DETAILED ACTION The preliminary amendment filed on 2/7/24 canceled claims 1-328 and added new claims 329-3 48 . Claims 329-3 48 are currently pending and under examination in the instant application. An action on the merits follows. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA Sequence Disclosures This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2); however, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth on the Notice To Comply With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino Acid Sequence Disclosures which is attached to this communication. Specifically, claim 335 recites an amino acid sequence which is not identified by a SEQ ID NO as required by 37 CFR 1.821. If this amino acid sequence is present within the on file sequence listing and has been accorded a SEQ ID NO, compliance may be achieved by amending the claim to recite the appropriate SEQ ID NO for this sequence. If the on file sequence listing does not contain this sequence, a new sequence listing in paper form and CRF, along with the required statement, must be filed-see the attached PTO-2301 for details. APPLICANT IS GIVEN A THREE MONTH EXTENDABLE PERIOD WITHIN WHICH TO COMPLY WITH THE SEQUENCE RULES, 37 CFR 1.821-1.825. Failure to comply with these requirements will result in ABANDONMENT of this application under 37 CFR 1.821 (g). Extension of time may be obtained by filing a petition accompanied by the extension fee under the provisions of 37 CFR 1.136. In no case may an applicant extend the period for response beyond the six-month statutory period. Applicant is requested to return a copy of the attached Notice To Comply with the response. Information Disclosure Statement The information disclosure statement (IDS) submitted on 2/7/24 is in compliance with the provisions of 37 CFR 1.97 and 1.98 . Accordingly, the information disclosure statement has been considered by the examiner, and an initialed and signed copy of the 1449 is attached to this communication. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 329-334, 340-342, and 346- 348 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception which is a product of nature without significantly more. The broadest reasonable interpretation of the claims based on independent claims 329 encompass any polypeptide which exhibits water-forming NADPH oxidase activity and which has one, two, three, four, or five specific amino acids in specific positions identified through alignment of the polypeptide with SEQ ID NO:1. Note that there is no limitation in the claims requiring that the polypeptide be based on SEQ ID NO:1 or have any percent homology to SEQ ID NO:1. The claims further do not recite that the polypeptide is mutated as compared to any other polypeptide sequence. The claims as written thus read on naturally occurring water-forming NADPH oxidases. A number of water-forming NADPH oxidases were in fact reported in the prior art, including the water forming T. kodakarensis NAD(P)H oxidase (TkNox) which includes four of the five recited amino acids at positions corresponding to those in SEQ ID NO:1 as claimed (see for example Petschacher et al. (2014) Computational and Structural Biotechnology Journal, Vol. 9(14),e201402005, https://doi.org/10.5936/csbj.201402005 , pages 1-11). Specifically, Petschacher teaches a naturally occurring water forming NADPH oxidase-TkNox- which has an A at a position corresponding to position 153 of SEQ ID NO:1, an R at a position corresponding to position 177 of SEQ ID NO:1, an S at a position corresponding to position 178 of SEQ ID NO:1, and an R at a position corresponding to position 183 of SEQ ID NO:1 (Petschacher et al., Figure 1). TkNox also has a GTGYIA motif which is a GxGXXG/A conserved motif as recited in claim 334 (Petschacher et al., Figure 1). It is further noted that naturally occurring T. kodakarensis are bacterial cells comprising nucleic acids which encode this polypeptide. In addition, this judicial exception is not integrated into a practical application because the claims are drawn to products and not any practical application. Further, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the following reasons. The additional elements include culture media. However, culture media is not taught in either the prior art or the specification to affect the structure or functionality of the polypeptide and as such does not amount to significantly more. Claim Rejections - 35 USC § 102 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. Claims 329-33 2 , 334, and 340-34 3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Petschacher et al. (2014) Computational and Structural Biotechnology Journal, Vol. 9(14),e201402005, https://doi.org/10.5936/csbj.201402005 , pages 1-11. Note that independent claim 329, while reciting a polypeptide with specific amino acids at positions which correspond to positions within SEQ ID NO:1, reads broadly on both naturally occurring polypeptides with the structural features and functional features claimed, and modified polypeptides in which the specific amino acids have been introduced through amino acid substitution. Petschacher et al. teaches cofactor engineering of Streptococcus Mutans water forming NADH oxidase (SmNOX) to utilize NADPH as a