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
Claims 1-2, 4-6 and 9-10 are pending.
Claims 3 and 7-8 are cancelled. Claims 6 and 9-10 are withdrawn.
Claims 1-2 and 4-5 are under examination.
The objection to the abstract is withdrawn in light of the submission of an updated abstract on 4/21/2026.
The objection to claims 1-5 is withdrawn in light of the correction of the informalities in the amended claim set dated 4/21/2026.
The previous rejection of claims 1-5 under 35 U.S.C. 101 is withdrawn in light of the cancellation of claim 3 and the amendment of claims 1-2 and 4-5 to recite a patent-eligible process containing active method steps in the response dated 4/21/2026.
The previous rejection of claims 1-5 under 35 U.S.C. 112(b) is withdrawn in light of the cancellation of claim 3 and the amendment of claims 1-2 and 4-5 to recite active method steps clarifying the quantification of ethanolamine phosphate; clarifying the number of oxidoreductase enzymes, and deleting the phrase “allowing” in the amendment dated 4/21/2026.
The previous rejection of claims 1 and 4 under 35 U.S.C. 103 as being unpatentable over May et al. in view of Narrod et al. is withdrawn in light of the claim amendment amending claim 4 into independent form and the requirement of quantifying the generated hydrogen peroxide in claim 4 in the response dated 4/21/2026.
Priority
This application, filed on 12/16/2022, is a CON of PCT/JP2021/022845 filed 6/16/2021, which claims priority to JAPAN 2020-104881 filed 6/17/2020. The effective filing date for prior art purposes is the filing date of the current application, December 16, 2022.
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.
Modified rejection necessitated by amendment: Claims 1-2 and 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et al. (JP 6868649 B2, published June 20, 2019; previously cited) in view of Imamura et al. (JP2005052034A, published on March 3, 2005; previously cited), and Mawatari et al. (JP2016045112A, published on April 4, 2016; previously cited). 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, 4th paragraph).
Sasaki does not teach adding a mediator in the sample, or adding at least one kind of oxidoreductase acting on the ethanolamine to produce a reaction product.
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). Imamura teaches that an oxidase acts on ethanolamine and generates hydrogen peroxide (English translation p.2, 3rd paragraph). Imamura further teaches an analysis reagent (R1) containing ethanolamine oxidase, catalase or peroxidase and a chromogen such as a phenol derivative, aniline derivative, or toluidine derivative and a reagent 2 composed of a component coupler such as phospholipase D, 4 aminoantipyrine, or 3-methyl-2-benzothiazolinone hydrazone (i.e. adding a mediator) (English translation p.2, paragraph 5). Imamura teaches hydrogen peroxide produced by the ethanolamine oxidase reaction simultaneously with the mixing of R1 and R2 produces a dye by oxidative condensation between the chromogen of the Trinder reagent and the coupler, and the absorbance of this dye can be measured spectroscopically (English translation p.2, paragraph 5).
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 treating choline with choline oxidase, then using peroxidase to produce a color, 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 and reagents R1 and R2 containing mediators 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.
Regarding claim 4, 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, 4th paragraph).
Sasaki does not teach adding at least one kind of oxidoreductase acting on the ethanolamine to produce a reaction product, or the reaction product is hydrogen peroxide.
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). Imamura teaches that an oxidase acts on ethanolamine and generates hydrogen peroxide (English translation p.2, 3rd paragraph). Imamura further teaches an analysis reagent (R1) containing ethanolamine oxidase, catalase or peroxidase and a chromogen such as a phenol derivative, aniline derivative, or toluidine derivative and a reagent 2 composed of a component coupler such as phospholipase D, 4 aminoantipyrine, or 3-methyl-2-benzothiazolinone hydrazone (English translation p.2, paragraph 5). Imamura teaches hydrogen peroxide produced by the ethanolamine oxidase reaction simultaneously with the mixing of R1 and R2 produces a dye by oxidative condensation between the chromogen of the Trinder reagent and the coupler, and the absorbance of this dye can be measured spectroscopically (English translation p.2, paragraph 5).
