METHODS AND CELLS FOR PRODUCTION OF VOLATILE COMPOUNDS

§103 §112

DETAILED ACTION 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 . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/1/2026 has been entered. Applicant’s amendment of claims 19, 28, 33, in the paper of 9/1/2026, is acknowledged. Applicants' arguments filed on 9/1/2026, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 19-37 are still at issue and are present for examination. Election/Restrictions Applicant's election without traverse of the following species: Species Group 1: acetone; Species Group 2: Slip_0880(SEQ ID NO:7) and Tle2 (subunit A, SEQ ID NO:19 and subunit B, SEQ ID NO:20) and Species Group 3: Geobacillus, in the paper of 9/2/2025, is acknowledged. Claims 23 and 25 are withdrawn from further consideration by the examiner, 37CFR 1.142(b), as being drawn to a non-elected invention. Claim Objections Claim 20, 24, 29, 34 are objected to because of the following informalities: Claims 20, 24, 29 and 34 depend form rejected claims 19, 28 and 33. Appropriate correction and/or comment is required. Claim Rejections - 35 USC § 112 The rejection of claim(s) 19-22, 24, 26-37 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or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 2/20/2026. The rejection of claim(s) 19-22, 24, 26-37 under 35 U.S.C. 112, first paragraph, based upon a lack of enablement is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 2/20/2026. Claim Rejections - 35 USC § 103 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. 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 rejection of claim(s) 19, 21, 22, 26-28, 30-33, 35-37 under 35 U.S.C. 103 as being unpatentable pver Zeldes et al. (Biotechnology and Bioengineering, Vol 115, No. 12, pp 2951-2961, Oct 23, 2018), Shaw et al., Biotechnology for Biofuels, Vol 8:75, May 2015, Sillers et al. US 20130273555, Uniprot Accession No. D7CLS5 Aug 2020, Uniprot Accession No. A8F7H7 Aug 2020 and Uniprot Accession No. A8F7H6 Aug 2020) is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 9/1/2026. Claim(s) 19, 21, 22, 26-28, 30-33, 35-37 is/are rejected under 35 U.S.C. 103 as being unpatentable Zeldes et al. (Biotechnology and Bioengineering, Vol 115, No. 12, pp 2951-2961, Oct 23, 2018), Shaw et al., Biotechnology for Biofuels, Vol 8:75, May 2015, Sillers et al. US 20130273555, Uniprot Accession No. D7CLS5 Aug 2020, Uniprot Accession No. A8F7H7 Aug 2020 and Uniprot Accession No. A8F7H6 Aug 2020 and Xue et al. (Biotechnology and Bioengineering, Vol 109., No. 11, Nov 2012). Zeldes et al. demonstrates a synthetic enzymatic pathway for extremely thermophilic acetone production that functions up to at least 70°C in vitro, comprising i) a thiolase (Thl) from Caldanaerobacter subterraneus, ii) heteromultimeric acetoacetyl-CoA:acetate CoA-transferase (CtfAB) complexes from Thermosipho melanesiensis and Caldanaerobacter subterraneus and iii) acetoacetate decarboxylase (Adc) from the mesophile C. acetobutylicum which has unusual thermostability. The Adc protein from C. acetobutylicum taught by Zeldes et al. is 100% identical to instant SEQ ID NO:28. This pathway can be used in an extremely thermophilic host organism (abstract; Fig. 6). Zeldes et al. as a part of their disclosure teach methods of providing a thermophilic cell comprising a i) a thiolase (Thl) from Caldanaerobacter subterraneus, ii) heteromultimeric acetoacetyl-CoA:acetate CoA-transferase (CtfAB) complexes from Thermosipho melanesiensis and Caldanaerobacter subterraneus and iii) acetoacetate decarboxylase (Adc) and nucleic acids and cells comprising a polynucleotide encoding a i) a thiolase (Thl) from Caldanaerobacter subterraneus, ii) heteromultimeric acetoacetyl-CoA:acetate CoA-transferase (CtfAB) complexes from Thermosipho melanesiensis and Caldanaerobacter subterraneus and iii) acetoacetate decarboxylase (Adc). In Shaw et al., the enzymes i) thiolase, ii) acetoacetate:acetate CoA-transferase, and iii) acetoacetate decarboxylase were assembled in the thermophilic anaerobe T. saccharolyticum with genes from thermophilic donor organisms that do not natively produce acetone. The resultant strain converted acetic acid to acetone and ethanol (page 5, col.1 , par. 2-page 6, col. 1 line 1). Thus Shaw et al. teach methods of producing acetone with the above enzymes