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 . 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.
Election/Restrictions
Applicant’s election of SEQ ID 8 and diabetics in the reply filed on 5 June, 2026 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 (MPEP § 818.01(a)).
The requirement is deemed proper and is therefore made FINAL.
Applicants have elected SEQ ID 8, and, in method claims, for treating diabetes. A search was conducted for this invention, and references rendering it obvious were found. As a result, claims 1-8, 10, and 12-14 were examined and claims 9, 11, 15, 19-40, 47, and 53 have been withdrawn from consideration.
During examination, a reference was found that anticipated at least one non-elected species. This reference is discussed below.
Claim Objections
Claim 10 is objected to because of the following informalities: claim 10 has an amino acid bhY, which is not defined in the claim. While it is defined in the disclosure (p12, 3d paragraph), this is not a standard amino acid and amino acid notation, and would be clearer if defined in the claim. Appropriate correction is required.
Claims Status
Claims 1-15, 19-40, 47 and 53 are pending.
Claim 12 has been amended.
Claims 9, 11, 15, 19-40, 47, and 53 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5 June, 2026.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 his invention.
Claim 12 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating pain and cancer, and preventing pain, does not reasonably provide enablement for all disorders associated with the α9α10 nicotinic acetylcholine receptor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The MPEP states “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue.’ These factors include, but are not limited to: 1) the breadth of the claims; 2) the nature of the invention; 3) the state of the prior art; 4) the level of one of ordinary skill; 5) the level of predictability in the art; 6) the amount of direction provided by the inventor; 7) the existence of working examples; and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure” (MPEP 2164.01(a).
1 and 2) the breadth of the claim and the nature of the invention: Applicants are claiming a method of treating or preventing any disorder associated with α9α10 nicotinic acetylcholine receptor, comprising administering a peptide that inhibits the receptor (p37, 2nd paragraph).
3) the state of the prior art: AlSharari et al (Eur. J. Pharmacol. (2020) 883:173320) states that the receptor targeted by these compounds inhibits inflammatory cytokine production when activated (2nd page, 2nd paragraph). In other words, inhibition of the receptor would counter its anti-inflammatory activity.
Pucci et al (Front. Cell. Neurosci. (2022) 15:806123) state that the natural ligand for these receptors does not initiate tumorogenesis, but does promote tumor growth and metastasis (1st page, 2nd paragraph). In other words, while inhibiting this receptor may provide a benefit to a cancer patient, it will do nothing to prevent cancer from developing.
Elgoyhen et al (Biochem. Pharmacol. (2009) 78(7) p712-719) discusses the α9α10 nicotinic acetylcholine receptor in the context of treatment of hearing loss (abstract). Note that a mouse with the α10 subunit knocked out was not able to amplify acoustic signals (4th page, 1st paragraph), indicating that inhibition of the receptor would not be beneficial. Note that this disorder is more common with age, (4th page, 3d paragraph), associating aging to the α9α10 nicotinic acetylcholine receptor.
4) the level of one of ordinary skill: The level of one of skill in the art is high.
5) the level of predictability in the art: 90% of clinical trials fail (Sun et al, Acta Pharmceut Sinica B (2022) 12(7) p3049-3062, title), indicating a limited level of predictability in the pharmaceutical arts.
6 and 7) the amount of direction provided by the inventor and the existence of working examples: Applicant’s experiments show analgesic activity (example 10, starting on p54), but no tests for other conditions are discussed.
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: The prior art shows that the natural ligand for the receptor does not cause cancer, indicating that inhibiting the receptor will not prevent cancer. The prior art also shows that activating the receptor will have an anti-inflammatory effect; inhibition of the receptor is not likely to be directly inhibitory to inflammation. Thus, it will take undue experimentation to prevent and treat inflammation and to prevent cancer.
Aging is associated with the receptor via hearing loss. Yet it is unclear how applicant’s invention will prevent and treat aging or hearing loss with the mechanism described by applicants. Thus, it will take undue experimentation to use the invention to prevent or treat aging.
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.
