Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
In response to Non-Final Office Action mailed on 03/04/2026, applicants' response, arguments and amendments filed on dated 07/02/2026 is acknowledged; in said response applicants’ have amended claims 1, 4, 7-8 and 12-16, canceled claims 3 and 11 and added new claims 17-18. Thus, amended claims 1-2, 4-10 and 12-18 are pending and are now under consideration. For the record, examiner made an attempt to reach the attorney on 07/14/2026, left a message regarding Office-position and no response has been received to date. Rejections and/or objections not reiterated from previous office action are hereby withdrawn.
Information disclosure statement
The information disclosure statement (IDS) submitted on 07/02/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Withdrawn-Claim Rejections: 35 USC § 112(b)
Previous rejections: I. Claims 13-14 rejected under 35 U.S.C. 112(b); and II. Claims 15-16 rejected under 35 U.S.C. 112(b), is being withdrawn due to claim amendments.
Withdrawn-Claim Rejections: 35 USC § 102 (AIA )
Previous rejections: I. Claims 3-4 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 II. Claims 15-16 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04/29/2015); and de Vries et al., (UniProtKB/TrEMBL database; Accession # A0A1L9U3A0, priority 03/15/2017), is being withdrawn due to claim amendments.
Withdrawn-Claim Rejections: 35 USC § 103
Previous rejection of claims 1-16 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), is being withdrawn due to claim amendments.
Maintained-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 1-2, 4-10 and 12-18 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 1-2, 4-10 and 12-18 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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14).
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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14).
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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14).
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.
Applicants’ have traversed the above written-description with the following arguments: (see pages 9-10 of Applicants’ REMARKS dated 07/02/2026).
Applicants’ argue: “…For example, the specification teaches that homologous proteins can comprise conservative amino acid substitutions, noting that "[i]n general, a conservative amino acid substitution will not substantially change the functional properties of a protein" See, p. 17, lines 5-10. The specification further provides the specific amino acids that serve as conservative substitutions for one another. See, p.17, lines 14-17. Accordingly, the specification provides ample description of variant amino acid sequences, such as those having at least 95% sequence identity to SEQ ID NOs. 3, 6, 9, or 12, that maintain the specified function of converting manooloxy to GAA…”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Examiner continues to maintain the rejection for reasons stated on record (dated 03/04/2026) and additionally for the following reasons.
On one hand to overcome the 35 USC 112(a) rejections, applicant’ present the following argument:
“…For example, the specification teaches that homologous proteins can comprise conservative amino acid substitutions, noting that "[i]n general, a conservative amino acid substitution will not substantially change the functional properties of a protein" See, p. 17, lines 5-10. The specification further provides the specific amino acids that serve as conservative substitutions for one another. See, p.17, lines 14-17. Accordingly, the specification provides ample description of variant amino acid sequences, such as those having at least 95% sequence identity to SEQ ID NOs. 3, 6, 9, or 12, that maintain the specified function of converting manooloxy to GAA…”;
and on the other hand to overcome 35 USC 103 rejection, applicants present the following argument:
“…These significant improvements demonstrate that selecting the amino acid sequences of SEQ ID NOS: 3, 6,9, or 12 was not merely an arbitrary choice among known monooxygenases, but rather a selection that yielded unexpectedly superior improvement in GAA production.”
Hence the arguments presented by the applicants’ are self-contradictory and supports examiner position in maintaining the 35 USC 112(a) rejections.
Examiner continues to maintain the following: The specification is limited to 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).
Therefore, the claims encompass a large genus of proteins which are substantially unrelated or completely unrelated and includes random mutants of SEQ ID NOs: 3, 6, 9 or 12 (see supporting evidence and arguments presented above in maintaining the written-description rejection) and not a single variant or mutant of SEQ ID NOs: 3, 6, 9 or 12 is disclosed in the specification. Hence, the scope of the instant claims are broad despite the guidance of the art and specification, the claims remain not commensurate with evidence of possession or in scope with the enabled invention. An important consideration is that structure is not necessarily a reliable indicator of function. Given this scenario, a skilled artisan needs to be provided with the specific structure associated with the function. The specification does not provide support for the full scope and breadth of the claims, thus examiner continues to hold the position the experimentation left to those skilled in the art is unnecessarily, and improperly extensive and undue. 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 changes and their 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, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims in the claimed method.
