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
Amended Claims 1-16 (dated 02/09/2024) are pending and now under consideration.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a 371 of PCT/US2022/073758 filed on 07/15/2022, which claims benefit of Provisional application 63/222,590 filed on 07/16/2021.
Information disclosure statement
The information disclosure statement (IDS) submitted on 03/11/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Objections-Abstract/Specification
The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
Claim Objections
Claim 4 is objected, due to the following informality: Claim 4 recites “convelting…” is a spelling/typographical error; should read as “converting…”. Correction and clarification is required.
Claim Rejections: 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
I. Claims 13-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Regarding claims 13-14, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949).
In the present instance, claims 13-14 recites the broad recitation “…the genetically modified host cell” and the claim also recites “…optionally an overlay…” which is the narrower statement of the range/limitation (range within range). It is not clear what the applicants’ intend to encompass in the rejected claims and the metes and bounds of the claims are unclear and as being indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired; as being indefinite because it is not clear whether the recitation following “optionally” is limiting. See MPEP 2173.05(h), which makes clear that “optionally” is another alternative format which requires some analysis before concluding whether or not the language is indefinite. In this regard, the term “optionally” in the context of the claim is analogous to the term “preferably.” When interpreted in this manner, it is unclear whether this narrower limitation following the recitation “optionally” is limiting. See MPEP 2173.05(d). Examiner suggests applicants’ consider writing additional new claims as dependent claims.
II. Claims 15-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Regarding claims 15-16, the phrase “A non-naturally occurring enzyme capable of converting manooloxy to GAA comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 (as in claim 15); and wherein the non-naturally occurring enzyme comprises the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 (as in claim 16) is confusing. Contrary to applicants’ assertions, SEQ ID NOs: 3, 9, or 12 are naturally-occurring, art discloses amino acid sequences having 100% sequence identity to SEQ ID NOs: 3, 9 and 12 of the instant application and obtained from specific sources (also see 35 U.S.C. 101 rejection below); and art also discloses a natural variant of SEQ ID NO: 6 having 98.7% sequence identity to SEQ ID NO: 6 of the instant application and obtained from specific source. Correction and clarification is required.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of 35 U.S.C. 112(a):
(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.
Written Description
I. Claims 1, 3-5 and 7-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 3-5 and 7-15 as interpreted is directed to encompass: any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “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”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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.
In the instant case the scope of the instant claims encompass a genus of host cells and a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
No information, beyond the characterization of isolated Baeyer-Villiger monooxygenase (BVMO) having the amino acid sequences of SEQ ID NOs: 3, 6, 9 or 12 and method of use in specific cellular context Saccharomyces cerevisiae comprising the biochemical pathway enzymes having specific structures (SEQ ID NOs: 17, 20, 23 and 26) for the conversion of substrate manooloxy to gamma-ambryl acetate (GAA) (see Examples 1-6, pages 29-33 of specification), has been provided by the applicants’, which would indicate that they had possession of the claimed genus of structures (no structural limitation) for polypeptides of interest with associated function and their encoding polynucleotides, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation).
The art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; 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. 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.
Hence, the recited genera of polypeptides and the encoding polynucleotides are interpreted to have widely variable structures, since minor changes may result in changes affecting function and no additional information correlating structure with function has been provided.
Therefore, given the lack of description of representative species encompassed by the genus of polypeptides, encoding polynucleotides and modifications, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants’ were in possession of the claimed invention. 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, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
II. Claims 1, 3-5 and 7-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, because the specification, while being enabling for characterization of isolated Baeyer-Villiger monooxygenase (BVMO) having the amino acid sequences of SEQ ID NOs: 3, 6, 9 or 12 and method of use in specific cellular context Saccharomyces cerevisiae comprising the biochemical pathway enzymes having specific structures (SEQ ID NOs: 17, 20, 23 and 26) for the conversion of substrate manooloxy to gamma-ambryl acetate (GAA) (see Examples 1-6, pages 29-33 of specification), does not reasonably provide enablement for a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above 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 make and or use the invention commensurate in scope with the claim.
