Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION This application is a 371 of PCT/EP2021/055319. The response filed on February 3, 2026 has been entered. Election/Restrictions Applicant’s election of Group I with a species election of ( i ) SEQ ID NO:169 as the ene reductase, (ii) hesperetin dihydrochalcone as a species of dihydrochalcone, (iii) hesper i din as a species of flavanone, chalcone, and/or glycoside, and (iv) SEQ ID NO:146 as the chalcone isomerase in the reply filed on February 3, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 7-10 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 3, 2026 . Status of Claims Claims 1- 20 are pending. Claims 7-10 and 17-20 are withdrawn. Claims 1-6 and 11-16 are under examination. Information Disclosure Statement The information disclosure statement (IDS) submitted on March 19, 2024 and February 6, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. Claim Objections Claim 11 is objected to because claim 11 depends from a non-elected claim, clam 7. However, in order to expedite the prosecution, the subject matter of claim 7 has been incorporated into claim 11. Appropriate correction, incorporating the limitations of the non-elected claim 7 into claim 11 is requested. Claim Rejections - 35 USC § 112 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 appl icant regards as his invention. Claim 3 is 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. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recite s the broad recitation “at least 5…minutes” and “at least …30 minutes”, which is the narrower statement of the range/limitation. T he claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. 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. Claims 1- 6 and 11- 16 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. MPEP 2111.01 states that ''[d] uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' In this case, the claims have been broadly to encompass a method of producing a ny dihydrochalcones or dihydrochalcone recited in claim 6 by incubating ( i ) any ene reductase having 90-100% sequence identity to SEQ ID NO:24-46, 169-175, or 176, (ii) any flavanone, any chalcone, and/or any corresponding glycoside or the flavanone, chalcone, and their corresponding glycosides recited in claim 4, and (iii) optionally a chalcone isomerase having at least 90% sequence identity to SEQ ID NO:145-156, 157, or 158. T herefore, the claims are drawn to a method of producing a genus of dihydrochalcone or the dihydrochalcone recited claim 6 by incubating ( i ) a genus of ene reductase, (ii) genus of flavanone, chalcone, and/or any glycoside or the flavanone, chalcone, and their corresponding glycosides recited in claim 4, and (iii) optionally a genus of chalcone isomerase. MPEP 2163 I. states that to “ satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. MPEP 2163. II.A.3.(a) sates that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention. According to MPEP 2163.II.A.3.(a).ii), “S atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’" The recitation of “ biocatalytical manufacturing of dihydrochalcone”, “ ene reductase”, “flavanone ” , “cha l cone”, “cha l cone isomerase” fails to provide a sufficient description of the genus of the enzymes, substrates, and product as it merely describes the functional features of the genus without providing any definition of the structural features of the species within the genus. The specification does not specifically define any of the species that fall within the genus. The specification does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. Some ene reductases were known in the art. Chavez ( Elucidation of the Function of Dihydrochalcones in Apple. Universita di Trento. Pages 1-190. 2019. - form PTO-892) discloses ene reductases, such as an Arabidopsis thaliana reductase ( AtDBR , At5g16970), that catalyze conversion of naringenin chalcone to phloretin (Figure 1-2 at page 7 and page 8). However, neither the prior art nor the instant specification provides guidance on which polypeptides having 90-100% sequence identity to any one of SEQ ID NO:24-46 and 169-176 have the function of producing the genus of dihydrochalcone or the dihydrochalcone recited claim 6 or which polypeptides having 90-100% sequence identity to any one of SEQ ID NO:145-158 have the function of producing a chalcone from the genus of flavanone, chalcone, and/or any glycoside or the flavanone, chalcone, and their corresponding glycosides recited in claim 4. Fransceus (J Ind Microbiol Biotechnol . 