the fusion position at 871 of the AA domain (LC-Hn) and fused to position 859 of the BB domain which Hc (Hcn and Hcc) through 1291(see wt BBBB). As such, the AABB fusion comprises residues 1-871 of A and residue 859-291 of B.
It is noted that the claims recite a nucleotide sequence encoding a chimeric neurotoxin comprising “an amino acid sequence of SEQ ID NO:12”. This language is deemed to read on subsequences of the full length amino acid sequence set forth in SEQ ID NO:12. As such, the nucleotide sequence, plasmid vectors, and cells of Rummel et al read on the instant claims. Amending the claims to recite “A nucleotide sequence encoding a chimeric neurotoxin comprising the amino acid sequence set forth in SEQ ID NO:12.” would obviate this issue.
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.
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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 24-27 are rejected under 35 U.S.C. 103 as being unpatentable over Rummel et al (FEBS Journal 278:4506-4515, 2011) in view of Dong et al (WO2013/180799;of record) and Uniprot Accession Number P0DPI1 which replaced A5HZZ9 cited in the specification as serotype A1 (SEQ ID NO:1) available 2010.
Rummel et al teach recombinantly expressed hybrid (i.e. chimeric) neurotoxins (see 4510, Figure 4 (AABB in particular). Rummel et al teach presence and construction of the hybrid neurotoxins from plasmids encoding wild-type Hc fragments and expression plasmids encoding full length BoNT/A; BoNT/B and BoNT/C. (see pages 4510, column 2 to page 4511, column 1 and Figure 4; and 4512, column 2). Rummel et al teach the formation of an AABB where the entire Hc fragment was B serotype and the remainder was A serotype (see page 4511, column 1 second paragraph). Rummel et al teach that HcnA and HccB harmonize well and that expansion the exchanged segment to the complete Hc fragment yielded a full-length hybrid with an identically increase potency was n the case of AAAB (see page 4511, column 2 second paragraph). The expression vectors were used to express the hybrid neurotoxins in E. coli strain M15 according to manufacturers instructions (see page 4513, column 1). Rummel et al does not teach the requirement for any linker or structure in the recombinant production of AABB or AAAB hybrids. Rummel et al differ by not teaching the amino acid sequence of hybrid AABB with the LC-Hn sequence from A1 and the Hc sequence from serotype B1.
Dong et al teach the wild type sequence of serotype B1 (Okra/strain 1), GenGank:AB232927.1; SEQ ID NO:1 in Figure 8. The OkraB1 strain si the same as the sequence set forth in B1lNP5 in Figure 1 of the instant allicaiton. which is identical with the serotype A1 sequence LC-Hn fragment found within of the instant SEQ ID NO:12. Dong et al teach the sequence of serotype B1 Figure 11, SEQ ID NO:4. Dong et al teach serotype A, but do not specify it is serotype A1.
UniProt Accession Number P0DPI1 teaches the sequence of BoNT/A1 which was previously known as A5HZZ9 and cited in the specification. P0DPI1 is 100% identical as compared with the disclosed SEQ ID NO:1.
It would have been prima facie obvious to one of ordinary skill in the art to use sequences of the serotype A1 and B1 as taught by the art in of dong et al and UniProt for the basis of the AABB fusion of Rummel et al to arrive at the instant nucleic acid encoding SEQ ID NO:12, vector and host cell as Rummell et al teach that the sequences of serotyope A and B were complementary and were fused to provide a hybrid (e.g. chimeric) that functioned better than either alone.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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