CTNF 18/294,327 CTNF 101689 DETAILED ACTION Status of Application Claims 16-33 are pending. 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. The cancellation of claims 1-15 and addition of claims 16-33 as submitted in a communication filed on 02/01/2024 is acknowledged. Applicant’s election without traverse of Group 2, claims 20-25 and 29, drawn to an aroma compound and compositions thereof comprising alpha-ionylideneethane, directed to subject matter as it relates to SEQ ID NO: 1, as submitted in communication filed on 05/13/2026 is acknowledged . 08-06 AIA Claim s 16-19, 26-28, and 30-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/13/2026 . Claims 20-25 and 29 are at issue and will be examined to the extent they encompass the elected invention . Priority Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to EP 21189182.5 filed on 08/02/2021. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file. This is the US national application which entered the national stage from Application No. PCT/EP2022/071567 filed on 08/01/2022. Information Disclosure Statement The information disclosure statements (IDS) submitted on 05/06/2024 and 09/10/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Drawings The drawings submitted on 02/01/2024 have been reviewed and are accepted by the examiner for examination purposes. Claim Objections Claims 20 and 29 are objected to because they are dependent from a non-elected claim (i.e., claim 19). Appropriate correction is required. Claim 20 is objected to because of the missing “alpha”. It should be amended to recite “alpha-ionylideneethane synthase”. Appropriate correction is required. Claim 21 is objected to due to the recitation of “A method for preparing one or more aroma compounds, comprising a) providing farnesyl diphosphate …b) converting farnesyl diphosphate… c) optionally, converting alpha-ionylideneethane … d) isolating alpha-ionylideneethane … e) optionally, purifying alpha-ionylideneethane.” It should be amended to recite “A method for preparing one or more aroma compounds, comprising a) providing a farnesyl diphosphate …b) converting the farnesyl diphosphate… c) optionally, converting the alpha-ionylideneethane … d) isolating the alpha-ionylideneethane … e) optionally, purifying the alpha-ionylideneethane.”. Appropriate correction is required. Claim 22 is objected to due to the recitation of “The method of claim 21, wherein the method includes the further steps of: f) exposing alpha-ionylideneethane to conditions suitable for oxidative cleavage of alpha-ionylideneethane … g) converting alpha-ionylideneethane to alpha-ionone”. It should be amended to recite “The method of claim 21, wherein the method includes further steps of: f) exposing the alpha-ionylideneethane to conditions suitable for oxidative cleavage of the alpha-ionylideneethane …g) converting the alpha-ionylideneethane to alpha-ionone.”. Appropriate correction is required. Claim 24 is objected to due to the recitation of “A method for… a) providing farnesyl diphosphate … b) converting farnesyl diphosphate … c) optionally, converting alpha-ionylideneethane … d) isolating alpha-ionylideneethane …e) optionally, purifying alpha-ionylideneethane … f) contacting the product with alpha-ionylideneethane”. It should be amended to recite “A method for… a) providing the farnesyl diphosphate … b) converting the farnesyl diphosphate … c) optionally, converting the alpha-ionylideneethane … d) isolating the alpha-ionylideneethane …e) optionally, purifying the alpha-ionylideneethane … f) contacting the product with the alpha-ionylideneethane”. Appropriate correction is required. Claim 24 is objected to due to the recitation of “aroma compound” in step f. It should be amended to recite “aroma compound s ”. Appropriate correction is required. Claim 25 is objected to due to the recitation of “The method of claim 24…i) exposing alpha-ionylideneethane … ii) converting alpha-ionylideneethane to”. It should be amended to recite “The method of claim 24… i) exposing the alpha-ionylideneethane … ii) converting the alpha-ionylideneethane to”. Appropriate correction is required. Claim 29 is objected to due to the recitation of “a) contacting farnesyl diphosphate”. It should be amended to recite “a) contacting a farnesyl diphosphate”. Appropriate correction is required. Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA) 07-30-02 AIA 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. 