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 treating choline with choline oxidase, then using peroxidase to produce a color, 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 combine the reaction of ethanolamine-containing phospholipid using tyramine oxidase and reagents R1 and R2 containing mediators 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 in a sample using colorimetric methods.
Response to Arguments
Applicant argues claim 1 includes the subject matter of previous claim 3, and now requires adding a mediator, using the oxidoreductase acting on ethanolamine to reduce the mediator, and determining ethanolamine phosphate concentration by quantifying the reduced mediator as the reaction product (See Remarks dated 4/21/2026, p.8 4th paragraph). Applicant argues that Sasaki’s ethanolamine-phosphate measurement generates ethanolamine from ethanolamine phosphate and uses an ethanolamine detection composition, but does not disclose oxidoreductase-based mediator reduction and quantification of a reduced mediator as the detected reaction product (See Remarks dated p.8 5th paragraph). Applicant argues that Imamura and Mawatari are directed to assays for ethanolamine-containing phospholipids/ether phospholipids and disclose oxidase/peroxidase colorimetric detection schemes that proceed via hydrogen peroxide, which are materially different from claim 1’s requirement that the oxidoreductase reduces an added mediator and that ethanolamine phosphate concentration is determined by quantifying the reduced mediator (See Remarks dated 4/21/2026, p.8 last paragraph). Applicant argues that May teaches phosphoethanolamine phosphatase activity and Narrod for ethanolamine oxidase, but neither May nor Narrod teaches or suggests the claimed mediator-based quantitation (See Remarks dated 4/21/2026, p.9 1st paragraph).
Applicant argues claim 4 is rewritten in independent form to include features of base claim 1, and Sasaki, Imamura and Mawatari are neither cited nor understood by Applicant to teach the features recited in previous Claim 4 (See Remarks dated 4/21/2026, p.9, 3rd paragraph). Applicant argues that May in view of Narrod does not teach or suggest determining a concentration of the ethanolamine phosphate by adding the at least one kind of oxidoreductase to act on the ethanolamine to produce hydrogen peroxide as the reaction product and quantifying the generated hydrogen peroxide by reacting with a coloring reagent by utilizing a catalytic reaction of peroxidase as set forth in amended claim 1 (See Remarks dated 4/21/2026, p.9 paragraph 6).
Applicant's arguments filed April 21, 2026 have been fully considered but they are not persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant’s arguments are directed towards newly added claim limitations, which were not recited in the previously rejected claims. As discussed in the rejection above, 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). Sasaki teaches that alkaline phosphatase is used as the enzyme for producing ethanolamine from PEA.
Imamura teaches a method for analyzing ethanolamine-containing phospholipid characterized by using at least phospholipase and tyramine oxidase (a.k.a. oxidoreductase). Imamura teaches that an oxidase acts on ethanolamine and generates hydrogen peroxide. Imamura further teaches an analysis reagent (R1) containing ethanolamine oxidase, catalase or peroxidase and a chromogen such as a phenol derivative, aniline derivative, or toluidine derivative and a reagent 2 composed of a component coupler such as phospholipase D, 4 aminoantipyrine, or 3-methyl-2-benzothiazolinone hydrazone. Imamura teaches hydrogen peroxide produced by the ethanolamine oxidase reaction simultaneously with the mixing of R1 and R2 produces a dye by oxidative condensation between the chromogen of the Trinder reagent and the coupler, and the absorbance of this dye can be measured spectroscopically.
Mawatari also teaches a method for quantifying ethanolamine ether phospholipid or choline ether phospholipid contained in a serum or blood sample. Mawatari further teaches processing ethanolamine generated by decomposition of ethanolamine ether phospholipid by phospholipase D by using amine oxidase (a.k.a. oxidoreductase) and treating choline with choline oxidase, then using peroxidase to produce a color, measuring the color developed using a spectrophotometer, and preparing a standard curve to quantify the ethanolamine ether phospholipid.
Thus, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the reaction of ethanolamine-containing phospholipid using tyramine oxidase and reagents R1 and R2 containing mediators 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 in a sample using colorimetric methods.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/DEEPA MISHRA/Examiner, Art Unit 1657
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