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 .
Remarks
The amendments and remarks filed on 05/12/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn. Claims 1, 3-14, 18, 23-27, and 29-30 are pending; Claims 2, 15-17, 19-22, and 28 are cancelled; Claims 14, 23, and 27 are amended; Claims 1, 3-13, 18, 25-26, and 29-30 are withdrawn; and Claims 14, 23-24, and 27 are under examination.
Priority
This application, U.S. Application number 18/007689, is a national stage entry of International Application Number PCT/JP2021/020923, filed on 06/02/2021, which claims the foreign priority under 35 U.S.C. 119(a)-(d) to JP 2020-096248 filed on 06/02/2020.
English translation of the certified foreign priority document was submitted on 5/14/2026. The priority date 06/02/2020 of foreign priority application is now granted to the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/03/2026 and 05/12/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97 and have been considered by the examiner.
Withdrawal of Objections
The objection to the abstract of the specification is withdrawn due to the amendment to the abstract filed on 05/12/2026.
Withdrawal of Rejections
The rejection of claims 23-24 and 27 under 35 U.S.C. 112(b) in the previous office action is withdrawn due to the amendment to the claims filed on 05/12/2026.
The rejection of Claims 14, 23-24, and 27 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Itoh et al. is withdrawn due to newly submitted English translation of the certified foreign priority document as well as Applicant’s statement about the common ownership in the 05/12/2026 response (page 8), which disqualifies Itoh et al. to be the prior art.
19. The rejection of Claims 14, 23-24, and 27 under 35 U.S.C. 103 over Satoh et al. in view of Arai et al. is withdrawn due to the amendment to the claims filed on 05/12/2026.
Claim Rejections - 35 USC § 112(b), or 112, Second Paragraph
Claims 14, 23-24, and 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. This rejection is maintained.
Claim 14 is indefinite due to the recitation of “the coupler and the hydrogen donor are not used in the same step”. It is noted that the term “coupler” recited in the claim is not defined in the specification. In the broadest and reasonable interpretation, a hydrogen donor can be considered as a coupler because the hydrogen donor is coupled with peroxidase and reacts with hydrogen peroxide for producing a quinone product (as evidenced by Satoh et al. of record, described in the 103 rejection of the previous non-final office action). However, the claim recites the limitation of the coupler and hydrogen donor are not used in the same step, implying they are not the same compound. It is unclear what specific compound can be considered as a coupler. Applicant is required to clarify the metes and boundary of the term “coupler”.
The remaining claims are rejected for depending on an indefinite claim.
Claim Rejections - 35 USC § 103
Claims 14, 23-24, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Matsui et al. (EP 0990904, 2000, cited in IDS) in view of Arai et al. (US Patent No. 5004685, 1991, of record).
Matsui et al. teach a method for quantification of LDL lipoprotein cholesterol in a sample, comprising: a first step of selectively eliminating/erasing lipoprotein cholesterol other than the LDL lipoprotein cholesterol to be quantified (i.e. leading lipoprotein cholesterol other than an analyte lipoprotein cholesterol to be quantified to outside of a reaction system) by the action of cholesterol esterase and cholesterol oxidase in the presence of a surfactant that acts on lipoprotein cholesterol other than LDL lipoprotein cholesterol, wherein hydrogen peroxide generated from the action is eliminated/erased (such that the hydrogen peroxide is not detected in subsequent step); and a subsequent second step of quantifying the LDL lipoprotein cholesterol remaining after the first step (abstract, paras 0014-0016); wherein the first step comprises eliminating/erasing the hydrogen peroxide by using a hydrogen donor and peroxidase to convert the hydrogen peroxide to a colorless quinone (paras 0017/lines 2-3, 0018/lines 5-6); and wherein the second step comprises adding a surfactant to act on the LDL lipoprotein cholesterol along with cholesterol esterase and cholesterol oxidase, and then quantifying hydrogen peroxide generated from the action for quantification of LDL lipoprotein cholesterol (para 0027). Overall, the method of Matsui et al. involves the use of cholesterol oxidase, cholesterol esterase, peroxidase, a hydrogen donor, and a surfactant; and the peroxidase and hydrogen donor are used in the first step.