07-34-01 Claims 20-25 and 29 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 20 provides for the making of producing one or more aroma compounds comprising utilizing an ionylideneethane synthase but since the claim does not set forth any steps involved in the method/process, it is unclear what method/process the applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Correction is required. Claims 20 and 29 are indefinite in the recitation in claim 19, from which they depend, of “…amino acid sequence selected from the group consisting of i) an amino acid sequence …ii) an amino acid sequence….; and iii) an enzymatically active fragment of the amino acid sequence of a) or b) ….d) any combination of a) to c) above” for the following reasons. The preamble prior to defining parts i)-iii) states that these parts are amino acid sequences. However, there are no amino acid sequences in a) or b). In addition, it is unclear as to how a single enzyme can be a combination of the enzymes listed in parts a) to c). For examination purposes, no patentable weight has been given to the term “d) any combination of a) to c) above”. Part iii) will be interpreted as “the amino acid sequence of a fragment of the amino acid sequence of i) or ii)”. Correction is required. Claims 21, 22, 24, 25, and 29 (claim 23 dependent thereon) are indefinite due to the term “conditions suitable”, for the following reason: suitable conditions are not described in the claims or specification. Therefore, it is unclear what conditions are required for the alpha-ionylideneethane synthase to produce alpha- ionylideneethane or for the oxidative cleavage of alpha-ionylideneethane to produce alpha-ionone in this case. For examination purposes, no patentable weight will be given to the term “conditions suitable”. Correction is required. Claims 21 and 24 (claims 22, 23, and 25 dependent thereon) are indefinite in the recitation of “converting alpha-ionylideneethane to one or more further aroma compounds”, for the following reason: “further” lacks clarity because it is unclear what is meant by further in this case. For examination purposes, “converting alpha-ionylideneethane to one or more further aroma compounds” with be interpreted as “converting alpha-ionylideneethane to other aroma compounds”. Correction is required. Claim 23 is indefinite in the recitation of “…amino acid sequence selected from the group consisting of i) an amino acid sequence …ii) an amino acid sequence….; and iii) an enzymatically active fragment of the amino acid sequence of a) or b) ….d) any combination of a) to c) above” for the following reasons. The preamble prior to defining parts i)-iii) states that these parts are amino acid sequences. However, there are no amino acid sequences in a) or b). In addition, it is unclear as to how a single enzyme can be a combination of the enzymes listed in parts a) to c). For examination purposes, no patentable weight has been given to the term “d) any combination of a) to c) above”. Part iii) will be interpreted as “the amino acid sequence of a fragment of the amino acid sequence of i) or ii)”. Correction is required. Claim 29 is indefinite in the recitation of “to produce at least one alpha- ionylideneethane, thereby producing the at least one alpha-ionylideneethane”, for the following reason: the redundancy of statement makes it unclear if there are multiple production steps or one step that produces alpha-ionylideneethane. For examination purposes, “to produce at least one alpha-ionylideneethane, thereby producing the at least one alpha-ionylideneethane” will be interrupted as “to produce at least one alpha- ionylideneethane”. Correction is required. Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA) 07-30-01 AIA The following is a quotation of the first paragraph 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. 07-31-01 AIA Claim s 20-25 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claims 20, 24, 29 depend from claim 19, they require in part a genus of alpha-ionylideneethane synthases having any structure, a genus of fungal or bacterial alpha-ionylideneethane synthase having any structure, a genus of variants of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, a genus of proteins that comprise the enzymatically active fragment of any alpha-ionylideneethane synthases having any structure, thus having any structure, a genus of proteins that comprise an enzymatically active fragment of the polypeptide of SEQ ID NO: 1, and a genus of proteins that comprise an enzymatically active fragment of a variant of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity. Claims 21-22, 25 require a genus of alpha-ionylideneethane synthases having any structure. Claim 23 requires in part a genus of alpha-ionylideneethane synthases having any structure, a genus of fungal or bacterial