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
Applicant’s election of Group I, encompassing claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 and as species Cellobionic acid (claim 2), and b-glucosidase activity encoded by NCU08755l (claim 23(a)) without traverse following in the reply filed on 09/30/2025 is acknowledged. Thus, claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-33 are pending in this application; elected Group I, encompassing claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 and as species Cellobionic acid (claim 2), and b-glucosidase activity encoded by NCU08755l (claim 23(a)) is now under consideration for examination; and claims 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Priority
This application claims the benefit of priority under 35 U.S.C. 119(e) to the US Provisional application 63/344,442 filed on 05/20/2022.
Information disclosure statement
The information disclosure statement (IDS) submitted on 09/30/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Claims Objections
I. Claim 1 and claims 2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 depending therefrom are objected: Recitation of “and/or” in claims 1-2, 9, 17, 23 and 31 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 …”.
II. Claim 16 is objected to for typographical error; Claim 16 recites “The method of claim l”; correction is required to “The method of claim 1”.
III. Claim 23 is objected and indefinite in the recitation of “having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell, for the following reasons. As taught in the specification and the prior art, the terms “NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641;… NCU09425 (NdvB); NCU08807 (CRE-1); … NCU09333 (ACE-1)” are Neurospora crassa gene(s) name which appear to encode b-glucosidase, cellobionate phosphorylase and transcription factors. However, as written, the terms appear to be generically used and not limited to a specific organism Neurospora crassa. While the gene nomenclature used may be appropriate for Neurospora crassa genes, the use of this nomenclature for genes encoding proteins of identical function in other organisms or fungi may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. It is suggested that if the sequences of the wild-type b-glucosidase, cellobionate phosphorylase and transcription factors is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claim. Furthermore, as written; the claim reads on yet to be discovered b-glucosidase, cellobionate phosphorylase and transcription factors and additionally it is not clear which specific version and the corresponding structure is being referred to in the claim, as public databases are constantly curated and revised. Correction and clarification is required.
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.
I. Claim 1 and claims 2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 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 1-2, 9, 17, 23 and 31 makes the claims indefinite, as it is not clear what limitations must be present. The metes and bounds of claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 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 …”.
II. Claims 5, 7, 9, 13, 23 and 29 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. Claims 5, 7, 9, 13, 23 and 29 recite the phrase “up to about”… “about”… at least about …”, the metes and bounds of the phrase “up to about”… “about”… at least about …” is not clear. The recitation of terms “at least” and “about” are inconsistent with each other and makes it unclear whether there is a discrete lower or upper limit to recited values in said claims (see Amgen Inc. v. Chugai pharmaceutical Co., F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). For example, In claim 23, the claim recites the phrase “at least about 80% sequence identity to a gene selected from the group consisting…”; the term “about” is a relative term which extends the metes and bounds of the claimed range, however, the disclosure does not recite the requisite degree or how one would objectively determine a percentage as being “about” (or not about) a certain value, for example 80% may by broadly and reasonably be interpreted above or below 80%, and as “‘about” 80% and thereby rendering the claims indefinite. Clarification and correction is required. Examiner suggests amending the phrase to recite “…at least …”. See MPEP § 2173.05(c).
III. Claim 23 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 23 is in the recitation of “having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell”, for the following reasons. As taught in the specification and the prior art, the terms “NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641;… NCU09425 (NdvB); NCU08807 (CRE-1); … NCU09333 (ACE-1)” are Neurospora crassa gene(s) name which appear to encode b-glucosidase, cellobionate phosphorylase and transcription factors. However, as written, the terms appear to be generically used and not limited to a specific organism Neurospora crassa. While the gene nomenclature used may be appropriate for Neurospora crassa gene, the use of this nomenclature for genes encoding proteins of identical function in other organisms or fungi may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. It is suggested that if the sequences of the wild-type b-glucosidase, cellobionate phosphorylase and transcription factors is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claim. Furthermore, as written; the claim reads on yet to be discovered b-glucosidase, cellobionate phosphorylase and transcription factors and additionally it is not clear which specific version and the corresponding structure is being referred to in the claim, as public databases are constantly curated and revised. Correction and clarification is required.
Additionally, claim 23 is rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 23 recites the phrase “reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell…”. For the record no specific structure for wildtype b-glucosidase activity…cellobionate phosphorylase and transcription factors is recited in the claims and no specific wild-type cell is recited in the claims, it is not clear to which wild-type cell the claimed structures are referred to and it is not clear variants are compared to specific corresponding b-glucosidase activity… cellobionate phosphorylase and transcription factors obtained from a specific source and furthermore the art teaches there could be more than one b-glucosidase activity… cellobionate phosphorylase and transcription factors, clarification is required. The phrase “reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell…” in claim 23 renders the claim indefinite and considered to be a relative term which renders the claim indefinite and the specification is limited to teaching b-glucosidase activity…cellobionate phosphorylase and transcription factors of specific wild-type cell Neurospora crassa, and one of ordinary skill in the art would not be able to reasonably determine the metes and bounds, as “reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell…” includes many undefined and unlimited structures, obtained from different wild-type cells and varies widely depending on the individual situation as well as the person making the determination and is dependent upon set of conditions defined by the individual situation. Clarification and correction is required. For examination purposes “reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell…” encompasses many undefined and unlimited structures and varied activity and wild-type cells.
