DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 6, 11-21 and 29-32 are pending in this application.
Applicant’s amendment to the claims filed 12/02/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 12/02/2025 in response to the non-final rejection mailed on 09/16/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The requirement for an election of invention among the inventions of:
Group I, corresponding to claims 1, 6, 11-14 and 29-32, drawn to the technical feature of a variant polypeptide having G4 amylase activity selected from the group consisting of: (a) a polypeptide having at least 80% sequence identity with SEQ ID NO: 1; (b) a polypeptide encoded by a polynucleotide having at least 80% sequence identity with SEQ ID NO: 2; (c) a polypeptide encoded by a polynucleotide that hybridizes under high stringency conditions with (i) a polynucleotide that encodes the amino acid sequence of SEQ ID NO: 1, or (ii) the full- length complement of (i); (d) a variant of the polypeptide of SEQ ID NO: 1 comprising a modification at one or more, and not exceeding 36 positions and having G4 amylase activity; (e) a polypeptide encoded by a polynucleotide that differs from SEQ ID NO: 1 due to the degeneracy of the genetic code; and (f) a fragment of the polypeptide (a), (b), (c), (d) or (e) having G4 amylase activity; wherein the variant amylase has G4 amylase activity, and compositions thereof, and a variant polypeptide having G-4-amylase activity, wherein the variant polypeptide is an amino acid sequence that is at least 80% identical to the amino acid sequence as set forth in SEQ ID NO:1 and the variant polypeptide has an increase in enzyme activity, thermostability, or any combination thereof when compared to the G4-amylase of SEQ ID NO:1, Group II, corresponding to claims 15-20, drawn to the technical feature of a method of making a variant polypeptide comprising: providing a template nucleic acid sequence encoding the polypeptide variant as in claim 1, transforming the template nucleic acid sequence into an expression host, cultivating the expression host to produce the variant polypeptide, and purifying the variant polypeptide, and Group III, corresponding to claim 21, drawn to the technical feature of a method for preparing dough or a baked product from the dough comprising adding the variant polypeptide of claim 1 to the dough and baking it, and
the requirement for an election of species among the species of amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R
are withdrawn in view of the amendment to claim 1 to recite “A synthetic variant polypeptide … having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 1 … wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”.
In view of the withdrawal of the restriction requirement as to the rejoined inventions and rejoined species, applicant(s) are advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Objections
The objection to claim 1 is withdrawn in view of the amendment to recite “when compared to the G4 amylase of SEQ ID NO: 1”.
Claim 15 is objected to for the phrase “the polypeptide variant as in claim 1”. In the interest of improving claim form, Applicant should consider amending the noted phrase to recite “the synthetic variant polypeptide of claim 1”.
Claim 19 is objected to for the phrase “selected from … a Saccharomyces, a Schizosaccharomyces” because there is no conjunction between “a Saccharomyces” and “a Schizosaccharomyces”. In the interest of improving claim form, Applicant should consider amending the noted phrase to recite “selected from … a Saccharomyces, and a Schizosaccharomyces”.
Claim 21 is objected to for the phrase “adding one of the variant polypeptides as claim 1, to the dough and baking it”. In the interest of improving claim form, Applicant should consider amending the noted phrase to recite “adding the synthetic variant polypeptide of claim 1 to a dough and baking it”.
Claim Rejections - 35 USC § 112(b)
The rejection of claim 6 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 is withdrawn in view of the amendment to recite “wherein the variant polypeptide comprises an amino acid sequence that shares at least 98.5%, at least 99%, or at least 99.5% sequence identity with the amino acid sequence set forth in SEQ ID NO: 1”.
Claims 16-20 are newly 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.
The instant rejections are necessitated by claim amendment.
Claim 16 (claims 17-20 dependent therefrom) is indefinite for the recitation of “the nucleic acid sequence as set forth in SEQ ID NO: 1”, as SEQ ID NO: 1 is an amino acid sequence. As written, it is unclear whether the claim is intending to limit the amino acid sequence of SEQ ID NO: 1, or a nucleotide sequence.
Claim 16 (claims 17-20 dependent therefrom) is indefinite for the recitation of “wherein the variant nucleotide is a nucleic acid sequence that is at least 80% identical to the nucleic acid sequence as set forth in SEQ ID NO: 1”, as claim 16 depends from claim 15 which recites “the polypeptide variant as in claim 1”, and claim 1 limits the sequence polypeptide variant to share at least 98% identity with SEQ ID NO: 1. As written, the requirement of a sequence sharing at least 80% identity with SEQ ID NO: 1 in claim 16 contradicts the requirement in claim 1 of a sequence sharing at least 98% identity with SEQ ID NO: 1.