cofactor (Petschacher et al., pages 1-5 and Table 2). Table 2 shows several mutants of SmNox including D192A/V193R with a Km of 5 uM for NADPH and 23 uM for NADH, and D192A/V193R/V194H/A199R with a Km of 3 uM for NADPH and 11 uM for NADH, with more than one mutation in the cofactor specificity loop (Petschacher et al., Table 2). Petschacher et al. further teaches that the SmNOX comprises a conserved sequence motif GxGXXG/A for dinucleotide binding with the specific sequence GAGYIG (Petschacher et al., Figure 1). Alignment of the SmNOX sequence with applicant’s SEQ ID NO:1 shows that the 192A mutation corresponds to the A at position 176 of SEQ ID NO:1 and the 193R mutation corresponds to position 177 of SEQ ID NO:1. Petschacher et al. also teaches a composition comprising the mutant SmNOX protein, NADH, and cell culture medium (Petschacher et al., pages 2-3). In addition, Petschacher et al. teaches nucleic acids and nucleic acid vectors encoding the mutant SmNOX and cells transfected with a vector encoding SmNOX (Petschacher et al., pages 2-3). Petschacher et al. also separately teaches a naturally occurring water forming NADPH oxidase-TkNox- which has an A at a position corresponding to position 153 of SEQ ID NO:1, an R at a position corresponding to position 177 of SEQ ID NO:1, an S at a position corresponding to position 178 of SEQ ID NO:1, and an R at a position corresponding to position 183 of SEQ ID NO:1 (Petschacher et al., Figure 1). In regards to claims 341-342, while Petschacher et al. teaches mutant SmNOX with Km values for NADH of no more than 100uM, Petschacher et al. did not test or report on the Kcat/Km of the mutant protein for NADH versus NADPH. I t is noted that the office does not have the facilities for examining and comparing applicant’s product with the product of the prior art in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed products are functionally different than those taught by the prior art and to establish patentable differences. See Ex parte Phillips , 28 USPQ 1302, 1303 (BPAI 1993), In re Best , 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray , 10 USPQ2d 1922, 1923 (BPAI 1989). Thus, for the reasons set forth above, Petschacher anticipates the products claimed in instant claims 329-33 2 , 334, and 340-343 . 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. 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. Claims 331-332 are rejected under 35 U.S.C. 103 as being unpatentable over Petschacher et al. (2014) Computational and Structural Biotechnology Journal, Vol. 9(14),e201402005, https://doi.org/10.5936/csbj.201402005 , pages 1-11. Petschacher et al. teaches cofactor engineering of Streptococcus Mutans water forming NADH oxidase (SmNOX) to utilize NADPH as a cofactor (Petschacher et al., pages 1-5 and Table 2). Table 2 shows several mutants of SmNox including D192A/V193R with a Km of 5 uM for NADPH and 23 uM for NADH, and D192A/V193R/V194H/A199R with a Km of 3 uM for NADPH and 11 uM for NADH, with more than one mutation in the cofactor specificity loop (Petschacher et al., Table 2). Petschacher et al. further teaches that the SmNOX comprises a conserved sequence motif GxGXXG/A for dinucleotide binding with the specific sequence GAGYIG (Petschacher et al., Figure 1). Alignment of the SmNOX sequence with applicant’s SEQ ID NO:1 shows that the 192A mutation corresponds to the A at position 176 of SEQ ID NO:1 and the 193R mutation corresponds to position 177 of SEQ ID NO:1. Petschacher et al. also teaches a composition comprising the mutant SmNOX protein, NADH, and cell culture medium (Petschacher et al., pages 2-3). While Petschacher et al. teaches an SmNOX mutant with two specific mutations corresponding to two of the recited amino acids from the list of 5 set forth in claim 329, Petschacher et al. does not specifically teach a third mutation and/or fourth mutation in an SmNOX mutant in which alanine (A) is present in a position corresponding to position 158 of SEQ ID NO:1 and/or R is present in a position corresponding to position 183 of SEQ ID NO:1. Position 158 of SEQ ID NO:1 is the last amino acid in the GxGXXG/A conserved sequence motif. In SEQ ID NO:1, this residue is an A. Although Petschacher et al. provides a sequence for SmNOX where this position is a G, Petschacher et al. also shows via comparison with a number of other NADH/NADPH oxidases that A can be present and fully functional in this position-see Figure 1 of Petschacher. Thus, in view of the teachings of Petschacher et al. that the position corresponding to position 158 of SEQ ID NO:1 can be an alanine instead of a glycine in the conserved sequence motif GxGXXG/A, it would have been prima facie obvious to the skilled artisan at the time of filing to produce an SmNOX mutant comprising an A at a position corresponding to position 158 of SEQ ID NO:1, an A at a position corresponding to position 176 of SEQ ID NO:1 and an R at a position corresponding to position 177 of SEQ ID NO:1 with a reasonable expectation that the resulting SmNOX mutant would be functional and exhibit water-forming NADPH oxidase activity. Further in regards to an R at a position corresponding to position 183 of SEQ ID NO:1, Petschacher et al. teaches that an R at this position in other