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: Election/Restrictions
Applicants’ election of Group II, claims 10-18 with traverse in the response dated 10/13/2025 is acknowledged, and the traversal is as follows: “Applicant hereby selects Group II, Claims 10-18 with traverse. All the claims of Group I contain most of the claim elements of Claim 10 of Group Il. There is little additional burden to search for prior art for Group I over a prior art search for Group II”.
At the outset examiner notes that the applicants’ response is incomplete and non-responsive, as no species election is made in the response dated 10/13/2025; in the interest of providing good service, examiner will limit the examination to the first species in claims 13-15, including the first species listed in Table 4 of claim 14.
This application contains claims directed to patentably distinct species in Group II, claims 13-15, the different genes recited in claims 13-15 and Table 4 are structurally and functionally independent. As such the genus of genes in each of claims 13-15 are not considered to constitute a proper genus, and is therefore subject to restriction. Furthermore, in this case, a search of more than one of the genes, encoded polypeptide sequence(s) and polynucleotide(s) claimed in claims 13-15 presents an undue burden on the Patent and Trademark Office due to the complex nature of the search in terms of computer time needed to perform the search and the subsequent analysis of the search results by the examiner. Regarding species in claims 13-15 i.e., MEALZ_RSO1195, MEALZ_RSO1280,… and multicopper oxidase domain-containing protein (gene- MEALZ_RS14455); type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045) are not considered to constitute a proper genus, and is therefore subject to restriction; examiner reiterates that claims 13-15 is not generic linking claims but instead an improper Markush group. A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate. In addition, these species are not obvious variants of each other based on the current record.
“Should applicant traverse on the ground that the species, or groupings of patentably indistinct species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.” No such argument is provided in the response dated 10/13/2025. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
Therefore, searching structurally distinct molecules like genes, encoded polypeptide(s) and polynucleotide(s) are not coextensive and the sequence search systems of the USPTO are at or near capacity, and search of multiple sequences in a significant number of patent applications is not practical, representing a real burden on the Office. Thus, a comphrensive search of each of the genes and encoded polypeptide(s) and polynucleotide(s) and their method of use would be a burden on the Office. The searches for any one invention are not required for and are not coextensive with the searches for any other invention, thereby creating an undue burden of search and examination. The results from a search of each of these inventions have different considerations with respect to the prior art. Burden Iies not only in the search of sequence databases, U.S. patents, but also in the search for Iiterature and foreign patents and in examination of the claim Ianguage and specification for compliance with the statutes concerning new matter, distinctness, written description and enablement. Thus, a comphrensive search of all inventions in Groups I-II would be a serious burden and contrary to applicants’ arguments, the requirement is still deemed proper and is therefore made FINAL.
Claims 1-18 are pending in this application, Group II, claims 10-18 and as species, examiner will limit the examination to the first species in claims 13-15, including the first species listed in Table 4 of claim 14 of the elected invention is now under consideration for examination; non-elected Group I claims 1-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/13/2025.
Priority
Acknowledgment is made of a claim for domestic priority under 35 U.S.C. 119(e) to the US Provisional Application 63/346,788 filed on 05/27/2022.
Information disclosure statement
The information disclosure statement (IDS) submitted on 08/24/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Claim Objections
I. Claim 10 and claims 11-18 depending therefrom are objected; Claim 10 and claims 13-15 is objected and indefinite in the recitation of “methanotroph comprising one or more of RhlYZAB (activity is not specified; for examination purposes RhlYZAB is interpreted as genes involved rhamnolipid synthesis), RhlYZAB are Pseudomonas aeruginosa genes involved in rhamnolipid synthesis or homologous enzyme(s) thereof;…methanotroph comprises mutations in one or more of the following genes: MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” are Methylotuvimicrobium alcaliphilum DSM19304 gene(s) names and no activity is specified and which appear be involved fatty acid synthesis in specific cellular context and strain Methylotuvimicrobium alcaliphilum DSM19 DASS strain. However, as written, the terms appear to be generically used and not limited to a specific organisms Pseudomonas aeruginosa and Methylotuvimicrobium alcaliphilum DSM19 DASS strain. While the gene nomenclature used may be appropriate for Pseudomonas aeruginosa and Methylotuvimicrobium alcaliphilum DSM19 DASS strain genes, the use of this nomenclature for genes encoding proteins of identical function/or any function, no activity is specified in claims in other organisms may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. It is suggested that if the sequences of the wild-type RhlYZAB and MEALZ_RSO1195… is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claims. Furthermore, as written; the claim reads on yet to be discovered type RhlYZAB and MEALZ_RSO1195… and additionally it is not clear which specific version and the corresponding structure is being referred to in the claims, as public databases are constantly curated and revised. Correction and clarification is required.
