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 .
Response to Amendment
Applicant's petition for revival under 37 CFR 1.136(a) filed on 10 September 2025, and the office's granting of this petition on 6 November 2025 are acknowledged.
Amendments filed on 10 September 2025 are acknowledged. Claims 1, 13, 16, 17, 19-21, 29, 61, and 68 are amended; claims 22, 39, 43, 62, 215, and 216 are newly canceled. A terminal disclaimer filed on 10 September 2025 is acknowledged. 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 amendments filed on 10 September 2025, an objection to the claims is added; the rejections under 35 U.S.C. 112(b), are partially withdrawn and modified; the rejections under 35 U.S.C. 112(a) regarding the written description requirement are withdrawn; the rejection under 35 U.S.C. 112(a) regarding the enablement requirement is withdrawn; and the rejections over the prior art are changed. Claims 15, 16, 20, 21, and 29 are directed to allowable subject matter.
In response to Applicant's statement pursuant to 35 U.S.C. 102(b)(2)(C), Beierle (WO 2019/089846 A1) is disqualified as prior art under 35 U.S.C. 102(a)(2), and the corresponding prior art rejections based upon Beierle have been withdrawn.
In response to the terminal disclaimer over 18/065282 filed on 10 September 2025, and the abandonment of co-pending application 16/760029, the nonstatutory double patenting rejections have been withdrawn.
Claim Objections
Claim 61 is objected to because of the following informalities: In the limitation "(1) contacting the guanidinyl derivative…" the number "1" must be reverted to "2". The number was changed without markup in this amendment. Appropriate correction is required.
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 "wherein the phenyl, 5-membered heteroaryl, 6-membered heteroaryl, and C1-6 alkyl are each optionally substituted with…" after the limitation beginning "wherein optional substituents of the optionally substituted group…" There is insufficient antecedent basis for the limitation "the phenyl, 5-membered heteroaryl, 6-membered heteroaryl" because the claim introduces "phenyl" "5-membered heteroaryl," and "6-membered heteroaryl" twice before. Compare the related rejection of claim 61 below.
Independent claims 1 and 61 recite the limitation "two R' or two R" on the same N form a 4-7 membered heterocyclic ring optionally containing an additional heteroatom selected from N, O and S as a ring member in addition to the nitrogen." There is insufficient antecedent basis for the limitation "the nitrogen" in the claim. It is recommended that this limitation be replaced by "the same N" to make the intended antecedent clear. Claims 20 and 21 are rejected for analogous reasons, with a suggested replacement of the limitation "the nitrogen" with "the same nitrogen."
Independent claims 1 and 61 recite the limitation "x=1 or 2; y=0 or 1; … each dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that R AA1 or R AA2 optionally cyclize onto the designated N atom." The grammar of the limitation "R AA1 or R AA2 optionally cyclize onto the designated N atom" supports two mutually contradictory interpretations of this limitation. The intended meaning of this limitation is unclear.
A first interpretation is that the limitation "…optionally cyclize onto…" describes a cyclic substructure of Formulae (I), (II), and (III). In other words, the first interpretation is optionally R AA1 and the designated N atom are part of a cycle. This interpretation is consistent with Formula (I), (II), and (III), when x=1 or y=0. Moreover, valence rules imply that such an interpretation is non-optional when x=1 or y=0. However, this interpretation is inconsistent with Formula (I), (II), and (III), in which each designated N atom is neutral and bonded to one or two hydrogen atoms, for when x=2 or y=1. Given valence rules, Formula (I), (II), and (III) appear to preclude either RAA1 or RAA2 from being the sidechain of proline when x=2 or y=1. 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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The specification addresses this first interpretation ([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.
A second interpretation is that the limitation "…optionally cyclize onto…" describes a functionality of R AA1 or R AA2. In other words, the second interpretation is that optionally R AA1 or RAA2 is a synthetic precursor that is capable of cyclizing onto the designated N atom. This interpretation is consistent with Formula (I), (II), and (III) for when x=2 or y=1, which are enabled to illustrate a precursor to a cyclization reaction rather than a cyclic structure itself. Moreover, valence rules imply that such an interpretation is non-optional when x=2 or y=1. However, this interpretation is inconsistent with Formula (I), (II), and (III), when x=1 or y=0.
