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 .
Application Status
In response to Non-Final Office Action mailed on 11/072025, applicants’ response and amendments dated 01/07/2026 is acknowledged; in said amendment applicants’ have amended claim 16 and added new claims 24-26. Thus, amended claims 16-26 are pending and are now under consideration. Rejections and/or objections not reiterated from previous office action are hereby withdrawn.
Amended Claims 16-26 are pending in this application, elected species “a) a deletion at two or three or four positions corresponding to positions R181, G182, H183 and G184, and b) a set of substitutions selected from the group consisting of: - K35A + A51T + N54A + G109A + R118T + W140Y + R172S + N174* + R181Q + E190P + 1206L + 1235L + Y243F + F267Y + Q280N + K281F + N299A + K302T + R320K + S334T + A339S + E345Q + E346P + V4101;” reading on the elected invention is now under consideration for examination (for details see applicants’ response dated 10/17/2025); non-elected species and on-elected sequences in claims 16-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/17/2025.
Maintained-Claim Rejections: 35 USC § 112(b)
The following is a quotation of the second paragraph of 35 U.S.C. 112:
(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.
I. Claim 16 and claims 17-26 depending therefrom are 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 applicant regards as the invention. Claim 16 recites the limitation “… using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%, at least 65%, at least 70%, at least 75%, at least 80% identical to SEQ ID NO: 2”, but less than 100% sequence identity to the amino acid sequence to the polypeptide of SEQ ID NO: 2”. At the outset examiner notes that claims as written is confusing, as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason; as the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410. Thus the scope of the claims are not clear. Clarification and correction is required.
II. Claim 16 and claims 17-26 depending therefrom are 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 applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
In the present instance, claim 16 recites the broad recitation “… has at least 60%,”, and the claim also recites “… at least 65%, at least 70%, at least 75%, at least 80% identical to SEQ ID NO: 2” which is the narrower statement of the sequence identity range/limitation (range within range). It is not clear what the applicants’ intend to encompass in the rejected claims and the metes and bounds of the claims are unclear and as being indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. Correction and clarification is required. Examiner suggests for the following sequence identities at least 65%, at least 70%, at least 75%, at least 80% identical to SEQ ID NO: 2” applicants’ consider writing additional new claims as dependent claims from claim 16.
In the present instance, claim 16 recites the broad recitation “… has at least 60% identical to SEQ ID NO: 2 …”, and claim 16 also recites “at least 65%, at least 70%, at least 75%, at least 80% identical to SEQ ID NO: 2” which is the narrower statement of range/limitation (range within range). It is not clear what the applicants’ intend to encompass in the rejected claims and the metes and bounds of the claims are unclear and as being indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. Correction and clarification is required.
Applicants’ have traversed the above 35 U.S.C. 112(b) rejection with the following arguments (see page 6 of Applicants’ REMARKS dated 01/27/2026).
Applicants’ argue “This rejection is respectfully traversed. The Office finds that recitation of the phrase "Improvement Factor (IF) > 1.0" renders the claim indefinite. Applicants strongly disagree. It is axiomatic that in a patent specification, an inventor may act as his own lexicographer and define a term used in the patent claims. As the Examiner himself has found, on page 7, lines 13-16, an improvement factor of greater than 1 is defined as improved wash performance. Further, methods of measuring wash performance of the alpha-amylases of the invention using an Automatic Mechanical Stress Assay are clearly described in the specification, beginning on page 141, line 14 in the section entitled "Wash performance of alpha amylase's using Automatic Mechanical Stress Assay", continuing through Examples 1 and 2, ending on page 145. Applicants respectfully request reconsideration and withdrawal of the rejection”.
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Applicants’ arguments filed on 01/27/2026 has not provided any argument or amendments for the following:
Claim 16 continues to recite the limitation “… using SEQ ID NO: 1 for numbering; and wherein said variant “… at least 65%, at least 70%, at least 75%, at least 80% identical to SEQ ID NO: 2”, but less than 100% sequence identity to the amino acid sequence to the polypeptide of SEQ ID NO: 2”. At the outset examiner notes that claims as written is confusing, as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason; as the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410; no argument is provided for the above issue.
Maintained-Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Written-description
Claims 16-26 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice . . ., reduction to drawings . . ., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, a “‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
The claims recite the following broadly claimed genera:
Claims 16-26 recite a genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410.
