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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3 August 2026 has been entered.
Response to Amendment
Amendments filed on 3 August 2026 are acknowledged. Claims 1, 19-21, and 61 are amended. Claims 1-3, 6, 13, 15-17, 19-21, 29, 61, and 68 are pending and are examined herein on the merits.
In response to the reply filed on 3 August 2026, the objection to the claims is withdrawn; the rejections under 35 U.S.C. 112(b) are changed; rejections under 35 U.S.C. 112(a) regarding scope of enablement are added; and the rejections over the prior art are withdrawn.
In response to Applicant's statement pursuant to 35 U.S.C. 102(b)(2)(C), Verespy (WO 2020/154208 A1) is disqualified as prior art under 35 U.S.C. 102(a)(2), and the corresponding prior art rejections based upon Verespy have been withdrawn.
In response to Applicant's statement pursuant to 35 U.S.C. 102(b)(2)(C), Chee (WO 2019/089836 A1) is disqualified as prior art under 35 U.S.C. 102(a)(2), and the corresponding prior art rejections based upon Chee have been withdrawn.
In response to Applicant's statement pursuant to 35 U.S.C. 102(b)(2)(C), by Desai (WO 2020/198264 A1) is disqualified as prior art under 35 U.S.C. 102(a)(2), and the corresponding prior art rejections based upon Desai have been withdrawn.
Claim Rejections - 35 USC § 112
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.
Claims 1-3, 6, 13, 15-17, 19-21, 29, 61, and 68 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Independent claim 1 recites the limitation "designated N atom indicates that…" after the definition of R2. It is unclear to what "designated N atom" refers. Accordingly, "designated N atom" lacks sufficient antecedent basis. It is noted that the limitation "a designated N atom is introduced later near the end of the claim."
Independent claim 1 recites the limitation "designated N atom indicates that RAA1 or RAA2 optionally cyclize onto the designated N atom." The intended meaning of this limitation is completely unclear. If this limitation is intended to define the term "designated N atom," then it is a circular definition.
Regarding the limitation that "RAA1 or RAA2 optionally cyclize onto the designated N atom," it is unclear whether this limitation describes a functionality of R AA1 or R AA2. In other words, it is unclear whether this limitation means that optionally R AA1 or RAA2 is a synthetic precursor that is capable of cyclizing onto the designated N atom. Such an interpretation contradicts the later claim 1 limitation that "each dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that RAA1 or RAA2 and the designated N atom are optionally part of a ring."
For purposes of evaluating the claims under 35 USC 112(a) below, the potentially contradictory claim 1 limitation "…RAA1 or RAA2 optionally cyclize onto the designated N atom" is not given weight. The examiner suggests removing the limitation "designated N atom indicates that RAA1 or RAA2 optionally cyclize onto the designated N atom; and" from claim 1.
Claim 1 recites the limitation "the designated N atom" within the definition of "each dashed semi-circle." There is insufficient antecedent basis for this limitation because the claim previously introduces both "designated N atom" and "a designated N atom."
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, independent claims 1 and 61 the broad recitation "wherein optional substituents of the optionally substituted group are one to three members selected from halo, …" , and the claim also recites "wherein the phenyl, 5- membered heteroaryl, 6-membered heteroaryl, and C 1-6 alkyl of the optionally substituted group are each optionally substituted with one or two members selected from halo, …," which is the narrower statement of the range/limitation.
Dependent claims 2, 3, 6, 13, 15-17, 19-21, 29, and 68 are rejected under 35 USC 112(b) for depending from claim 1 or 61.
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.
Claims 1-3, 6, 13, 15-17, 19-21, 29, 61, and 68 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a semi-circle connecting RAA1 or RAA2 to a designated N atom indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=1 or when y=0, and also enabling for a semi-circle connecting RAA1 or RAA2 to a designated N atom not indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=2 or when y=1, does not reasonably provide enablement for a semi-circle connecting RAA1 or RAA2 to a designated N atom indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=2 or when y=1, or for a semi-circle connecting RAA1 or RAA2 to a designated N atom not indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=1 or when y=0. 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.
Factors to be considered when determining whether the claimed invention would require undue experimentation are given in MPEP 2164.01 (a). In re Wands, 858 F. 2d 731,737; 8 USPQ 2d 1400, 1404 (Fed. Cir. 1988).
(A) The breadth of the claims.
Independent claims 1 and 61, and dependent claims 19 and 20, recite the limitations "x=1 or 2; y=0 or 1" and "each dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that RAA1 or RAA2 and the designated N atom are optionally part of a ring."
Accordingly, the scope of the claim permits a semi-circle connecting RAA1 or RAA2 to a designated N atom to indicate that RAA1 or RAA2 and the designated N atom are part of a ring when x=2 or when y=1, which is the part of the rejected scope of the claims.
