CTNF 18/067,158 CTNF 96631 Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. DETAILED ACTION Claims 1-10 are pending. Priority This application is a CON of PCT/JP2021/022845 filed 6/16/2021, which claims priority to JAPAN 2020-104881 filed 6/17/2020. As no certified English translation of the priority documents have been filed, the effective filing date of the current application is the filing date of the current application, December 16, 2022. Information Disclosure Statement The information disclosure statements filed on 12/16/2022; 1/20/2023; 6/26/2024; and 7/11/2025 all comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. All references were considered. Election/Restrictions 08-25-02 Applicant’s election of Group I: claims 1-5 in the reply filed on September 10, 2025 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the election has been treated as an election without traverse (MPEP § 818.01(a)). 08-06 AIA Claim s 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions , there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 10, 2025 . Claims 1-5 are being examined . Specification The abstract of the disclosure is objected to because the abstract contains line numbers in the left column (line 5). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Claim Objections 07-29-01 AIA Claim s 1-5 are objected to because of the following informalities: There are line numbers in the left column of the claims (lines 5, 10, 15, 20 and 25) . Appropriate correction is required. Claim Rejections - 35 USC § 101 07-04-01 AIA 07-04 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 1-5 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because the claims are directed towards the natural phenomenon of phosphatase converting ethanolamine phosphate to ethanolamine, and allowing oxidoreductase to act on ethanolamine. The claims recite a quantitation method comprising allowing phosphatase to act on a sample to convert ethanolamine phosphate to ethanolamine, and allowing oxidoreductase to act on ethanolamine. Phosphatase enzymes remove phosphate groups from ethanolamine phosphate to produce ethanolamine, which is a natural phenomenon. Oxidoreductase enzymes catalyze the transfer of electrons from one molecule to another, which is a natural phenomenon. May et al . ( Arabidopsis thaliana PECP1 — Enzymatic characterization and structural organization of the first plant phosphoethanolamine/phosphocholine phosphatase”, Biochimica et Biohphysica Acta, 2012, Vol. 1824, Issue 2, pp.319-325) teaches a phosphoethanolamine phosphatase that is likely to be involved in the liberation of inorganic phosphate (abstract). May further teaches incubating the enzyme with substrates and measuring the amount of phosphate generated by enzymatic reactions p.320, 1 st column – 3.2. Enzyme activity assay, protein quantification and mass spectrometry), demonstrating that phosphatase acting to remove phosphate from ethanolamine phosphate substrates is a natural phenomenon. Narrod et al. (“Metabolism of Ethanolamine”, Journal of Biological Chemistry, 1964, Vol. 239, Issue 7, pp.2189-2193) teaches that the initial step of ethanolamine utilization which is catalyzed by ethanolamine oxidase is described by the over-all equation: PNG media_image1.png 39 455 media_image1.png Greyscale (p.2189, 1 st column, 1 st paragraph), demonstrating that oxidase acting on ethanolamine is a natural phenomenon. Thus, claims 1-5 are directed towards natural phenomena and are not patent-eligible subject matter. 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. Claims 1-5 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention. Claim 1 recites “allowing phosphatase to act” in line 2 and “allowing oxidoreductase to act” in line 4. It is unclear whether “allowing” means phosphatase or oxidoreductase are already present in a sample, or are added externally to a sample. It is further unclear what is meant by the phrase “allowing”, which will be interpreted very broadly to mean “to act”. It is further unclear how the claimed method is a “quantitation method” because there are no active quantification steps recited. Claims 2-5 are rejected for depending from rejected claim 1 but failing to remedy the indefiniteness therein. Claim 2 recites “wherein the sample includes at least one kind of amine other than the ethanolamine phosphate, the oxidoreductase is an oxidoreductase acting on at least the amine” in lines 2- 4. It is unclear whether “the amine” is referring to the ethanolamine phosphate or the at least one kind of amine other than ethanolamine phosphate. Claim 3 recites a mediator is reduced by allowing the oxidoreductase to act on the ethanolamine. It is uncertain whether a mediator is a reagent compound to be added to the sample, or naturally pre-existing in the same environment with the sample. Claim 5 recites “wherein the first oxidoreductase allowed to act on the ethanolamine, and a second oxidoreductase allowed to act on the at least one kind of amine are contained”. It is unclear what is meant by “contained”. It is further unclear whether there is one or more