alpha-ionylideneethane synthase having any structure, a genus of variants of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, a genus of proteins that comprise the enzymatically active fragment of any alpha-ionylideneethane synthases having any structure, thus having any structure, a genus of proteins that comprise an enzymatically active fragment of the polypeptide of SEQ ID NO: 1, and a genus of proteins that comprise an enzymatically active fragment of a variant of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity. See claim rejections under 35 usc 112(b) for claim 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. The claims encompass a large genus of proteins which are structurally unrelated or substantially unrelated. A polypeptide having at least 40 % sequence identity with the polypeptide of SEQ ID NO: 1 allows for any combination of 264 amino acid modifications within SEQ ID NO: 1 (264 = 0.6x440; SEQ ID NO: 1 has 440 amino acids). The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula N!x19 A /(N-A)!/A!, where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. Thus, the total number of variants having at least 40% sequence identity with the polypeptide of SEQ ID NO: 1 that result from amino acid substitutions is 440!x19 264 /(440-264)!/264! or 6.09x10 464 variants. A sufficient written description of a genus of polypeptides may be achieved by a recitation of a representative number of polypeptides defined by their amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is either no recited structural feature which is representative of all the members of the genus of alpha-ionylideneethane synthases recited in the claims, or the recited structural feature, i.e., 40% sequence identity to SEQ ID NO: 1, is not representative of all the members of the genus of alpha-ionylideneethane synthases recited, since there is no information as to which are the structural elements within the polypeptide of SEQ ID NO: 1 that are essential for the recited activity, which are the remaining structural elements required in the recited polypeptides in addition to those recited in the claims such that the desired alpha-ionylideneethane synthase activity is displayed, or a correlation between structure and function which would provide those unknown structural features. Furthermore, while one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation (Abstract), therefore having different function. Since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all the alpha-ionylideneethane synthases required by the claimed methods. Therefore, one of ordinary skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention . 07-31-03 AIA Claim s 20-25 and 29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for using alpha-ionylideneethane synthase with SEQ ID NOs: 1-17 and SEQ ID NOs: 19-33 in preparing aroma compounds, the specification does not reasonably provide enablement for a method for preparing aroma compounds comprising utilizing (a) alpha-ionylideneethane synthases having any structure, (b) fungal or bacterial alpha-ionylideneethane synthase having any structure, (c) variants of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, (d) proteins that comprise the enzymatically active fragment of any alpha-ionylideneethane synthases having any structure, (e) proteins that comprise an enzymatically active fragment of the polypeptide of SEQ ID NO: 1, and (f) proteins that comprise an enzymatically active fragment of a variant of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity . 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 these claims. Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of 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. The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below. The breadth of the claims . Claims 20-25 and 29 broadly encompass a method for preparing aroma compounds comprising a genus of alpha-ionylideneethane synthases having any structure, a genus of fungal or bacterial alpha-ionylideneethane synthase having any structure, a genus of variants of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, a genus of proteins that comprise the enzymatically active fragment of any alpha-ionylideneethane synthases having any structure, thus having any structure, a genus of proteins that comprise an enzymatically active fragment of the polypeptide of SEQ ID NO: 1, and a genus of proteins that comprise an enzymatically active fragment of a variant of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the structural features that are representative of all the members of the genus of alpha-ionylideneethane synthases, the