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/Restriction
Applicants’ election with traverse of Group I directed to claims 1-12 and 33-38 and as species Methylthio-alkane reductase (claim 5) and Nitrospiraceae phylum (Nitrospinota; claims 9-12) following claim amendments and addition of new claims for prosecution in their response dated 12/11/2025 is acknowledged; in said amendment applicants’ have amended claims 1-3, 11, 13-17, 20-21, 23 and 37, canceled claim 4 and added new claims 39-41. The traversal is on the grounds that “… Applicant requests that the restriction requirement be reconsidered because the Office Action has not shown that a serious burden would be required to examine all of the claims”. Applicants’ arguments have been considered, however examiner respectfully disagrees for the following reasons. Examiner continues to maintain the position for the reasons made of record in the Restriction dated 08/27/2025 i.e., “Inventions’ I-II and the method of Groups’ III-IV are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make other and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP § 806.05(f)). In the instant case the product of Groups’ III-IV made by the claimed method can be made by biochemical methods as opposed to the use of engineered microorganism of Groups’ I-II; and there is an examination and search burden for these patentably distinct species due to their mutually exclusive characteristics. The species require a different field of search (e.g., searching different classes/subclasses or electronic resources, or employing different search queries); and/or the prior art applicable to one species would not likely be applicable to another species; and/or the species are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph. Examiner would like to reiterate that elected claims 1-3, 5-12 and 33-41 are directed to a broad genera of engineered microorganisms (genus of cellular contexts) comprising a broad genera of S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures, since each encoded S-Adenosyl-L-methionine (SAM) pathway enzyme(s) claimed is structurally and functionally independent and distinct for the following reasons: each of these S-Adenosyl-L-methionine (SAM) pathway enzyme(s) has a unique and separate structures. As such the Markush/genus of polypeptides/S-Adenosyl-L-methionine (SAM) pathway enzyme(s) in each of elected claims 1-3, 5-12 and 33-41 are not considered to constitute a proper genus, and is therefore subject to restriction; examiner reiterates that elected claims 1-3, 5-12 and 33-41 are 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. Furthermore, in this case, a search of more than one (1) cellular context and S-Adenosyl-L-methionine (SAM) pathway enzyme(s) in each of the elected claims 1-3, 5-12 and 33-41 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. Searching structurally distinct molecules in a genus of cellular context are not coextensive, and search of multiple structures in a significant number of patent applications is not practical, representing a real burden on the Office; and a search for any one of the S-Adenosyl-L-methionine (SAM) pathway enzyme and engineered cellular context would not encompass any other S-Adenosyl-L-methionine (SAM) pathway enzyme and engineered cellular context. Thus, a comphrensive search of each of the encoded S-Adenosyl-L-methionine (SAM) pathway enzyme(s) and engineered cellular contexts and their method of use would be a burden on the Office. Additionally, 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. Accordingly, non-elected species in claims 5 and 9-12 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3 and 5-41 are pending in this application, Group I, claims 1-12 and 33-41 and as species Methylthio-alkane reductase (claim 5) and Nitrospiraceae phylum (Nitrospinota; claims 9-12) of the elected invention is now under consideration for examination; non-elected species in claims 5 and 9-12 of Group I and the non-elected Groups’ II-IV, claims 13-32 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 12/11/2025.
Priority
This application claims the benefit of priority under 35 U.S.C. 119(e) to the US Provisional application 63/365,503 filed on 05/31/2022.
Information disclosure statement
The information disclosure statements (IDS) submitted on 06/22/2023 and 1020/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statements are considered and initialed by the examiner.
Objections to Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Claim Objections
I. Claim 1 and 2-12 and 33-41 are objected to for the following informality: Claims 1-2 recite “C2.4 alkene…C2.4 alkanol” is confusing and a typographical error; examiner suggests the following amendments for claims 1-2: “C2-4 alkene…C2-4 alkanol”.
II. Claims 5 (claim 6 depending therefrom) and 7 are objected are objected to for the following informality: Recitation of “and/or” in claims 5 and 7, 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 …” and for examination purposes the claims 2 and 9 are interpreted as “…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. Claims 5 (claim 6 depending therefrom) and 7 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 6-7 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 claims 5 and 7 makes the claim indefinite, as it is not clear what limitations must be present. The metes and bounds of claims 5-7 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 …”.
