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 .
Response to Amendment
Applicant’s amendment and remark filed on 05/07/26 has been entered. Claims 1, 4-5, 9-21 remain pending and are examined herein. Applicant’s amendment and remark have overcome each and every rejection under 112(b) set forth in Office Action mailed on 02/09/26.
The 112(b) rejection of claims 5, 13, and 17 is withdrawn in view of Applicant’s amendment.
The 103 rejection is maintained.
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.
Claim(s) 1, 4, 5, and 9-21 is/are rejected under 35 U.S.C. 103 as being obvious by Takatsuma (JP 2001204495A) in view of Provigate (WO 2019221264 A1) as cited in the Office Action mailed on 02/09/26.
Regarding claim 1, Takatsuma discloses a method for evaluating a degree of glycation of albumin (para. [0048]), the method comprising:
(a) providing a solution potentially containing albumin ( <Substrate solution> HSA substrate solution; Albumin Human, para. [0049])
(b) bringing the solution into contact with a color indicator (Take 1.2 ml of the reaction solution in a test tube and add 0.06 ml of HSA substrate solution or distilled water…and the absorption spectrum is measured with a spectrophotometer. The results are shown in FIGS. As can be seen from Figures 1 to 3, HABA can be used at pH 4.0 to 9.0 (Figure 1), BCG at pH 5.5 or below (Figure 2), and BCP at pH 4.5 to 7.5 (Figure 3). is there; para. [0050]);
(c) subsequently or simultaneously, bringing the solution into contact with protease (para.[0052]) in a state where the color indicator is present in the solution (The procedure for combining the protein quantification reagent, the proteolytic reagent, and the glycated amino acid coloring reagent includes, for example, selecting the type of chromogenic reagent so that the detection wavelengths of the protein quantification reagent and the glycated amino acid quantification reagent are equal, para. [0041]; also see para. [0007]-[0009] where Takatsuma discloses the objective is conducting the two reactions within the same tank);
(d) using a first reaction between the color indicator and the albumin to determine a concentration of the albumin in the solution (As shown in Fig. 5, color development was confirmed by the reaction of the albumin quantification reagent immediately after the start of the reaction…It was clarified that the albumin quantification was performed; para. [0057]);
(e) using a second reaction between the protease and the albumin in the solution containing the color indicator (para. [0007]-[0009] and [0041]) to determine a concentration of glycated albumin, and including:
using the protease to degrade the albumin to generate peptides (and then albumin was decomposed by the reaction of the protease and settled to the level almost before the sample addition in the vicinity of 200 seconds, para. [0057])
causing the generated peptides to react with ketoamine oxidase (Examples of the enzyme acting on the glycated glycated amino acid having an ε-amino…Debaryomyces genus-derived ketoamine oxidase; para. [0023]) to generate hydrogen peroxide (…investigate the relationship between the absorbance and the produced hydrogen peroxide, and the amount of enzyme that produces 1 µM hydrogen peroxide at 37°C-1 min was defined as 1U. The calculation formula is shown below. Enzyme activity (U/ml) = (As-Ab) x 2.32 x enzyme dilution rate; para.[0027]),
measuring a concentration of the generated hydrogen peroxide (The amount of the hydrogen peroxide may be quantified by, for example, coloring, luminescence, fluorescence, etc. by using a POD or the like to generate a dye or the like, and using catalase or the like to generate an aldehyde from an alcohol, The amount may be quantified. Para.[0037]), and determining, based on the concentration of the hydrogen peroxide, the concentration of the glycated albumin (Therefore, for colorimetric quantification of hydrogen peroxide generated by R-FOD, for example, 480 to 550 nm A combination of dyes having sufficient sensitivity in the vicinity, for example, a dye having an absorption maximum at 400 to 630 nm (4-AA and TOOS, etc.; λmax=555 nm) may be selected. Para. [0042]. The intensity of color is directly proportional to the amount of glycated amino acids, which corresponds to the concentration of glycated albumin); and
(f) determining a degree of glycation of the albumin, based on the concentration of the albumin and the concentration of the glycated albumin (para. [0066]).
Takatsuma does not disclose measuring a concentration of hydrogen peroxide by using a hydrogen peroxide electrode. Rather, the concentration of hydrogen is measured by colorimetric detection or by a dye (The amount of the hydrogen peroxide may be quantified by, for example, coloring, luminescence, fluorescence, etc. by using a POD or the like to generate a dye or the like, para. [0037]). However, Takatsuma discloses that dye/color indicator for the first albumin quantification reaction will not interfere with the detection in the second reaction by carefully adding sufficient amount of protease to terminate the proteolysis reaction (…add a sufficient amount of protease to terminate the proteolysis reaction before adding the glycated amino acid quantification reagent, para. [0041]) and optimizing the pH of the reaction vessel (so the pH of the reaction should be carefully selected so that the protein quantification reagent does not affect the glycated protein quantification. Para. [0041]).
Analogous art Provigate discloses a glycated protein sensor comprising a hydrogen peroxide detection part and an enzyme layer disposed on the hydrogen peroxide detection part, the enzyme layer including an immobilized protease and an immobilized ketoamine oxidase, where the hydrogen peroxide detection part includes a hydrogen peroxide electrode (translated description para. 34-35 and 37). Since Takatsuma’s procedure is uniquely designed so that the color indicator for the albumin quantification does not interfere with the second reaction (para. [0009] and [0041]), it would have been obvious to one of ordinary skill in the art before the effective filing date to have substituted the measurement method of glycated albumin via colorimetric determination of hydrogen peroxide of the method of Takatsuma with the electrode device of Provigate to derived the claimed invention as an alternative for determining hydrogen peroxide and glycated albumin concentration as Takatsuma discloses that any quantification method of hydrogen peroxide is suitable for assaying method (para. [0037]) and using an electrode detector would have eliminate complexity of adding two dyes in the same reaction vessel.
