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 .
Detailed Action
Amended claims 1-12 and 14-25 (dated 12/19/2023) are pending and now under consideration. Examiner also notes that there are two sets of claims designated as 11 and 12 and thus the claim numbering of claims is incorrect (see claim objections below).
Priority
Acknowledgment is made of applicants’ claim for foreign priority under 35 U.S.C. 119(a)-(d). This application is a 371 of PCT/CN2022/102201 filed on 06/29/2022 and claims the priority date of China application PCT/CN2021/103075 filed on 06/29/2021; however, said foreign priority application has not been provided, and the Office is unable to retrieve said foreign priority application and no English translation of said foreign priority application has been provided. Therefore, the priority date for instant claims under consideration is deemed to be the filing date of 371 of PCT/CN2022/102201 filed on 06/29/2022.
Information disclosure statement
The information disclosure statements (IDS) submitted on 12/19/2023, 05/01/2024, 06/03/2024, 04/22/2025, 04/29/2025 and 08/22/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Objections-Abstract/Specification
I. The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
II. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. The specification contains hyperlinks to various site domains, for example, pages 12, line 10 of the instant application. Applicants’ are required to thoroughly scrutinize the specification and delete all embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01. Appropriate correction is required.
Claims Objections
I. Amended Claims 1-12 and 14-25 (dated 12/19/2023) are objected, due to the following informality: The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not). In claims (dated 12/19/2023), there are two sets of claims designated as 11 and 12 and thus misnumbered. Misnumbered claims 11-12 and 14-25 should be renumbered.
II. Claims 4, 9 and 17 are objected: Recitation of “and/or” in claims 4, 9 and 17 makes the claim indefinite, as it is not clear what limitations must be present. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
Claim Rejections: 35 USC § 112(b)
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 4, 9 and 17 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 the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention; recitation of “and/or” in claims 4, 9 and 17 makes the claims indefinite, as it is not clear what limitations must be present. The metes and bounds of claims 4, 9 and 17 are not clear and thus, it would not be possible to one of ordinary skill in the art to define the metes and bounds of the desired patent protection. The rejection may be overcome by amending the claims to recite “… or …”. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
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.
Claims 1-12 and 14-25 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 1-12 and 14-25 (examiner notes that claims are misnumbered) as interpreted are directed to a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation).
The structural elements recited in claims 1-12 and 14-25 are not sufficient structure to form a “alpha-amylase activity” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity”, 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., “xylanase” activity and possibly fall within the claims and those amino acid sequences that do not have “alpha-amylase activity” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity”. As such, claims 1-12 and 14-25 recite a genera of biomolecules described only by a functional characteristics (i.e., being an “alpha-amylase activity” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity”), 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” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity”, in claims 1-12 and 14-25 have no defined outer bounds for the scope of “alpha-amylase activity” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity”, 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 i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase) and the encoding polynucleotides, isolated host cells comprising the encoding polynucleotides, method of making and method of use said specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase), has been provided by the applicants’, which would indicate that they had possession of the claimed (examiner notes that claims are misnumbered) genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation).
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 NOs: 1-6 and 14 and the encoding polynucleotides, 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 i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase) and the encoding polynucleotides, isolated host cells comprising the encoding polynucleotides, method of making and method of use said specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase), has been provided by the applicants’, which would indicate that they had possession of the claimed (examiner notes that claims are misnumbered) genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation). 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.
Enablement
Claims 1-12 and 14-25 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 i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase) and the encoding polynucleotides, isolated host cells comprising the encoding polynucleotides, method of making and method of use said specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase). However, specification does not reasonably provide enablement for (examiner notes that claims are misnumbered) a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation). 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 1-12 and 14-25 are so broad as to encompass: (examiner notes that claims are misnumbered) a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation). 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 the characterization of specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase) and the encoding polynucleotides, isolated host cells comprising the encoding polynucleotides, method of making and method of use said specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides i.e., (examiner notes that claims are misnumbered) a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation). The specification but 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: (examiner notes that claims are misnumbered) a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1-5); isolated polypeptides (as in claims 6-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any “alpha-amylase activity” and a “mature polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity” 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 i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase) and the encoding polynucleotides, isolated host cells comprising the encoding polynucleotides, method of making and method of use said specific structures i.e., comprising the amino acid sequences of SEQ ID NO: 14 (alpha-amylase); SEQ ID NOs: 1-3 (cellobiohydrolase I); SEQ ID NO: 4 (cellobiohydrolase II); SEQ ID NO: 5 (endoglucanase); and SEQ ID NO: 6 (beta-glucosidase), however, the scope of claims 1-12 and 14-25 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).