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 and 7-15 are so broad as to encompass: a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation). The scope of the claims is not commensurate with the enablement provided by the disclosure with regard to the extremely large number polypeptides and encoding polynucleotides broadly encompassed by the claims. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires knowledge 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. In view of the broad breadth of the claims, the amount of experimentation required to determine the structure of all the polypeptides or the encoding polynucleotides from any plant source including variants, mutants and recombinants, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (e.g., see Whisstock et al., Q Rev Biophys. 2003 Aug; 36(3): 307-340), practicing the claimed invention would require undue experimentation. As such, the specification fails to enable the entire scope of the claimed invention.
However, in this case the disclosure is limited to characterization of isolated Baeyer-Villiger monooxygenase (BVMO) having the amino acid sequences of SEQ ID NOs: 3, 6, 9 or 12 and method of use in specific cellular context Saccharomyces cerevisiae comprising the biochemical pathway enzymes having specific structures (SEQ ID NOs: 17, 20, 23 and 26) for the conversion of substrate manooloxy to gamma-ambryl acetate (GAA) (see Examples 1-6, pages 29-33 of specification), but provides no guidance with regard to the making and using of a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation) or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make the claimed polypeptides and encoding polynucleotides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure (e.g., see Whisstock et al., Q Rev Biophys. 2003 Aug; 36(3): 307-340), 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 polypeptides and encoding polynucleotides encompassed by the claims.
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 claim, 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 or deletions.
The specification does not support the broad scope of the claims which encompass: a genus of structures (no structural limitation) for polypeptides and the encoding polynucleotides of interest with associated function, i.e., any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation), because the specification does not establish: (A) encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claims 1); and regions of the protein/polynucleotide structure which may be modified without affecting the activity of the encoded enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9) (B) the general tolerance of the polypeptide and the polynucleotide encoding claimed enzymes to modification and extent of such tolerance; (C) a rational and predictable scheme for modifying any amino acid residue or the respective codon in the polynucleotide with an expectation of obtaining the desired biological function; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
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 claim broadly including polypeptides and encoding polynucleotides with an enormous number of modifications including variants, mutants and recombinants of undefined structure with the associated function. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of polypeptides 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).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or 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 claims. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The breadth of claims includes overly broad genus, applicants’ disclose no direction or guidance on how to design and make any polypeptide and the encoding polynucleotide of undefined structure having desired activity as noted in the breadth above. Thus, instant specification and prior art failed to describe how to make and use the claimed genus of polypeptides and encoding polynucleotides sufficiently. Although, it is possible to display and create any protein structure in computer (in silico) and manipulate in any possible way, such as inserting any amino acid(s) into preexisting three-dimensional scaffold; the creation of desired catalytic/biologic activity in a solution is highly unpredictable.
According to MPEP § 2164.02: “All questions of enablement are evaluated against the claimed subject matter. The focus of the examination inquiry is whether everything within the scope of the claim is enabled.”; “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Nevertheless, not everything necessary to practice the invention need be disclosed. In fact, what is well-known is best omitted. In re Buchner, 929 F.2d 660, 661, 18 USPQ2d 1331, 1332 (Fed. Cir. 1991). All that is necessary is that one skilled in the art be able to practice the claimed invention, given the level of knowledge and skill in the art. Further the scope of enablement must only bear a “reasonable correlation” to the scope of the claims. See, e.g., In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”; and “As concerns the breadth of a claim relevant to enablement, the only relevant concern should be whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. > AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); < In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). See also Plant Genetic Sys., N.V. v. DeKalb Genetics Corp., 315 F.3d 1335, 1339, 65 USPQ2d 1452, 1455 (Fed. Cir. 2003) (alleged “pioneer status” of invention irrelevant to enablement determination).”