II. Claim 35 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. Claim 35 recites the phrase “at least about ”, the metes and bounds of the phrase ““at least about ”is not clear. The recitation of terms “at least” and “about” are inconsistent with each other and makes it unclear whether there is a discrete lower or upper limit to recited values in said claims (see Amgen Inc. v. Chugai pharmaceutical Co., F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). For example, in claim 35, the claim recites the phrase “at least about 1 x105 CFU/g ”; the term “about” is a relative term which extends the metes and bounds of the claimed range, however, the disclosure does not recite the requisite degree or how one would objectively determine a CFU as being “about” (or not about) a certain value, for example 1 x105 CFU/g may by broadly and reasonably be interpreted above or below 1 x105 CFU/g, and thereby rendering the claims indefinite. Clarification and correction is required. Examiner suggests amending the phrase to recite “…at least …”. See MPEP § 2173.05(c).
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 5-12 and 33-41 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 1-3, 5-12 and 33-41 recite a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5).
The structural elements recited in claims 1-3, 5-12 and 33-41 are not sufficient structure to form “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” having no specific structural elements of any kind and having associated activity. There in inherent unpredictability in regards to encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/engineered host cell i.e., “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” and possibly fall within the claims and those amino acid sequences that do not have “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” activity. As such, claims 1-3, 5-12 and 33-41 recite a genera of biomolecules described only by a functional characteristics (i.e., encoding polynucleotides and encodes polypeptides/which amino acid sequences may have the associated function in any undefined cellular context/engineered host cell i.e., “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” activity, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.” Further, without any structural limitations for structural features that actually provide for “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” activity, claims 1-3, 5-12 and 33-41 have no defined outer bounds for the scope of “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” 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 Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use of said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification) has been provided by the applicants’, which would indicate that they had possession of the a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5).
The genus of polynucleotides and encoded polypeptides required in the claimed invention is an extremely large structurally and functionally variable genus in the claimed genera of engineered host cells. While the argument can be made that the recited genus of polypeptides is adequately described by the disclosure of the structures of amino acid sequences and the encoding polynucleotides as disclosed in the characterization of specific cellular context/engineered Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use of said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification), since one could use structural homology to isolate those polypeptides and the encoding polynucleotides recited in the claims. The art clearly teaches the “Practical Limits of Function Prediction”: (a) Devos et al., (Proteins: Structure, Function and Genetics, 2000, Vol. 41: 98-107), teach that the results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and plasticity of proteins (Abstract, page 98) and the analysis poses interesting questions about the reliability of current function prediction exercises and the intrinsic limitation of protein function prediction (Column 1, paragraph 3, page 99) and conclude that “Despite widespread use of database searching techniques followed by function inference as standard procedures in Bioinformatics, the results presented here illustrate that transfer of function between similar sequences involves more difficulties than commonly believed. Our data show that even true pair-wise sequence relations, identified by their structural similarity, correspond in many cases to different functions (column 2, paragraph 2, page 105).
(b) Whisstock et al., (Quarterly Reviews of Biophysics 2003, Vol. 36 (3): 307-340) also highlight the difficulties associated with “Prediction of protein function from protein sequence and structure”; “To reason from sequence and structure to function is to step onto much shakier ground”, closely related proteins can change function, either through divergence to a related function or by recruitment for a very different function, in such cases, assignment of function on the basis of homology, in the absence of direct experimental evidence, will give the wrong answer (page 309, paragraph 4), it is difficult to state criteria for successful prediction of function, since function is in principle a fuzzy concept. Given three sequences, it is possible to decide which of the three possible pairs is most closely related. Given three structures, methods are also available to measure and compare similarity of the pairs. However, in many cases, given three protein functions, it would be more difficult to choose the pair with most similar function, although it is possible to define metrics for quantitative comparisons of different protein sequences and structures, this is more difficult for proteins of different functions (page 312, paragraph 5), in families of closely related proteins, mutations usually conserve function but modulate specificity i.e., mutations tend to leave the backbone conformation of the pocket unchanged but to affect the shape and charge of its lining, altering specificity (page 313, paragraph 4), although the hope is that highly similar proteins will share similar functions, substitutions of a single, critically placed amino acid in an active-site residue may be sufficient to alter a protein’s role fundamentally (page 323, paragraph 1).
(c) This finding is reinforced in the following scientific teachings for specific proteins in the art that suggest, even highly structurally homologous polynucleotides and encoded polypeptides do not necessarily share the same function. For example, Witkowski et al., (Biochemistry 38:11643-11650, 1999), teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Seffernick et al., (J. Bacteriol. 183(8): 2405-2410, 2001), teaches that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Broun et al., (Science 282:1315-1317, 1998), teaches that as few as four amino acid substitutions can convert an oleate 12-desaturase into a hydrolase and as few as six amino acid substitutions can transform a hydrolase to a desaturase.
