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 with traverse of the invention of Group I, claims 1-8 and 21, in the reply filed on 04/17/2026 is acknowledged. The traversal is on the ground(s) that Bradshaw does not teach the feature “wherein a sequence of a third domain of first, second, third, and fourth domains in a botulinum toxin type A light chain, which is other than botulinum toxin type A4, is substituted with a sequence of a third domain of botulinum toxin type A4” (remarks, pages 6-7). This argument has been fully considered but has not been found persuasive because claim 1 does not in any way limit what is present in the claimed recombinant recombinant botulinum toxin type A light chain except that a third domain of botulinum toxin type A4 or a variant thereof must be present. The claims are drawn to a composition, not to a method, and so whatever has been “substituted” to give a protein comprising the recited third domain of BoNT A4 is not relevant to the claim drawn to a protein comprising a third domain of BoNT A4. See full discussion below under Claim Interpretation.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
The amendment of 04/17/2026 has been entered. Claims 1-13, 16, 19, 21, and 25-28 are pending in this US patent application. Claims 9-13, 16, 19, and 25-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/17/2026.
Claims 1-8 and 21 are currently under examination and were examined on their merits.
Information Disclosure Statement
The information disclosure statements filed in this application on 12/28/2023, 03/07/2025, and 11/25/2025 have been received and considered.
Claim Interpretation
Instant claim 1 is drawn to a recombinant botulinum toxin comprising a recombinant botulinum toxin type A light chain. Within the claimed light chain, a third domain of a botulinum toxin type A light chain “which is other than botulinum toxin type A4, is substituted with a sequence of a third domain of botulinum toxin type A4 or a variant thereof.” The Examiner notes that the instant claims are drawn to a composition and not to a process of substituting a third domain of botulinum toxin type A4 into another protein. The Examiner further notes that instant claims 1-8 and 21 do not require that any domains of any other botulinum toxin type A light chains that are not of type A4 be present. Rather, instant claim 1 recites a composition comprising the following characteristics: 1) it is recombinant; 2) it is a botulinum toxin; 3) the botulinum toxin comprises a recombinant botulinum toxin type A light chain; and 4) the botulinum toxin type A light chain comprises a third domain of botulinum toxin type A4. Instant claim 2 adds the limitation that the toxin comprises a fourth domain of botulinum toxin type A4 or a variant thereof. Claims 3-4 limit the type A light chain that was present prior to substitutions. A product-by-process claim is limited only to the structure implied by the recited steps, not to the specific manipulations of the steps. See MPEP § 2113. Once a sequence has been “substituted” into a protein, which indicates that a previous sequence has been removed and a new sequence has been inserted into its place, the structure of the previous sequence has no effect whatsoever on the structure of the new sequence. As such, any protein that meets the four structural characteristics recited above will be interpreted to read on claims 1-4 in their entirety, regardless of whether the prior art teaches a method of substituting the recited domains into other proteins.
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.
Claims 1-7 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bradshaw et al., Appl. Environ. Microbiol. 80(23): 7415-7422 (2014).
Bradshaw teaches a full-length recombinant botulinum toxin of type A4 with mutations at positions 260 and 264 (see entire document, including page 7416, right column, paragraph 3; reads on claims 1-4; as discussed above under Claim Interpretation, claim 1 as written only requires the presence of a third domain of type A4 BoNT and does not require the presence of any other domains of other types of botulinum neurotoxin). The protein comprises the BoNT A4 heavy chain (page 7420, Figure 3; reads on claims 5-7). The mutations mildly increased the activity of the toxin in vitro (page 7421, Figure 4 and left column, paragraph 2; reads on claim 21).
Therefore, claims 1-7 and 21 are anticipated by Bradshaw and are rejected under 35 U.S.C. 102(a)(1).
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by international patent application WO 2018/132423 filed by Johnson et al., published 07/19/2018 (cited on the IDS filed 12/28/2023).
Johnson teaches chimeric botulinum neurotoxins comprising a light chain polypeptide from a first subtype and a heavy chain polypeptide from a second subtype (see entire document, including page 3, lines 26-32). In a specific embodiment, the molecule is an A4/A1 botulinum neurotoxin (page 4, line 6; page 7, lines 20-23; reads on claims 1-8; see above under Claim Interpretation for the Examiner’s interpretation of claims 1-4).
Therefore, claims 1-8 are anticipated by Johnson and are rejected under 35 U.S.C. 102(a)(1).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 07/02/2026