Instant claims are so broad such that, instant disclosure of instant specification and a general knowledge in the art are not commensurate with the scope of instant claims for one skilled in the art to make and use claimed invention without undue experimentation. As noted above, the breadth of instant claims encompass an overly broad genus of undefined structure including variants, mutants and homologs.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, and the high degree of unpredictability of the prior art in regard to structural variability and its effect on function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. 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. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of any genetically modified host cell capable of producing gamma-ambryl acetate (GAA) (genera of host cells; as in claims 1, 3-5, 7-11 and 13); said genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants (no specific activity is recited for amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12, as in claim 1); said genetically modified host cell further comprising one or more of: a) one or more heterologous nucleic acids that each, independently, encodes an enzyme capable of converting one or more IPP, DMAPP, GPP, FPP, or GGPP into GPP, FPP, GGPP, or CPP… (no structure is provided; as in claim 8); said genetically modified host cell further comprising one or more of: a) a CPP synthase; b) an Erg20; c) a GPP synthase; d) a GGPP synthase; e) a CPP pyrophosphatase; f) an alcohol dehydrogenase; or g) an enal-cleaving enzyme including variants, mutants and recombinants (no structure is provided; as in claim 9); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14; also see claims objections and 35 U.S.C. 112(b) rejection above for claims interpretation), 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).
Claim Rejections: 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title
Claims 15-16 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 15-16 are directed to a law of nature or a natural phenomenon: non-naturally occurring enzyme capable of converting manooloxy to GAA comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs:. 3, 6, 9, or 12; and wherein the non-naturally occurring enzyme comprises the amino acid sequence of SEQ ID NOS. 3, 6, 9, or 12 (also see 35 U.S.C. 112(b) rejection above for claims interpretation).The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons stated below.
The “2014 Interim Guidance on Patent Subject Matter Eligibility” 79 FR 74618 (Dec. 16, 2014) directs that claims drawn to 1) a composition of matter, 2) a law of nature or a natural phenomenon and 3) lacking recitation of additional elements that make the claims directed to significantly more than a judicial exception are ineligible for patenting under 35 U.S.C. 101. See, 79 FR, page 74621 (flow chart). Nature-based compositions of matter are not directed to significantly more than a judicial exception when the claimed "naturally occurring products and some man-made products ... are essentially no different from a naturally occurring product ... that fall under the laws of nature or natural phenomena exception.” 79 FR, page 74623, left column. That is, a patent-eligible composition of matter must be "markedly different" in terms of the "product's structure, function, and/or other properties." 79 FR, page 74623, center column. Further, processes directly to isolating nature-based compositions of matter have also been found to be directed to nothing more than a judicial exception when only routine purification techniques are employed. 79 FR, page 74622, center column (e.g. isolating DNA or other nature-based products).
Claims 15-16 are directed to naturally-occurring protein(s) or composition thereof, whether isolated, synthetic or recombinant or not, that are not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc., 106 USPQ2d 1972 (June 13, 2013), as they are not markedly different than the naturally-occurring protein(s), or composition thereof protein of SEQ ID NOs:. 3, 6, 9, or 12 obtained from fungal source. Examiner would like to point out that fungi endogenously comprises the protein and having 100% sequence identity to SEQ ID NO: 3 (UniProtKB/TrEMBL database; Accession # A0A8E2EGY4; see provided sequence alignment); fungi endogenously comprises the protein and having 98.7% sequence identity to SEQ ID NO: 6 (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020; see provided sequence alignment); fungi endogenously comprises the protein and having 100% sequence identity to SEQ ID NO: 9 (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015; see provided sequence alignment); and fungi endogenously comprises the protein and having 100% sequence identity to SEQ ID NO: 12 (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017; see provided sequence alignment); While claim 15 recites polypeptides comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOs:. 3, 6, 9, or 12… and having an activity to capable of converting manooloxy to GAA, the occurrence of mutations/variants within naturally occurring proteins is well known in the art; the reference polypeptide isolated from reference fungal sources and endogenously comprises the protein and having 98.7% sequence identity to SEQ ID NO: 6 (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020; see provided sequence alignment), and as the claims do not specify any particular position at which the substitution must occur, thus the proteins of claim 15 are also directed to natural products (see, the recent Office Guidance For Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products, available from http://www.uspto.gov/patents/law/exam/examguide.jsp).