MPEP 2163.II.A.2. (a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”;
Examiner would like to reiterate
“The basic quid pro quo contemplated by the Constitution and the Congress for granting a patent monopoly is the benefit derived by the public from an invention with substantial utility”, [u]nless and until a process is refined and developed to this point-where specific benefit exists in currently available form-there is insufficient justification for permitting an applicant to engross what may prove to be a broad field”, and “a patent is not a hunting license”,[i]t is not a reward for the search, but compensation for its successful conclusion.”
Maintained-Enablement
II. Claims 1-2, 4-10 and 12-18 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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14). 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 1-2, 4-10 and 12-18 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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14). 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 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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14) 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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14), because the specification does not establish: (A) encodes an enzyme comprising an amino acid sequence that is at least 95% 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 95% 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 7); 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 8) (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 1-2, 4-5, 7-11 and 13-18); 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 95% identical to the amino acid sequence of SEQ ID NOs: 3, 6, 9, or 12 including variants, mutants and recombinants, wherein the enzyme is capable of converting manooloxy to GAA, and wherein the genetically modified host cell is a yeast cell or a yeast strain; 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 7); 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 8); and a method of producing gamma-ambryl acetate (GAA) (as in claim 14), 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).
Applicants’ have traversed the above enablement rejection with the following arguments: (see pages 10-11 of Applicants’ REMARKS dated 07/02/2026).
Applicants’ argue: “…As acknowledged by the Office, the specification discloses the characterization of the isolated BVMOs (SEQ ID NOs: 3, 6, 9, or 12) and their method of use in Saccharomyces cerevisiae for the conversion of manooloxy to GAA (Examples 1-6, pages 29-33 of the specification). The specification describes how to achieve enzyme variants having at least 95% sequence identity through conservative amino acid substitutions, which will not substantially change the functional properties of a protein" See, p.17, lines 5-10. The specification provides detailed instructions for one of skill in the art to identify the enzyme variants and to make and use the claimed genetically modified host cells. It provides detailed protocols for constructing a yeast test strain to assess the ability of enzymes to convert manooloxy into GAA. See, Example 2. Furthermore, it teaches the precise analytical methods, specifically gas chromatography, including the specific detection settings, necessary to measure the substrate (manooloxy) and the product (GAA). See, Example 5. The specification also provides ample description of how to prepare the genetically modified host cells. See, pp.22-23.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Applicants’ arguments filed on 07/02/2026 for the traversal of enablement rejection is on similar lines to the arguments presented for traversing the written-description, said arguments have been fully considered but they are not persuasive. Examiner continues to maintain the rejection for reasons stated on record, supporting evidence and arguments presented above in maintaining the written-description rejection also applies to enablement rejection.
For the above cited reasons, examiner is maintaining the written-description and enablement rejection for claims 1-2, 4-10 and 12-18.
Maintained-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 95% identical to the amino acid sequence of SEQ ID NOs:. 3, 9, or 12, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NOs 3, 9, or 12; and wherein the non-naturally occurring enzyme comprises the amino acid sequence that is at least 99% identical of SEQ ID NO. 6, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NO 6.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. While claim 15-16 recites polypeptides comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NOs:. 3, 9, or 12, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NOs 3, 9, or 12; and 99% identical to SEQ ID NO: 6 and having an activity to capable of converting manooloxy to GAA, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NO 6 and as the claims do not specify any particular position at which the substitution must occur, thus the proteins of claims 15-16 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.
Applicants’ have traversed the above 35 USC § 101 rejection with the following arguments: (see pages 11-13 of Applicants’ REMARKS dated 07/02/2026).
Applicants’ argue: “…Amended claim 15 is directed to a non-naturally occurring enzyme capable of converting manooloxy to GAA comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NOs. 3, 9, or 12, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NOs 3, 9, or 12…
Amended claim 16 is directed to a non-naturally occurring enzyme capable of converting manooloxy to GAA, comprising an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 6, wherein the non-naturally occurring enzyme comprises an amino acid sequence having one or more amino acid substitutions, deletions, or insertions compared to SEQ ID NO: 6.”