Moreover, the scope of the claim permits a semi-circle connecting RAA1 or RAA2 to a designated N atom to not indicate that RAA1 or RAA2 and the designated N atom are part of a ring when x=1 or when y=0, which is also part of the rejected scope of the claims.
As set forth above in the rejections under 35 USC 112(b), the potentially contradictory indefinite limitation "…RAA1 or RAA2 optionally cyclize onto the designated N atom" in claim 1 is not given weight for purposes of evaluating the claims under 35 USC 112(a).
(B) The nature of the invention.
The invention is a method of peptide sequencing using N-terminal degradation.
(C) The state of the prior art.
The closest prior art of record are WO 2017/192633 (IDS) nor Hamada ("A novel N-terminal degradation reaction of peptides via N-amidination," Bioog. Med. Chem. Lett. 2016, 26, 1690-1695; IDS).
The prior art of record does not disclose peptides that violate the valence rules that are the subject of this rejection.
(D) The level of one of ordinary skill.
One of ordinary skill in the art would understand that a semi-circle connecting RAA1 or RAA2 to a designated N atom indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=1 or when y=0 is necessary (non-optional) for the formula of the claims to satisfy valence rules. Moreover, one of ordinary skill in the art would understand that a semi-circle connecting RAA1 or RAA2 to a designated N atom not indicating that RAA1 or RAA2 and the designated N atom are part of a ring when x=2 or when y=1 is required for the formula of the claims to satisfy valence rules, in which each designated N atom is neutral and bonded to one or two hydrogen atoms, for when x=2 or y=1. As an example, the claimed formula appear to preclude either RAA1 or RAA2 from being the sidechain of proline when x=2 or y=1, given valence rules. A comparison of the hydrogen substituents of the nitrogen atoms for Formula (I) with the proline nitrogen atoms of a Pro-Pro-AA tripeptide is shown below:
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(E) The level of predictability in the art.
Valence rules of organic chemistry are highly predictable.
(F) The amount of direction provided by the inventor.
The specification teaches the following ([0126], page 66; bolding and italics added):
The terminal amino acid at one end of the peptide chain that has a free amino group is referred to herein as the “N-terminal amino acid” (NTAA). Note that, as depicted in some of the structures herein, the side chain of an amino acid, including the NTAA, can optionally cyclize onto the amine; so the free amino group may not be -NH2 if the side chain (like that of proline) cyclizes onto the amine. It is nevertheless an accessible and nucleophilic amine, subject to functionalization according to the methods described herein, and the functionalized NTAA is still subject to elimination under the cleavage conditions of the methods.
The above passage states that the amino acid can be proline in the context of "the side chain… cyclizes onto the amine." However, the specification also correctly points out that if the N-terminal amino acid is proline, the N-terminus is not -NH2, which contradicts Formula (I) of the claims when x=2 and the semi-circle indicates a ring.
(G) The existence of working examples.
No working examples are provided of the rejected scope of the claims.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In view of the clear violation of valence rules for the rejected scope of the claims, it would require undue experimentation for one of ordinary skill in the art to use the rejected scope of the claimed invention.
Allowable Subject Matter
Claims 1-3, 6, 13, 15-17, 19-21, 29, 61, and 68 would be allowable if rewritten to overcome the rejections under 35 U.S.C. 112(b) set forth in this Office action and to overcome the rejections under 35 U.S.C. 112(a) by limiting the scope of the claims to the enabled scope indicated below:
x=1 or 2; y=0 or 1; […]
when x=1 or y=0, each corresponding dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that R AA1 or R AA2 and the designated N atom are part of a ring;
when x=2 or y=1, each corresponding dashed semi-circle connecting RAA1 or RAA2 to a designated N atom does not indicate that R AA1 or R AA2 and the designated N atom are part of a ring;
Neither WO 2017/192633 (IDS) nor Hamada ("A novel N-terminal degradation reaction of peptides via N-amidination," Bioog. Med. Chem. Lett. 2016, 26, 1690-1695; IDS) suggest by themselves a modification of their respective guanidinylation procedure to provide a guanidinyl derivative of Formula (II) or a tautomer thereof as recited in independent claim 1.
Response to Arguments
Applicant's arguments filed on 29 May 2026 and 3 August 2026 have been considered and are moot in view of the new grounds of rejection.
With respect to the previous rejections under 35 USC 112(b), Applicant's arguments address amendments to claim 61 that are not evident to the examiner (no relevant mark-ups are present).
Applicant's representative is encouraged to contact the examiner if there are any questions on overcoming the remaining rejections.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE ADAMS whose telephone number is (571)270-5043. The examiner can normally be reached M, T, Th, and F, 12-4 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, Lyle Alexander can be reached on (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MICHELLE ADAMS/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797
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