Prosecution Insights
Last updated: April 19, 2026
Application No. 18/353,673

ACID TOLERANT CLOSTRIDIA

Non-Final OA §102§103§112
Filed
Jul 17, 2023
Examiner
RAGHU, GANAPATHIRAM
Art Unit
1652
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Alliance for Sustainable Energy, LLC
OA Round
1 (Non-Final)
74%
Grant Probability
Favorable
1-2
OA Rounds
2y 8m
To Grant
99%
With Interview

Examiner Intelligence

Grants 74% — above average
74%
Career Allow Rate
944 granted / 1285 resolved
+13.5% vs TC avg
Strong +26% interview lift
Without
With
+26.3%
Interview Lift
resolved cases with interview
Typical timeline
2y 8m
Avg Prosecution
39 currently pending
Career history
1324
Total Applications
across all art units

Statute-Specific Performance

§101
2.1%
-37.9% vs TC avg
§103
44.1%
+4.1% vs TC avg
§102
10.5%
-29.5% vs TC avg
§112
10.0%
-30.0% vs TC avg
Black line = Tech Center average estimate • Based on career data from 1285 resolved cases

Office Action

§102 §103 §112
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- 14 and as species ( Claim 3 ) CTKRS02840; ( Claim 4 ) CTKRS02860; ( Claim 5 ) CTKRS09785; ( Claim 6 ) CTKRS09915; ( Claim 7 ) heterologous gene encoding for an amino acid decarboxylase ; ( Claim 8 ) heterologous gene encoding for lysine decarboxylase; ( Claim 9 ) heterologous gene encoding for lysine decarboxylase enzymes from C. tyrobutyricum ; ( Claim 12 ) heterologous amino acid decarboxylase; ( Claim 13 ) heter o logous amino acid selected from the group consisting of lysine decarboxylase and a glutamine decarboxylase; and ( Claim 14 ) heterologous amino acid decarboxylase selected from the group consisting of lysine decarboxylase from C. tyrobutyricum, a lysine decarboxylase from Clostridium celluvorans, and a glutamine decarboxylase from Clostridium perfringens in the reply filed on 12 /0 8 /2025 is acknowledged. Examiner would like to point out that applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, and because applicants’ did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).The restriction requirement is still deemed proper and is therefore made FINAL. Claims 1- 20 are pending in this application; and claims 1- 1 4 and the elected species reading on the elected invention is now under consideration for examination; claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention, 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 63/389,432 filed on 0 7 / 15 /2022 ; however note elected claims 3- 6 are only given the priority date Non-provisional application filed on 07/17/2023 . Information disclosure statement The information disclosure statement (IDS) submitted on 11 / 28 /202 3 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner. Claims Objections Claim 3-6 are objected and indefinite in the recitation of “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ”, for the following reasons. No specific structure and the associated activity is recited in the claims for the claimed genes . It is suggested that if the sequences of the “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claim s and additionally it is not clear which specific version and the corresponding structure is being referred to in the claim s , 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 2-1 4 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. Claim 1 is not clear for the following reason: it is not clear whether the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid … is being compared to the corresponding wild-type Clostridium sp. cell from which the non-naturally occurring Clostridium sp. was gene rated or the claimed non-naturally occurring Clostridium sp. is compared to any wild-type Clostridium sp. cell of undefined genotype and phenotype? ; clarification and correction is required. Additionally, Claim s 3-6 are indefinite in the recitation of “ derived ”. The metes and bounds of the term “ derived ” is not clear in the context of the claim. It is not clear to the examiner what are the structures encompassed in “ derived” ? or is a representative member of a genus/merely exemplary. Furthermore, in claim s 3-6 are indefinite in the recitation of “ derived ”; as written, one cannot determine if the term refers to ‘functions of several real variables” or ‘structural variables’ of claimed “ derived ” genes i.e., unlimited structures or structurally undefined molecules or functionally variable molecules and the extent of variability is unclear , no structure and associated function is recited in the claims ). The metes and bounds of the claims are unclear. For examination purposes, no patentable weight will be given to the terms. It is not clear to the examiner as to what the phrase “ derived ” means in the context of the above claims, is this synonymous with “ obtained from specific source or having specific structures ? or does it include natural and man-made variants of unlimited/undefined structures thereof from any source? Examiner suggests amending the claims to recite ”obtained from…” and to recite the structure/SEQ ID NO: with the associated function . Clarification and correction required. II. Claim s 3-6 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim s 3 -6 are rejected in the recitation of “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ”, for the following reasons. No specific