NAD(P)H oxidases is typical for NADPH converting enzymes. As such, since an R at a position corresponding to position 183 of SEQ ID NO:1 is considered a typical residue for an NADPH converting enzyme, it would have been prima facie obvious to the skilled artisan at the time of filing to further modify the SmNOX mutant with NADPH converting enzyme activity to include an R at a position corresponding to position 183 with a reasonable expectation of success or both an R at a position corresponding to position 183 and the R at an A at a position corresponding to position 158 of SEQ ID NO:1 such that the skilled artisan would have had a reasonable expectation that the resulting SmNOX mutant would be functional and exhibit water-forming NADPH oxidase activity. Claim Rejections - 35 USC § 112 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 329-3 48 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The applicant broadly claims a genus of polypeptides based on the functional activity of 1) water forming NADPH activity- claims 329-3 48 , or 2) water forming NADH activity- claims 356-357. Note that all claimed polypeptides may exhibit both water forming NADPH and NADH activity. Claim 329 reads broadly on any polypeptide, naturally occurring or synthetic, with the only structural feature being 1, 2, 3, 4, or 5 specific amino acids within a polypeptide of any structure, sequence, etc. Certain claims further limit the polypeptide of claim 329 to one which has a cofactor specificity sequence having the amino acid sequence ARSARVMR, or where the polypeptide has a sequence at least 85% identical to SEQ ID NO:329. Claim 343 reads more narrowly on a genus of NADH oxidases with one or more amino acids mutation in the dinucleotide-binding motif and/or a cofactor specificity loop of a water with render the oxidase selective for NADPH over NADH. The specification does not provide adequate disclosure for the broad genus of polypeptides with the claimed functional property of water forming NADPH oxidase activity and/or NADH oxidase activity, for the narrower genus of mutated water forming NADH oxidases with NADPH oxidase activity, or for the narrowest genus of polypeptides with at least 85% sequence identity to SEQ ID NO:1 or SEQ ID NO:329 with water forming NADPH oxidase activity. The specification provides a description of a number of what appear to be naturally occurring water-forming NADH oxidases from a number of different bacteria, including different strains of the same bacteria (SEQ ID NOS 1-273), and sequences with 85% sequence identity or more with any one of these sequences. The specification also generally discloses sequences based on these bacterial NADH with the specific functional properties of selective oxidization of NADPH over NADH, a kcat/KM for NADPH that is increased by 10-fold or more relative to the kcat/Km exhibited for NADH, Km values for NADH and O2 of no more than about 100 pM and 20 pM, respectively, and/or the production of less than about 2% by mole of H2O2 compared to H2O production during the catalytic cycle of the polypeptide. Please note that the specification does not disclose a single polypeptide which is not a bacterial water-forming NADH oxidase which has water-forming NADH oxidase activity, NADPH oxidase activity, or any other claimed activity. Further, of all of the generally disclosed bacterial NADH oxidizing polypeptides, the specification only provides a detailed description of the functional properties of SEQ ID NO:1, a water forming NADH oxidase from Lactobacillus brevis (LbNox), and specific mutants of SEQ ID NO:1 including mutants of SEQ ID NO:1 with one or more of G158A, D176A, A177R, M178S, and P183R amino acid substitutions relative to SEQ ID NO: 1. The specification does not disclose the ability of other water forming NADH oxidases to oxidize NADPH, the Km or kcat/Km of any of these enzymes for NADH versus NADPH, or the Km values of these NADH oxidases for O2, or the percent production of H2O2 versus H2O. In addition, the specification does not teach the effects of any mutations on any bacterial water forming NADH oxidase other than LbNox. Turning to the working examples, it is noted that the working examples are solely focused on the properties of LbNox (SEQ ID NO:1) and mutants of LbNox. The working examples disclose the sequence and the crystal structure of LbNox, and the functional properties of wild type LbNox which include high selectivity for NADH over NADPH, negligible H2O2 production relative to H2O, a very low Km of O2. The working examples also describe the production of a single mutant of LbNox (SEQ ID NO:329), a sequence based on SEQ ID NO:1 which contains all five of the specific amino acid substitutions recited in claim 329. This mutant, referred to as TPNOX in the specification, was designed based on the crystal structure of TPNOX and previous modifications to other bacterial NADH oxidases in the prior art, and exhibits a kcat of 268/s and a Km of 22 uM for NADPH, whereas the kcat for NADH was virtually non-reactive. Neither the working examples nor the remainder of the specification provides any further description of the activity of an LbNox polypeptide with only 1, 2, 3, or 4 of the claimed amino acid substitutions, or