The method of Matsui et al. differs from the method of claims 14 and 23-24 in that Matsui et al. do not teach the second step involves the use of an iron complex and a coupler.
Arai et al. teach a process for determining/measuring an analyte cholesterol in a sample by measuring an amount of hydrogen peroxide generated from the interaction between the analyte cholesterol and catalytic enzymes, wherein the hydrogen peroxide (H2O2) is measured in a process involved with the use of a ferrocyanide compound (reading on the “iron complex”) and a colorless chromogen (reading on the “coupler”), in which the ferrocyanide compound reacts with H2O2 to generate water (H2O) and a ferricyanide compound, and the generated ferricyanide compound then converts the colorless chromogen to a color/pigment product to be optically detected for measuring the analyte cholesterol (see the reaction formula in col. 2/lines 15-33; col. 1/lines 36-41, col. 3/lines 25-32; and col. 8/lines 37-38).
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify the method of Matsui et al. by using an iron complex, specifically a ferrocyanide compound, in combination with a colorless chromogen (coupler) in the second step for measuring an amount of hydrogen peroxide producing from the LDL lipoprotein cholesterol to be quantified, thereby quantifying the LDL lipoprotein cholesterol, because it is well known in the art that a ferrocyanide iron complex compound n is effective at converting hydrogen peroxide and a colorless chromogen respectively to water and a pigment product that can be optically detected, thus allowing a analyte lipoprotein cholesterol in a sample to be quantitatively measured, as supported by Arai et al.
Regarding the claim 27, Arai et al. teach including catalase in the first step for eliminating/erasing hydrogen peroxide generated from un-targeted lipoprotein cholesterol (para 0017/lines 1-2). Thus, the claimed limitation would have been obvious over the cited prior art.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Double Patenting
Claims 14, 23-24, and 27 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 9-11, 13-14, and 16-28 of copending Application No. 18/007690 in view of Higuchi et al. (US 2013/0171674, 2013, cited in IDS). This rejection is maintained.
The claims of the ‘690 application are directed in part to a method of quantifying cholesterol in a lipoprotein other than small dense low density lipoprotein (sd LDL) in a sample, comprising: a first step [step (a)] of causing a first reagent composition having a cholesterol esterase activity (cholesterol esterase) and a cholesterol oxidase activity (cholesterol oxidase) to act on the sample, wherein the first reagent composition further comprises a surfactant; a second step [step (b)] of causing a second reagent composition to act on the sample to quantify cholesterol in a remaining lipoprotein after the first step; wherein: (i) the first reagent composition satisfies one or two of the following three conditions: containing a coupler, containing an iron complex, and having peroxidase activity, and (ii) the second reagent composition satisfies the remaining one or two of the conditions, which are not satisfied by the first reagent composition; wherein the first reagent composition comprises at least one of peroxidase activity (peroxidase) and catalase activity (catalase); wherein the second reagent composition contains a surfactant; wherein the lipoprotein contains LDL cholesterol, HDL cholesterol, HDL3 cholesterol, remnant cholesterol, or apoE-containing HDL cholesterol; wherein the first reagent composition comprises both cholesterol esterase activity (cholesterol esterase) and cholesterol oxidase activity (cholesterol oxidase), and further comprises peroxidase activity (peroxidase) and/or catalase activity (catalase); wherein the first reagent composition further comprises a protein having no enzymatic activity; wherein a measurement target is the HDL or the HDL3; and wherein a measurement target is the sd LDL or the apoE-containing HDL; wherein the coupler is one or more selected from 4-aminoantipyrine, an aminoantipyrine, vanillindiaminesulfonic acid, methylbenzthiazolinone hydrazone, and sulfonated methylbenzthiazolinone hydrazone.
Given the claims of the ‘690 application define the first reagent composition comprises peroxidase activity (i.e. the condition 3), the second reagent composition used in the second step accordingly satisfies the remaining conditions 1 and 2, i.e. comprising a combination of a coupler and iron complex, thus meeting the limitation of using the coupler and iron complex in the second step, as recited in the instant claim 14. Overall, a coupler, an iron complex, a peroxidase, a surfactant, cholesterol oxidase, cholesterol esterase, and catalase are collectively used in the two steps of the claimed method of the ‘690 application, thus meeting the claimed limitation.
