IMMUNOLOGICALLY OPTIMIZED BOTULINUM TOXIN LIGHT CHAIN VARIANTS

DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Applicants’ Amendment 1) Acknowledgment is made of Applicants’ amendment filed 06/22/26 in response to the non-final Office Action mailed 01/22/26. Status of Claims 2) Claims 2, 104, 105, 109-111, 113, 116 and 117 have been canceled via the amendment filed 06/22/26. Claims 1, 16-18, 22, 24, 28, 83-85, 87, 90, 94, 98, 99 and 103 have been amended via the amendment filed 06/22/26. New claims 118-127 have been added via the amendment filed 06/22/26. Claims 1, 16-18, 22, 24, 28, 83-85, 87, 90, 94, 98, 99, 103 and 118-127 are pending. Claims 1, 85, 87, 90, 99 and 103, as amended, and the newly added claims 118 and 123-127 dependent from claim 1, do not cover the previously elected S156G mutation within the elected SEQ ID NO: 1 BoNT/A-LC species and therefore are withdrawn from consideration as not being directed to a species elected by original presentation. See 37 C.F.R 1.142(b) and M.P.E.P § 821.03. Claims 17 and 22, as amended, do not cover the previously elected S156G mutation within the elected SEQ ID NO: 1 BoNT/A-LC species and therefore these claims and the newly added claims 120 and 121 that depend from the amended claim 17, are withdrawn from consideration as not being directed to a species elected by original presentation. See 37 C.F.R 1.142(b) and M.P.E.P § 821.03. Claims 18, 24, 83, 84, 94 and 98 were previously withdrawn from consideration as being directed to a non-elected invention or species. See 37 C.F.R 1.142(b) and M.P.E.P § 821.03. Claims 16, 28, 119 and 122 are under examination. Prior Citation of Title 35 Sections 3) The text of those sections of Title 35 U.S. code not included in this action can be found in a prior Office Action. Prior Citation of References 4) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record. Objection(s) Withdrawn 5) The objection to claim 16 set forth at paragraph 13(d) of the Office Action mailed 01/22/26 is withdrawn in light of Applicants’ claim amendment. 6) The objections to claims 1, 17, 85, 87 and 99 set forth at paragraph 13 of the Office Action mailed 01/22/26 are withdrawn in light of Applicants’ claim amendments. These amended claims are now withdrawn from consideration. See paragraph 2) supra. Objection(s) to Specification and Claims 7) The specification and claims 16 and 28, as amended, and the new claim 122, are objected to for the following reason(s): 37 CFR 1.75(d)(1) provides, in part, that ‘the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description.’. The terms or limitations identified below lack antecedent basis in the as-filed specification. Furthermore, 35 U.S.C § 132 states that no amendment shall introduce new matter into the disclosure of the invention. Claim 16, as amended, is set forth below, which includes the following added limitations shown by Applicants via underlining: PNG media_image1.png 41 525 media_image1.png Greyscale PNG media_image2.png 17 433 media_image2.png Greyscale ............... S156G ......... as PNG media_image3.png 16 146 media_image3.png Greyscale . Thus, the product claimed in the amended claim 16 is a deimmunized BoNT/A-LC comprising: (1) the amino acid sequence of SEQ ID NO: 1; and (2) further comprising the S156G mutation (the elected species) as relating to SEQ ID NO: 1. However, while there is descriptive support and antecedent basis in the as-filed specification for a deimmunized botulinum toxin A light chain (BoNT/A-LC) comprising the amino acid sequence of SEQ ID NO: 1 comprising therein the S156G mutation, there is no descriptive support and antecedent basis in the as-filed specification and the original claims for a deimmunized BoNT/A-LC comprising: (1) the amino acid sequence of SEQ ID NO: 1; and (2) further comprising the S156G mutation as relating to SEQ ID NO: 1. Claim 28, as amended, is set forth below, which includes the following added limitations shown by Applicants via underlining: PNG media_image4.png 41 512 media_image4.png Greyscale .......... PNG media_image5.png 39 521 media_image5.png Greyscale ....... PNG media_image6.png 34 536 media_image6.png Greyscale ..... PNG media_image7.png 35 522 media_image7.png Greyscale ......... PNG media_image8.png 59 528 media_image8.png Greyscale .......... Thus, the dependent claim 28 reciting multiple limitations “S156 ...... as relating to SEQ ID NO: 1” requires the deimmunized BoNT/A-LC of claim 16 to comprise at least S156 of broader scope, i.e., any generic amino acid residue being present at S156. Due to the lack of a coordinating conjunction limitation –and-- or –or-- between the last two elements recited at the end of the claim, i.e., between the last two paragraphs, the claimed deimmunized BoNT/A-LC encompasses one comprising all the multiple S156 mutations as recited. However, there is no descriptive support and antecedent basis in the as-filed application for the deimmunized BoNT/A-LC now claimed in the amended claim 28. New claim 122 is set forth below, which includes the following limitations: PNG media_image9.png 14 487 media_image9.png Greyscale comprises ........ PNG media_image10.png 35 490 media_image10.png Greyscale ........... PNG media_image11.png 38 507 media_image11.png Greyscale .......... PNG media_image12.png 35 524 media_image12.png Greyscale ....... PNG media_image13.png 60 523 media_image13.png Greyscale ......... PNG media_image14.png 84 519 media_image14.png Greyscale ....... or .... Thus, the dependent new claim 122 requires the deimmunized BoNT/A-LC of claim 16 to comprise the S156G mutation as relating to SEQ ID NO:1. However, there is no descriptive support and antecedent basis in the as-filed application for the deimmunized BoNT/A-LC now claimed in new claim 122. It is noted that Applicants do not point to specific parts of the as-filed specification for descriptive support and/or antecedence for the deimmunized BoNT/A-LC as claimed currently and for the full scope of the claims identified supra. Rejection(s) Moot 8) The rejection of claim 2 set forth at paragraph 9 of the Office Action mailed 01/22/26 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite is moot in light of Applicants’ cancellation of the claim. 9) The rejection of claim 2 set forth at paragraph 12 of the Office Action mailed 01/22/26 under 35 U.S.C § 102(a) as being anticipated by WO 2015177312 A1 (of record) is moot in light of Applicants’ cancellation of the claim. Rejection(s) Withdrawn 10) The rejections of claims 1, 22, 28, 85, 87, 90, 99 and 103 set forth at paragraph 9 of the Office Action mailed 01/22/26 under 35 U.S.C § 112(b) or 35 U.S.C § 112 (pre-AIA ), second paragraph, as being indefinite are withdrawn in light of Applicants’ claim amendments. These amended claims are now withdrawn from consideration. See paragraph 2) supra. 11) The rejection of claims 1, 17, 22, 85, 87, 90, 99 and 103 set forth at paragraph 12 of the Office Action mailed 01/22/26 under 35 U.S.C § 102(a) as being anticipated by WO 2015177312 A1 (of record) is withdrawn in light of Applicants’ claim amendments. These amended claims are now withdrawn from consideration. See paragraph 2) supra. 12) The rejection of claims 16 and 28 set forth at paragraph 12 of the Office Action mailed 01/22/26 under 35 U.S.C § 102(a) as being anticipated by WO 2015177312 A1 (of record) is withdrawn in light of Applicants’ claim amendments. Rejection(s) under 35 U.S.C § 112(b) or (Pre-AIA ), First Paragraph 13) The following is a quotation of 35 U.S.C § 112(a): (a) IN GENERAL.- The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of 35 U.S.C. § 112 (pre-AIA ), first paragraph: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out the invention. 14) Claims 16 and 28, as amended, the dependent claim 119, and the new claim 122 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for the (pre-AIA ), the Applicant. This is a new matter rejection. PNG media_image1.png 41 525 media_image1.png Greyscale PNG media_image2.png 17 433 media_image2.png Greyscale ............... S156G ......... as PNG media_image3.png 16 146 media_image3.png Greyscale . Thus, the product claimed in the amended claim 16 is a deimmunized BoNT/A-LC comprising: (1) the amino acid sequence of SEQ ID NO: 1; and (2) further comprising the S156G mutation (the elected species) as relating to SEQ ID NO: 1. However, while there is descriptive support in the as-filed specification for a deimmunized botulinum toxin A light chain (BoNT/A-LC) comprising the amino acid sequence of SEQ ID NO: 1 comprising therein the S156G mutation, there is no descriptive support in the as-filed specification and the original claims for a deimmunized BoNT/A-LC comprising: (1) the amino acid sequence of SEQ ID NO: 1; and (2) further comprising the S156G mutation as relating to SEQ ID NO: 1. Claim 28, as amended, is set forth below, which includes the following added limitations shown by Applicants via underlining: PNG media_image4.png 41 512 media_image4.png Greyscale .......... PNG media_image5.png 39 521 media_image5.png Greyscale ....... PNG media_image6.png 34 536 media_image6.png Greyscale ..... PNG media_image7.png 35 522 media_image7.png Greyscale ......... PNG media_image8.png 59 528 media_image8.png Greyscale .......... Thus, the dependent claim 28 including multiple limitations “S156 ...... as relating to SEQ ID NO: 1” requires the deimmunized BoNT/A-LC of claim 16 to comprise at least S156 of broader scope, i.e., any generic amino acid residue being present at S156. Due to the lack of a coordinating conjunction limitation –and-- or –or-- between the last two elements recited at the end of the claim, i.e., between the last two paragraphs, the claimed deimmunized BoNT/A-LC encompasses one comprising all the multiple S156 mutations as recited. However, there is no descriptive support in the as-filed application for the deimmunized BoNT/A-LC now claimed in the amended claim 28. New claim 122 is set forth below, which includes the following limitations: PNG media_image9.png 14 487 media_image9.png Greyscale comprises ........ PNG media_image10.png 35 490 media_image10.png Greyscale ........... PNG media_image11.png 38 507 media_image11.png Greyscale .......... PNG media_image12.png 35 524 media_image12.png Greyscale ....... PNG media_image13.png 60 523 media_image13.png Greyscale ......... PNG media_image14.png 84 519 media_image14.png Greyscale ....... or .... Thus, the dependent new claim 122 requires the deimmunized BoNT/A-LC of claim 16 to comprise the S156G mutation as relating to SEQ ID NO:1. However, there is no descriptive support in the as-filed application for the deimmunized BoNT/A-LC now claimed in new claim 122. It is noted that Applicants do not point to specific parts of the as-filed specification for descriptive support for the deimmunized BoNT/A-LC as claimed currently and for the full scope of the claims identified supra. Therefore, the above-identified limitations and the currently claimed scope of the claims constitute new matter. See M.P.E.P 608.04 to 608.04(c). Applicants are requested to point to the descriptive support in the specification as filed, for the new limitation(s), or alternatively, remove the new matter from the claim(s). Applicants should specifically point out the support for any amendments made to the disclosure. See MPEP 714.02 and 2163.06, which, with respect to newly added or amended claims, requires Applicants to show support in the original disclosure for the new or amended claims. Rejection(s) under 35 U.S.C § 112(b) or (Pre-AIA ), Second Paragraph 15) 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. 16) Claims 16, 28, 119 and 122 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 inventor or a joint inventor, or for the pre-AIA the Applicant regards as the invention. (a) The limitations: “S156G ..... as relating to SEQ ID NO: 1” in claim 16, as amended, and new claim 122 render the claims ambiguous and indefinite. The limitation “as relating to SEQ ID NO: 1” is not defined in the specification and therefore, one of ordinary skill in the art cannot understand in an unambiguous way the structural boundaries of the claimed product and thus the scope of the claims. (b) Analogous rejection applies to claim 28, as amended, with regard to the multiple limitations “S156 ...... as relating to SEQ ID NO: 1”. Claim 28, as amended, is also ambiguous and incomplete because it lacks a coordinating conjunction limitation –and-- or –or-- between the last two elements recited at the end of the claim, i.e., between the last two paragraphs, rendering the scope of the claim indeterminate. (c) The dependent claims 119 and 122 are indefinite for having incorrect antecedence in the limitation(s) “the mutation”. These claims depend from claim 16, which as amended currently includes the limitation “at least one” mutation. For proper antecedence, it is suggested that Applicants replace said limitation in claims 28, 119 and 122 with the limitation --the at least one mutation--. (d) The dependent claim 28 is ambiguous, confusing and indefinite in the limitations: The deimmunized BoNT/A-LC of claim 16 “comprising: ...... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, ..... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, ..... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, ..... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, ..... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, ..... at least one mutation .... S156 .... as relating to SEQ ID NO: 1, .....”. Since the deimmunized BoNT/A-LC of claim 16 already comprises S156G as relating to SEQ ID NO: 1, are all the multiple ‘at least one mutation .... S156 .... as relating to SEQ ID NO: 1’ of broader scope recited in instant claim 28 in addition to the at least one S156G mutation from claim 16? One of ordinary skill in the art cannot understand in an unambiguous way the structural boundaries of the claimed product and thus the scope of the claim. The metes and bounds of the claim are indeterminate. (e) Claims 28, 119 and 122, which depend from claim 16, are also rejected as being indefinite because of the indefiniteness identified above in the base claim. Conclusion 17) No claims are allowed. 18) Applicant’s amendment necessitated the new ground(s) of rejection presented in this Office action. THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 C.F.R 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Correspondence 19) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 8.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the supervisory examiner, Jeffrey Stucker can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300. 20) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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. /S. DEVI/ S. Devi, Ph.D.Primary Examiner Art Unit 1645 September, 2026