activity or the corresponding structure is recited in the claims for the claimed genes and i t is suggested that if the sequences of the “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claim s . Furthermore, as written , 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(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. I. Claims 1- 14 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- 14 recite a genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid . The structural elements recited in claims 1- 14 are not sufficient structure to form a n “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs” . There in inherent unpredictability in regards to encoding polynucleotides /genes and encode d polypeptides/ which amino acid sequences may have the associated function i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs” . As such, claims 1- 14 recite a genera of biomolecules described having any activity or only by functional characteristics (i.e., being “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs” ), 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 “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs” , claims 1- 14 have no defined outer bounds for the scope of “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs” 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 genes and encoded 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 c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ) ; said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [ 0017-0022 ], page s 5 -6 of specification) has been provided by the applicants’, which would indicate that they had possession of the claimed genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid. The genus of polynucleotides /genes and encoded 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 , i.e., characterization of c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ); said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [0017-0022], pages 5-6 of specification) , since one could use structural homology to isolate those polypeptides and the encoding polynucleotides /genes 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 c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ); said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [0017-0022], pages 5-6 of specification) , has been provided by the applicants’, which would indicate that they had possession of the claimed genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid . As the claimed genera of polypeptides and encoding polynucleotides /genes having widely variable structures and associated function in a genera of cellular context , 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 II. Claims 1- 14 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 c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ); said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [0017-0022], pages 5-6 of specification) . However, specification does not reasonably provide enablement for a genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid . 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- 14 are so broad as to encompass: a genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid . The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polynucleotides /genes and encoded polypeptides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to characterization of c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ); said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [0017-0022], pages 5-6 of specification) . It would require undue experimentation of the skilled artisan to make and use the claimed polynucleotides/genes and encoded polypeptides i.e., a genera of cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid ) . 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 cellular contexts (Clostridium sp.; as in claims 1-2 and 7-14 ); genera of polynucleotides /genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” ( no structure is recited as in claims 3-6 ) and said Clostridium sp., further comprising any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homologs (as in claims 7-11 and 13-14 ) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid , because the specification does not establish: (A) a rational and predictable scheme for modifying specific nucleotides or amino acid residues in any “ CTKRS02840 … CTKRS02860 … CTKRS09785 … CTKRS09915 ” having no specific structural elements of any kind and having any unspecified activity and “any amino acid decarboxylase or an amino acid deaminase of undefined and unlimited structures including variants, mutants and homolog 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 c hemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG ); said mutated strain of C. tyrobutyricum overexpressing f our genes comprising native lysine decarboxylase obtained from C. tyrobutyricum (CTK RS05660), a lysine decarboxylase obtained from Clostridium celluvorans (CLOCELRS05175), an agmatine deaminase obtained from Clostridium beijerinckii (CBEI_RS09960), and a glutamine decarboxylase obtained from Clostridium perfringens (CPF_RS11275), designated as pLAR208, pLAR217, pLAR219, and pLAR214 plasmids respectively (see ¶ [0017-0022], pages 5-6 of specification) , however, the scope of claims 1 - 14 is so broad