genus of fungal or bacterial alpha-ionylideneethane synthase having any structure, the genus of variants of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, the genus of proteins that comprise the enzymatically active fragment of any alpha-ionylideneethane synthases having any structure, thus having any structure, the genus of proteins that comprise an enzymatically active fragment of the polypeptide of SEQ ID NO: 1, and the genus of proteins that comprise an enzymatically active fragment of a variant of the protein of SEQ ID NO: 1 having at least 40% sequence identity to the polypeptide of SEQ ID NO: 1 having alpha-ionylideneethane synthase activity, recited in the claims. In the instant case, the specification enables using alpha-ionylideneethane synthase with SEQ ID NOs: 1-17 and SEQ ID NOs: 19-33 in preparing aroma compounds. The amount of direction or guidance presented and the existence of working examples . The specification discloses using alpha-ionylideneethane synthase with SEQ ID NOs: 1-17 and SEQ ID NOs: 19-33 in preparing aroma compounds. However, the specification fails to provide any clue as to the structural elements required in any alpha-ionylideneethane synthase or SEQ ID NO: 1 polypeptide variants to prepare aroma compounds. No correlation between structure and function has been presented. The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art . The structure of an agent determines its structural and functional properties. While the art discloses a limited number alpha-ionylideneethane synthases or SEQ ID NO: 1 polypeptide variants, neither the specification nor the art provides a correlation between structure and function such that one of skill in the art can envision the structure of any alpha-ionylideneethane synthases or any SEQ ID NO: 1 polypeptide variants that can prepare aroma compounds. The art clearly teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function (Abstract). The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of determining the function and activity of polypeptide variants were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of alpha-ionylideneethane synthases and polypeptide variants to find an alpha-ionylideneethane synthase or polypeptide variant with the desired activity to prepare aroma compounds. In the absence of (i) a rational and predictable scheme for selecting the alpha-ionylideneethane synthases or polypeptide variants most likely to have the desired functional features, (ii) a correlation between structure and the recited activity to prepare aroma compounds, one of skill in the art would have to test an infinite number of alpha-ionylideneethane synthases and polypeptide variants. Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, the high degree of unpredictability in the prior art regarding enzymatic activity and polypeptide variance, 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. Claim Rejections - 35 USC § 102 (AIA) 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 20, 21, 23 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Takino et al. (Cited in the IDS; here by “Takino”) . Claims 20, 21, 23 as interpreted are directed in part to a method for preparing one or more aroma compounds, comprising a) providing a farnesyl diphosphate and an alpha-ionylideneethane synthase, b) converting the farnesyl diphosphate to alpha-ionylideneethane, in vitro or in a host cell, c) optionally, converting the alpha-ionylideneethane to other aroma compounds, d) isolating the alpha-ionylideneethane and, e) optionally, purifying the alpha-ionylideneethane; wherein the alpha-ionylideneethane synthase is SEQ ID NO: 1. Takino teaches that BcABA3 (Uniprot: ABA3_BOTFB) is an alpha-ionylideneethane synthase (Page 12392, left column, first paragraph). Takino teaches that BcABA3 converts farnesyl diphosphate (FPP) to alpha-ionylideneethane (Page 12392, Scheme 1). Takino teaches the purification of BcABA3 (12393, left column, lines 1-10) (Figure 1. (single peak)). Takino teaches that BcABA3 is a sesquiterpene synthase (Page 12392, Abstract). In regards to claim 23, it is directed in part to the method on claim 21 wherein the alpha-ionylideneethane has the amino acid sequence of SEQ ID NO: 1. It is noted that SEQ ID NO: 1 has 100% sequence identity with an Alpha-ionylideneethane synthase (Uniprot: ABA3_BOTFB). See alignment below. It is noted that claim 20 does not require any steps, and claim 21 does not require the making of additional aroma compounds. Therefore, the teachings of Tankino et al. anticipate the instant claims as written/interpreted. RESULT 1 ABA3_BOTFB (NOTE: this sequence has 2 duplicates in the database searched) ID ABA3_BOTFB Reviewed; 440 AA. AC A0A384JQC9; DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot. DT 07-NOV-2018, sequence version 1. DT 28-JAN-2026, entry version 17. DE RecName: Full=Alpha-ionylideneethane synthase aba3 {ECO:0000303|PubMed:16820452}; DE EC=4.2.3.