The specification describes at least two such cyclization reactions ([0126, page 66; bolding and italics added):
In another example, a peptide may form a pyroglutamate when treated with a chemical reagent (e.g., diheterocyclic methanimine). For example, under conditions where the N-terminal amino acid is glutamine (Gln; Q) a cyclization stemming from the N-terminal amine readily occurs on the primary amide of the glutamine side chain resulting in pyroglutamate formation. During this step, the P1 amino acid is eliminated and newly formed N-terminal glutamine may cyclize to form pyroglutamate... In another example, under conditions where the N-terminal amino acid is serine (Ser, S), a cyclization stemming from the serine side-chain on to the modified N-terminal amine results in iminooxazolidine formation…
Under the second interpretation, the limitation "R AA1 or R AA2 optionally cyclize onto the designated N atom" means that R AA1 or R AA2 can be, for example, the side chain of glutamine or the side chain of serine. It does not mean that the claimed Formula (I), (II), and (III) comprises a pyroglutamate structure or an iminooxazolidine structure because such structures, like that of proline, have different nitrogen substitution than the claimed formulae.
Given that both the first interpretation and the second interpretation find some support in the specification, it is unclear whether Formula (I), (II), and (III) optionally include cyclic substructure(s) (first interpretation) or whether Formula (I), (II), and (III) optionally are precursors to cyclic substructure(s) (second interpretation). The claims are interpreted as follows when considering compliance with 35 USC 112(a):
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 is part of a cycle with the designated N atom;
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 is part of a cycle with the designated N atom;
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.
Claim 19 recites the limitation "x=1 or 2; y=0 or 1; … each dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that R AA1 or R AA2 optionally cyclize onto the designated adjacent N atom." This is indefinite for reasons analogous to those set forth above regarding the similar limitation in claims 1 and 61.
Claim 19 recites the limitation "the designated adjacent N atom." There is insufficient antecedent basis for this limitation in the claim.
Claim 20 recites the limitation "the dashed semi-circle [singular] connecting RAA1 and RAA2 to the nearest N atom indicates that R AA1 and/or R AA2 optionally cyclize onto the designated N atom." There is insufficient antecedent basis for the limitations "the dashed semi-circle," "the nearest N atom," and "the designated N atom." This limitation is henceforth interpreted as follows:
each dashed semi-circle connecting RAA1 or RAA2 to a designated N atom indicates that R AA1 or R AA2 optionally cyclize onto the designated N atom;
This interpretation of the limitation of claim 20 is indefinite for reasons analogous to those set forth regarding independent claims 1 and 61.
Independent claim 61 recites the limitation "wherein the phenyl, 5-membered heteroaryl, 6-membered heteroaryl, and C1-6 alkyl of the optionally substituted group are each optionally substituted with…" after the limitation beginning "wherein optional substituents of the optionally substituted group…" There is insufficient antecedent basis for the limitation "the phenyl, 5-membered heteroaryl, 6-membered heteroaryl" because the claim introduces "phenyl" "5-membered heteroaryl," and "6-membered heteroaryl" twice before (immediately after "an optionally substituted group" and immediately after "optional substituents of the optionally substituted group"). Is the limitation "the phenyl, 5-membered heteroaryl, 6-membered heteroaryl, and C1-6 alkyl of the optionally substituted group …" meant to refer to the early limitation "R6 is an optionally substituted group…" rather than to the later limitation "optional substituents of the optionally substituted group…"?
Claim Rejections - 35 USC § 102
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.
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)(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.
Claims 1- 3, 6, 13, 17, 19, 61, and 68 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Verespy (WO 2020/154208; previously cited).