(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.
first rejection
Claim(s) 1, 3-5, 12, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McIntosh (US 20160122388).
McIntosh discusses α-conotoxin peptides that can be used to treat pain (abstract). Among the sequences discussed are Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Cit-iodoTyr-Gln-Cys-Tyr-Arg (SEQ ID 10) and Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Arg-iodoTyr-Gln-Cys-Arg-Arg-Arg (SEQ ID 12) (paragraphs 19 and 20). Note that these sequences anticipate claim 1, with X1=Cys, X2=Cit or Arg, R-3-Y=iodotyrosine (presume to be the 3 isomer), X3=Tyr or Arg, and X4=Arg. Note that these also anticipate claims 3-5. They are taught to treat pain, anticipating claims 12 and 13.
second rejection
Claim(s) 1, 3-5 and 12-14 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by McIntosh et al (US 20230391838, priority date June 3, 2020).
Please note that this reference appears to be applicant’s own work. It is possible that applicants can disqualify this reference as prior art with one of the exceptions under 35 USC 102(b)(2).
McIntosh et al discuss peptides that can be used to treat diabetic neuropathic pain, (paragraph 188), relevant to claims 12-14. One of the sequences synthesized (paragraph 318, table 2a-1) is SEQ ID 24, with the sequence Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Arg-3-IodoTyr-Gln-Cys-β-homoTyr-Arg (table 1, p16), anticipating claims 1, 3-5 and 12-14. Note that disulfide scrambling by dithiol exchange can be a problem (paragraph 115).
Claim Rejections - 35 USC § 103
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 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.
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.
Claims 1-8, 10, and 12-14 are rejected under 35 U.S.C. 103 as being obvious over McIntosh et al (US 20230391838) in view of Zheng et al (J. Am. Chem. Soc. (2015)137 p15094-15097).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
McIntosh et al discuss peptides that can be used to treat diabetic neuropathic pain, (paragraph 188). One of the sequences synthesized (paragraph 318, table 2a-1) is SEQ ID 24, with the sequence Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Arg-3-IodoTyr-Gln-Cys-β-homoTyr-Arg (table 1, p16). Note that disulfide scrambling by dithiol exchange can be a problem (paragraph 115). As noted above, this reference anticipates claims 1, 3-5, and 12-14.
The difference between this reference and the remaining claims is that this reference does not discuss a Pen residue.
Zheng et al discuss the orthogonal disulfide pairing (title). A mix of Pen and Cys residues under oxidizing conditions selectively formed heterodimers, but negligible amounts of homodisulfides (p15094, 2nd column, 3d paragraph). This is exploited to direct the disulfide bond formation of peptides comprising multiple disulfide bonds (p15095, 2nd column, 2nd paragraph). This also prevented disulfide isomerization (p15096, 2nd column, 2nd paragraph). This allows synthesis of multiple disulfide bonds avoiding protecting group chemistry to direct the synthesis (p15097, 1st column, 3d paragraph). This reference discusses using Pen residues to direct disulfide bond formation.
Therefore, it would be obvious to replace the various Cys residues with Pen residues, to generate congeners that are resistant to the disulfide bond shuffling discussed by McIntosh et al. As Zheng et al clearly shows that the Pen-Cys disulfide bond will not exchange with a Cys-Cys disulfide bond, an artisan in this field would attempt this substitution with a reasonable expectation of success.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
first rejection
Claims 1-8, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/760,668 (US 20230391838) (reference application) in view of Zheng et al (J. Am. Chem. Soc. (2015)137 p15094-15097).
Competing claim 1 claims SEQ ID 24, with the sequence Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Arg-3-IodoTyr-Gln-Cys-β-homoTyr-Arg. Note that this anticipates claims 1 and 3-5. While the competing claims do not specify treatment of diabetic pain, the disclosure does (paragraph 188). Note that the utility of an invention is one of the few places the disclosure can be relied upon for a double patenting rejection (MPEP 804(II)(B)(1)).
The difference between the competing claims and the remaining claims is that the competing claims do not have a Pen residue.