II. Claim 14 is objected to, due to the following informality: Claim 14 recites “… as indicated in Table 4” in the claim. Examiner suggests incorporating the specific SEQ ID NO in the claim. Appropriate correction is required.
MPEP 2173.05(s) provides the following guidance:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
III. Claim 18 is objected: Recitation of “and/or” in claim 18 makes the claim indefinite, as it is not clear what limitations must be present. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
Claim Rejections: 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
I. Claim 10 and claims 11-18 depending therefrom is 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.
In Claim 10 and claims 13-15 the recitation of “methanotroph comprising one or more of RhlYZAB or homologous enzyme(s) thereof (activity is not specified; for examination purposes RhlYZAB is interpreted as genes involved rhamnolipid synthesis), are RhlYZAB are Pseudomonas aeruginosa genes involved in rhamnolipid synthesis;…methanotroph comprises mutations in one or more of the following genes: MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” are Methylotuvimicrobium alcaliphilum DSM19304 gene(s) names and no activity is specified and which appear be involved fatty acid synthesis in specific cellular context and strain Methylotuvimicrobium alcaliphilum DSM19 DASS strain. However, as written, the terms appear to be generically used and not limited to a specific organisms Pseudomonas aeruginosa and Methylotuvimicrobium alcaliphilum DSM19 DASS strain. While the gene nomenclature used may be appropriate for Pseudomonas aeruginosa and Methylotuvimicrobium alcaliphilum DSM19 DASS strain genes, the use of this nomenclature for genes encoding proteins of identical function/or any function, no activity is specified in claims in other organisms may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. For example, the ARO4 gene of Candida albicans encodes a DAHP synthase, whereas the E. coli counterpart is the AroF gene. See Sousa et al. (Microbiology, 2002, Vol. 148: 1291-1303; reference not enclosed). As such, the use of gene terminology which is applicable to some microorganisms and not to others is confusing since the claims use this gene nomenclature with respect to any microbial organism. It is suggested that if the sequences of RhlYZAB and MEALZ_RSO1195… is disclosed and to incorporate the corresponding sequence identifier (i.e., SEQ ID NO: X; SEQ ID NO: Y) be used in the claims. Furthermore, as written; the claim reads on yet to be discovered type RhlYZAB and MEALZ_RSO1195… and additionally it is not clear which specific version and the corresponding structure is being referred to in the claims, as public databases are constantly curated and revised. Correction and clarification is required.
II. Claim 18 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention; recitation of “and/or” in claim 18 makes the claims indefinite, as it is not clear what limitations must be present. The metes and bounds of claim 18 is not clear and thus, it would not be possible to one of ordinary skill in the art to define the metes and bounds of the desired patent protection. The rejection may be overcome by amending the claims to recite “… or …”. Correction and clarification is required. Examiner suggests amending the claim to recite “…or …”.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 10-18 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 10-18 recite a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
The structural elements recited in claims 10-18 are not sufficient structure to form a “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” having no specific structural elements of any kind and having associated activity or any undefined activity. There in inherent unpredictability in regards to encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/genetically modified methanotroph, genera of host cell i.e., “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” and possibly fall within the claims and those genes and encoded amino acid sequences that do not have “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)”. As such, claims 10-18 recite a genera of biomolecules described only by a functional characteristics (i.e., encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/genetically modified methanotroph host cell i.e., “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)”, 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 “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” activity, claims 10-18 have no defined outer bounds for the scope of “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” activity that fall within the scope of the claims. Due to the literal unlimited structural scope of the claims, it is not possible to provide for a representative number of species that adequately described are representative of the entire genus having no fixed structural outer boundaries. Further, such genera of altered enzymes as recited lack “a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials” and without any required structure that is sufficient for providing the recited enzyme activity, the recited genera lack disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. The claims lack adequate written description in the as-filed specification for the reasons stated.