The applied reference has a common applicant and common joint inventors 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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
Regarding claims 1, 2, and 19, Verespy discloses the following reaction steps ([0160], page 57), where R2 is C1-6 alkyl and R1 is H or C1-6 alkyl ([0154], page 54), thereby disclosing (1) converting a peptidic compound of Formula (I) or (IA) to a guanidinyl derivative of Formula (II), and (2) contacting the guanidinyl derivative with a medium to produce a compound of Formula (III) or (IIIA):
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In the alternative regarding claims 1, 2, and 19, Verespy discloses the following reaction steps ([0166], page 59), where R4 is C1-6 alkyl ([0163], page 57), thereby disclosing (1) converting a peptidic compound of Formula (I) or (IA) to a guanidinyl derivative of Formula (II), and (2) contacting the guanidinyl derivative with a medium to produce a compound of Formula (III) or (IIIA):
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In the alternative regarding claims 1, 2, and 19, Verespy discloses the following reaction steps ([0184], page 63), where R7 is C1-6 alkyl and R6 is H or C1-6 alkyl ([0178], page 61), thereby disclosing (1) converting a peptidic compound of Formula (I) or (IA) to a guanidinyl derivative of Formula (II), and (2) contacting the guanidinyl derivative with a medium to produce a compound of Formula (III) or (IIIA):
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Regarding claims 3 and 19, Verespy discloses that the polypeptide attached to a solid support ([0061]).
Regarding claim 6, Verespy discloses that the polypeptide is attached to a nucleic acid (binding agent, [0087]).
Regarding claim 13, Verespy discloses that elimination of the functionalized NTAA is performed at pH of about 9 (pH 10.5, [0489]).
Regarding claim 17, Verespy discloses that contacting the guanidinyl derivative with the medium at step (2) occurs at temperature between 40° C and 100° C (95° C, [0489]).
Regarding claim 61, Verespy discloses the limitations of claim 1, as set forth above. Beierle further discloses the production of the claimed cleavage product ([0161], [0167]), [0185]). Verespy discloses a method to identify the N-terminal amino acid residue of a peptidic compound of the Formula (I), and identifying the N-terminal amino acid of the polypeptide by determining the structure or identity of the at least one cleavage product ([0033], [0038], [0061], [0311]).
Regarding claim 68, Verespy discloses that Z is an amino acid or polypeptide attached to a solid support ([0061]).
Claims 1- 3, 6, 13, 17, and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chee (WO 2019/089836 A1; newly cited).
The applied reference has a common applicant and common joint inventors 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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
Regarding claims 1, 2, and 19, Chee discloses a method for analyzing a polypeptide comprising "(b) functionalizing the N-terminal amino acid (NTAA) of the polypeptide with a chemical reagent to yield a functionalized NTAA, wherein the chemical reagent comprises a compound selected from the group consisting of (i) a compound of Formula (I)," ([0387], page 60), where R2 is C1-6 alkyl and R1 is H or C1-6 alkyl (ibid.).
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It is inherent or implicit to Chee that functionalizing the NTAA of the polypeptide with a chemical reagent of Formula (I), where R2 is C1-6 alkyl and R1 is H or C1-6 alkyl, to yield a functionalized NTAA results in a guanidinyl derivative of Formula (II) or a tautomer thereof.
In the alternative, Chee discloses that the chemical reagent comprises a compound of Formula (II), where R4 is C1-6 alkyl ([0387], page 61).
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It is inherent or implicit to Chee that functionalizing the NTAA of the polypeptide with a chemical reagent of Formula (II), where R4 is C1-6 alkyl, to yield a functionalized NTAA results in a guanidinyl derivative of Formula (II) or a tautomer thereof.
In the alternative, Chee discloses that the chemical reagent comprises a compound of Formula (IV), where R7 is C1-6 alkyl and R6 is H or C1-6 alkyl ([0387], page 62).