2017 May;44(4-5):687-695. – form PTO-892) reviews protein engineering techniques, such as random mutagenesis and recombination, directed evolution and iterative or combinatory saturation “hotspots”. Fransceus states that “a recurring problem, however, is choosing which amino acid positions should be targeted. Answering this question is not an easy feat and requires substantial insight in the relationship between an enzyme’s sequence or structure and its properties.” Sanavia (Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 1968-1979. – form PTO-892) discloses challenge s in the prediction of protein stability in the occurrence of multiple mutations. “ Multiple-point mutations are common variations of the protein sequence that may be needed in protein engineering when a single-point mutation is not enough to yield the desired stability change. Dealing with multiple-site variations adds another level of complexity beyond the prediction of the effect of a single variant on protein stability, since it requires the learning of many types of combinatorial effects ”. The specification is limited to description of a method of producing hesperetin dihydrochalcone , naringenin dihydrochalcone, or eriodictyol dihdrochalcone by incubating ( i ) Arabidopsis thaliana ene reductase variants having the amino acid sequence of any one of SEQ ID NO:169-176 , (ii) hesperetin , naringenin, or eriodictyol , and (iii) chalcone isomerase having the amino acid sequence of any of SEQ ID NO : 145-158. While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant specie s encompassed by the genus, the examples described above are not enough and does not constitute a representative number of species to describe the whole genus . Therefore, the specification fails to describe a representative spe cies of the claimed genus. The claimed invention requires a defined set of ( i ) ene reductase, (ii) flavanone or chalcone, and (iii) chalcone isomerase to produce a dihydrochalcone. Although the specification discloses exemplary ene reductases, flananone and chalcones , and chalcone isomerases, a “laundry list” disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not “reasonably lead” those skilled in the art to any particular species, see Fujikawa v. Wattanasin , 93 F.3d 1559, 1571, 39 USPQ2d 1895, 1905 (Fed. Cir. 1996) or MPEP 2163. While the exemplary CPR/F3' H and host cells were known in the art, this knowledge alone would not allow one level of skill in the art to immediately envisage the claimed genus Further, one of skill in the art could identify polypeptides having at least 90-95 % sequence identity to SEQ ID NO:196 or 146. However, there is no teaching regarding which 5 or 10 % of the amino acids can vary from SEQ ID NO: 169 or 146 and result in polypeptide having ene reductase activity or chalcone isomerase activity, respectively. An important consideration is that structure is not necessarily a reliable indicator of function. In the instant case, there is no disclosure relating similarity of structure to conservation of function. Conservation of structure is not necessarily a surrogate for conservation of function. Since the claimed invention is that of enzyme s , and there is no disclosure of t he domains responsible for ene reductase activity or chalcone isomerase activity , the absence of information may be persuasive that those of skill in the art would not take the disclosure as generic. Given this lack of description of the representative species encompassed by the genus of the claims, 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 inventions of claims 1- 6 and 11-16 . Claim Rejections - 35 USC § 102 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention. Claim(s) 1 -6 and 14-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gall ( Enzymatic conversion of flavonoids using bacterial chalcone isomerase and enoate reductase. Angew Chem Int Ed Engl. 2014 Jan 27;53(5):1439-42 - form PTO- 1449 ). Regarding claim 1, Gall discloses a method for the biocatalytical manufacturing of a dihydrochalcone by ( i ) providing an enoate reductase, synonymous with ene reductase , (ii) providing a flavanone, (iii) incubating the ene reductase with the flavanone, and (iv) obtaining a dihydrochalcone ( abstract, Scheme 1 at page 1439, 1 st and 3 rd full paragraph at page 1441, and Table 1). Regarding claim 2, the method of Gall uses a cell extract comprising the ene reductase and therefore the ene reductase is partially purified ( page 1441 ). Regarding claim 3, the method of Gall discloses