No information, beyond the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification) has been provided by the applicants’, which would indicate that they had possession of the a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
The genus of polynucleotides and encoded polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus in the claimed genera of genetically modified methanotroph host cells. While the argument can be made that the recited genus of polynucleotides and encoded polypeptides is adequately described by the disclosure of the structures of amino acid sequences and the encoding polynucleotides as disclosed in the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification), since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. 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. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
As stated above, no information beyond the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation). As the claimed genera of polypeptides and encoding polynucleotides having widely variable structures and associated function in the claimed genera of genetically modified methanotroph host cells, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
Claims 10-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification). However, specification does not reasonably provide enablement for a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 10-18 are so broad as to encompass: a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation). The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of polynucleotides and encoded polypeptides broadly encompassed by the claims in a genus of engineered host cells. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides and engineered host cells i.e., a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation). The specification but provides no guidance with regard to the making of variants and mutants or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (for example, see Whisstock et al., Prediction of protein function from protein sequence and structure. Q Rev Biophys. 2003, Aug. 36 (3): 307-340. Review), the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to make and use the full scope of the polypeptides encompassed by the claims. However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b). Here, the claims read on a significant number of inoperative embodiments.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any “RhlYZAB or homologous enzyme(s) thereof activity… MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” activity having no specific structural elements and an expectation of obtaining the desired biological/biochemical function; (B) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (C) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
While as discussed above, the specification provides guidance with regard to the characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (see Example 1, Table 6, pages 34-50 of specification), however, the scope of claims 10-18 is so broad and the lack of guidance either in the specification or in the prior art, the claims remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including polynucleotides and encoded polypeptides with an enormous number of modifications in a genera of cellular context. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of genes, polynucleotides and encoded polypeptides/enzymes having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Claim Rejections: 35 USC § 102 (AIA )
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 (or as subject to pre-AIA 35 U.S.C. 102) 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 10-18 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Awasthi et al., (J. Indus. Microbiol. Biotechnol., 2022, Vol. 49, kuac002; pages 1-12; publication date 02/03/2022; the priority date for instant claims under consideration is deemed to be the filing date US Provisional Application 63/346,788 filed on 05/27/2022).
Claims 10-18 as interpreted are directed to a genera of genetically modified methanotroph host cells/genera of cellular context (methanotroph of undefined genotype and phenotype) comprising any undefined genetic modification in the cellular machinery (as in claims 10-15); i.e., comprising one or more of RhlYZAB or homologous enzyme(s) thereof of undefined and undefined structures including variants, mutants and homologs wherein the genetically modified methanotroph comprises any genetic undefined genetic modification/mutation in one more following genes “MEALZ_RSO1195, MEALZ_RSO1280, (no activity is specified)… type IV pilus secretin PilQ (pilQ; gene-MEALZ_RS15795); and, FAD-dependent oxidoreductase/hypothetical protein/NAD(P)/FAD-dependent oxidoreductase (gene-MEALZ_RS 18045)” (as in claims 10-15); and said genera of genetically modified methanotroph is resistant or able to grow in a medium having rhamnolipid as compared to a corresponding wild-type cell (as in claims 16-18; also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
Awasthi et al., (J. Indus. Microbiol. Biotechnol., 2022, Vol. 49, kuac002; pages 1-12; publication date 02/03/2022) disclose characterization of specific cellular context/engineered Methylotuvimicrobium alcaliphilum DSM19 DASS strain comprising specific structures codon optimized polynucleotide sequence of SEQ ID NOs: 1-4 encoding RhlYZAB involved rhamnolipid synthesis, method of making and method of use said Methylotuvimicrobium alcaliphilum DSM19 DASS strain for the production of rhamnolipid (Abstract; Fig. 1, page 2; Fig. 2, Table 1, page 5; Fig. 6, Table 3, page 9; entire document; and Supplemental Supporting information, Table S2). Therefore, the disclosure of Awasthi et al., (J. Indus. Microbiol. Biotechnol., 2022, Vol. 49, kuac002; pages 1-12; publication date 02/03/2022); the priority date for instant claims under consideration is deemed to be the filing date US Provisional Application 63/346,788 filed on 05/27/2022) anticipate the instant claims 10-18 as written/interpreted.
III. “BY OTHERS”
“Others” Means Any Combination of Authors or Inventors Different Than the Inventive Entity
The term “others” in 35 U.S.C. 102(a) refers to any entity which is different from the inventive entity. The entity need only differ by one person to be “by others.” This holds true for all types of references eligible as prior art under 35 U.S.C. 102(a) including publications as well as public knowledge and use. Any other interpretation of 35U.S.C. 102(a) “would negate the one year [grace] period afforded under § 102(b).”
The applied reference has a common inventors (Deepika Awasthi and Steven W. Singer) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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