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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 18, 2026 has been entered.
Status of Objections and Rejections
All rejections under 35 U.S.C. §103 are maintained.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 3-6, and 10-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sato (JP 2001157597, a machine translation used for citation) in view of Geisler (US 4613569), supported by PMS-PubChem for claim 4.
Regarding claim 1, Sato teaches a kit for detecting histamine (¶21: (a) histamine dehydrogenase, (b) an electron carrier and (c) a reduced electron carrier, a reagent for measuring at least one of the group consisting of 4-imidazolylacetaldehyde and ammonia for determining histamine), comprising
(i) histamine dehydrogenase (¶21: lines 1-2).
Sato further discloses component composition of histamine quantification reagent (¶78, Table 3), including WST-8 as a reduced electron carrier color former (¶78). WST-8 is a tetrazolium salt (¶78: Note 2: (2-methoxy-4-nitrophenyl)- 3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium-1 sodium).
Sato does not explicitly disclose the kit comprising boric acid.
However, Geisler teaches a stabilized preparation of tetrazolium salts for analytical purposes (Col. 1, lines 8-9). It has found that less acidic but complex-forming acids, such as boric acid, possess a very considerable stabilising effect not only against temperature stressing of the composition but also against illumination (Col. 1, lines 60-65). The stabilising agents, i.e., tetrazolium salts, are used as indicators for detection of various analytes with their corresponding dehydrogenase, e.g., lactate dehydrogenase for detection of lactic acid, alcohol dehydrogenase for detection of alcohol, acetaldehyde dehydrogenase for detection of acetaldehyde (col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sato by incorporating boric acid as taught by Geisler because boric acid would stabilize tetrazolium salt, one component of the histamine quantification reagent, for detection of an analyte (e.g., histamine) using a dehydrogenase enzyme (e.g., histamine dehydrogenase), and thus maintain the stabilising effect against temperature stressing and illumination (Geisler, Col. 1, lines 60-65) for the detection of reducing materials for analytical purposes (Col. 1, lines 8-13). Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
In claim 1, the boronic acid represented by the formula (I) or (II) and/or alkyl sulfate recited in claim 1 are optional, and do not required in the prior art.
Regarding claim 3, Sato teaches a mediator (¶64: tetrazolium-based electron carrier).
Regarding claim 4, Sato teaches the mediator is phenazinium methyl sulfate (¶64: phenazine methosulfate). As evidenced by PMS-PubChem, phenazinium methyl sulfate and phenazine methosulfate are synonyms (see page 2, number 33).
Regarding claim 5, Sato teaches a coloring reagent (¶20: a reducing color-developing reagent) that develops a color when histamine is oxidized by the histamine dehydrogenase (¶20: to cause an enzymatic action and quantifying a dye produced; (¶22: the histamine dehydrogenase used in the method for determining histamine by oxidative deamination; histamine dehydrogenase is allowed to act on a histamine-containing sample).
Regarding claim 6, Sato teaches wherein the coloring reagent is tetrazolium salt (¶64: a tetrazolium-based reducing color reagent).
Regarding claim 10, Sato and Geisler disclose all limitations of claim 1 as applied to claim 1, including the kit comprising the boric acid or the salt thereof (Geisler, Col. 1, lines 60-65). Sato and Geisler do not explicitly disclose such that a final concentration of said boric acid or the salt thereof at the time of measurement is 120 mM or lower.
However, Geisler discloses 1 to 10 moles, and preferably 1 to 2 moles of the complex-forming acid (e.g., boric acid), as a stabilizing acid, soluble in polar solvents per mol of tetrazolium salt (Col. 1, lines 37-40), rendering the concentration of boric acid is a result-effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sato and Geisler by adjusting the concentration of the boric acid within the claimed range because it is a result-effective variable and can be optimized through routine experimentation to obtain the optimal stabilization effect. MPEP 2144.05 (II)(B).
Regarding claim 11, the limitation “wherein the alkyl sulfate is sodium lauryl sulfate” is optional in the kit claimed in claim 1, and thus not required in the prior art.
Claim(s) 7-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sato in view of Geisler, and further in view of Ono (JP 2009039015, a machine translation for citation), supported by Wikipedia (MOPSO 2-Hydroxy-3-morpholinopropanesulfonic acid - Wikipedia) for claims 7-9.
Regarding claim 7, Sato and Geisler disclose all limitations of claim 1 as applied to claim 1. Sato and Geisler do not explicitly disclose a buffer comprising a compound having a zwitterion and having no carboxy group, the buffering being MOPSO.
However, Ono teaches a method for measuring objective substance using tetrazolium compound as a chromogen (title). Examples of buffers include MOPSO (page 5, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sato and Geisler by substituting its buffer with MOPSO as taught by Ono. The suggestion for doing so would have been that MOPSO is a suitable material for being buffer for measuring a sample using tetrazolium compound as chromogen and the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07. Here, the buffer MOPSO disclosed by Ono is the same buffer used in the specification (page 16, para. 2, lines 1-5), and would have the same structure, i.e., having a zwitterion and having no carboxy group (also see Wikipedia as an evidence: MOPSO is a zwitterionic organic chemical buffering agent; there is no carboxy group in the structure of MOPSO).