A “product that is purified or isolated, for example, will be eligible when there is a resultant change in characteristics sufficient to show a marked difference from the product’s naturally occurring counterpart. If the claim recites a nature-based product limitation that does not exhibit markedly different characteristics, the claim is directed to a ‘product of nature' exception.” 79 FR, page 74623, right column. A change in biological activity, chemical or physical properties, and structure and form are given as non-limiting examples of possible “markedly different characteristics.” 79 FR, page 74623, right column. Here, as stated, the claims encompass naturally-occurring rhamnose synthases having the same structure, and therefore biological activity, chemical and physical properties, as a naturally-occurring product. As such, the claims appear to be directed towards nothing more than a judicial exception for the reasons stated. The claims recite ineligible subject matter for the reasons stated.
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.
I. Claims 3-4 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Schalk et al., (US 12,486,499 B2; priority 07/10/2019) and disclose basic biosynthetic strategy for converting isomer of copalol in order to provide structurally related isomers of manooloxy to gamma-ambryl acetate (see Abstract; Figs 2, 9-10, 26, 30 & 33; 13. col. 5, lines 1-5; Examples 1-2 & 18, in vivo conversion of manooloxy to gamma-ambryl acetate (GAA) using BVMOs) and entire document); said reference discloses genetically modified S. cerevisiae comprising an enzyme capable of converting manooloxy to GAA is a Baeyer-Villiger monooxygenase (BVMO; see Figure in col. 3-4; reproduced below; col. 17, lines 3-25; col. 104, lines 50-67 to col. 112, lines 1-45); said reference discloses genetically modified S. cerevisiae comprising enzymes that convert a terpene precursor molecule to the respective terpene target molecule, like in particular a processed target terpene alcohol or terpene hydrocarbon and examples of such terpene precursor molecules are for example non-cyclic compounds, selected from farnesyl pyrophosphate (FPP), geranylgeranyl-pyrophosphate (GGPP), or a mixture of isopentenyl pyrophosphate (IPP) and dimethyl allyl pyrophosphate (DMAPP; see col. 14, lines 59-67 to col. 15,lines 1-12); said biosynthetic pathway enzymes comprising polypeptides and having 100% sequence identities to SEQ ID NOs: 18, 21, 24 and 27 of the instant application (see provided sequence alignments) and expression of said enzymes in genetically modified S. cerevisiae and under the control of transcriptional regulatory elements (col. 90, lines 30-67 to col. 94, lines 1-30); said reference also discloses providing an overlay/isopropyl myristate (IPM) overlay and recovering GAA from the genetically modified host cell, the overlay, or the medium (col. 112, lines 25-45). Certain relevant sections from Schalk et al., (US 12,486,499 B2) reproduced below:
cols. 3-4
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122
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Therefore, the reference of Schalk et al., (US 12,486,499 B2; priority 07/10/2019) is deemed to anticipate claims 3-4 as written and when given the broadest reasonable interpretation.
II. Claims 15-16 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017).
Fungi endogenously comprises the protein and having 98.7% sequence identity to SEQ ID NO: 6 (Kjaerbolling et al., UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020; see provided sequence alignment); fungi endogenously comprises the protein and having 100% sequence identity to SEQ ID NO: 9 (Cuomo et al., UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015; see provided sequence alignment); and fungi endogenously comprises the protein and having 100% sequence identity to SEQ ID NO: 12 (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017; see provided sequence alignment).
Therefore, the references of Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017) is deemed to anticipate claims 15-16 as written and when given the broadest reasonable interpretation.
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 1-16 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schalk et al., (US 12,486,499 B2; priority 07/10/2019) as applied to claims 3-4 see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) above); and further in view Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017) as applied to claims 15-16 (also see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) above).