an LbNox polypeptide with additional amino acid substitutions, deletions, or insertions which has 85% sequence identify to SEQ ID NO:1 or SEQ ID NO:329. Thus, of the universe of polypeptide sequences encompassed by the claims, including non-bacterial NADH based polypeptides with 1 to 5 specified amino acid residues that exhibit NAPDH oxidase activity, bacterial water forming NADH oxidase polypeptides-wild type or mutated with NAPDH oxidase activity- and sequences with 85% sequence homology to SEQ ID NO:1 or SEQ ID NO:329 with specific NADH oxidase and/or NADPH oxidase activity, the specification only provides a specific description of the activity of two specific polypeptides, LbNox (SEQ ID NO:1) and TPNOX (SEQ ID NO:329) towards NADH and NADPH respectively which meet the claimed functional limitations. Turning to the state of the prior art, it is noted that despite crystal structure guidance and comparison to other bacterial NADH and NADPH oxidases, identification of mutations which convert an NADH oxidase to and NADPH oxidase cannot be determine a priori , and mutants with high levels of NADPH oxidation as compared to NADH may not be found for all bacterial water forming NADH oxidases. Petschacher et al., for example, shows that mutant S. mutans NADH oxidases with amino acid substitutions in the cofactor specificity sequence did not generally result in enzymes with higher activity of NADPH over NADH ( Petschacher et al. (2014) Computational and Structural Biotechnology Journal, Vol. 9(14),e201402005, https://doi.org/10.5936/csbj.201402005 , pages 1-11 , see in particular, Table 2). In particular, note that no single amino acid substitutions produced an enzyme with marked levels of NADPH oxidase activity. It is further noted that the prior art is silent as to effects of mutations outside of the cofactor specificity sequence, and in particular mutations in the GxGXXG/A dinucleotide binding motif required for enzyme activity. Vas-Cath Inc. v. Mahurkar , 19 USPQ2d 1111, clearly states that "applicant must convey with reasonable clarity to those skilled the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is claimed." (See page 1117). The instant specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116). An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may also be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc. , 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Regents of the University of California v. Eli Lilly , 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); Amgen, Inc. v. Chugai Pharmaceutical , 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). The applicant has not provided sufficient description or a reduction to practice of polypeptides and mutant polypeptides with NADH or NADPH activity as claimed other than SEQ ID NO:1 and SEQ ID NO:329. Further, based on the applicant's specification, the skilled artisan cannot envision which additional changes in the sequence of SEQ ID NOS:1 or 329 or any other polypeptide that can be made without affecting the functional properties of polypeptides, and as such cannot envision the detailed chemical structure of the genus of polypeptides encompassed by the claims. Therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. See Fiers v. Revel, 25 USPQ2d 1602 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Thus, for the reasons outlined above, claims 329-352, and 356-357 do not meet the requirements for written description under 35 U.S.C. 112, first paragraph. 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 . Claims 329-348 are rejected on the ground of nonstatutory double patenting a s being unpatentable over claims 1-5 of U.S. Patent No. 11,866,736, hereafter referred to as th e ‘736 patent, alone or in view of Petschacher et al. (2014) Computational and Structural Biotechnology Journal, Vol. 9(14),e201402005, https://doi.org/10.5936/csbj.201402005 , pages 1-11 . Instant claim 329 recites a polypeptides which exhibits water-forming NADPH oxidase activity and has one or more specific amino acid substitutions corresponding to positions within SEQ ID NO:1, where SEQ ID NO:1 is the amino acid sequence of a Lactobacillus Brevis NADH water-forming NADH oxidase . Claim 343 recites a polypeptide produced by introducing one or more mutations into a dinucleotide-binding motif and/or a cofactor specificity loop of a water-forming NADH oxidase, where the one or more mutations renders the water-forming NADH oxidase selective for the oxidation of NADPH over NADH. Note that the instant claimed polypeptides encompass a water-forming oxidase with both NADH and NADPH oxidation activity as specifically recited in instant dependent claims 341-342. The ‘736 patent claims are drawn to a mammalian cell comprising a nucleic acid encoding a water- forming NADH oxidase bound to a targeting peptide that localizes the water-forming NADH oxidase to mitochondria, where the water-forming NADH oxidase comprises an NADH-binding sit e comprising a R ossman fold domain having a dinucleotid e -binding motif defined by the peptide G-x-G-x-x-G/A and a cofactor specificity loop, and wherein the water-forming NADH oxidase is a bacterial water-forming NADH oxidase. In addition, the ‘736 patent claims recite that the NADH oxidase