The structural elements recited in claims 16-26 are not sufficient structure to form an “alpha-amylase” having no specific structural elements of any kind and having associated activity. There in inherent unpredictability in regards to which amino acid sequences may have the associated function i.e., “alpha-amylase” activity and possibly fall within the claims and those amino acid sequences that do not have “alpha-amylase” activity. As such, claims 16-26 recite a genera of biomolecules described only by a functional characteristics (i.e., being an “alpha-amylase”), without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.” Further, without any structural limitations for structural features that actually provide for “alpha-amylase” activity, claims 16-26 have no defined outer bounds for the scope of “alpha-amylase” that fall within the scope of the claims. Due to the literal unlimited structural scope of the claims, it is not possible to provide for a representative number of species that adequately described are representative of the entire genus having no fixed structural outer boundaries. Further, such genera of altered enzymes as recited lack “a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials” and without any required structure that is sufficient for providing the recited enzyme activity, the recited genera lack disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. The claims lack adequate written description in the as-filed specification for the reasons stated.
No information, beyond the characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, page 143 of specification) has been provided by the applicants’, which would indicate that they had possession of the claimed genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410.
The genus of polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures and the characterization of the variants/mutants of amino acid sequences of SEQ ID NO: 1, since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase.
As stated above, no information beyond the characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, page 143 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410. As the claimed genera of polypeptides and encoding polynucleotides having widely variable structures and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Maintained-Enablement
Claims 16-26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, page 143 of specification). However, specification does not reasonably provide enablement for a genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410. 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 in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 16-26 are so broad as to encompass: a genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410. The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polynucleotides and encoded polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, pages 143 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides i.e., a genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410. The specification provides no guidance with regard to the making of variants and mutants or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340. Review), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to make and use the full scope of the polypeptides encompassed by the claims. However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b). Here, the claims read on a significant number of inoperative embodiments.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410, because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any alpha-amylase having no specific structural elements and an expectation of obtaining the desired biological/biochemical function; (B) a rational and predictable scheme for modifying any amino acid residue with an expectation of obtaining the desired biological/biochemical function; (C) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (D) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (E) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
While as discussed above, the specification provides guidance with regard to the characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, page 143 of specification), however, the scope of claims 16-26 is so broad and the lack of guidance either in the specification or in the prior art, the claims remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed (guided mutants). Such guidance has not been provided in the instant specification or in the prior art. The art also teaches the following regarding complexity of the structure/function relationship: The reference of Chica et al., (Curr. Opin. Biotechnol., 2005, Vol. 16: 378-384) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Sen et al., (Appl. Biochem. Biotechnol., 2007, Vol.143: 212-223), teaches in vitro recombination techniques such as DNA shuffling, staggered extension process (STEP), random chimera genesis on transient templates (RACHITT), iterative truncation for the creation of hybrid enzymes (ITCHY), recombined extension on truncated templates (RETT), and so on have been developed to mimic and accelerate nature's recombination strategy. However, such rational design and directed evolution techniques only provide guidance for searching and screening for the claimed polypeptide which is not guidance for making and/or using the claimed polypeptide. Additionally, knowledge is not extant in the art to assay all possible enzymatic activities, how to express all possible enzymes or how predictably assay for such activities. For example, the reference of Banerjee et al., (Bioenerg. Res. 2010, Vol. 3: 82-92), on page 84, right column, second paragraph, describe that “enzymes have critical properties besides specific activity and thermal tolerance that must be considered but which can be difficult to assay in vitro. For example, besides catalyzing a particular chemical reaction, enzymes must be efficiently translated and secreted, able to resist proteases, act cooperatively with other enzymes, and have low product and feedback inhibition. One can easily imagine that an “improved” enzyme, based on assay in isolation on a model substrate, might perform poorly in a real-world situation”.
Thus, 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 broadly including polynucleotides and encoded polypeptides with an enormous number of modifications. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes 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).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Applicants’ have traversed the above written-description rejection and enablement with the arguments following claim amendments (see page 7 of Applicants’ REMARKS dated 01/27/2026).
