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 .
Claim Status
Claims 1-3, 5-17, and 21-24 are pending.
Claims 4 and 18-20 are cancelled.
Claims 6-17 are withdrawn as being directed to a non-elected invention, the election having been made on 12/30/2025.
Claims 1-3, 5 and 21-24 have been examined.
Priority
This application has PRO 63/329,329 04/08/2022.
Withdrawn Objection and Rejection
The objection to claims 4-5 is withdrawn because the amendment to claim 1 and cancellation of claim 4 overcome the objection.
The rejection of claims 1-5 under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. is withdrawn because the amendment to claim 1 overcomes the rejection.
The rejection of claims 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Black et al. is withdrawn because the amendment to claim 1 overcomes the rejection.
Modified Rejection
Claim Rejections - 35 USC § 112
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.
Claims 1-3, 5 and 21-23 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention for the reasons as follows.
actual reduction to practice
Applicant disclosed SEQ ID Nos: 1-6 are highly homologous peptide sequences and satisfy actual reduction to practice. Furthermore, the specification disclosed screening a polypeptide library is required to identify the claimed polypeptides [0022, 0094-0095]; thus, the limited disclosure are insufficient to represent the entire genus of the known or unknown polypeptide sequences comprising 1-12 amino acid substitutions in the instant SEQ ID NO: 2.
disclosure of drawings or structural chemical formulas:
Figures 3-7 suggest a protein folding structure may be used to facilitate mutant
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polypeptide design before screening a polypeptide library. Fig. 6A shows results of screening a polypeptide library are unpredictable based on amino acid substitution in the mutant polypeptides in the following. Furthermore, the disclosed method of screening a polypeptide library comprising amino acid substitutions does not translate to sufficient disclosure of the polypeptide sequences with 1-12 amino acid substitutions compared to a reference polypeptide (a wild-type or parent polypeptide or a thermostable variant) in the claims.
(c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure.
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The claimed noncanonical cofactors do not share structural similarity as shown in the following, suggesting a single polypeptide is unlikely to improve catalytic efficiency of all structurally distinct noncanonical cofactors as claimed.
Furthermore, Figures 3-7 suggest a protein folding structure may be used to facilitate mutant polypeptide design for screening a polypeptide library. A prior art, Zhao et al. (WO 2006/074194 A2), teaches the use of error-prone (EP) PCR for site-directed mutagenesis (SDM) to identify mutant with improve or desired function [00050, Fig 20] based on phosphite
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dehydrogenase (PTDH) pathway shown in figure 18. Zhao’s recombinant peptide SEQ ID NO: 35 (Fig 31, claim 7) highly homologous to the instant SEQ ID NO: 2, but does not contain A155N suggesting A115N is not absolutely required to improve catalytic efficiency of noncanonical cofactors.
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The other reference, Black et al. (Nat Chem Biol. 2020 January; 16(1): 87–94, cited in IDS), teaches the use of folding structure of glucose dehydrogenase.to facilitate design a mutant polypeptide. However, a bioassay is required to prove the concept of polypeptide design due to the unpredictability of protein design according to Black’s figure (p21). Unfortunately, Black et al. did not show the mutant glucose dehydrogenase polypeptide sequence. Thus, the prior art references known in the art are insufficient to establish correlation of structure and function to support the entire genus of the claimed polypeptide sequences as claimed due to the unpredictability of polypeptide design and screening a polypeptide library.
representative number of samples.
The limited disclosure of SEQ ID Nos of SEQ ID NO: 3-6 are highly homologous
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peptide sequence as shown follows and insufficient to represent 1-12 amino acid substitutions of SEQ ID NO: 2 for the entire genus of the polypeptides as claimed. Furthermore, the claimed noncanonical cofactors do not share structural similarity and the specification did not provide evidence that a given polypeptide can improve catalytic efficiency for all the noncanonical cofactors as claimed.
Because claim 1 fails to satisfy the written description requirements, claim 1 is rejected under 112 (a).