III. Claims 11-12 and 14-22 (examiner notes claims are misnumbered) recites “A host cell…”, as interpreted is directed to the use of multicellular organisms including transgenic animals and plants and is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as failing to comply with the enablement requirement when given the broadest reasonable interpretation, because, while claims 11-12 and 14-22 is enabling for an isolated prokaryotic or eukaryotic host cell transformed with the recombinant expression vector encoding polypeptide(s) of interest, does not reasonably provide enablement for any transgenic multi-cellular organisms or host cells within a multi-cellular organism that have been transformed with the synthetic nucleic acid/expression vector or any transgenic plant that have been transformed with the synthetic nucleic acid/expression vector and expressing the polypeptide of interest. 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 the claims.
Claims 11-12 and 14-22 is so broad as to encompass transgenic multi-cellular organisms and host cells transformed with specific nucleic acids, including cells in vitro culture as well as within any multi-cellular organism and transgenic plants. The enablement provided is not commensurate in scope with the claim due to the extremely large number of transgenic multicellular organisms encompassed by the claims which the specification fails to teach how to generate. While methods for transforming cells in vitro are well known in the art, methods for successfully transforming cells within complex multi-cellular organisms are not routine and are highly unpredictable. Furthermore, methods for producing a successfully transformed cell within the multi-cellular organism are unlikely to be applicable to transformation of other types of multi-cellular organism, as multi-cellular organisms vary widely. However, in this case the disclosure is limited to only isolated cells in vitro. Thus, applicant has 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 the use of host cells within a multi-cellular organism for the production of said polypeptides in the claimed method. The scope of claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA)). Without sufficient guidance, expression of genes in a particular host cell and having the desired biological characteristics is unpredictable, 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 USPQ 2nd 1400 (Fed. Cir., 1988). It is suggested that the applicant limit the claim to “An isolated transformed host cell …”.
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).
Claim Rejections: 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title
Claims 6-10 are rejected 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. Claims 6-7 and 9-10 are directed to a law of nature or a natural phenomenon. Claims 6-7 and 9-10 as interpreted are directed to a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities (also see claims objections, 35 U.S.C. 112(b) above and 35 U.S.C. 112(a) rejections above for claims interpretation).The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons stated below.
The “2014 Interim Guidance on Patent Subject Matter Eligibility” 79 FR 74618 (Dec. 16, 2014) directs that claims drawn to 1) a composition of matter, 2) a law of nature or a natural phenomenon and 3) lacking recitation of additional elements that make the claims directed to significantly more than a judicial exception are ineligible for patenting under 35 U.S.C. 101. See, 79 FR, page 74621 (flow chart). Nature-based compositions of matter are not directed to significantly more than a judicial exception when the claimed "naturally occurring products and some man-made products ... are essentially no different from a naturally occurring product ... that fall under the laws of nature or natural phenomena exception.” 79 FR, page 74623, left column. That is, a patent-eligible composition of matter must be "markedly different" in terms of the "product's structure, function, and/or other properties." 79 FR, page 74623, center column. Further, processes directly to isolating nature-based compositions of matter have also been found to be directed to nothing more than a judicial exception when only routine purification techniques are employed. 79 FR, page 74622, center column (e.g. isolating DNA or other nature-based products).
Here, naturally-occurring variant polypeptides comprising “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities corresponding to SEQ ID NOs: 1-6 of the instant application is disclosed by the following references: UniProtKB/TrEMBL Accesion#Q8TFL9, Collins et al., disclose a cellobiohydrolase having 86.4% sequence identity to SEQ ID NO: 1; UniProtKB/TrEMBL Accesion#Q8NK02, Lockington et al., disclose a cellobiohydrolase having 100% sequence identity to SEQ ID NO: 2; UniProtKB/TrEMBL Accesion#A0A9W9UEA3, Petersen et al., disclose a cellobiohydrolase having 89.9% sequence identity to SEQ ID NO: 3; UniProtKB/TrEMBL Accesion#A0A1L2TQP9, Gusakov et al., disclose a cellobiohydrolase having 98.2% sequence identity to SEQ ID NO: 4; UniProtKB/TrEMBL Accesion#A0AB34KW61, Gioti et al., disclose a endoglucanase having 80.6% sequence identity to SEQ ID NO: 5; UniProtKB/TrEMBL Accesion#A0A6V8HCI3, Fujii et al., disclose a beta-glucosidase having 80.6% sequence identity to SEQ ID NO: 6 (see provided sequence alignments). The features of claims 6-10 are met by the reference polypeptides of SEQ ID NOs: 1-6 in the disclosed references above. Since the features of the claims are met by the structure of polypeptides of SEQ ID NOs: 1-6 and the claims do not recite additional features or elements that amount to significantly more than the judicial exception, since the structure recited in claims 6-10 is "essentially no different from a naturally occurring product” such that there is no marked difference in the "product's structure, function, and/or other properties. As such, the claims 6-10 recite patent ineligible subject matter for the reasons stated.