that conversion of flavanone to dihydrochalcone at 1 hr , 2hr or 17 hr of reaction time, which reads on an incubation time of at least 30 minutes (Table 1 at page 1441). Regarding claim 4, the flavanone of Gall is naringenin (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 5, the flavanone of the method of Gall is provided as a purified flavanone (page 1441). Regarding claim 6, the method of Gall produces naringenin dihydrochalcone (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 14, the method of Gall provides a chalcone isomerase ( KF154734) between steps ( i ) and (ii) (Scheme 1 at page 1439 and page 1441). The chalcone isomerase of Gall has at least 90% sequence identity to SEQ ID NO:146 of the instant application (see the sequence alignment below). Regarding claim 15, the method of Gall comprises incubating (a) the ene reductase, (b) a chalcone isomerase, and (c) a flavanone (Scheme 1 at page 1439 and page 1441). Regarding claim 16, the method of Gall further comprises purifying the dihydrochalcone (Table 1) . Therefore, the reference of Gall anticipates claims 1-6 and 14-16. Claim(s) 1, 3-6 and 14-16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hilmer ( US 9,359,622 - form PTO- 1449 ). Regarding claim 1, Hilmer discloses a method for the biocatalytical manufacturing of a dihydrochalcone by using a transgenic microorganism comprising ( i ) providing a n enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) adding a flavanone and cultivating transgenic microorganism, and (iv) obtaining a dihydrochalcone (claim 15). Regarding claim 3, the method of Hilmer discloses that conversion of naringenin ( flavanone ) to phloretin ( dihydrochalcone ) after 0.25 to 26 hr , which reads on an incubation time of at least 15- 30 minutes (Table 5 at Column 21 ). Regarding claim 4, the flavanone of Hilmer is naringenin , hesperedin or hesperetin ( Column 4, line 24 through Column 6, line 54 and claim 19 ) . Regarding claim 5, the flavanone of the method of Hilmer is provided as a purified flavanone ( claim 18 ). Regarding claim 6, the method of Hilmer produces a pholoretin or hesperetin dihydrochalcone ( Column 5 line 45 through Column 6, line 60 and claim 19 ). Regarding claim 14, the method of Hilmer provides a plant chalcone isomerase of SEQ ID NO: 3 between steps ( i ) and (ii) ( claim 18) . The chalcone isomerase of Hilmer has at least 90% sequence identity to SEQ ID NO:146 of the instant application ( claim 27 and see the sequence alignment below). Regarding claim 15, the method of Hilmer comprises incubating (a) the ene reductase, (b) a chalcone isomerase, and (c) a flavanone ( claim 18 ). Regarding claim 16, the method of Hilmer further comprises purifying the dihydrochalcone ( claim 18 ). Therefore, the reference of Gall anticipates claims 1 , 3-6, and 14-16. Claim Rejections - 35 USC § 103 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 . This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim (s) 1-6 , 12, and 14-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gall ( Enzymatic conversion of flavonoids using bacterial chalcone isomerase and enoate reductase. Angew Chem Int Ed Engl. 2014 Jan 27;53(5):1439-42 - form PTO- 1449 ) and Naesby (“ Evolva SA” WO 2016/193504 - form PTO-1449). Regarding claim 1, Gall discloses a method for the biocatalytical manufacturing of a dihydrochalcone by ( i ) providing an enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) incubating the ene reductase with the flavanone, and (iv) obtaining an dihydrochalcone (abstract, Scheme 1 at page 1439, 1 st and 3 rd full paragraph at page 1441, and Table 1). Regarding claim 2, the method of Gall uses a cell extract comprising the ene reductase and therefore the ene reductase is partially purified (page 1441). Regarding claim 3, the method of Gall discloses that conversion of flavanone to dihydrochalcone at 1 hr , 2hr or 17 hr of reaction time, which reads on an incubation time of at least 30 minutes (Table 1 at page 1441). Regarding claim 4, the flavanone of Gall is naringenin (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 5, the flavanone of the method of Gall is provided as a purified flavanone (page 1441). Regarding claim 6, the method of Gall produces a naringenin dihydrochalcone (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 14, the method of Gall provides a chalcone isomerase (KF154734) between steps ( i ) and (ii) (Scheme 1 at page 1439 and page 1441). The chalcone isomerase of Gall has at least 90% sequence identity to SEQ ID NO:146 of