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It is inherent or implicit to Chee that functionalizing the NTAA of the polypeptide with a chemical reagent of Formula (IV), where R7 is C1-6 alkyl and R6 is H or C1-6 alkyl, to yield a functionalized NTAA results in a guanidinyl derivative of Formula (II) or a tautomer thereof.
Chee further discloses that the method comprises "(e) eliminating the functionalized NTAA to expose a new NTAA" ([0387], page 63). This step inherently or implicitly involves contact with a medium and formation of a compound of Formula (III) or (IIIA).
Accordingly, Chee discloses a method to cleave an N-terminal amino acid residue from a peptidic compound of Formula (I) or (IA), wherein the method comprises (1) converting a peptidic compound of Formula (I) or (IA) to a guanidinyl derivative of Formula (II) or a tautomer thereof, and (2) contacting the guanidinyl derivative with a medium to produce a compound of Formula (III) or (IIIA).
Regarding claims 3 and 19, Chee discloses that the polypeptide attached to a solid support ([0389]).
Regarding claim 6, Chee discloses that the polypeptide is attached to a nucleic acid (the polypeptide being associated with a recording tag, step (a), [0387], page 60, the recording tag comprising a nucleic acid, [0124]) that is optionally covalently joined to a solid support ([0389]).
Regarding claim 13, Chee discloses that the NTAA is eliminated by mild Edman degradation ([0465]) using triethylammonium acetate ([0468]) at pH 8.5 ([1510]).
Regarding claim 17, Chee discloses that contacting the guanidinyl derivative with the medium at step (2) occurs at temperature between 40° C and 95° C (60 °C, [1439]).
Claims 1- 3, 6, 13, 17, and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Desai (WO 2020/198264 A1; previously cited).
The applied reference has a common applicant and common joint inventors 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. 102(a)(2) 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) if the same invention is not being claimed; 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 in the reference 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.
Regarding claims 1, 2, and 19, Desai discloses a method for analyzing labeling an N-terminal amino acid (NTAA) of a peptide and removing the labeled terminal amino acid with a modified cleavase ([0085]).
Desai teaches that the reagent for modifying or labeling the amino acid for removal by the modified cleavase comprises a compound selected from the group consisting of a compound of Formula (I) ([0150]), where R2 is C1-6 alkyl and R1 is H or C1-6 alkyl (ibid.).
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It is inherent or implicit to Desai that labeling the NTAA of the polypeptide with a chemical reagent of Formula (I), where R2 is C1-6 alkyl and R1 is H or C1-6 alkyl, results in a guanidinyl derivative of Formula (II) or a tautomer thereof.
In the alternative, Desai discloses that the chemical reagent comprises a compound of Formula (II), where R4 is C1-6 alkyl ([0157]).
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It is inherent or implicit to Desai that labeling the NTAA of the polypeptide with a chemical reagent of Formula (II), where R4 is C1-6 alkyl, results in a guanidinyl derivative of Formula (II) or a tautomer thereof.
Desai further discloses that the method comprises stepwise removal of the labeled N-terminal amino acid from the polypeptide ([0022]). This step inherently or implicitly involves contact with a medium and formation of a compound of Formula (III) or (IIIA).
Accordingly, Desai discloses a method to cleave an N-terminal amino acid residue from a peptidic compound of Formula (I) or (IA), wherein the method comprises (1) converting a peptidic compound of Formula (I) or (IA) to a guanidinyl derivative of Formula (II) or a tautomer thereof, and (2) contacting the guanidinyl derivative with a medium to produce a compound of Formula (III) or (IIIA).
Regarding claims 3 and 19, Desai discloses that the polypeptide attached to a solid support ([0056], [0237]).
Regarding claim 6, Desai discloses that the polypeptide is attached to a nucleic acid (a nucleic acid molecule that may form a covalent association or non-covalent association with the polypeptide, [0042]).
Regarding claim 13, Desai discloses that enzymatic cleavage ([0026]) is performed at pH 7.5 ([0389]).
Regarding claim 17, Desai discloses that contacting the guanidinyl derivative with the medium at step (2) (the enzymatic cleavage of terminal amino acids) occurs at temperature of "about 50° C to 90°" ([0222]).