The claimed method of the ‘690 application differs from the instantly claimed method in that the claims of the ‘690 application are silent about whether a hydrogen donor is included along with peroxidase in the first reagent composition of the first step.
It would have been obvious to include a hydrogen donor in the first reagent composition in the method of the ‘690 application for quantifying cholesterol in a lipoprotein, because it is a common practice in the art to include a hydrogen donor along with peroxidase in a reagent composition for acting on hydrogen peroxide generated from the interaction between the cholesterol and cholesterol oxidase.
In support, Higuchi et al. teach a method for quantifying cholesterol in HDL3 lipoprotein in a sample, wherein the lipoprotein cholesterol (other than LDL3) is eliminated in a first step such that the cholesterol does not affect the reaction for measurement of cholesterol in a subsequent step; and wherein cholesterol esterase and cholesterol oxidase are allowed to act on the lipoprotein cholesterol (other than LDL3) to generate hydrogen peroxide, which is then reacted with a hydrogen donor in the presence of peroxidase and converted to a colorless quinone (paras 0024, 0028, 0029/lines 1-7 and 9-11).
It is noted that the modified method of the ‘690 application meets the limitation that “the coupler and the hydrogen donor are not used in the same step” in the instant claim 14.
Therefore, in view of the teachings of the cited prior art, the method of Claims 14, 23-24, and 27 of the instant application is deemed obvious over the method of Claims 9-11, 13-14, and 16-28 of the copending Application No. 18/007690.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 14, 23-24, and 27 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 13, 18, and 21 of copending Application No. 17/641689. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons. This rejection is maintained.
The claims of the ‘689 application are directed in part to a method of quantifying cholesterol in small, dense LDL in a sample obtained from a subject in two steps, comprising: (1) a first step of leading cholesterol in lipoproteins other than small, dense LDL to outside of a reaction system in the presence of cholesterol esterase activity, cholesterol oxidase activity, and a surfactant that acts on lipoproteins other than small, dense LDL; and (2) a second step of quantifying cholesterol in lipoproteins remaining after the first step in the presence of a surfactant that acts on at least small, dense LDL, wherein,(i) in either the step (1)/(2), at least a coupler, an iron complex, peroxidase, catalase, electron donor and a surfactant are used; (ii) the coupler and the electron donor are not used simultaneously in the same step; (iii) the coupler and iron complex are used simultaneously in one of the first and second steps, and the peroxidase is used in another step; and (iv) the coupler, iron complex and peroxidase are not used simultaneously in the same step; wherein the first step involves the use of the peroxidase and an electron donor (in a first reagent), and the second step involves the use of the coupler and the iron complex (in a second reagent); and wherein the first step further involves the use of catalase (in a first reagent).
Regarding the limitation “hydrogen donor” that is used in the first step of the instant claim 14, the claims of the ‘689 application define using the electron donor, not hydrogen donor, along with peroxidase in the first step. The electron donor of the ‘689 application appears to be an alternative term used by the claims of the ‘689 application for representing the hydrogen donor, as evidenced by the specification of the ‘689 application (see para 0030 in pages 14-15) and the specification of the instant application (see para 0036 in page 14), which both disclose exactly the same chemical compounds (i.e. TOOS, MAOS, TOPS, HDAOS, HALPS, and HMMPS) as the electron donor and the hydrogen donor, respectively. Thus, the teachings of the ‘689 application meet the limitation about the hydrogen donor in the instantly claimed method.
Therefore, the method of Claims 14, 23-24, and 27 of the instant application is deemed obvious over the method of over claims 13, 18, and 21 of copending Application No. 17/641689.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 14, 23-24, and 27 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 7-12 of US Patent No. 12209270 in view of Higuchi et al. (US 2013/0171674, 2013, cited in IDS). This rejection is maintained.