and the lack of guidance either in the specification or in the prior art, the claims remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed (guided mutants) . Such guidance has not been provided in the instant specification or in the prior art. The art also teaches the following regarding complexity of the structure/function relationship: The reference of Chica et al., (Curr. Opin. Biotechnol., 2005, Vol. 16: 378-384) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Sen et al., (Appl. Biochem. Biotechnol., 2007, Vol.143: 212-223), teaches in vitro recombination techniques such as DNA shuffling, staggered extension process (STEP), random chimera genesis on transient templates (RACHITT), iterative truncation for the creation of hybrid enzymes (ITCHY), recombined extension on truncated templates (RETT), and so on have been developed to mimic and accelerate nature's recombination strategy. However, such rational design and directed evolution techniques only provide guidance for searching and screening for the claimed polypeptide which is not guidance for making and/or using the claimed polypeptide . Additionally, knowledge is not extant in the art to assay all possible enzymatic activities, how to express all possible enzymes or how predictably assay for such activities. For example, the reference of Banerjee et al., (Bioenerg. Res. 2010, Vol. 3: 82-92), on page 84, right column, second paragraph, describe that “enzymes have critical properties besides specific activity and thermal tolerance that must be considered but which can be difficult to assay in vitro . For example, besides catalyzing a particular chemical reaction, enzymes must be efficiently translated and secreted, able to resist proteases, act cooperatively with other enzymes, and have low product and feedback inhibition. One can easily imagine that an “improved” enzyme, based on assay in isolation on a model substrate, might perform poorly in a real-world situation ”. Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including polynucleotides and encoded polypeptides with an enormous number of modifications. The scope of the claim must bear a reasonable correlation with the scope of enablement ( In re Fisher , 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5). Enablement III. Claims 1-14 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Claims 1-14 recite specific strain “ non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to a wild type Clostridium sp. in the same conditions ” and “ wherein the organism is derived from Clostridium tyrobutyricum (WT ATCC25795) and comprises at least one non-naturally occurring Clostridium tyrobutyricum (WT ATCC25795) gene selected from the group consisting of CTKRS02840 …” . It is apparent that specific strain “ non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to a wild type Clostridium sp. in the same conditions ” and “ wherein the organism is derived from Clostridium tyrobutyricum (WT ATCC25795) and comprises at least one non-naturally occurring Clostridium tyrobutyricum (WT ATCC25795) gene selected from the group consisting of CTKRS02840 …” is required to practice the claimed invention. As such the biological material must be readily available or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public . If it is not so obtainable or available, the requirements of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, may be satisfied by a deposit of “ non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to a wild type Clostridium sp. in the same conditions ” and “ wherein the organism is derived from Clostridium tyrobutyricum (WT ATCC25795) and comprises at least one non-naturally occurring Clostridium tyrobutyricum (WT ATCC25795) gene selected from the group consisting of CTKRS02840 …” . The specification does not disclose a repeatable method to obtain “ non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to a wild type Clostridium sp. in the same conditions ” and “ wherein the organism is derived from Clostridium tyrobutyricum (WT ATCC25795) and comprises at least one non-naturally occurring Clostridium tyrobutyricum (WT ATCC25795) gene selected from the group consisting of CTKRS02840 …” , and there is no indication in the specification as to the public availability . If the deposit was made under the terms of Budapest Treaty, then a statement, affidavit or declaration by applicants’, or a statement by an attorney of record over his/her signature and registration number, or someone empowered to make such a statement, stating that the invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. In order to certify that the deposit meets the criteria set forth in 37 CFR 1.801-1.809 and MPEP 2402-2411.05, applicants’ may provide assurance of compliance by statement, affidavit or declaration, or by someone empowered to make same, or by a statement by an attorney of record over his/her signature and registration number showing that: (a) during the pendency of the application, access to the invention will be afforded to the Commissioner upon request; (b) all restrictions upon availability to the public will be irrevocably removed upon granting the patent; (c) the deposit will be maintained in public depository for a period of 30 years, or 5 years after the last request or for the enforceable life of the patent, whichever is longer; (d) a test of the viability of the biological material at the time of deposit (see 37 CFR 1.807); and the deposit will be replaced if it should ever become inviable. 