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 61 and 68 are rejected under 35 U.S.C. 103 as being obvious over Chee (WO 2019/089836 A1; newly cited) in view of Hamada ("A novel N-terminal degradation reaction of peptides via N-amidination," Bioog. Med. Chem. Lett. 2016, 26, 1690-1695; IDS).
The applied reference to Chee has a common applicant and common joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, they constitute 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.
Regarding claims 61 and 68, Chee discloses the limitations of claims 1 and 3, as set forth above.
Chee further discloses that the NTAA is eliminated by mild Edman degradation ([0465]-[0473]). It is implicit or inherit that the eliminating the functionalized NTAA discussed above in the rejection of claim 1 to expose a new NTAA by this mild Edman degradation is a step of contacting the guanidinyl derivative with a medium to induce cleavage of the modified N-terminal amino acid and produce at least one cleavage product of the claimed cleavage products.
Chee further discloses "identifying the N-terminal amino acid of the polypeptide" ([0749], page 124).
Chee does not disclose that the step of identifying the N-terminal amino acid of the polypeptide is done by determining the structure or identity of the at least one cleavage product.
However, Chee cites Hamada in the context of cleaving guanidinylated NTAA and incorporates it by reference ([0861], [1184], [1198]).
In the analogous art of guanidinylation of N-terminal amino acids, Hamada discloses determining the structure or identity of at least one cleavage product to identify the N-terminal amino acid of an analogue of the compound of Formula (I) ("all products released from N-amidinopeptides 1–8 were identified using ESI-Mass analysis," page 1694, last para.; Fig. 1).
The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
For the benefit of selecting a known method of identifying the guanidinylated N-terminal amino acid of the polypeptide, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify the method of Chee with Hamada's step of identifying the N-terminal amino acid of the polypeptide by determining the structure or identity of the at least one cleavage product.
Allowable Subject Matter
Claims 15, 16, 20, 21, and 29 would be allowable if rewritten to overcome the rejections under 35 U.S.C. 112(b) set forth in this Office action and to include the non-redundant limitations of the claim 1. As noted in the rejections under 35 U.S.C. 112(b), the claims have been interpreted as follows when considering compliance with 35 USC 112(a):
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 is part of a cycle with the designated N atom;
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 is part of a cycle with the designated N atom;
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.
Regarding claim 15, Chee (WO 2019/089836 A1), Desai (WO 2020/198264 A1), and Verespy (WO 2020/154208 A1) fail to teach or suggest that the medium of step 15 comprises a diheteronucleophile.
Regarding claim 16, Chee (WO 2019/089836 A1), Desai (WO 2020/198264 A1), and Verespy (WO 2020/154208 A1) fail to teach or suggest the recited guanidinyl derivative of Formula (I) or a tautomer thereof.
Regarding claims 20, 21, and 29, Chee (WO 2019/089836 A1), Desai (WO 2020/198264 A1), and Verespy (WO 2020/154208 A1) fail to teach or suggest that the guanidinyl derivative of Formula (II) is produced by converting the peptidic compound of Formula (I) to a compound of the formula (IV), although Desai ([0190]) and Verespy ([0223]) disclose producing a compound of formula (IV).
Response to Arguments
Applicant's arguments filed on 10 September 2025 have been considered and are not fully persuasive and/or are moot in view of the new grounds of rejection.
Regarding the IDS filed 2 June 2022, Applicant states "a legible copy the foreign document number 3 is submitted with this response." However, no foreign document or IDS was submitted on 10 September 2025.
Applicant's arguments do not specifically address the maintained or modified grounds of rejection under 35 USC 112(b). Applicant's representative is encouraged to contact the examiner if there are any questions on overcoming the remaining rejections under 35 USC 112(b).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 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.
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.
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/MICHELLE ADAMS/ Examiner, Art Unit 1797
/JENNIFER WECKER/ Primary Examiner, Art Unit 1797