and nucleic acids and cells comprising polynucleotides encoding above enzymes. Sillers et al. describes genetically modified thermophilic microorganisms converting acetate to acetone or isopropanol, wherein the acetyl-CoA is converted to acetoacetyl-CoA by i) a thiolase, the acetoacetyl-CoA is converted to acetoacetate by ii) a CoA transferase, and the acetoacetate is converted to acetone by iii) an acetoacetate decarboxylase (paragraphs [0018] and [0019]; claims 42, 112). Sillers et al. disclose cultivating the above thermophilic cells in a bioreactor at 55oC in cultivation broth thereby producing acetone and recovering the acetone produced. Zeldes et al., Shaw et al., and Sillers et al. each relate to a thermophilic microorganism comprising three acetone pathway enzymes j), ii) and iii) as functionally defined in claim 1. The cited prior art does however not explicitly disclose a thermophilic cell expressing a combination of the specific enzymes i), ii) and iii), wherein i) is selected from SEQ ID NOs 1,2,3,4,7,59 or functional variants thereof with at least 70% sequence identity, ii) is selected from SEQ ID NOs 19/20 (Tle2) and SEQ ID NO: 21 (Dde2) or functional variants thereof with at least 70% sequence identity, and iii) is according to SEQ ID NO:28 or functional variants thereof with at least 70% sequence identity. Uniprot Accession No. D7CLS5 Aug 2020 teaches thiolase from Syntrophothermus lipocalidus which has 100% sequence identity to the protein having the instant amino acid sequence of SEQ ID NO:7. Uniprot Accession No. A8F7H7 Aug 2020 teaches acetate-CoA transferase subunit a from Thermotoga lettingae which has 100% sequence identity to the protein having the instant amino acid sequence of SEQ ID NO:19. Uniprot Accession No. A8F7H6 Aug 2020 teaches acetate-CoA transferase subunit b from Thermotoga lettingae which has 100% sequence identity to the protein having the instant amino acid sequence of SEQ ID NO:20. Xue et al. (Biotechnology and Bioengineering, Vol 109., No. 11, Nov 2012) teach a strain of Clostridium acetobutylicum, JB200, that has been engineered to produce high levels of butanol (approx.. 20 g/L) and acetone (10.8 g/L) (see Figure 4 and supporting text). Xue et al. teach that this strain was created to produce a high titer of butanol and acetone. One of skill in the art before the effective filing date would have been motivated to substitute the enzymes taught by Uniprot Accession No. D7CLS5 (thiolase), Uniprot Accession No. A8F7H7 (acetate-CoA transferase subunit a), Uniprot Accession No. A8F7H6 (acetate-CoA transferase subunit b) and the Adc protein from C. acetobutylicum as taught by Zeldes et al. in the Clostridium acetobutylicum, JB200, strain taught by Xue et al. using the methods taught by Shaw et al. for producing acetone. One of skill in the art before the effective filing date would have been motivated to substitute the polynucleotides encoding the above enzymes for use in the methods taught by Shaw et al. for their use in transforming the Clostridium acetobutylicum, JB200, strain taught by Xue et al. In view of the teachings provided in any of Zeldes et al., Shaw et al., and Sillers et al. it would be obvious for a skilled person to select a suitable combination of i) acetyl-CoA acetyltransferase, ii) acetate CoA-transferase, and iii) acetoacetate decarboxylase for providing a synthetic pathway for the production of acetone. The expectation of success is high based upon the high level of skill in the art in the area of genetic engineering and protein expression as exemplified by the teachings of Zeldes et al., Shaw et al., Sillers et al. and Xue et al. Thus claim(s) 19, 21, 22, 26-28, 30-33, 35-37 is/are rejected under 35 U.S.C. 103 as being unpatentable Zeldes et al. (Biotechnology and Bioengineering, Vol 115, No. 12, pp 2951-2961, Oct 23, 2018), Shaw et al., Biotechnology for Biofuels, Vol 8:75, May 2015, Sillers et al. US 20130273555, Uniprot Accession No. D7CLS5 Aug 2020, Uniprot Accession No. A8F7H7 Aug 2020 and Uniprot Accession No. A8F7H6 Aug 2020 and Xue et al. (Biotechnology and Bioengineering, Vol 109., No. 11, Nov 2012). Remarks No claim is allowed. . Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri. 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. rgh 10/6/2026 /RICHARD G HUTSON/Primary Examiner, Art Unit 1652