As stated above, no information beyond the characterization of specific cellular context/engineered Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use of said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase of including variants, mutants and homologs of undefined and unlimited structures (as in claim 5). As the claimed genera of polypeptides and encoding polynucleotides having widely variable structures and associated function in the claimed genera of engineered host cells, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
Claims 1-3, 5-12 and 33-41 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 Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use of said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification). However, specification does not reasonably provide enablement for a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5). 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 1-3, 5-12 and 33-41 are so broad as to encompass: a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5). 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 Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification). It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides and engineered host cells i.e., a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5). 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 and the encoding polynucleotides encompassed by the claims. However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b). Here, the claims read on a significant number of inoperative embodiments.
While enzyme isolation techniques, recombinant and mutagenesis techniques are known, and it is not routine in the art to screen for multiple substitutions or multiple modifications as encompassed by the instant claims, the specific amino acid positions within a protein's sequence where amino acid modifications can be made with a reasonable expectation of success in obtaining the desired activity/utility are limited in any protein and the result of such modifications is unpredictable. In addition, one skilled in the art would expect any tolerance to modification for a given protein to diminish with each further and additional modification, e.g. multiple substitutions.
The specification does not support the broad scope of the claims which encompass: a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-12 and 33-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates; as in claims 1-3, 5-12 and 33-37) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-12 and 33-41; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any “any S-Adenosyl-L-methionine (SAM) pathway enzymes… any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol … and any methylthio-alkane reductase” 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 Saccharomyces cerevisiae ATCC 96581 strain comprising specific structures, a Oleate hydratase encoded by the polynucleotide sequence of SEQ ID NO: 1, and a Linalool dehydratase encoded by the polynucleotide sequence of SEQ ID NO: 2, method of making and method of use said Saccharomyces cerevisiae ATCC 96581 strain for the production of ethanol (see Examples 1-2, ¶ [0068-0076], pages 18-21 of specification), however, the scope of claims 1-3, 5-12 and 33-41 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 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 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 1-3, 5-9, 12, 33-34, 36-37 and 39-40 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by North et al., (US 2024/0060037 A1; priority 03/25/2021) when given the broadest reasonable interpretation.
Claims 1-3, 5-9, 12, 33-34, 36-37 and 39-40 as interpreted are directed to a genera of host cells/genera of cellular context (fermenting organisms producing C2-4 alkene from C2-4 alkanol; as in claims 1-3, 5-9 and 33-34, 36-37 and 39-40); comprising a cellular machinery able to produce any C2-4 alkene from any C2-4 alkanol (genera of products and substrates) and comprising any undefined genetic modification i.e., wherein the engineered host cell comprises S-Adenosyl-L-methionine (SAM) pathway enzymes including variants, mutants and homologs of undefined and unlimited structures and any non-native enzyme of undefined and unlimited structures catalysing the conversion of C2-4 alkanol (as in claims 1-3, 5-9 and 33-34, 36-37 and 39-40; also see claims objections and 35 U.S.C. 112(b) for claims interpretation); said pathway enzyme comprises any methylthio-alkane reductase including variants, mutants and homologs of undefined and unlimited structures (as in claim 5).
North et al., (US 2024/0060037 A1; priority 03/25/2021) disclose non-naturally occurring microbial organisms capable of producing ethylene, ethane, and/or methane, as well was methods for producing ethylene, ethane, and/or methane using the same; said non-naturally occurring microbial organism is genetically engineered to express Methylthio-alkane reductase (Abstract; Fig. 1A, reproduced below; ¶ [0075]; Claims; and entire document); said non-naturally occurring microbial organism is Rhodobacter capsulatus, Rp, Rhodopseudomonas palustris; Ru, Rhodospirillum rubrum, R. rubrum (¶ [0018], [0030-0033], [0038], [0227-0232]); and carbon sources including ethanol the one or more carbon sources may be selected from one or more in combination of: carbon dioxide and carbon monoxide, mono and disaccharide sugars, organic acids (for example, malate, succinate, pyruvate, and fumarate), volatile fatty acids (for example, formate, acetate, propionate, and butyrate), alcohols (for example, ethanol and glycerol), (¶ [0152]). Certain relevant sections from North et al., (US 2024/0060037 A1; priority 03/25/2021) is reproduced below:
PNG
media_image1.png
499
398
media_image1.png
Greyscale
PNG
media_image2.png
611
406
media_image2.png
Greyscale
PNG
media_image3.png
400
262
media_image3.png
Greyscale
PNG
media_image4.png
106
278
media_image4.png
Greyscale
Therefore, the reference of North et al., (US 2024/0060037 A1; priority 03/25/2021) is deemed to anticipate claims 1-3, 5-9, 12, 33-34, 36-37 and 39-40 as written and when given the broadest reasonable interpretation and is rejected under rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
Claim Rejections: 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 5-12 and 33-41 are rejected under 35 U.S.C. 103(a) as being unpatentable over North et al., (US 2024/0060037 A1; priority 03/25/2021) as applied to claims 1-3, 5-9, 12, 33-34, 36-37 and 39-40 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Voight et al., (US 9,040,266 B2), Wood et al., (US 2020/0337314 A1) and Begmatov et al., (Microorganisms, 2021, Vol. 9,2362, pages 1-21).