Applicants’ argue “These rejections are respectfully traversed. To advance prosecution, claims have been amended. Applicants respectfully request reconsideration and withdrawal of the rejection.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for reasons made of record in the Office-action dated 11/27/2025 and additionally for the following reasons. Contrary to applicants arguments, claims as written encompass and reads on a genera of modified/variants polypeptides having alpha-amylase activity using SEQ ID NO: 1 for numbering; and wherein said variant has at least 60%,at least 65%, at least 70%, at least 75%, at least 80%...95% identical to SEQ ID NO: 2 and having the recited amino acid substitutions at the recited positions (as in claims 16-17 and 19-26); a method of producing and a method of use of said variant alpha-amylase (as in claims 18 and 22; also see 35 U.S.C. 112(b) rejection above claims interpretation; examiner notes that claims as written is confusing and as SEQ ID NO: 2 does not conform to the original amino acid residues of SEQ ID NO: 1 listed in the claims and for the following reason, as in the wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 2 has the following amino acid residues in the following positions: D190; M206; A235; K267; T280; N281; S299; G302; P320; P334; E339; W345; F346; and G410 as opposed to the amino acid residues of SEQ ID NO: 1 used for numbering the amino acid residues i.e., SEQ ID NO: 1 has E190; I206; I235; Y243; F267; Q280; K281; N299; K302; R320; S334; A339; E345; E346; and V410 and a genera modified parent alpha-amylases comprising the polypeptide of “SEQ ID NO: 2, SEQID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12 or SEQ ID NO: 13”. Examiner continues to maintain specification is limited to characterization of specific structures/mutants and having the recited amino acid residue substitutions in the recited positions of wild-type polypeptide comprising the amino acid sequence of SEQ ID NO: 1, method of making and method of use said specific mutant/variants (see Example 1, page 143 of specification).
As interpreted by the examiner above and the evidence provided in the cited references/scientific findings supports examiner’s position and for the following reasons: (i) random mutations affect the inter or intra molecular interactions and said interactions determine the folding, 3-D configurations and affect function; and (ii) although there are homologies between known domains of a protein i.e., conserved motifs, each of the structure/variant or any fragment thereof has its own specificity with regards to the folding, 3-D configurations and the associated activity and will not tolerate random mutations/truncations/insertions/substitution/deletions” i.e., structure correlated to function is not recited. Therefore, the scope of the instant claims are broad despite the guidance of the art and specification, the claims remain not commensurate with evidence of possession or in scope with the enabled invention. Hence, claims are reading on significant numbers of inoperative embodiments would render claims non-enabled/lack of written-description, when the specification does not clearly identify the operative embodiments or evidence of possession and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b).
Summary of Pending Issues
The following is a summary of issues pending in the instant application
Claim 16 and claims 17-26 depending therefrom are rejected under 35 U.S.C. 112(b).
Claims 16-26 are rejected under 35 U.S.C. 112(a).
Conclusion
None of the claims are allowable. Claims 16-26 are rejected for the reasons identified in the Rejections and Summary sections of this Office Action. Applicants’ must respond to the rejections in each of the sections in this Office Action to be fully responsive for prosecution.
THIS ACTION IS MADE FINAL. 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 extension fee 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.
Regarding filing an After Final amendment, Applicants are directed to MPEP 714.13, which states:
II. ENTRY NOT A MATTER OF RIGHT
It should be kept in mind that applicant cannot, as a matter of right, amend any finally rejected claims, add new claims after a final rejection (see 37 CFR 1.116) or reinstate previously canceled claims. Except where an amendment merely cancels claims, adopts examiner suggestions, removes issues for appeal, or in some other way requires ONLY A CURSORY REVIEW by the examiner (e.g., typographical errors), compliance with the requirement of a showing under 37 CFR 1.116(b)(3) is expected in all amendments after final rejection. An affidavit or other evidence filed after a final rejection, but before or on the same date of filing an appeal, may be entered upon a showing of good and sufficient reasons why the affidavit or other evidence is necessary and was not earlier presented in compliance with 37 CFR 1.116(e). See 37 CFR 41.33 and MPEP § 1206 for information on affidavit or other evidence filed after appeal. (Examiner's emphasis) If more than a cursory review is required, Applicants are referred to CFR §1.114.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHIRAMA RAGHU whose telephone number is (571)272-4533. The examiner can normally be reached on M-F 8:30am-5pm EST.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652