Reply: Applicants' arguments have been considered but are found to be non-persuasive for the following reasons. Applicants’ arguments filed on 07/02/2026 for the traversal of 35 USC § 101 rejection is based on “high generality” and as the claims and specification do not specify any particular position at which the substitution must occur in SEQ ID NOs: 3, 6, 9 or 12, thus the proteins of claims 15-16 are directed to natural products.
New-Claim Rejections: 35 USC § 103
Necessitated by claim amendments
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-10, 12-15 and 17-18 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) 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).
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).
Certain relevant sections from Schalk et al., (US 12,486,499 B2) reproduced below:
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in vivo conversion of manooloxy to gamma-ambryl acetate (GAA) using BVMOs
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Regarding new claims 17-18; overlay and recovering GAA from the genetically modified host cell, the overlay, or the medium (col. 112, lines 25-45)
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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 95% identical to the amino acid sequence of SEQ ID NOS. 3, 6, 9, or 12 (as in claims 1-2 and 15).
Regarding claims 1-2 and 15, 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 1-2, 4-10, 12-15 and 17-18 prima facie obvious to one of ordinary skill in the art.
Hence, claims 1-2, 4-10, 12-15 and 17-18 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) 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).
Applicants’ have traversed the above 35 U.S.C. 103(a) rejection following claim amendments and said arguments are relevant to the new rejection (see pages 14-16 of Applicants’ REMARKS dated 07/02/2026).
Applicants’ argue: “…Kjaerbolling, Cuomo, de Vries are mere genomic database entries. They provide no functional characterization regarding GAA production, nor do they teach or suggest that SEQ ID NOs. 3, 9 and 12 would lead to improved GAA production. It is only the present application that demonstrates that the claimed enzymes provide unexpectedly superior GAA production compared to a control BVMOs known in the art. As detailed in Example 6 and Table 1 of the specification, yeast strains expressing the enzymes of SEQ ID NOS: 3, 6, 9, or 12 exhibit dramatic improvements in both GAA titers and the molar conversion of manooloxy to GAA. Specifically, compared to a control strain expressing the known AspWeBVMO enzyme (SEQ ID NO: 15), the claimed enzymes achieved an improvement in relative GAA produced (titers) ranging from 90% to 138% over the control, as well as an improvement in the proportion of manooloxy converted to GAA by roughly 70% (from a 0.54 conversion rate in the control to 0.90-0.92 using the claimed enzymes). These significant improvements demonstrate that selecting the amino acid sequences of SEQ ID NOS: 3, 6,9, or 12 was not merely an arbitrary choice among known monooxygenases, but rather a selection that yielded unexpectedly superior improvement in GAA production. For these reasons, the amended claims are not obvious over the cited references. Applicant respectfully requests withdrawal of the rejection.
Reply: Examiner continues to maintain the rejection for reasons stated on record (dated 03/04/2026) and additionally for the following reasons. Applicants’ arguments are directed to limitations not recited in the claims and furthermore the specification 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), does not reasonably provide enablement for a genus of structures for polypeptides and the encoding polynucleotides of interest with associated function.
On one hand to overcome the 35 USC 112(a) rejections, applicant’ present the following argument:
“…For example, the specification teaches that homologous proteins can comprise conservative amino acid substitutions, noting that "[i]n general, a conservative amino acid substitution will not substantially change the functional properties of a protein" See, p. 17, lines 5-10. The specification further provides the specific amino acids that serve as conservative substitutions for one another. See, p.17, lines 14-17. Accordingly, the specification provides ample description of variant amino acid sequences, such as those having at least 95% sequence identity to SEQ ID NOs. 3, 6, 9, or 12, that maintain the specified function of converting manooloxy to GAA…”;
and on the other hand to overcome 35 USC 103 rejection, applicants present the following argument:
“…These significant improvements demonstrate that selecting the amino acid sequences of SEQ ID NOS: 3, 6,9, or 12 was not merely an arbitrary choice among known monooxygenases, but rather a selection that yielded unexpectedly superior improvement in GAA production.”