the instant application (see the sequence alignment below). Regarding claim 15, the method of Gall comprises incubating (a) the ene reductase, (b) a chalcone isomerase, and (c) a flavanone (Scheme 1 at page 1439 and page 1441). Regarding claim 16, the method of Gall further comprises purifying the dihydrochalcone (Table 1). Gall does not disclose an ene reductase having at least 90 -95 % sequence identity to SEQ ID NO:41. Regarding claim s 1 and 12 , Naesby discloses a method of producing phloretin, a dihydrochalcone, by cultivating a host cell expressing a Rubus idaeus ene reductase (ZS1) having the amino acid sequence of SEQ ID NO:62 (Example 5 and page 101). Said ene reductase of SEQ ID NO:62 of Naesby has 100% sequence identity to amino acids 3-349 amino acids of the ene reductase of SEQ ID NO:41 of the instant application (see the sequence alignment below). Regarding claim 4, Naesby discloses that phloretin is produced from the flavanone naringenin (Example 5). Regarding claim 16, Naesby discloses purifying the dihydrochalcone ([0230] and [0240]). Therefore, in combining the above references , it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to modify the method of Gall by replacing the ene reductase with the Rubus idaeus ene reductase of Naesby because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable . One having ordinary skill in the art would have been motivated to do so in order to further increase production of the dihydrochalcone . One of ordinary skill in the art would have had a reasonable expectation of success since Gall discloses a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone and Naesby discloses an ene reductase that can used to produce dihydrochalcone. T he rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element ( ene reductase ) for another yields predictable results (conversion of chalcone to dihydrochalcone) to one of ordinary skill in the art . See MPEP 2143. Therefore, the above references render claims 1-6, 12, and 14-16 prima facie obvious. Claim (s) 1-6 and 11-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gall ( Enzymatic conversion of flavonoids using bacterial chalcone isomerase and enoate reductase. Angew Chem Int Ed Engl. 2014 Jan 27;53(5):1439-42 - form PTO- 1449 ) and Chavez (Elucidation of the Function of Dihydrochalcones in Apple. Universita di Trento. Pages 1-190. 2019. - form PTO-892). Regarding claim 1, Gall discloses a method for the biocatalytical manufacturing of a dihydrochalcone by ( i ) providing an enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) incubating the ene reductase with the flavanone, and (iv) obtaining an dihydrochalcone (abstract, Scheme 1 at page 1439, 1 st and 3 rd full paragraph at page 1441, and Table 1). Regarding claim 2, the method of Gall uses a cell extract comprising the ene reductase and therefore the ene reductase is partially purified (page 1441). Regarding claim 3, the method of Gall discloses that conversion of flavanone to dihydrochalcone at 1 hr , 2hr or 17 hr of reaction time, which reads on an incubation time of at least 30 minutes (Table 1 at page 1441). Regarding claim 4, the flavanone of Gall is naringenin (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 5, the flavanone of the method of Gall is provided as a purified flavanone (page 1441). Regarding claim 6, the method of Gall produces a naringenin dihydrochalcone (Scheme 1 at page 1439 and Table 1 at page 1441). Regarding claim 14, the method of Gall provides a chalcone isomerase (KF154734) between steps ( i ) and (ii) (Scheme 1 at page 1439 and page 1441). The chalcone isomerase of Gall has at least 90% sequence identity to SEQ ID NO:146 of the instant application (see the sequence alignment below). Regarding claim 15, the method of Gall comprises incubating (a) the ene reductase, (b) a chalcone isomerase, and (c) a flavanone (Scheme 1 at page 1439 and page 1441). Regarding claim 16, the method of Gall further comprises purifying the dihydrochalcone (Table 1). Gall does not disclose an ene reductase having at least 90-95% sequence identity to SEQ ID NO:169. Regarding claim s 1 and 11-12 , Chavez discloses ene reductases, such as an Arabidopsis thaliana reductase ( AtDBR , At5g16970), that catalyze conversion of naringenin chalcone to phloretin ( Figure 1-2 at page 7 and page 8 ). Said Arabidopsis thaliana reductase ( AtDBR , At5g16970) e ne reductase is identical to the Arabidopsis thaliana ene reductase of SEQ ID NO:25 of the instant application by 1 amino acid and has at least 90% sequence