The claims of the ‘270 patent are directed in part to a method of quantifying small dense LDL cholesterol (sdLDL-C) in a sample, comprising: a first step [step (a)] of allowing a first reagent composition having cholesterol esterase activity and cholesterol oxidase activity to act on the sample; and a second step [step (b)] allowing a second reagent composition for quantifying the sdLDL-C to act to quantify cholesterol in a remaining lipoprotein, wherein the first reagent composition satisfies one or two conditions of Conditions 1 to 3, and wherein the second reagent composition satisfies the remaining one or two conditions of Conditions 1 to 3, wherein Condition 1 comprises a coupler, wherein Condition 2 comprises an iron complex; and wherein Condition 3 possesses a peroxidase activity; wherein the first reagent composition further has catalase activity; wherein the first reagent composition contains a surfactant that acts on lipoproteins other than the sdLDL; and wherein the second reagent composition contains a surfactant that acts on the sdLDL.
It is noted when the first reagent solution in the first step of the claimed method of the ‘270 patent comprises peroxidase (i.e. satisfies the condition 3), the second reagent solution in the second step would accordingly comprises a coupler and an iron complex (i.e. satisfies conditions 1 and 2), Thus, the teachings of the ‘270 patent renders the instantly claimed limitation of using coupler and iron complex in the second step to be obvious. Overall, a coupler, an iron complex, a peroxidase, a surfactant, and catalase are collectively used in the two steps of the claimed method of the ‘270 patent.
The claimed method of the ‘270 patent differs from the instantly claimed method in that the claims of the ‘270 patent are silent about whether a hydrogen donor is included along with peroxidase in the first reagent composition of the first step.
The teachings of Higuchi et al. are described above.
It would have been obvious to include a hydrogen donor in the first reagent composition in the method of the ‘270 patent for quantifying the sdLDL cholesterol in a sample, because it is a common practice in the art to include a hydrogen donor along with peroxidase in a reagent composition for acting on hydrogen peroxide generated from the interaction between the cholesterol and cholesterol oxidase, as supported by Higuchi et al.
It is noted that the modified method of the ‘270 patent meets the limitation that “the coupler and the hydrogen donor are not used in the same step” in the instant claim 14.
Therefore, in view of the teachings of the cited prior art, the method of Claims 14, 23-24, and 27 of the instant application is deemed obvious over the method of claims 7-12 of US Patent No. 12209270.
Response to Arguments
Applicant's arguments about the 112(b) rejection in the response filed on 05/12/2026 (pages 6-7) are based on newly submitted claim amendment. The arguments have been fully considered, and they are found to be persuasive in part because the claim amendment overcomes the 112(b) rejection over claims 23-24 and 27, but it is not sufficient to overcome the rejection over claim 14. Specifically, Applicant failed to address the issue related to the term “coupler” in the limitation “the coupler and the hydrogen donor are not used in the same step” of the claim 14. As such, the 112(b) rejection over the claim 14 is maintained in this office action, as indicated above.
Applicant's arguments about the rejection of claims 14, 23-24, and 27 under 35 USC 102(a)(1) and 102(a)(2) as being anticipated by Itoh in the 05/12/2026 response (page 8) have been fully considered but they are moot, because the rejection has been withdrawn as indicated above.
Applicant's arguments about the rejection of claims 14, 23-24, and 27 under 35 USC 103 over Satoh in view of Arai in the 05/12/2026 response (pages 8-10) have been fully considered but they are moot because the 103 rejection has been withdrawn, and the ground of the rejection in this office action is different from that in the previous office action (see pages 5-7 for details). Overall, the conclusion of the obviousness of the newly amended claims 14, 23-24, and 27 has been established for all the reasons indicated above.
Applicant’s arguments about the double patenting rejections in the response filed on 05/12/2026 (page 10/last paragraph) have been fully considered but they are not persuasive. Applicant’s arguments are based on those arguments presented against the prior art references cited in the 103 rejection (in pages 9-10 of the response). However, none of the double patenting rejections are relevant to the prior art references (Saitoh and Arais) cited in the 103 rejection. Thus, the arguments based on Saitoh and Arais are moot to the double patenting rejections. Accordingly, the double patenting rejections are maintained in this office action.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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