Claim 19 recites the phrase “the method of claim 16, wherein the yeast expression system”. There is insufficient antecedent basis for the limitation “the yeast expression system” in claim. Applicant should consider amending claim 19 to depend from claim 17 to provide antecedent basis for this limitation.
Claim 20 recites the phrase “the method of claim 16, wherein the fungal expression system”. There is insufficient antecedent basis for the limitation “the fungal expression system” in claim. Applicant should consider amending claim 20 to depend from claim 17 to provide antecedent basis for this limitation.
Response to remarks: beginning on page 5 of Applicant’s response to rejections under 35 USC 112; Applicant in summary contends the amendments to the claims obviate the rejections of record.
Applicant’s remarks are considered and found not convincing, as claims 16-20 were not amended. The amendment to claim 1 has necessitated the rejoinder of previously elected inventions, and therefore the rejections of the claims of the rejoined inventions above are necessitated by claim amendment.
Claim Rejections - 35 USC § 112(a)
The rejection of claims 1-4, 6, 11-14 and 29-30 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of the amendment to claim 1 to recite “wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”, as the amendment limits the locations of the claimed substitutions to the variant such that one of skill in the art would reasonably conclude that the disclosure provides a representative number of species to describe the genus, and thus, that the applicant was in possession of the recited genus of variant polypeptides.
Claim Interpretation: Claims 31-32 are drawn to a synthetic variant polypeptide encoded by a polynucleotide having at least 96.5% sequence identity with the nucleotide sequence of SEQ ID NO: 2. As the claims do not recite any function of the polypeptides, the function of said polypeptides are considered to be unlimited.
Claims 31-32 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a synthetic variant polypeptide having G4 amylase activity and being encoded by a polynucleotide having at least 96.5% sequence identity with the nucleotide sequence of SEQ ID NO: 2,, does not reasonably provide enablement for polypeptides with any function or being non-functional as encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The instant rejection is maintained from a previous Office action.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)) as follows: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a). The Factors considered to be most relevant to the instant rejection are addressed in detail below.
The nature of the invention: According to the specification at para 0003, “the disclosure relates to polypeptides having amylase activity, polynucleotides comprising the coding sequences for these polypeptides, and methods for making and using these polypeptides and polynucleotides”. The object of the invention is therefore to provide polypeptides with amylase activity, polynucleotides encoding these polypeptides and methods of making the polypeptides.
The breadth of the claims: The claims recite a synthetic variant polypeptide encoded by a polynucleotide having at least 96.5% sequence identity with the nucleotide sequence of SEQ ID NO: 2, and are considered to be drawn to polypeptides having any function or being non-functional, and as such the function of said polypeptide is unlimited.
The state of the prior art; The level of one of ordinary skill; and The level of predictability in the art: According to MPEP 2164.03, “…what is known in the art provides evidence as to the question of predictability” and “[I]f one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art.”
The reference of Singh (supra) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top).
The unpredictability associated with amino acid modification is exemplified by the reference of Zhang (supra) which discloses that even a mutation that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
As such, one of skill in the art would recognize a high level of unpredictability that the polynucleotides with the sequence limitations recited by the claims would produce a polypeptide that maintains the desired unlimited functional activity.
The amount of direction provided by the inventor and The existence of working examples: The specification discloses the following working examples of the recited variant polypeptides: 49 variants of SEQ ID NO: 1, each bearing a mutation from the group of T31C-G190R, P111T, G123F, G136M, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, S394E, S401Y, and A206D-R348G-Q422R relative to SEQ ID NO: 1. Other than these working examples, the specification fails to disclose any other variant polypeptide.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure: While methods of generating polynucleotides encoding polypeptides were known at the time of the invention, it was not routine in the art to make and determine a use for polypeptides bearing all functions as recited by the claims. Additionally, it was not routine in the art to make and determine a use for polypeptides that are non-functional.
In view of the overly broad scope of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability, and the state of the prior art, undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Response to remarks: beginning on page 5 of Applicant’s response to rejections under 35 USC 112; Applicant in summary contends the amendments to the claims obviate the rejections of record.
Applicant’s remarks are considered and found not convincing, as claims 31-32 have not been amended. Therefore the rejection of claims 31-32 under 35 USC 112(a) is maintained.
Claim Rejections - 35 USC § 101
The rejection of claims 1-4, 6, 12-14 and 29-30 under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more is withdrawn in view of the amendment to claim 1 to recite “wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”, as the amended limitations distinguish the claimed variant polypeptide as markedly different from its naturally occurring counterpart
Claim Rejections - 35 USC § 102
The rejection of claims 1-4, 6 and 29-30 under 35 U.S.C. 102(a)(1) as being anticipated by UniProt Accession No. A4XX23_PSEMY (1 page, 05/10/2017, cited on the Form PTO-892 mailed 09/16/2025; herein referred to as UNI2) is withdrawn in view of the amendment to claim 1 to recite “wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”, as UNI2 does not disclose a polypeptide with the recited sequence limitations.