Regarding claim 8, Sato, Geisler, and Ono disclose all limitations of claim 7 as applied to claim 7, including the buffer being MOPSO. Here, the buffer MOPSO disclosed by Ono is the same buffer used in the specification (page 16, para. 2, lines 1-5), and would have the same structure, i.e., having a zwitterion and having a sulfo group (also see Wikipedia as an evidence: MOPSO is a zwitterionic organic chemical buffering agent; there is a sulfo group in the structure of MOPSO).
Regarding claim 9, Sato, Geisler, and Ono disclose all limitations of claim 8 as applied to claim 8, including the buffer being MOPSO. Here, the buffer MOPSO disclosed by Ono is the same buffer used in the specification (page 16, para. 2, lines 1-5), and would have the same structure, i.e., having a zwitterion, having a sulfo group, and having a hydroxy group at position 2 (also see Wikipedia as an evidence: MOPSO is a zwitterionic organic chemical buffering agent; there is a sulfo group in the structure of MOPSO; a hydroxyl group on the C-2 of the propane moiety).
Regarding claim 10, Sato and Geisler disclose all limitations of claim 1 as applied to claim 1, including the kit comprising the boric acid or the salt thereof (Geisler, Col. 1, lines 60-65). Sato and Geisler do not explicitly disclose such that a final concentration of said boric acid or the salt thereof at the time of measurement is 120 mM or lower. Geisler merely discloses 1 to 10 moles, and preferably 1 to 2 moles of the complex-forming acid (e.g., boric acid) soluble in polar solvents per mol of tetrazolium salt (Col. 1, lines 37-40).
However, Ono teaches a method for measuring objective substance using tetrazolium compound as a chromogen (title), and the presence of boric acid or its salt in the measurement reaction solution suppresses non-specific color development of the tetrazolium compound that caused by dehydroascorbic acid and accurately determines the concentration of the measurement target substance in the sample (page 2, para. 4, lines 4-7). The concentration of boric acid or a salt thereof is preferably in the range of 50 mM to 1M (page 4, para. 2), which overlaps the claimed range.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sato and Geisler by adjusting the concentration of the boric acid or the salt thereof for measurement of a substance within the claimed range because it provides a suitable concentration of boric acid to suppressing the nonspecific color development of a tetrazolium compound. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sato in view of Geisler, and further in view of Small (U.S. Patent Pub. 2002/0004213).
Regarding claim 12, Sato and Geisler disclose all limitations of claim 1 as applied to claim 1. Sato and Geisler do not explicitly disclose wherein the kit comprises a sample collection part and a reaction part.
However, Small teaches an enzymatic method for determining concentration of an analyte, such as LysoPA, in samples of biological fluids ([0008]). The detection of LysoPA includes sample collection ([0053]) so that blood was collected in BD vacutainer tubes ([0054]). The enzyme assay uses a 96 well microtiter plate ([0064] line 1) for enzyme reaction ([0064]: containing all reagents including dehydrogenase for the sample) to determine the level of LysoPA ([0065] line 1). Thus, Small teaches a sample collection part ([0053]: BD vacutainer tubes) and a reaction part ([0064]: the wells of a 96-well microtiter plate).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Sato and Geisler by incorporating the sample collection part and the reaction part into the kit to carry out the method of Sato and Geisler as taught by Small because the sample collection part and the reaction part are suitable means for carrying out an enzymatic method of determining an analyte concentration. Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A). Further, the combined Sato, Geisler, and Small would necessarily result in the reaction part comprising the reagents for determining histamine as disclosed by Sato and Geisler, including histamine dehydrogenase and boric acid or a salt thereof.
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive.
Applicant argues the machine translation was not correct and points out inconsistency between different paragraphs (Response, pp. 2-3). To avoid such confusion, Examiner cites explicit disclosures in Sato for an exemplified component composition of histamine quantification reagent (¶78, Table 3). It is clear that the histamine quantification reagent includes WST-8, which is a tetrazolium salt, indicated as a reduced electron carrier color former (¶78) or a tetrazolium-based reduced color-forming reagent (¶64).
Since the reagent of Sato contains the tetrazolium salt (e.g., WST-8), the stabilizer, boric acid, as taught by Geisler would be an obvious choice for one of ordinary skill in the art to use for stabilizing Sato’s reagent. Applicant’s argument that Geisler is limited to reaction involving NAD and NADH (p. 5, para. 1) is unpersuasive because Geisler teaches the stabilizing agent is used for tetrazolium salts in various detection systems, for dehydrogenase enzymes tailored to various analyte, e.g., lactate dehydrogenase for detection of lactic acid, alcohol dehydrogenase for detection of alcohol, acetaldehyde dehydrogenase for detection of acetaldehyde (Geisler, col. 2, para. 2).
Applicant argues Geisler is irrelevant to the claimed subject matter (p. 5, para. 5). This argument is unpersuasive because Geisler teaches a stabilizer for tetrazolium salts when they are used for analytical purpose based on dehydrogenase enzymes.
Applicant argues Ono is related to suppressing nonspecific color development of a tetrazolium compound due to dehydroascorbic acid (p. 6, para. 5). Examiner notes that Ono is no longer relied on for rejection of claim 1 in the previous Office actions starting from the one sent on February 6, 2025.
Conclusion
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/C. SUN/Primary Examiner, Art Unit 1795