is bound to the mitochondrial targeting sequence from subunit IV of human cytochrome c oxidase, and more specifically where the targeting sequence peptide has the amino acid sequence of SEQ ID NO:298. While the ‘736 patent claims are drawn to a cell and not specifically to the oxidase polypeptide itself, the cells produce a genus of bacterial water-forming NADH oxidases which encompasses bacterial water-forming NADH oxidases with both NADH oxidase activity and NADPH oxidase activity. Further, the specification of the ‘736 patent, which is largely identical to the specification of the instant application, discloses embodiments of the bacterial water-forming NADH oxidase which includes the specific amino acid substitutions recited in the instant claims , including an oxidase sequence as set forth in SEQ ID NO:329, and which have the same NADPH oxidase activity as recited in instant claims 340-343 . The MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for obvious-type double patenting rejections. In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. See In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). In particular, those portions of the specification which provide support for the reference claims may be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized “that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,” but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first “determine how much of the patent disclosure pertains to the invention claimed in the patent” because only “[t]his portion of the specification supports the patent claims and may be considered.” The court pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103 , since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The MPEP gives the example that if the reference patent discloses several species within the scope of the reference genus claim, that portion of the disclosure should be analyzed to properly construe the reference patent claim and determine whether it anticipates or renders obvious the claim in the application being examined. Because that portion of the disclosure of the reference patent is an embodiment of the reference patent claim, it may be helpful in determining the full scope and obvious variations of the reference patent claim. Thus, the ‘736 patent claims, whi le broader than the instant claims, encompass the subspecies of water-forming NADPH oxidases as claimed in the instant claims, and based on the portion of the disclosure of the ‘736 specification which describes the claimed invention of the ‘736 patent claims, the specific species of water-forming NADPH oxidases with the amino acid mutations recited in the instant claims are obvious variants of the water-forming NADH oxidases recited in the ‘736 patent claims. As such, the ‘736 patent claims render obvious instant claims 329-348. Furthermore, or alternatively, Petschacher et al. supplements the ‘736 patent claims by teach ing cofactor engineering of Streptococcus Mutans water forming NADH oxidase (SmNOX) to utilize NADPH as a cofactor (Petschacher et al., pages 1-5 and Table 2). Table 2 shows several mutants of SmNox including D192A/V193R with a Km of 5 uM for NADPH and 23 uM for NADH, and D192A/V193R/V194H/A199R with a Km of 3 uM for NADPH and 11 uM for NADH, with more than one mutation in the cofactor specificity loop (Petschacher et al., Table 2). Petschacher et al. further teaches that the SmNOX comprises a conserved sequence motif GxGXXG/A for dinucleotide binding with the specific sequence GAGYIG (Petschacher et al., Figure 1). Alignment of the SmNOX sequence with applicant’s SEQ ID NO:1 shows that the 192A mutation corresponds to the A at position 176 of SEQ ID NO:1 and the 193R mutation corresponds to position 177 of SEQ ID NO:1. Petschacher et al. also teaches a composition comprising the mutant SmNOX protein, NADH, and cell culture medium (Petschacher et al., pages 2-3). In addition, Petschacher et al. teaches another naturally occurring water forming NADPH oxidase-TkNox- which has an A at a position corresponding to position 153 of SEQ ID NO:1, an R at a position corresponding to position 177 of SEQ ID NO:1, an S at a position corresponding to position 178 of SEQ ID NO:1, and an R at a position corresponding to position 183 of SEQ ID NO:1 (Petschacher et al., Figure 1). Thus, based on the breadth of the ‘736 patent claims, and the motivation provided by Petschacher et al. to modify specific amino acids within the cofactor specificity loop, including specific amino acids recited in instant claims 329-33 2 , it would have been obvious to the skilled artisan at the time of filing to make a mammalian cell which expresses a bacterial water-forming NADH oxidase as set forth in the ‘736 patent claims which further has one or more of the specific amino acid s recited in instant claim 329 either naturally occurring or introduced through amino acid substitution in the cofactor specificity loop and which exhibits preferential NADPH to NADH oxidase activity with a reasonable expectation of success . No claims are allowed. Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547. 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. Dr. A.M.S. Wehbé /ANNE MARIE S WEHBE/ Primary Examiner, Art Unit 1634