Claims 2-3, 5, and 21-23 are rejected as depending on claim 1.
The rejection may be overcome by distinctly claiming the peptide sequence fully supported by the specification.
Applicant’s Arguments
A person having ordinary skill in the relevant art would recognize that applicant had possession of a recombinantly engineered polypeptide that has improved catalytic efficiency for an oxidized form of a noncanonical cofactor because applicant's application teaches methodologies, assays and techniques that allowed for the discovery and production of recombinantly engineered polypeptides that exhibited improved catalytic efficiency for using noncanonical cofactors (Remarks, p4, para 2-3 bridging to p5, para 1).
Response to Arguments
Applicant's arguments filed 6/22/2026 have been fully considered but they are not persuasive because the argument is not commensurate in scope of the claims for the reasons as follows.
Figures 3-7 suggest a protein folding structure may be used to facilitate mutant polypeptide design before screening a polypeptide library. Fig. 6A shows results of screening a polypeptide library are unpredictable based on amino acid substitution in the mutant
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polypeptides in the following. Furthermore, the disclosed method of screening a polypeptide library comprising amino acid substitutions does not translate to sufficient disclosure of the polypeptide sequences with 1-12 amino acid substitutions compared to a reference polypeptide (a wild-type or parent polypeptide or a thermostable variant) in the claims. Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See MPEP 2145(I).
The claimed noncanonical cofactors do not share structural similarity as shown follows. A single polypeptide is unlikely to be able to improve catalytic efficiency for noncanonical cofactors as claimed.
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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.
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.
Claims 1-3, 5 and 21-23 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 the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is unclear with respect to the claimed polypeptide sequences. The metes and bounds are unclear because it is unclear whether a given polypeptide can improve catalytic efficiency of all the noncanonical cofactors or only improve some of the noncanonical cofactors as claimed. In one claim interpretation a polypeptide improve catalytic efficiency for all claimed noncanonical cofactors. In another claim interpretation, a polypeptide (e.g., SEQ ID NO: 3) can improve some but NOT all of the noncanonical cofactor as claimed. Since (a) Fig. 6A shows results of screening a polypeptide library are unpredictable based on amino acid substitutions in the polypeptides and (b) the claimed noncanonical cofactors do not share structural similarity suggesting a give polypeptide is unlikely to improve all of the structurally distinct noncanonical cofactors, rendering the metes and bounds of the polypeptide sequences in claim 1 indefinite. Claims 2-3, 5 and 21-23 are further rejected as depending on claim 1.
Response to Arguments
Applicant's arguments of “mutations like A 155N in comparison to TS-PTDH (SEQ ID NO:2), promote utilization of noncanonical cofactors, such as NMN+, by the recombinantly engineered polypeptides (Remarks, p14, para 1-2) filed 6/22/2026 have been fully considered but they are not persuasive because the claimed noncanonical cofactors do not share structural similarity; thus, a single polypeptide is unlikely to be able to improve catalytic efficiency for noncanonical cofactors as claimed, rendering the metes and bounds are unclear because it is unclear whether a given polypeptide can improve catalytic efficiency of all the noncanonical cofactors or only improve some of the noncanonical cofactors as claimed.
New Ground of Objection
Claim Objections
Claim 24 is objected to as being dependent upon a rejected claim 5.
Allowable Subject Matter
Claim 24 is objected to as being dependent upon a rejected claim 5, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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The closest prior art reference, Zhao et al. (WO 2006/074194 A2), show a polypeptide of SEQ ID NO; 35 (Fig 31) with a single amino acid mismatch in comparison to the reference polypeptide of SEQ ID NO: 2 as shown follows. However, Zhao’s SEQ ID NO: 35 does not contain a substitution of A155N.
Conclusion
No claim is allowed.
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.
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/J.L/Examiner, Art Unit 1658
04-September-2026
/Melissa L Fisher/ Supervisory Patent Examiner, Art Unit 1658
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