identity to the Arabidopsis thaliana ene reductase variant (V285Q) of SEQ ID NO:169 of the instant application (see the sequence alignment s below). Regarding claim 4, Chavez discloses that phloretin is produced from the flavanone naringenin ( Figure 1-2 at page 7 and page 8 ). Therefore, in combining the above references , it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to modify the method of Gall by replacing the ene reductase with the Arabidopsis ene reductase of Chavez because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable . One having ordinary skill in the art would have been motivated to do so in order to further increase production of the dihydrochalcone . One of ordinary skill in the art would have had a reasonable expectation of success since Gall discloses a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone and Chavez discloses an ene reductase that can used to produce phloretin, a dihydrochalcone. T he rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element ( ene reductase ) for another yields predictable results (conversion of chalcone to dihydrochalcone) to one of ordinary skill in the art . See MPEP 2143. Therefore, the above references render claims 1-6, 11- 12, and 14-16 prima facie obvious. Claim(s ) 1, 3-6, 11-12, and 14-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hilmer ( US 9,359,622 - form PTO-1449) and Chavez (Elucidation of the Function of Dihydrochalcones in Apple. Universita di Trento. Pages 1-190. 2019. - form PTO-892). Regarding claim 1, Hilmer discloses a method for the biocatalytical manufacturing of a dihy drochalcone by using a transgenic microorganism comprising ( i ) providing an enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) adding a flavanone and cultivating transgenic microorganism, and (iv) obtaining an dihydrochalcone (claim 15). Regarding claim 3, the method of Hilmer discloses that conversion of naringenin (flavanone) to phloretin (dihydrochalcone) for 0.25 to 26 hr , which reads on an incubation time of at least 15-30 minutes (Table 5 at Column 21). Regarding claim 4, the flavanone of Hilmer is naringenin, hesperedin or hesperetin (Column 4, line 24 through Column 6, line 54 and claim 19). Regarding claim 5, the flavanone of the method of Hilmer is provided as a purified flavanone (claim 18). Regarding claim 6, the method of Hilmer produces a pholoretin or hesperetin dihydrochalcone (Column 5 line 45 through Column 6, line 60 and claim 19). Regarding claim 14, the method of Hilmer provides a plant chalcone isomerase of SEQ ID NO:3 between steps ( i ) and (ii) (claim 18). The chalcone isomerase of Hilmer has at least 90% sequence identity to SEQ ID NO:146 of the instant application (claim 27 and see the sequence alignment below). Regarding claim 15, the method of Hilmer comprises incubating (a) the ene reductase, (b) a chalcone isomerase, and (c) a flavanone (claim 18). Regarding claim 16, the method of Hilmer further comprises purifying the dihydrochalcone (claim 18). Hilmer also does not disclose using an ene reductase having at lest 90-95% sequence identity to SEQ ID NO:25 or 169. Regarding claims 1 and 11-12, Chavez discloses ene reductases, such as an Arabidopsis thaliana reductase ( AtDBR , At5g16970), that catalyze conversion of naringenin chalcone to phloretin (Figure 1-2 at page 7 and page 8). Said Arabidopsis thaliana reductase ( AtDBR , At5g16970) ene reductase is identical to the Arabidopsis thaliana ene reductase of SEQ ID NO:25 of the instant application by 1 amino acid and has at least 90% sequence identity to the Arabidopsis thaliana ene reductase variant (V285Q) of SEQ ID NO:169 of the instant application (see the sequence alignments below). Regarding claim 4, Chavez discloses that phloretin is produced from the flavanone naringenin (Figure 1-2 at page 7 and page 8). Therefore, in combining the above references , it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to modify the method of Hilmer by replacing the ene reductase with the Arabidopsis ene reductase of Chavez because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable . One having ordinary skill in the art would have been motivated to do so in order to further increase production of the dihydrochalcone . One of ordinary skill in the art would have had a reasonable expectation of success since Hilmer discloses a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone and Chavez discloses an ene reductase that can used to produce phloretin, a dihydrochalcone. T he rationale to support a conclusion that the claims would have been obvious is that the substitution of one known element ( ene reductase ) for another yields predictable results (conversion of chalcone to dihydrochalcone) to one of ordinary skill in the art . See MPEP 2143. Therefore, the above references render claims 1 , 3- 6, 11-12, and 14-16 prima facie obvious. Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hilmer (US 9,359,622 - form PTO-1449) and Chavez (Elucidation of the Function of Dihydrochalcones in Apple. Universita di Trento. Pages 1-190. 2019. - form PTO-892) as applied to claim s 1, 3-6, 11-12, and 14-16 above, and further in view of Carvalho ( Enzymatic and whole cell catalysis: finding new strategies for old processes. Biotechnol Adv. 2011 Jan-Feb;29(1):75-83. – form PTO-892). Hilmer and Chavez do not disclose a method of converting a flavanone to dihydrochalcone by incubating the flavanone, a purified ene reductase, and a purified chalcone isomerase. Regarding claim 2, Hilmer discloses purification of an ene reductase and chalcone isomerase expressed from E. coli (Example 1.2 and Example 3). Carvalho discloses advantages of using enzym atic catalysis over whole cell catalysis. Carvalho discloses that enzymes are able to catalyze reactions at a rate far more rapid than it would occur without and continue to function under in vitro conditions and catalyze reactions in conditions not suitable for cell growth (3 rd full paragraph at page 75). Therefore, in combining the above references , it would have been obvious to one having ordinary skill in the art before the time the claimed invention was effectively filed to modify the method of Hilmer by incubating a flavanone with a purified ene reductase of Hilmer or Chavez and a purified chalcone isomerase of Hilmer . One having ordinary skill in the art would have been motivated to do so in order to optimize the conversion of the flavanone to dihydrochalcone since enzym atic reactions are able to catalyze reactions at a rate far more rapid than it would occur without and continue to function under in vitro conditions and catalyze reactions in conditions not suitable for cell growth . One of ordinary skill in the art would have had a reasonable expectation of success since Hilmer discloses a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone , Chavez discloses an ene reductase that can used to produce phloretin, a dihydrochalcone , and Carvalho discloses advantages of enzymatic catalysis compared to whole cell catalysis . Therefore, the above references render claims 1 -6, 11-12, and 14-16 prima facie obvious. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claim s 1, 4 -6 and 14-16 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claim s 1-39 of U.S. Patent No. 9,359,622 (reference patent) . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the reference patent recite a method of producing dihydrochalcone. Regarding claim 1 of the instant application, claim 16 of the reference patent recites a method for the biocatalytical manufacturing of a dihydrochalcone by using a transgenic microorganism comprising ( i ) providing an enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) adding a flavanone and cultivating transgenic microorganism, and (iv) obtaining an dihydrochalcone . Therefore, claim 1 of the instant application anticipated by claim 16 of the reference patent. Regarding claim 4 of the instant application , claim 19 of the reference patent recites that the flavanone is naringenin. Therefore, claim 4 of the instant application anticipated by claim 19 of the reference patent. Regarding claim 5 of the instant application , claim 18 of the reference patent recites the flavanone is added, and therefore reads on a purified flavanone (claim 18). Therefore, claim 5 of the instant application anticipated by claim 18 of the reference patent. Regarding claim 6 of the instant application , claim 19 of the reference patent recites that the dihydrochalcone produced is a phloretin . Therefore, claim 6 of the instant application anticipated by claim 19 of the reference patent. Regarding claim 14 of the instant application , claim 27 of the reference patent recites that the plant chalcone isomerase of SEQ ID NO:3 is added between steps ( i ) and (ii) (claim 18). The chalcone isomerase of the reference patent has at least 90% sequence identity to SEQ ID NO:146 of the instant application ( see the sequence alignment below). Therefore, claim 14 of the instant application anticipated by claim 27 of the reference patent. Regarding claim 15 of the