The disclosures of North et al., (US 2024/0060037 A1; priority 03/25/2021) as applied to claims 1-3, 5-9, 12, 33-34, 36-37 and 39-40 is described above. However, North et al., are silent regarding wherein the microorganism is an engineered version of a fungal strain (as in claims 10-11 and 41); wherein the composition comprises the engineered microorganism in an amount of at least about 1 x 105 CFU/g (as in claim 35); and wherein the composition comprises the engineered microorganism as part of a consortium (as in claim 38).
Regarding claims 10-11 and 41, the following reference, Voight et al., (US 9,040,266 B2) discloses a recombinant organism, such as a yeast/Saccharomyces cerevisiae, expressing a heterologous S-adenosylmethionine (SAM)-dependent pathway enzyme and a carbon source in a cultivation medium under conditions to increase flux through a S-adenosyl-methionine (SAM) biosynthetic pathway (Abstract; Summary of invention, col. 1, lines 55-67 to col. 7, lines 1-6; Claims; and entire document) and suggest said genetically engineered yeast/Saccharomyces cerevisiae for the production of ethylene (col. 18, lines 29-45).
Regarding claims 35 and 38, the following reference Wood et al., (US 2020/0337314 A1) teaches microbial based compositions including yeast/Saccharomyces cerevisiae in a consortium with other microorganisms; cocultured in consortium in culture medium and wherein microorganisms of interest are in an amount of at least about 1 x 105 CFU/g depending on the experimental need (see Abstract; ¶ [0003-0006], [0010], CFU/g [0020-0023]; and entire document).
Regarding elected species of claim 9, Begmatov et al., (Microorganisms, 2021, Vol. 9,2362, pages 1-21) also provide teaching, suggestion and motivation to a skilled artisan for the selection of Nitrospiraceae phylum (Nitrospinota) and modify the primary reference as the engineered microorganism, as said Nitrospiraceae phylum (Nitrospinota) possess the cellular machinery/metabolic pathway for methane, sulfur and nitrogen cycling (see Abstract; last ¶, page 9; third ¶, page 12; ¶ 4.3, page 13; Conclusions; Fig. 5, page 16; and entire document).
As such, disclosure of strategy and methods for “a recombinant organism, such as a yeast/Saccharomyces cerevisiae, expressing a heterologous S-adenosylmethionine (SAM)-dependent pathway enzyme and a carbon source in a cultivation medium under conditions to increase flux through a S-adenosyl-methionine (SAM) biosynthetic pathway and suggest said genetically engineered yeast/Saccharomyces cerevisiae for the production of ethylene”; and “compositions including yeast/Saccharomyces cerevisiae in a consortium with other microorganisms”; as in claims 9-11, 35, 38 and 41, such as that of references of Voight et al., Wood et al., and Begmatov et al., teaching the advantages of said modifications, clearly suggests to a skilled artisan to modify the teachings of North et al., and incorporate the structural and functional elements of Voight et al., Wood et al., and Begmatov et al., in the claimed engineered host cell and method of use for the production of ethylene from ethanol as claimed in the instant invention. One of ordinary skill in the art would have a reasonable expectation of success, since engineered host cell, method of use for the production of ethylene are well known in the art.
Therefore, claims 1-3, 5-12 and 33-41 are rejected under 35 U.S.C. 103(a) as being unpatentable over North et al., (US 2024/0060037 A1; priority 03/25/2021) as applied to claims 1-3, 5-9, 12, 33-34, 36-37 and 39-40 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Voight et al., (US 9,040,266 B2), Wood et al., (US 2020/0337314 A1) and Begmatov et al., (Microorganisms, 2021, Vol. 9,2362, pages 1-21).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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