Claim Rejections: 35 USC § 102 (AIA )
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(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.
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 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.
I. Claims 6-10 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liu et al., (US 9,481,897) disclose a cellobiohydrolase having 100% sequence identity to SEQ ID NO: 1; Mort et al., (US 10,266,814) disclose a cellobiohydrolase having 100% sequence identity to SEQ ID NO: 2; Daniell H., (US 10,676,751) disclose a cellobiohydrolase having 88.5% sequence identity to SEQ ID NO:3; Yamanobe et al., (US 6,127,160) disclose a cellobiohydrolase having 95.6% sequence identity to SEQ ID NO: 4; Coleine et al., UniProtKB/TrEMBL Accession# A0A1V8TEB5, disclose a endoglucanase having 73.2% sequence identity to SEQ ID NO: 5; and Fukasawa et al., (US 7,256,031) disclose a beta-glucosidase having 99.7% sequence identity to SEQ ID NO: 6 (see provided sequence alignments).
Therefore, the references of Liu et al., (US 9,481,897), Mort et al., (US 10,266,814), Daniell H., (US 10,676,751), Coleine et al., UniProtKB/TrEMBL Accession# A0A1V8TEB5; and Fukasawa et al., (US 7,256,031) are deemed to anticipate claims 6-10 as written and when given the broadest reasonable interpretation.
II. Claims 1, 3-6, 9-12, 14 and 17-25 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liu et al., (WO 2021/055395 A1, in IDS), when given the broadest reasonable interpretation.
Claims 1, 3-6, 9-12, 14 and 17-25 (examiner notes that claims are misnumbered) as interpreted are directed a genera of polypeptides having alpha-amylase activity (no structure is provided; unlimited and undefined structures), and a genera of “mature” polypeptides having cellobiohydrolase activity, endoglucanase activity, or beta-glucosidase activity, said genera of polypeptides having a sequence identity of at least 70% to SEQ ID NOs: 1-6 or any functional fragment(s) of undefined and unlimited structures or comprising any substitution, any deletion, and/or any insertion at one or more positions of undefined and unlimited structures and having associated activities, said genera of polypeptides utilized in a process for producing any fermentation product/a genera of products (as in claims 1 and 3-5); isolated polypeptides (as in claims 6 and 9-10); isolated polynucleotides encoding said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising polynucleotides encoding said genera of polypeptides and method of producing said genera of polypeptides (as in claims 11-12); and any recombinant host cell comprising said encoding genera of polynucleotides (as in claims 14 and 17-25; and also see claims objections, and 35 U.S.C. 112(b) for claims interpretation).
Liu et al., (WO 2021/055395 A1, in IDS; see Abstract; and entire document) disclose a process for producing fermentation products from starch-containing material comprising the steps of: i) liquefying the starch-containing material at a temperature above the initial gelatinization temperature using an alpha-amylase; ii) saccharifying using a carbohydrate-source generating enzyme; iii) fermenting using a fermenting organism; wherein at least one polypeptide having beta-1, 6-glucanase activity and/or at least one polypeptide having endo- and/or exo-beta-1, 3-glucanase activity are present or added during saccharifying step ii) or fermenting step iii) (see claim 22). Liu et al., also discloses that enzymatic hydrolysis of cellulose to glucose requires the use of endo beta-glucanases (e.g. EC 3.2.1.4), cellobiohydrolases (e.g. EC 3.2.1.91) and beta-glucosidases (e.g. EC 3.2.1.21) (see description, paragraph 8). Liu et al., further discloses a recombinant host cell, wherein the cell is a yeast cell such as Saccharomyces, Rhodotorula, Schizosaccharomyces, Kluyveromyces, Pichia, Hansenula, Rhodosporidium, Candida, Yarrowia, Lipomyces, Cryptococcus, or Dekkera sp. Cell (see claims 33,39,40 and see Abstract; cols. 45-51; and entire document). Liu et al., (WO 2021/055395 A1, in IDS) also disclose a cellobiohydrolase having 78.2% sequence identity to SEQ ID NO:1; disclose a cellobiohydrolase having 75.8% sequence identity to SEQ ID NO:2; disclose a cellobiohydrolase having 80.0% sequence identity to SEQ ID NO:3; and disclose a cellobiohydrolase having 76.9% sequence identity to SEQ ID NO:4 of the instant invention (see provided sequence alignments).
Therefore, claims 1, 3-6, 9-12, 14 and 17-25 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Liu et al., (WO 2021/055395 A1, in IDS) as written and when given the broadest reasonable interpretation.
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652