Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
In response to Non-Final-Office Action mailed on 12/22/2025, applicants’ response dated 06/22/2026 is acknowledged; in said response applicants’ have amended claims 1-9 and 12-14. Thus, amended claims 1-20 are pending in this application; and elected claims 1-14 and the elected species reading on the elected invention is now under consideration for examination; claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim. Rejections and/or objections not reiterated from previous office action are hereby withdrawn.
Maintained-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 07/15/2022; however note elected claims 3-6 are only given the priority date Non-provisional application filed on 07/17/2023.
New-Matter/Objection to Specification
Necessitated by claim amendments
Upon further review of claims amendment; amended new claims 3-6 (dated 06/22/2026) are objected to under 35 U.S.C. 132(a), because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: Amended claims 3-6 recites “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6)” and broadens the scope of the claims and as claimed was not contemplated in the specification as originally filed dated 07/17/2023 or in the original claim set dated 07/17/2023. The instant amended new claims dated 06/22/2026 as interpreted encompass new-matter.
New Matter-Claim Rejections: 35 USC § 112 (a)
Necessitated by claim amendments
Amended new claims 3-6 (dated 06/22/2026) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter, 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(s), at the time the application was filed, had possession of the claimed invention. Amended new claims 3-6 (dated 06/22/2026) are rejected because, new claims 3-6 (dated 06/22/2026), recites the following subject matter: “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6)”and broadens the scope of the claims and as claimed was not contemplated in the specification as originally filed dated 07/17/2023 or in the original claim set dated 07/17/2023; see Purdue Pharma L.P. v. Faulding Inc., 230 F .3d 1320, 1326, 56 USPQ2d 1481, 1486 (Fed. Cir. 2000). The court noted that with respect to In Re Rusching 379 F.2d 990, 154 USPQ 118 (CCPA 1967) that “Rusching makes clear that one cannot disclose a forest in the original application, and then later pick a tree out of the forest and say “here is my invention”. In order to satisfy the written description requirement, the blaze marks directing the skilled artisan to that tree must be in the originally filed disclosure”.
Maintained-Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
I. Amended 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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 an “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” 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 encoded polypeptides/which amino acid sequences may have the associated function i.e., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” 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 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) in the claimed non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid” 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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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.
Applicants’ have traversed the above written-description and enablement with the following common arguments: (see page 8 of Applicants’ REMARKS dated 06/22/2026).
Applicants’ argue: “…as allegedly failing to comply with the written description requirement. Applicant respectfully disagrees. Merely in an additional effort to promote the efficient prosecution of the Application, Applicant has specified the nucleotide and amino acid sequences of the genes in the specification as originally filed in a sequence listing filed herewith.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 12/22/2025) and additionally for the following reasons. Contrary to applicants’ argument, claims 1-2 and 7-14 do not recite any specific structure, i.e., “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” and a genera of cellular contexts i.e., any Clostridium sp.; and
regarding claims 3-6, examiner takes the following position: “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)”. The disclosure of the specification is still insufficient to enable the claimed Clostridium sp., to its full scope or evidence of possession. Therefore, the scope of the instant claims are broad despite the guidance of the art and specification, the claims remain not commensurate with evidence of possession or in scope with the enabled invention.
There are no examples provided to encompass the numerous characteristics of the whole genus claimed. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals applicants’ hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of structures with the associated function in the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
MPEP 2163.II.A.2. (a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”;
Examiner would like to reiterate
“The basic quid pro quo contemplated by the Constitution and the Congress for granting a patent monopoly is the benefit derived by the public from an invention with substantial utility”, [u]nless and until a process is refined and developed to this point-where specific benefit exists in currently available form-there is insufficient justification for permitting an applicant to engross what may prove to be a broad field”, and “a patent is not a hunting license”,[i]t is not a reward for the search, but compensation for its successful conclusion.”