Hence the arguments presented by the applicants’ are self-contradictory and supports examiner position in maintaining the 35 USC 103(a) rejection.
Some of the Applicants' arguments are based on superior/unexpected results by the Applicants’ method (see response pages 15-16, dated 07/02/2026). This argument is not found particularly persuasive because the evidence necessary to overcome a prima facie case of obviousness must not only be clear and convincing, but must also be commensurate in scope with the claimed subject matter. Examiner would like to point out that specification 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). Further, it is well recognized that “unexpected” effects are highly unpredictable and are very dependent on the specific conditions including particular structures and examiner has also provided ample evidence regarding structural and functional heterogeneity in the claimed enzymes (for details see 35 U.S.C. 112(a) rejection for written-description and enablement above). Thus, any combination for which synergism or “unexpected” effect is not clearly established would be properly rejected because non-obviousness would not have been established. The scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results, for example. In re Dill, 202 USPQ 805 (CCPA, 1979), In re Lindner 173 USPQ 356 (CCPA 1972), In re Hyson, 172 USPQ 399 (CCPA 1972), In re Boesch, 205 USPQ 215, (CCPA 1980), In re Grasselli, 218 USPQ 769 (Fed. Cir. 1983), In re Clemens, 206 USPQ 289 (CCPA 1980). It should be clear that the probative value of the data is not commensurate in scope with the degree of protection sought by the claim.
Therefore, examiner continues to take the position that each and every element of the instant invention is taught in the combination of cited references and that the combined teachings in the cited prior art provides a reasonable expectation of success and predictability for the claimed method herein and the claimed benefits are very much expected and predictable.
The Supreme Court has acknowledged: When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation...103 likely bars its patentability...if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person's skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions ...... the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
Examiner continues to hold the position that the cited references render claims 1-2, 4-10, 12-15 and 17-18 prima facie obvious to one of ordinary skill in the art when one applies the Teaching, Suggestion and Motivation (TSM) test under the rationale for arriving at a conclusion of obviousness as suggested by the KSR ruling. The rationale applied for this rejection is as follows:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try”–choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
The combined teachings in the cited prior art provides a reasonable expectation of success and predictability for the claimed invention. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Summary of Pending Issues
The following is a summary of issues pending in the instant application.
Claims 1-2, 4-10 and 12-18 are rejected under 35 U.S.C. 112(a) for written-description and enablement.
Claims 15-16 are rejected under 35 U.S.C. 101.
Claims 1-2, 4-10, 12-15 and 17-18 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) 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).
Conclusion
None of the claims are allowable. Claims 1-2, 4-10 and 12-18 are rejected for the reasons identified in the Rejections and Summary sections of this Office Action. Applicants’ must respond to the rejections in each of the sections in this Office Action to be fully responsive for prosecution.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Regarding filing an After Final amendment, Applicants are directed to MPEP 714.13, which states:
II. ENTRY NOT A MATTER OF RIGHT
It should be kept in mind that applicant cannot, as a matter of right, amend any finally rejected claims, add new claims after a final rejection (see 37 CFR 1.116) or reinstate previously canceled claims. Except where an amendment merely cancels claims, adopts examiner suggestions, removes issues for appeal, or in some other way requires ONLY A CURSORY REVIEW by the examiner (e.g., typographical errors), compliance with the requirement of a showing under 37 CFR 1.116(b)(3) is expected in all amendments after final rejection. An affidavit or other evidence filed after a final rejection, but before or on the same date of filing an appeal, may be entered upon a showing of good and sufficient reasons why the affidavit or other evidence is necessary and was not earlier presented in compliance with 37 CFR 1.116(e). See 37 CFR 41.33 and MPEP § 1206 for information on affidavit or other evidence filed after appeal. (Examiner's emphasis) If more than a cursory review is required, Applicants are referred to CFR §1.114.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHIRAMA RAGHU whose telephone number is (571)272-4533. The examiner can normally be reached on M-F 8:30am-5pm EST.
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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.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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