- {ECO:0000269|PubMed:30226766, ECO:0000269|PubMed:39747870}; DE EC=4.2.3.47 {ECO:0000269|PubMed:30226766, ECO:0000269|PubMed:39747870}; DE AltName: Full=Abscisic acid biosynthesis cluster protein 3 {ECO:0000303|PubMed:16820452}; DE AltName: Full=Sesquiterpene synthase aba3 {ECO:0000303|PubMed:30226766}; GN Name=aba3 {ECO:0000303|PubMed:16820452}; ORFNames=BCIN_08g03880; OS Botryotinia fuckeliana (strain B05.10) (Noble rot fungus) (Botrytis OS cinerea). OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Leotiomycetes; OC Helotiales; Sclerotiniaceae; Botrytis. OX NCBI_TaxID=332648; [6] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PATHWAY. RX PubMed=30226766; DOI=10.1021/jacs.8b08925; RA Takino J., Kozaki T., Sato Y., Liu C., Ozaki T., Minami A., Oikawa H.; RT "Unveiling biosynthesis of the phytohormone abscisic acid in fungi: RT unprecedented mechanism of core scaffold formation catalyzed by an unusual RT sesquiterpene synthase."; RL J. Am. Chem. Soc. 140:12392-12395(2018). Query Match 100.0%; Score 2328; Length 440; Best Local Similarity 100.0%; Matches 440; Conservative 0; Mismatches 0; Indels 0; Gaps 0; Qy 1 MQQVITQTLVDDRFIQISDSKKSEGLATDSTKRQSQEQPIHDKDPIKAATAAMAATPLVK 60 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 1 MQQVITQTLVDDRFIQISDSKKSEGLATDSTKRQSQEQPIHDKDPIKAATAAMAATPLVK 60 Qy 61 EHQDTWYYPPDIANDLQSINLPAELKGEIFACAWEYTRCVIPNYTNWNRYVAFMRIIIMG 120 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 61 EHQDTWYYPPDIANDLQSINLPAELKGEIFACAWEYTRCVIPNYTNWNRYVAFMRIIIMG 120 Qy 121 IIAEFRGEMVDVTASNNLLGYDLDATLAALFEGTPGHKEMAREYKTFLLITADKASERRD 180 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 121 IIAEFRGEMVDVTASNNLLGYDLDATLAALFEGTPGHKEMAREYKTFLLITADKASERRD 180 Qy 181 GELFRRYVNALAQSPRHWFRMRDCDALARFTIASALACNDLDDIWFTEDQFEILTEIGDT 240 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 181 GELFRRYVNALAQSPRHWFRMRDCDALARFTIASALACNDLDDIWFTEDQFEILTEIGDT 240 Qy 241 LYDAVAFYKHRAEGETNSTFAYMPEDLRIKAYSECREILWALDAAWARNPKLANVINFVR 300 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 241 LYDAVAFYKHRAEGETNSTFAYMPEDLRIKAYSECREILWALDAAWARNPKLANVINFVR 300 Qy 301 FFGGPIHMMMRRYRFVEENLTIGKSETDKVVDQTRKNFKLWNRVDANKRSVLNTQRYKAL 360 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 301 FFGGPIHMMMRRYRFVEENLTIGKSETDKVVDQTRKNFKLWNRVDANKRSVLNTQRYKAL 360 Qy 361 IARSEELMFPGLAEFLEMGGDGICDKCKYRESYGAELSHQFGGVELCSECRLSWRKYLEC 420 |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||| Db 361 IARSEELMFPGLAEFLEMGGDGICDKCKYRESYGAELSHQFGGVELCSECRLSWRKYLEC 420 Qy 421 FVERATKVFPELKTHFEVPV 440 |||||||||||||||||||| Db 421 FVERATKVFPELKTHFEVPV 440 Claim Rejections - 35 USC § 103 (AIA) 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-06 AIA 15-10-15 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 (i.e., changing from AIA to pre-AIA) 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. 07-21-aia AIA Claim s 20-25, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Takino et al. (Cited in the IDS; hereby “Takino”), in view of Simeis ( Chemistry 3.3: 821-830 published 07/28/2021; hereby “Simeis”) as evidenced by Masyita et al. ( Food chemistry: X 13: 100217 published 01/19/22; hereby “Masyita”), McQuinn et al. Current opinion in plant biology 27: 172-179 published 08/21/2015; hereby “McQuinn”), Paparella et al ( Plants 10.4 (2021): 754; hereby “Paparella”) . The teachings of Takino have been discussed above. Takino fails to teach the conversion of alpha-ionylideneethane to alpha ionone to make an aroma compound. Simeis teaches that terpenoid compounds can be converted into aroma compounds by oxidative cleavage reactions (Page 822, Figure 1). Simeis teaches that the terpenoids valencene, α-ionone, β-ionone and theaspirane produce derivatives of huge interest in the flavor and fragrances industry (Page 821, second paragraph). Simeis teaches that α-ionone are natural organic molecules derived from carotenoid (Page 821, second paragraph). Simeis teaches that α-ionone oxidative modification produces different natural flavors (Page 821, Figure 2). Simeis teaches the purification of α-ionone by chromatography (Page 823, sixth paragrapgh). Carotenoids (tetraterpeniods) and sesquiterpenes are both terpenes, but differ in carbon backbone length, as carotenoids have 40 carbon atoms and sesquiterpenes have 15 carbon atoms as evidenced by Masyita (Page 2, last paragraph). Caroteniods produce apocarotenoid