Maintained-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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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/genes and encoded polypeptides of undefined and unlimited structures including variants, mutants and homologs and having any activity i.e., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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., “CTK_RS02840…CTK_RS02860… CTK_RS09785…CTK_RS09915” (no structure is recited as in claims 1-2); “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1) (amened claim 3); …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS02860 (SEQ ID NO: 23), RS02840 (SEQ ID NO: 1) (amened claim 4);… gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09785 (SEQ ID NO: 33), RS02840 (SEQ ID NO: 1) (amened claim 5); and …gene comprising a nucleotide sequence that is greater than 90 percent identical to CTK_RS09915 (SEQ ID NO: 5), RS02840 (SEQ ID NO: 1) (amened claim 6; also see rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter)” 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 7-14) 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 chemical mutagenesis of C. tyrobutyricum performed in an anaerobic chamber using N-methyl-N'-nitro-N-nitrosoguanidine (NTG); said mutated strain of C. tyrobutyricum overexpressing four 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).
Applicants’ have traversed the above written-description and enablement with the following common arguments: (see page 8 of Applicants’ REMARKS dated 06/22/2026).
Applicants’ argue: “…as allegedly failing to comply with the written description requirement. Applicant respectfully disagrees. Merely in an additional effort to promote the efficient prosecution of the Application, Applicant has specified the nucleotide and amino acid sequences of the genes in the specification as originally filed in a sequence listing filed herewith.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 12/22/2025) and additionally for the following reasons. Applicants’ arguments filed on 06/22/2026 for the traversal of enablement rejection is on similar lines to the arguments presented for traversing the written-description, said arguments have been fully considered but they are not persuasive. Examiner continues to maintain the rejection for reasons stated on record, supporting evidence and arguments presented above in maintaining the written-description rejection also applies to enablement rejection.
For the above cited reasons, examiner is maintaining the written-description and enablement rejection for claims 1-14.
Maintained-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 CTK_RS02840…”. 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.
Applicants’ have traversed the above enablement with the following common arguments: (see pages 8-9 of Applicants’ REMARKS dated 06/22/2026).
Applicants’ argue: “Applicants are in the process of depositing the engineered strains disclosed in the Application into the international depositary authority at the Agricultural Research Service Culture Collection (NRRL) located at 1815 North University Street, Peoria, Illinois 61604 in order to satisfy the requirements for the furnishing of samples according to 37 CFR 1.808 under the rules for microorganism deposit under the Budapest Treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure (Budapest Treaty) so that the public may have access to the claimed strains. The NRRL accession numbers will be communicated to the Office for the accession and viability date deposit of Applicant's engineered strains. In addition, Applicant will file a declaration of Jeffrey Linger, Ph.D. under 37 CFR 1.132 declaring that the engineered strains were mailed to and viably deposited in the international depositary authority at the Agricultural Research Service Culture Collection (NRRL). The affidavit will also state that the deposited strains are the same as originally disclosed in the application as filed…”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 12/22/2025) and additionally for the following reasons. To date no Affidavit has been filed by applicants.
Maintained-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 any non-naturally occurring Clostridium sp. organism exhibiting increased growth and production of butyric acid at pHs lower than 7.0 when compared to any 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 producing 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, pages 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).
Therefore, the references 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).
Applicants’ have traversed the above 35 USC § 102 (AIA ) with the following arguments: (see page 9 of Applicants’ REMARKS dated 06/22/2026).
Applicants’ argue: “Liu and Zhou. Applicants respectfully disagree. As mentioned above, Applicant is filing herewith a sequence listing that contains the sequences of the genes disclosed in the Application as filed. Applicant has amended the claims to recite that the non-naturally occurring genes claimed are greater than 90 percent identical to the particular sequences of the referenced genes. Neither Liu or Zhou disclose non-naturally occurring genes with sequences that are 90 percent or more identical to the particular non- naturally occurring genes as
Applicant currently claims. Accordingly, since neither Liu or Zhou has disclosed the claimed subject matter of Applicant's claimed invention, neither Liu or Zhou can anticipate Applicant's invention as currently claimed.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 12/22/2025) and additionally for the following reasons. Contrary to applicants’ argument, claims 1-2 and 10-11 do not recite any specific structure or SEQ ID NO: i.e., “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” and a genera of cellular contexts i.e., any Clostridium sp.