Regarding claims 3-14, the disclosure of Schalk et al., (US 12,486,499 B2; priority 07/10/2019) disclose basic biosynthetic strategy for converting isomer of copalol in order to provide structurally related isomers of manooloxy to gamma-ambryl acetate (see Abstract; Figs 2, 9-10, 26, 30 & 33; 13. col. 5, lines 1-5; Examples 1-2 & 18, in vivo conversion of manooloxy to gamma-ambryl acetate (GAA) using BVMOs; and entire document); said reference discloses genetically modified S. cerevisiae comprising an enzyme capable of converting manooloxy to GAA is a Baeyer-Villiger monooxygenase (BVMO; see Figure in col. 3-4; reproduced below; col. 17, lines 3-25; col. 104, lines 50-67 to col. 112, lines 1-45); said reference discloses genetically modified S. cerevisiae comprising enzymes that convert a terpene precursor molecule to the respective terpene target molecule, like in particular a processed target terpene alcohol or terpene hydrocarbon and examples of such terpene precursor molecules are for example non-cyclic compounds, selected from farnesyl pyrophosphate (FPP), geranylgeranyl-pyrophosphate (GGPP), or a mixture of isopentenyl pyrophosphate (IPP) and dimethyl allyl pyrophosphate (DMAPP; see col. 14, lines 59-67 to col. 15,lines 1-12); said biosynthetic pathway enzymes comprising polypeptides and having 100% sequence identities to SEQ ID NOs: 18, 21, 24 and 27 of the instant application (see provided sequence alignments) and expression of said enzymes in genetically modified S. cerevisiae and under the control of transcriptional regulatory elements (col. 90, lines 30-67 to col. 94, lines 1-30); said reference also discloses providing an overlay/isopropyl myristate (IPM) overlay and recovering GAA from the genetically modified host cell, the overlay, or the medium (col. 112, lines 25-45).
However, Schalk et al., is silent regarding said reference genetically modified host cell capable of producing gamma-ambryl acetate (GAA), wherein the genetically modified host cell comprises one or more heterologous nucleic acids that each, independently, encodes an enzyme comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NOS. 3, 6, 9, or 12 (as in claims 1-2 and 15-16).
Regarding claims 1-2 and 15-16, Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017) provide structural and functional elements of the instant invention and having 98.7%-100% sequence identities to SEQ ID NOs: 6, 9 and 12 of the instant invention and having monooxygenase activities (see provided sequence alignments).
Therefore, using the indications of Schalk et al., as a reference, it would have been easy for a person skilled in the art to use the encoding polynucleotides that encode for polypeptides having monooxygenase activities (BVMOs) as disclosed by Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017 for in vivo conversion of manooloxy to gamma-ambryl acetate (GAA) and as suggested by Schalk et al., and generate a transformant to produce gamma-ambryl acetate (GAA). As such, disclosures of Schalk et al., Kjaerbolling et al., Cuomo et al., and de Vries et al., provide the structural and functional elements in the claimed compositions and method of use as claimed in the instant invention. One of ordinary skill in the art would have a reasonable expectation of success, since basic biosynthetic strategy for converting isomer of copalol in order to provide structurally related isomers of manooloxy to gamma-ambryl acetate and in vivo conversion of manooloxy to gamma-ambryl acetate (GAA) using BVMOs are well known in the art. Therefore, the above reference renders claims 1-16 prima facie obvious to one of ordinary skill in the art.
Therefore, claims 1-16 are rejected under 35 U.S.C. 103(a) as being unpatentable over Schalk et al., (US 12,486,499 B2; priority 07/10/2019) as applied to claims 3-4 see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) above); and further in view Kjaerbolling et al., (UniProtKB/TrEMBL database; Accession # A0A5N7BV18, priority 04/22/2020); Cuomo et al., (UniProtKB/TrEMBL database; Accession # A0A0D2JC84, priority 04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652