by oxidative cleavage as evidenced by McQuinn (Page 175, Figure 3). Ionones are ketones with a monocyclic terpenoid backbone made up of 13 carbon atoms as evidenced by Paparella (Page 1, Paragraph 3). Claims 20-25 and 29 are directed in part to a method for preparing one or more aroma compounds, including producing alpha-ionone, comprising a) providing a farnesyl diphosphate and an alpha-ionylideneethane synthase to produce alpha- ionylideneethane, b) converting the farnesyl diphosphate to alpha-ionylideneethane, in vitro or in a host cell, c) optionally, converting the alpha-ionylideneethane to other aroma compounds, d) isolating the alpha-ionylideneethane and/or the optionally other aroma compounds and, e) optionally, purifying the alpha-ionylideneethane and/or the optionally other aroma compounds, wherein the method includes the further steps of: f) the alpha-ionylideneethane oxidative cleavage of alpha- ionylideneethane to produce alpha-ionone, and g) converting the alpha-ionylideneethane to alpha-ionone; and h) optionally, purifying the alpha-ionone; wherein the alpha-ionylideneethane synthase is selected from the group consisting of: a) the subclass of carbon-oxygen lyases acting on phosphates (EC 4.2.3); b) a fungal or bacterial alpha-ionylideneethane synthase; and c) an amino acid sequence selected from the group consisting of: i) an amino acid with the sequence of SEQ ID NO: 1, ii) an amino acid sequence having at least 40% sequence identity at the amino acid level with SEQ ID NO: 1 having alpha- ionylideneethane synthase activity; iii) the amino acid sequence of a fragment of the amino acid sequence of i) or ii). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of Takino to produce alpha-ionylideneethane to produce the known flavor and fragrance compound, alpha-ionone. A person of ordinary skill in the art is motivated to use the method of Takino to produce alpha-ionylideneethane and subsequently apply oxidative cleavage conditions taught by Simeis to produce the known flavor and fragrance compound, alpha-ionone, because oxidative modification of terpenoid compounds yields ionone aroma compounds useful in flavor and fragrance. One of ordinary skill in the art has a reasonable expectation of success in performing oxidative cleavage on alpha-ionylideneethane to produce alpha-ionone because all that is required is applying known oxidative cleavage conditions after producing the alpa-ionylideneethae according to Takino and add oxidative cleavage after the production of alpha-ionylideneethane with BcABA3. Furthermore, a person of ordinary skill in the art has a reasonable expectation of success because it is evidenced that terpenoid compounds undergo predicable oxidative cleavage reactions to form ionone products. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention. Conclusion No claim is in condition for allowance. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SYNPHANE SHELTON whose telephone number is (571)272-6318. The examiner can normally be reached 9:00am-7pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Mondesi can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /S.L.S./Examiner, Art Unit 1652 /ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652 Application/Control Number: 18/294,327 Page 2 Art Unit: 1652 Application/Control Number: 18/294,327 Page 3 Art Unit: 1652 Application/Control Number: 18/294,327 Page 4 Art Unit: 1652 Application/Control Number: 18/294,327 Page 5 Art Unit: 1652 Application/Control Number: 18/294,327 Page 6 Art Unit: 1652 Application/Control Number: 18/294,327 Page 7 Art Unit: 1652 Application/Control Number: 18/294,327 Page 8 Art Unit: 1652 Application/Control Number: 18/294,327 Page 9 Art Unit: 1652 Application/Control Number: 18/294,327 Page 10 Art Unit: 1652 Application/Control Number: 18/294,327 Page 11 Art Unit: 1652 Application/Control Number: 18/294,327 Page 12 Art Unit: 1652 Application/Control Number: 18/294,327 Page 13 Art Unit: 1652 Application/Control Number: 18/294,327 Page 14 Art Unit: 1652 Application/Control Number: 18/294,327 Page 15 Art Unit: 1652 Application/Control Number: 18/294,327 Page 16 Art Unit: 1652 Application/Control Number: 18/294,327 Page 17 Art Unit: 1652 Application/Control Number: 18/294,327 Page 18 Art Unit: 1652 Application/Control Number: 18/294,327 Page 19 Art Unit: 1652 Application/Control Number: 18/294,327 Page 20 Art Unit: 1652 Application/Control Number: 18/294,327 Page 21 Art Unit: 1652 Application/Control Number: 18/294,327 Page 22 Art Unit: 1652 Application/Control Number: 18/294,327 Page 23 Art Unit: 1652
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