Zheng et al discuss the orthogonal disulfide pairing (title). A mix of Pen and Cys residues under oxidizing conditions selectively formed heterodimers, but negligible amounts of homodisulfides (p15094, 2nd column, 3d paragraph). This is exploited to direct the disulfide bond formation of peptides comprising multiple disulfide bonds (p15095, 2nd column, 2nd paragraph). This also prevented disulfide isomerization (p15096, 2nd column, 2nd paragraph). This allows synthesis of multiple disulfide bonds avoiding protecting group chemistry to direct the synthesis (p15097, 1st column, 3d paragraph). This reference discusses using Pen residues to direct disulfide bond formation.
Therefore, it would be obvious to sequentially modify the Cys residues with Pen residues, to find congeners that allow for synthesis without multiple protection/deprotection steps to generate the correct disulfide bonds. As Zheng et al states that this is a general process for such peptides, an artisan in this field would attempt this modification with a reasonable expectation of success. Alternatively, the rationale could be to prevent disulfide bond isomerization, same reasonable expectation of success.
Note that if the 2nd Cys of the competing claims is mutated to Pen, it regenerates SEQ ID 8, applicant’s elected species.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
second rejection
Claims 1-8, 10, and 12-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,947,274. Although the claims at issue are not identical, they are not patentably distinct from each other because the competing claims anticipate or render obvious the examined claims.
Competing claim 1 describes a number of sequences, including SEQ ID 35, which differs from applicants’ elected species in that X2 is a Cit residue rather than an Arg, anticipating claims 1, 2, 4, and 5. While the competing claims do not specify treatment of diabetic pain, the disclosure does (paragraph 57). Note that the utility of an invention is one of the few places the disclosure can be relied upon for a double patenting rejection (MPEP 804(II)(B)(1)), anticipating claims 12-14. The difference between Cit and Arg is a single methylene residue, which, absent secondary considerations, is not considered a patentable difference (MPEP 2144.09(II)), rendering obvious claims 3, 6-8, and 10.
third rejection
Claims 1-5, 12, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of U.S. Patent No. 10,633,417 in view of Zheng et al (J. Am. Chem. Soc. (2015)137 p15094-15097).
Competing claim 1 describes a genus of sequences, while competing claim 7 lists a Markush group of sequences, including SEQ ID 8, with the sequence Gly-Cys-Cys-Thr-Asp-Pro-Arg-Cys-Cit-iodoTyr-Gln-Cys-Tyr-Arg-Arg. Note that this anticipates claims 1, 4, and 5. While the competing claims do not specify treatment of pain, the disclosure does column 11, line 4-12). Note that the utility of an invention is one of the few places the disclosure can be relied upon for a double patenting rejection (MPEP 804(II)(B)(1)), anticipating claims 12 and 13. The Cit residue at position 9 differs from the Arg of claim 3 by a single methylene residue, which, absent secondary considerations, is not considered a patentable difference (MPEP 2144.09(II)), rendering obvious claims 3.
The difference between the competing claims and the remaining examined claim is a Cys-Pen mutation.
Zheng et al discuss the orthogonal disulfide pairing (title). A mix of Pen and Cys residues under oxidizing conditions selectively formed heterodimers, but negligible amounts of homodisulfides (p15094, 2nd column, 3d paragraph). This is exploited to direct the disulfide bond formation of peptides comprising multiple disulfide bonds (p15095, 2nd column, 2nd paragraph). This also prevented disulfide isomerization (p15096, 2nd column, 2nd paragraph). This allows synthesis of multiple disulfide bonds avoiding protecting group chemistry to direct the synthesis (p15097, 1st column, 3d paragraph). This reference discusses using Pen residues to direct disulfide bond formation.
Therefore, it would be obvious to replace the various Cys residues with Pen residues, to generate congeners that are resistant to the disulfide bond shuffling discussed by McIntosh et al. As Zheng et al clearly shows that the Pen-Cys disulfide bond will not exchange with a Cys-Cys disulfide bond, an artisan in this field would attempt this substitution with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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