Claim Rejections - 35 USC § 103
The rejection of claim 11 under 35 U.S.C. 103 as being unpatentable over UNI2 in view of Shibuya et al. (Biosci Biotech Biochem, 1992, 56:884; cited on the Form PTO-892 mailed 02/10/2025; herein referred to as Shibuya), and
the rejection of claims 12-14 under 35 U.S.C. 103 as being unpatentable over UNI2 in view of BASF et al. (US 2015/0017707 A1; cited on the Form PTO-892 mailed 07/24/2024; herein referred to as BASF),
are withdrawn in view of the amendment to claim 1 to recite “wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”, as UNI2, Shibuya and BASF do not teach or suggest a polypeptide with the recited sequence limitations.
Double Patenting
The double patenting rejections set forth on pp. 24-36 of the previous office action are withdrawn in view of the amendment to claim 1 to recite “wherein the synthetic variant polypeptide comprises a modification comprising one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1”.
Allowable Subject Matter
The closest prior art of record to claims 1, 6, 11-21 and 29-30 is considered to be UniProt Accession No. A4XX23_PSEMY (1 page, 05/10/2017, cited on the Form PTO-892 mailed 09/16/2025; herein referred to as UNI2), which discloses a glucan 1,4-alphamaltotetraohydrolase from Pseudomonas mendocina that shares 98.7% sequence identity with SEQ ID NO: 1 and has a T143N substitution at the position corresponding to 143 of SEQ ID NO: 1 [see Appendix A].
The teachings of UNI2 alone or in combination with the other prior art of record do not teach or suggest “a synthetic variant polypeptide having G4 amylase activity and comprising an amino acid sequence having at least 98% sequence identity with SEQ ID NO: 1, wherein the synthetic variant polypeptide has an increase in enzyme activity, thermostability, or a combination thereof when compared to G4-amylase of SEQ ID NO: 1, and wherein the modification is at one or more amino acid substitutions selected from T31C, P111T, G123F, G136M, G136R, G136K, G136C, D141M, D141I, D141P, T143E, T143P, T143A, T143Y, T143F, P145Y, Y148W, A149P, C152P, C152T, D153S, D156G, G160N, G160M, D162E, D178N, A181E, A181N, A181R, R184A, G190R, A206D, H213D, N215P, G227S, G227D, G227H, G227E, G227N, G227W, G227Q, H309R, H309K, A315S, A315C, A315Y, D345E, F346L, R348G, S394E, S401Y, and Q422R relative to SEQ ID NO: 1” recited in claim 1. Therefore claims 1, 6, 11-21 and 29-30 are free of the prior art of record.
The prior art of record does not teach or suggest the subject matter of claims 31 and 32 of a synthetic variant polypeptide encoded by a polynucleotide having at least 96.5% sequence identity with the nucleotide sequence of SEQ ID NO: 2. The closest prior art of record is NCBI Accession No. PTLV01000064.1 (46 pages, 02/25/2018; cited on the Form PTO-892 mailed 07/24/2024; herein referred to as NCBI1) which discloses the polypeptide glucan 1,4-alpha-maltohexaosidase encoded by the nucleotide sequence region 25268..26908 [p 7, sequence on p 29] that shares 95.9% sequence identity with SEQ ID NO: 2 [see Appendix B]. There is no teaching or suggestion in the prior art of record of a synthetic variant polypeptide encoded by a polynucleotide having at least 96.5% sequence identity to SEQ ID NO: 2 as recited in claim 31. Therefore, claims 31-32 are free of the prior art of record.
Conclusion
Status of the Application:
Claims 1, 6, 11-21 and 29-32 are pending.
Claims 16-20 and 31-32 are rejected.
Claims 15 and 21 are objected to for minor informalities.
Claims 1, 6, 11-14, and 29-30 are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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, Manjunath Rao can be reached at (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
Appendix A
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613
666
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Sequence alignment of SEQ ID NO: 1 with the amino acid sequence of UniProt Accession No. A4XX23_PSEMY (reference UNI2), wherein * denotes position 143 of SEQ ID NO: 1.
Appendix B
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402
638
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Sequence alignment of SEQ ID NO: 2 with the nucleic acid sequence of glucan 1,4-alpha-maltohexaosidase from PTLV01000064.1 (reference NCBI1).