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 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 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 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 recite a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
The structural elements recited in claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 are not sufficient structure to form a “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity” having no specific structural elements of any kind and having associated activity. There in inherent unpredictability in regards to encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/engineered host cell i.e., “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity” and possibly fall within the claims and those amino acid sequences that do not have “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity”. As such, claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 recite a genera of biomolecules described only by a functional characteristics (i.e., encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/engineered host cell i.e., “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase 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 “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity” activity, claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 have no defined outer bounds for the scope of “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity” 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 cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification) has been provided by the applicants’, which would indicate that they had possession of the a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
The genus of polynucleotides and encoded polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus in the claimed genera of engineered host cells. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures of amino acid sequences and the encoding polynucleotides as disclosed in the characterization of specific cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification), 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.
(d) Specifically regarding production of any aldonic acid from cellulosic biomass requires specific defined cellular context and defined cellular metabolic machinery: see (i) Mehtio et al., Crit. Rev. Biotechnol., 2016, Vol. 36(5): 904-916; especially see Abstract; Fig. 1, page 905; col. 2, page 907 to col. 1, page 911; and entire document; and the following reference clearly provide evidence that specific genetic modifications in specific cellular context/engineered host is required for the production of cellobionate and cellobionic acid: see (ii) Znameroski et al., (US 9,822,373; entire document); and (iii) Fan et al., (US 10,358,668; entire document).
As stated above, no information beyond the characterization of specific cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; 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 in the claimed genera of engineered host cells, 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 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 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 cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification). However, specification does not reasonably provide enablement for a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; 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 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 are so broad as to encompass: a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; 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 in a genus of engineered host cells. 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 cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides and engineered host cells i.e., a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; 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: a genera of host cells/genera of cellular context (fermenting organisms) comprising a cellular machinery able to hydrolyze cellulosic biomass and to produce any sugar acid/aldonic acid (genera of sugar acids) and any biofuel (genera of biofuels) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises: (a) reduced activity of one or more polypeptides having b-glucosidase activity as compared to a corresponding wild-type cell, wherein each of the one or more polypeptides having b-glucosidase activity are encoded by a gene that has at least about 80% sequence identity to a gene selected from the group consisting of NCU00130, NCU04952, NCU05577, NCU07487, NCU08755, and NCU03641; (b) reduced activity of a polypeptide having cellobionate phosphorylase activity as compared to a corresponding wild-type cell, wherein the polypeptide having cellobionate phosphorylase activity is encoded by a gene that has at about least 80% sequence identity to NCU09425 (NdvB); (c) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU08807 (CRE-1) as compared to a corresponding wild-type cell; and(d) reduced activity of a polypeptide encoded by a gene that has at least about 80% sequence identity to NCU09333 (ACE-1) as compared to a corresponding wild-type host cell; and/or (e) an increased expression or activity of any laccase protein as compared to a corresponding wild-type cell and said host cell comprising a genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs in the claimed recombinant engineered cell (no structure is recited in claims; 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 “b-glucosidase activity… cellobionate phosphorylase… transcription factors; and laccase activity” having no specific structural elements and an expectation of obtaining the desired biological/biochemical function; (B) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (C) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (D) 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 cellular context/engineered Neurospora crassa HL strain comprising specific structures as disclosed in the prior art (see 35 U.S.C. 102 and 35 U.S.C. 103 rejection below), method of making and method of use said Neurospora crassa HL strain for the production of ethanol (see Examples 1-2, pages 32-40 of specification), however, the scope of claims 1-2, 4-5, 7, 9, 13, 16-17, 20, 23 and 25-31 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.
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 in a genera of cellular context. 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).
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.
Claims 1-2, 4-5, 7, 9, 13, 16-17 and 27-31 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Han et al., (Biores. Technol., 2020, Vol. 307, 123200, pages 1-7) when given the broadest reasonable interpretation.
Claims 1-2, 4-5, 7, 9, 13, 16-17 and 27-31 as interpreted are directed to a method for producing any fuel or any commodity chemical from a cellulosic biomass, the method comprising: (a) pretreating a composition comprising the cellulosic biomass with any sugar acid (genera of sugar acids), thereby producing a pretreated composition; (b) fermenting at least some of the pretreated composition in a first fermentation process, thereby producing a first fermented composition, wherein the first fermented composition comprises the sugar acid (genera of sugar acids); (c) separating the first fermented composition into a first fraction and a second fraction, wherein the first fraction comprises at least some of the sugar acid and the second fraction comprises at least some of the sugar acid; and (d) fermenting the second fraction isolated in step (c) in a second fermentation process, thereby producing the fuel and/or commodity chemical; wherein the sugar acid comprises an oligosaccharide aldonic acid, a disaccharide aldonic acid, a monosaccharide aldonic acid, a heteropolysaccharide aldonic acid, or a combination thereof; and/or wherein the sugar acid is selected from the group consisting of cellobionic acid (CBA), gluconic acid (GA), glucuronic acid, xylonic acid, glucaric acid, and a combination thereof…; wherein the amount of cellulase inhibitory compounds that are produced during the pretreatment in step (a) is lower compared to when the sugar acid is not used to pretreat the cellulosic biomass; and … wherein the amount of hemicellulose and/or lignin that is removed from the cellulosic biomass