New-Claim Rejections: 35 USC § 103
Necessitated by claim amendments
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 1-3 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 Kim et al., (Accession#KM108103, 2014, obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention) and 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 “…gene comprising a nucleotide sequence that is greater than 90 percent identical to selected from the group consisting of CTK RS02840 (SEQ ID NO: 1; amened claim 3); and 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 12-13).
Regarding claim 3, Kim et al., provide evidence in Accession#KM108103, 2014, obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention.
Regarding claims 12-13, the 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 i.e., obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention and overexpressing heterologous amino acid decarboxylase or heterologous amino acid deaminase, and an agmatine deaminase, such as that of Kim et al., and 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 Kim et al., and 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 genetically 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 1-3 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 Kim et al., (Accession#KM108103, 2014, obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention) and Milan et al., (US 2019/0040417 A1).
Applicants’ have traversed the above 35 USC § 103 following claim amendments with the following arguments (see pages 9-10 of Applicants’ REMARKS dated 06/22/2026).
Applicants’ argue: “…Neither Liu, Zhou or Milan disclose or teach all of the limiting elements of Applicant's currently amended claims 1-2 and 10-11 nor their dependent claims that contain specific sequences of non-naturally occurring genes.
Accordingly, no combination of Liu, Zhou or Milan can obviate Applicant's claimed invention at least because Liu, Zhou or Milan do not disclose or teach all of the limiting elements of Applicant's claimed invention.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 12/22/2025) and additionally for the following reasons. Contrary to applicants’ argument, claims 1-2 and 10-13 do not recite any specific structure, i.e., “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” and a genera of cellular contexts i.e., any Clostridium sp.
Examiner has provided a new reference that discloses the structural and functional elements of claim 3 of the instant invention: Kim et al., (Accession#KM108103, 2014, obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention).
Summary of Pending Issues
Upon further review of claims amendment; amended new claims 3-6 (dated 06/22/2026) are objected to under 35 U.S.C. 132(a), because it introduces new matter into the disclosure.
Amended new claims 3-6 (dated 06/22/2026) are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA )/new-matter, as failing to comply with the written description requirement.
Claims 1-14 are rejected under 35 U.S.C. 112(a) for written-description, enablement and Biologic-Deposit.
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 1-3 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 Kim et al., (Accession#KM108103, 2014, obtained from Clostridium tyrobutyricum and annotated as major facilitator superfamily MFS1(nark) gene and having 99.6% sequence identity to SEQ ID NO: 1 of the instant invention) and Milan et al., (US 2019/0040417 A1).
Claims 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention.
Conclusion
None of the claims are allowable. Claims 1-14 are objected/rejected for the reasons identified in the Rejections and Summary sections of this Office Action. Applicants must respond to the rejections in each of the sections in this Office Action to be fully responsive for prosecution.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Regarding filing an After Final amendment, Applicants are directed to MPEP 714.13, which states:
II. ENTRY NOT A MATTER OF RIGHT
It should be kept in mind that applicant cannot, as a matter of right, amend any finally rejected claims, add new claims after a final rejection (see 37 CFR 1.116) or reinstate previously canceled claims. Except where an amendment merely cancels claims, adopts examiner suggestions, removes issues for appeal, or in some other way requires ONLY A CURSORY REVIEW by the examiner (e.g., typographical errors), compliance with the requirement of a showing under 37 CFR 1.116(b)(3) is expected in all amendments after final rejection. An affidavit or other evidence filed after a final rejection, but before or on the same date of filing an appeal, may be entered upon a showing of good and sufficient reasons why the affidavit or other evidence is necessary and was not earlier presented in compliance with 37 CFR 1.116(e). See 37 CFR 41.33 and MPEP § 1206 for information on affidavit or other evidence filed after appeal. (Examiner's emphasis) If more than a cursory review is required, Applicants are referred to CFR §1.114.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHIRAMA RAGHU whose telephone number is (571)272-4533. The examiner can normally be reached on M-F 8:30am-5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached on 408-918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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