instant application , claim 18 of the reference patent recites incubating (a) an ene reductase, (b) a chalcone isomerase, and (c) a flavanone . Therefore, claim 15 of the instant application anticipated by claim 18 of the reference patent. Regarding claim 16 of the instant application , claim 18 of the reference patent recites purifying the dihydrochalcone (claim 18). Therefore, claim 16 of the instant application anticipated by claim 18 of the reference patent. Therefore, the conflicting claims are not patentably distinct from each other. Claims 1 -3 and 11-12 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-39 of U.S. Patent No. 9,359,622 (reference patent) in view of Hilmer ( US 2014/0045233 – form PTO-892 ), Carvalho ( Enzymatic and whole cell catalysis: finding new strategies for old processes. Biotechnol Adv. 2011 Jan-Feb;29(1):75-83. – form PTO-892) , and C havez (Elucidation of the Function of Dihydrochalcones in Apple. Universita di Trento. Pages 1-190. 2019. - form PTO-892 ) . Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application and the claims of the reference patent recite a method of producing dihydrochalcone. Regarding claim 1 of the instant application, claim 16 of the reference patent recites a method for the biocatalytical manufacturing of a dihydrochalcone by using a transgenic microorganism comprising ( i ) providing an enoate reductase, synonymous with ene reductase, (ii) providing a flavanone, (iii) adding a flavanone and cultivating transgenic microorganism, and (iv) obtaining an dihydrochalcone . Therefore, claim 1 of the instant application anticipated by claim 16 of the reference patent. The claims of the reference patent do not recite a method of converting a flavanone to dihydrochalcone by incubating the flavanone, a purified ene reductase, and a purified chalcone isomerase. The claims of the reference patent does not disclose using an ene reductase having at least 90-95% sequence identity to SEQ ID NO:25 or 169. Regarding claim 2, Hilmer discloses a method of producing dihydrochalcone by incubating a transgenic microorganism expressing an ene reductase and a chalcone isomerase (claim 1). Hilmer disclsoes purification of an ene reductase and chalcone isomerase expressed from E. coli (Example 1.2 and Example 3). Carvalho discloses advantages of using enzymatic catalysis over whole cell catalysis. Carvalho discloses that enzymes are able to catalyze reactions at a rate far more rapid than it would occur without and continue to function under in vitro conditions and catalyze reactions in conditions not suitable for cell growth (3 rd full paragraph at page 75). Regarding claim 3, the method of Hilmer discloses that conversion of naringenin (flavanone) to phloretin (dihydrochalcone) for 0.25 to 26 hr , which reads on an incubation time of at least 15-30 minutes (Table 5 page 12 ). Regarding claims 1 and 11-12, Chavez discloses ene reductases, such as an Arabidopsis thaliana reductase ( AtDBR , At5g16970), that catalyze conversion of naringenin chalcone to phloretin (Figure 1-2 at page 7 and page 8). Said Arabidopsis thaliana reductase ( AtDBR , At5g16970) ene reductase is identical to the Arabidopsis thaliana ene reductase of SEQ ID NO:25 of the instant application by 1 amino acid and has at least 90% sequence identity to the Arabidopsis thaliana ene reductase variant (V285Q) of SEQ ID NO:169 of the instant application (see the sequence alignments below). Regarding claim 4, Chavez discloses that phloretin is produced from the flavanone naringenin (Figure 1-2 at page 7 and page 8). Therefore, it would have been obvious to one having ordinary skill in the art to modify the claims of the reference patent by incubating a flavanone with a purified ene reductase and a purified chalcone isomerase . Also, t t would have been obvious to one having ordinary skill in the art to modify the claims of the reference patent by replacing the ene reductase of the reference patent with the Arabidopsis ene reductase of Chavez because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable . One having ordinary skill in the art would have been motivated to modify the claims of the reference patent i n order to further increase production of the dihydrochalcone and/or to optimize the conversion of the flavanone to dihydrochalcone since enzymatic reactions are able to catalyze reactions at a rate far more rapid than it would occur without and continue to function under in vitro conditions and catalyze reactions in conditions not suitable for cell growth . One of ordinary skill in the art would have had a reasonable expectation of success since the claims of the reference patent recite a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone , Hilmer discloses a biocatalytical method of producing a dihydrochalcone by incubating a chalcone isomerase, ene reductase, and a flavanone, Chavez discloses an ene reductase that can used to produce phloretin , and Carvalho discloses advantages of enzymatic catalysis compared to whole cell catalysis. Therefore, the conflicting claims are not patentably distinct from each other. Conclusion Claims 1-20 are pending. Claims 7-10 and 17-20 are withdrawn. Claims 1-6 and 11-16 are rejected. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT YONG D PAK whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-0935 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-Th: 5:30 am - 3:30 pm . 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, FILLIN "SPE Name?" \* MERGEFORMAT Robert Mondesi can be reached on FILLIN "SPE Phone?" \* MERGEFORMAT 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. /YONG D PAK/ Primary Examiner, Art Unit 1652 Sequence alignment between the chalcone isomerase of SEQ ID NO: 146 of the instant application (“ Qy ”) and the chalcone isomer ase of Gal l/ KF154734 (“Db”) V9P0A9_EUBRA ID V9P0A9_EUBRA Unreviewed; 283 AA. AC V9P0A9; DT 19-MAR-2014, integrated into UniProtKB / TrEMBL . DT 19-MAR-2014, sequence version 1. DT 08-OCT-2025, entry version 38. DE SubName : Full=Chalcone isomerase {ECO:0000313|EMBL:AGS82960.1}; DE EC=5.5.1.6 {ECO:0000313|EMBL:AGS82960.1}; DE SubName : Full=Taxifolin isomerase {ECO:0000313|EMBL:AIS36173.1}; GN Name=tai {ECO:0000313|EMBL:AIS36173.1}; OS Eubacterium ramulus . OC Bacteria; Bacillati ; Bacillota ; Clostridia; Eubacteriales ; Eubacteriaceae ; OC Eubacterium. OX NCBI_TaxID =39490 {ECO:0000313|EMBL:AGS82960.1}; RN [1] {ECO:0000313|EMBL:AGS82960.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=DSM 16296 {ECO:0000313|EMBL:AGS82960.1}; RA Gall M., Bornscheuer U.T.; RT "Biologic pathways of E. ramulus ."; RL Submitted (MAY-2013) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000313|EMBL:AIS36173.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=DSM 16296 {ECO:0000313|EMBL:AIS36173.1}; RA Braune A., Engst W., Blaut M.; RT "Purification and characterization of taxifolin isomerase, an enzyme from RT Eubacterium ramulus catalyzing a unique ring contraction."; RL Submitted (JUN-2014) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0007829|PDB:4C9S, ECO:0007829|PDB:4C9T} RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 2-283. RX PubMed=25849401; DOI=10.1107/s1399004715001935; RA Thomsen M., Tuukkanen A., Dickerhoff J., Palm G.J., Kratzat H., RA Svergun D.I., Weisz K., Bornscheuer U.T., Hinrichs W.; RT "Structure and catalytic mechanism of the evolutionarily unique bacterial RT chalcone isomerase."; RL Acta Crystallogr . D 71:907-917(2015). RN [4] {ECO:0007829|PDB:4D4F, ECO:0007829|PDB:8B7R} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS). RX PubMed=36432010; DOI=10.3390/molecules27227909; RA Palm G.J., Thomsen M., Berndt L., Hinrichs W.; RT "Structural Basis for (2< i >R</ i >,3< i >R</ i >)-Taxifolin Binding and Reaction RT Products to the Bacterial Chalcone Isomerase of < i >Eubacterium RT ramulus </ i >."; RL Molecules 27:7909-7909(2022). CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; KF154734; AGS82960.1; -; Genomic_DNA . DR EMBL; KM067454; AIS36173.1; -; Genomic_DNA . DR PDB; 4C9S; X-ray; 1.80 A; A/B/C/D/E/F=2-283. DR PDB; 4C9T; X-ray; 1.98 A; A/B/C/D/E/F=2-283. DR PDB; 4D06; X-ray; 2.00 A; A/B/C/D/E/F=1-283. DR PDB; 4D4F; X-ray; 2.34 A; A/B/C/D/E/F=1-283. DR PDB; 8B7R; X-ray; 2.15 A; A/B/C/D/E/F=1-283. DR PDB; 8B7U; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=1-283. DR PDB; 8B7Z; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=1-283. DR PDBsum ; 4C9S; -. DR PDBsum ; 4C9T; -. DR PDBsum ; 4D06; -. DR PDBsum ; 4D4F; -. DR SASBDB; V9P0A9; -. DR SMR; V9P0A9; -. DR KEGG; ag:AIS36173; -. DR BRENDA; 5.5.1.6; 17131. DR GO; GO:0045430; F:chalcone isomerase activity; IEA:UniProtKB-EC . DR InterPro ; IPR040518; Chalcone_N . DR Pfam ; PF18232; Chalcone_N ; 1. PE 1: Evidence at protein level; KW 3D-structure {ECO:0007829|PDB:4C9S, ECO:0007829|PDB:4C9T}; KW Isomerase {ECO:0000313|EMBL:AGS82960.1}. FT DOMAIN 6..106 FT /note="Chalcone isomerase N-terminal" FT /evidence="ECO:0000259|Pfam:PF18232" SQ SEQUENCE 283 AA; 32503 MW; F590D5C34EC186BF CRC64; Query Match 98.6%; Score 1526; Length 283; Best Local Similari