oxidoreductase, because claims 1 and 2 from which claim 5 depends, both recite “oxidoreductase” as a singular enzyme, and does not indicate that more than one oxidoreductase is present in or required by the reaction. Claim Rejections - 35 USC § 103 07-20-aia AIA The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1-2 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et al. (JP 6868649 B2, published June 20, 2019) in view of Imamura et al. (JP2005052034A, published on March 3, 2005) and Mawatari et al. (JP2016045112A, published on April 4, 2016). As the original JP 6868649 B2, JP2005052034A and JP2016045112A documents are in Japanese, English translations are relied upon for support . Regarding claim 1 , Sasaki teaches a method for measuring phosphoethanolamine (PEA) in a sample with high sensitivity, with the method comprising (2a) a step for removing ethanolamine in a sample; (2b) a step for adding an enzyme to the sample obtained in step (2a) to produce ethanolamine from PEA included in the sample; (2c) a step for adding a composition for detecting ethanolamine to the sample obtained in the step (2b); and (2d) a step for detecting ethanolamine in the sample obtained in step (2c) (English translation claims; p.5, paragraphs 4-7). Sasaki teaches that alkaline phosphatase is used as the enzyme for producing ethanolamine from PEA (English translation p.5, 4 th paragraph). Sasaki does not teach allowing oxidoreductase to act on the ethanolamine. However, Imamura teaches a method for analyzing ethanolamine-containing phospholipid characterized by using at least phospholipase and tyramine oxidase (a.k.a. oxidoreductase) (English translation claims; p.1 last sentence to p.2 top paragraph). Mawatari teaches a method for quantifying ethanolamine ether phospholipid or choline ether phospholipid contained in a serum or blood sample (English translation, claims). Mawatari further teaches processing ethanolamine generated by decomposition of ethanolamine ether phospholipid by phospholipase D by using amine oxidase (a.k.a. oxidoreductase) and then using peroxide, measuring the color developed using a spectrophotometer, and preparing a standard curve to quantify the ethanolamine ether phospholipid (English translation claims; p.6, paragraphs 4-5). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the reaction of ethanolamine-containing phospholipid using tyramine oxidase taught by Imamura with the reaction of alkaline phosphatase with a sample to produce ethanolamine from PEA taught by Sasaki using the color detection method taught by Mawatari to arrive at the claimed invention. Each of Sasaki, Imamura and Mawatari teach the detection of ethanolamine from a sample. One of ordinary skill in the art would reasonably expect that combining known elements together in a predictable way would result in a method to quantify ethanolamine ether phospholipid in a sample. Regarding claims 2 and 5 , Sasaki does not teach any amine other than ethanolamine, or a second oxidoreductase acting on the amine other than the ethanolamine phosphate. However, Imamura teaches monoamine and diamine that are removed by a combination of tyramine oxidase, monoamine oxidase, and diamine oxidase (English translation p.2, paragraph 4). Mawatari teaches that free amines existing in serum or blood plasma can be removed prior to performing the processing by phospholipase D (English translation p.6, paragraph 7). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add oxidoreductases taught by Imamura to remove monoamine and diamine, and free amines from the sample as taught by Mawatari, in the method of Sasaki to improve the accuracy and detection sensitivity of PEA. One of ordinary skill in the art would have found it beneficial to remove free amines from a blood plasma or serum sample to improve the detection of PEA and be able to better detect depression in a patient . 07-21-aia AIA Claims 1 and 4 are r ejected under 35 U.S.C. 103 as being unpatentable over M ay et al. (“ Arabidopsis thaliana PECP1 — Enzymatic characterization and structural organization of the first plant phosphoethanolamine/phosphocholine phosphatase”, Biochimica et Biophysica Acta, 2012, Vol. 1824, pp.319-325) in view of Narrod et al. (“Metabolism of Ethanolamine”, Journal of Biological Chemistry, 1964, Vol. 239, Issue 7, pp.2189-2193) . Regarding claim 1 , May teaches a phosphoethanolamine/phosphocholine phosphatase (abstract). May teaches enzyme activity was measured by a discontinuous colorimetric method by incubating the enzyme with substrates and calculating the amount of phosphate generated by enzymatic reactions (p.320, 1 st column 2.3. Enzyme activity assay, protein quantification and mass spectrometry). May teaches the enzyme is likely to be involved in the liberation of inorganic phosphate from intracellular sources and is especially in demand under phosphate-deprived conditions (abstract). May does not teach allowing oxidoreductase to act on the ethanolamine. Narrod teaches ethanolamine utilization is catalyzed by ethanolamine oxidase (i.e. oxidoreductase) (p.2189, 1 st column 2 nd paragraph). Narrod further teaches appropriate amounts of enzyme were incubated with ethanolamine and aliquots were removed at appropriate time intervals for glycolaldehyde assay (p.2189, 2 nd column – Analytical Procedures). Narrod teaches that metabolism of isotopically labeled ethanolamine led to the proposal of a pathway including oxidative deamination, and deamination of ethanolamine, the primary step of the proposed pathway, was indicated by the recovery of 15 N (p.2189 1 st column 1 st paragraph). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined phosphoethanolamine phosphatase taught by May and ethanolamine oxidase taught by Narrod. One of ordinary skill in the art would have been motivated to do so because May teaches the removal of phosphate from phosphoethanolamine which would produce ethanolamine, and Narrod teaches that ethanolamine is the substrate of ethanolamine oxidase. One of ordinary skill in the art would have found it beneficial to couple phosphoethanolamine phosphatase and ethanolamine oxidase together in a single reaction using colorimetric methods to detect phosphate to quantify the amount of ethanolamine phosphate in a sample. Regarding claim 4 , May does not teach wherein the oxidoreductase is an oxidase, or a concentration of the ethanolamine phosphate is determined by allowing the oxidoreductase to act on the ethanolamine and quantifying consumed oxygen. However, Narrod teaches ethanolamine oxidase (title). Narrod further teaches that the conversion of ethanolamine to glycolaldehyde is dependent on the presence of air, and because of the low activity of the enzyme preparation, oxygen consumption was followed with a standardized oxygen electrode (p.2191, 1 st column – Stoichiometry). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have quantified consumed oxygen because Narrod teaches that oxygen consumption could be measured using a standardized oxygen electrode. One of ordinary skill in the art would have found it beneficial to measure oxygen consumption to determine enzyme activity if enzyme activity was low to reliably determine the presence of the enzyme in the sample . 07-22-aia AIA Claim 2 is r ejected under 35 U.S.C. 103 as being unpatentable over M ay et al. (“ Arabidopsis thaliana PECP1 — Enzymatic characterization and structural organization of the first plant phosphoethanolamine/phosphocholine phosphatase”, Biochimica et Biophysica Acta, 2012, Vol. 1824, pp.319-325) in view of Narrod et al. (“Metabolism of Ethanolamine”, Journal of Biological Chemistry, 1964, Vol. 239, Issue 7, pp.2189-2193) as applied to claim 1 above, and further in view of Ohga et al. (US 9,631,224 issued on April 25, 2017) . The teachings of May et al. and Narrod et al. are discussed above. Regarding claim 2 , May and Narrod are silent on whether the sample includes at least one kind of amine other than ethanolamine phosphate. May and Narrod do not teach wherein the oxidoreductase is allowed to act on the at least one kind of amine before allowing phosphatase to act. Ohga teaches identifying a component in a body fluid of a patient as an objective guideline for diagnosis of depression (Column 1, lines 26-28). Ohga teaches that as a predictive marker, the level of tryptophan or its degradation product or the like in a body fluid can be determined (Column 1, lines 30-33). Ohga teaches that ethanolamine phosphate level in blood is useful as a biomarker for diagnosing depression (Column 1, lines 34-36). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected a blood or bodily fluid sample taught by Ohga as a sample in the method of May and Narrod, because Ohga teaches the detection of ethanolamine phosphate levels in blood is useful as a biomarker for diagnosing depression. One of ordinary skill would reasonably expect that a sample of blood or bodily fluid sample would predictably contain at least one kind of amine other than the ethanolamine phosphate as required by the claim. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEEPA MISHRA whose telephone number is (571) 272-6464. The examiner can normally be reached Monday - Friday 9:30am - 3:30pm EST. 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, Louise W. Humphrey can be reached at (571) 272-5543. 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. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657 /DEEPA MISHRA/Examiner, Art Unit 1657 Application/Control Number: 18/067,158 Page 2 Art Unit: 1657 Application/Control Number: 18/067,158 Page 3 Art Unit: 1657 Application/Control Number: 18/067,158 Page 4 Art Unit: 1657 Application/Control Number: 18/067,158 Page 5 Art Unit: 1657 Application/Control Number: 18/067,158 Page 6 Art Unit: 1657 Application/Control Number: 18/067,158 Page 7 Art Unit: 1657 Application/Control Number: 18/067,158 Page 8 Art Unit: 1657 Application/Control Number: 18/067,158 Page 9 Art Unit: 1657 Application/Control Number: 18/067,158 Page 10 Art Unit: 1657 Application/Control Number: 18/067,158 Page 11 Art Unit: 1657 Application/Control Number: 18/067,158 Page 12 Art Unit: 1657 Application/Control Number: 18/067,158 Page 13 Art Unit: 1657