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 and 10-11 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by I. Liu X., (PhD., Thesis, 2005, Ohio State Univ., pages 1-220); and II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, pages 1-15) when given the broadest reasonable interpretation. Claims 1-2 and 10-11 as interpreted are directed to a ny non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to a ny wild type Clostridium sp. in the same conditions … wherein the organism generates butyric acid at a rate that is 50% greater than that of a wild type Clostridium sp. organism ; wherein the organism generates butyric acid at a rate of up to 0.48 g/L/h . I. Liu X ., ( PhD., Thesis, 2005, Ohio State Univ., pages 1- 220 ) disclose a genetically modified C. tyrobutyricum prod ucing high levels of butyric acid as compared to the corresponding wild-type cell with butyrate yield of 0.63g/L.h and at a rate of >50% compared to the wild-type cell (see Table 3.2, page 82) and fermentation kinetics (Fig. 3.7-3.8, pages 89-90 and Table 4.1-4.2, pages107-108; and entire document) . II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, page s 1-15) disclose a genetically modified C. tyrobutyricum producing high levels of butyric acid as compared to the corresponding wild-type cell with high butyrate yield and at a rate of >68% compared to the wild-type cell (see Abstract; Fig. 4, page 7; Conclusions , page 10; and entire document). T herefore, the reference s of I. Liu X., (PhD., Thesis, 2005, Ohio State Univ., pages 1-220) and II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, pages 1-15) is deemed to anticipate claims 1-2 and 10-11 as written and when given the broadest reasonable interpretation and is rejected under rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2). Claim Rejections: 35 USC § 103 The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a). The factual inquiries set forth in Graham v. John Deere Co. , 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. Claims 1-2 and 10 - 13 are rejected under 35 U.S.C. 103(a) as being unpatentable over I. Liu X., (PhD., Thesis, 2005, Ohio State Univ., pages 1-220) or II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, pages 1-15) as applied to claims 1-2 and 10-11 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Milan et al., ( US 2019/0040417 A1 ) . The disclosures of I. Liu X., (PhD., Thesis, 2005, Ohio State Univ., pages 1-220) or II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, pages 1-15) as applied to claims 1-2 and 10-11 is described above. However, Liu X., or Zhou et al., are silent regarding wherein the organism expresses at least one heterologous amino acid decarboxylase or heterologous amino acid deaminase ; comprising at least one heterologous amino acid decarboxylase or amino acid deaminase selected from the group consisting of lysine decarboxylase, an agmatine deaminase , and a glutamine decarboxylase (as in claims 12 -1 3 ) . Regarding claims 12-13 , t he following reference Milan et al., ( US 2019/0040417 A1) disclose strategy and methods for production of butyric acid in genetically modified microorganisms including Clostridial sp., comprising and overexpressing heterologous amino acid decarboxylase or heterologous amino acid deaminase , and an agmatine deaminase ( see Abstract; ¶ [0081-0082], [0090], [0143], [0146], [0216] ; and entire document . As such, disclosure of strategy and methods for production of butyric acid in genetically modified microorganisms including Clostridial sp., comprising and overexpressing heterologous amino acid decarboxylase or heterologous amino acid deaminase , and an agmatine deaminase , such as that of Milan et al., clearly suggests to a skilled artisan to modify the teachings of Liu X., or Zhou et al., and incorporate the structural and functional elements of Milan et al., in the claimed recombinant genetically modified Clostridial sp., and method of use for the production of butyric acid as claimed in the instant invention . One of ordinary skill in the art would have a reasonable expectation of success, since g enetically modified microorganisms including Clostridial sp., comprising the biochemical pathway genes for the production of butyric acid and a method of production of butyric acid are well known in the art. Therefore, claims 1-2 and 10 - 13 are rejected under 35 U.S.C. 103(a) as being unpatentable over I. Liu X., (PhD., Thesis, 2005, Ohio State Univ., pages 1-220) or II. Zhou et al., (Biotechnol. Biofuel, 2014, Vol. 7:22, pages 1-15) as applied to claims 1-2 and 10-11 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Milan et al., ( US 2019/0040417 A1) . Allowable Subject Matter/Conclusion None of the claims are allowable. Any inquiry concerning this communication or earlier communications from the examiner shou
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Prosecution Timeline

Jul 17, 2023
Application Filed
Dec 17, 2025
Non-Final Rejection — §102, §103, §112 (current)

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2y 8m
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