Regarding claim 4, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses measuring the first reaction between the color indicator and the albumin includes measuring an absorbance of the color indicator (Take 1.2 ml of the reaction solution in a test tube and add 0.06 ml of HSA substrate solution or distilled water…and the absorption spectrum is measured with a spectrophotometer. The results are shown in FIGS. As can be seen from Figures 1 to 3, HABA can be used at pH 4.0 to 9.0 (Figure 1), BCG at pH 5.5 or below (Figure 2), and BCP at pH 4.5 to 7.5 (Figure 3). is there; para. [0050]);
Regarding claim 5, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses measuring of the absorbance of the color indicator includes measuring a change in the absorbance with time (Ten seconds after the start of the reaction, the absorbance (A1) at 545 nm was measured for the purpose of obtaining the protein quantitative value, and then the proteolytic reaction was continued at 37°C. After 270 seconds (4.5 minutes) after the start of the reaction, the absorbance (A2) at 545 nm was measured; para.[0056]).
Regarding claim 9, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Provigate discloses measuring of the concentration of the hydrogen peroxide includes bringing the hydrogen peroxide having passed through an ion-exchange resin, into contact with the hydrogen peroxide electrode (translated description, paragraph 63).
Regarding claim 10-11, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses the color indicator is pH indicator BCP or BCG (Figure 2 or 3).
Regarding claim 12, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses the color indicator is BCP,
the method further comprising adjusting, during the first reaction, a pH of the solution to a range of 4.5 to 7.5 (After stirring, the mixture is allowed to stand at room temperature for 1 minute or longer…and BCP at pH 4.5 to 7.5 (Figure 3). is there. Para. [0050]) and adjusting, during the second reaction (the pH of the glycated protein quantification reagent added directly to the protein quantification reagent… para. [0050]), a pH of the solution to a range of pH 4.5 to 7.5 (and pH 4.5 to 7.5 when BCP is used. Para. [0050]).
The ranges cited overlapped with the claimed range of 4.5 to 8.5 for the first reaction and 6.0 to 9.0 for the second reaction. It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by Takatsuma because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I.
Regarding claim 13, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses wherein, when the first reaction between the color indicator and the albumin and the second reaction between the protease and the albumin are performed at the same time, a pH of the solution is adjusted to a range suitable for both of the first reaction and the second reaction (In addition, for example, albumin quantification reagents such as BCP, BCG, BPB, and MO have alkaline and violently colored dyes, so the pH of the reaction should be carefully selected so that the protein quantification reagent does not affect the glycated protein quantification. Para. [0041]).
Regarding claim 14, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses the color indicator is BCP, and
the pH is adjusted to a range of 4.5 to 7.5 (After stirring, the mixture is allowed to stand at room temperature for 1 minute or longer…and BCP at pH 4.5 to 7.5 (Figure 3). is there. Para. [0050]). The ranges cited overlapped with the claimed range of 7.0 to 8.5. It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by Takatsuma because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I.
Regarding claim 15, Modified Takatsuma discloses the claimed invention as discussed above in claim 12. Takatsuma discloses in the first reaction, a mixture solution of the solution does not contain a protein denaturing agent (<R-1> 10mM Tris buffer pH7.258mM 4-AA (manufactured by Wako Pure Chemical Industries, Ltd.) 15U/ml POD (manufactured by Sigma) 10mg/ml Alkaline protease (manufactured by Nagase & Co., 3000PU/) ml)1% CHAPSO0.4mM AlCl310mM EDTA0.001675% BCP0.5% Tween20; para.[0058]).
Regarding claim 16, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses wherein the color indicator is BCP or BCG (para. [0050]), the method further comprising adjusting, during the first reaction, a temperature of the solution to room temperature (para. [0050]), and adjusting, during the second reaction, a temperature of the solution to 37
℃
(para. [0052]).
Regarding claim 17, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses wherein, when the first reaction between the color indicator and the albumin and the second reaction between the protease and the albumin are performed at least partially at the same time (para. [0056]), a temperature of the solution is adjusted to a range suitable for both of the first reaction (270 μl of the above R-1 (protein quantification reagent, proteolytic reagent) was placed in a cell and incubated at 37° C., 9 μl of a sample was added, and the reaction was started at 37° C. with stirring. Para. [0056]) and the second reaction (…and then the proteolytic reaction was continued at 37°C. After 270 seconds (4.5 minutes) after the start of the reaction, the absorbance (A2) at 545 nm was measured, and after 300 seconds (5 minutes) after the start of the reaction, 90 μl of the above R-2 was added and stirred, and further at 37°C for 300 seconds (5 minutes). Para. [0056]).
Regarding claim 18, Modified Takatsuma discloses the claimed invention as discussed above in claim 12. Takatsuma discloses the temperature is adjusted to room temperature (After stirring, the mixture is allowed to stand at room temperature for 1 minute or longer…and BCP at pH 4.5 to 7.5 (Figure 3). is there. Para. [0050]).
Regarding claim 19, Modified Takatsuma discloses the claimed invention as discussed above in claim 1. Both Takatsuma and Provigate disclose enzyme and ketoamine oxidase can be used at room temperature (Takatsuma, para. [0050]); Provigate, translated description para. 115).
Regarding claim 20, Modifeid Takatsuma discloses the claimed invention as discussed above in claim 1. Takatsuma discloses the ketoamine oxidase is an oxidase that acts on an amino acid or peptide in which an epsilon-amino group is glycated (Examples of the enzyme acting on the glycated glycated amino acid having an ε-amino…Debaryomyces genus-derived ketoamine oxidase; para. [0023]) and the measuring the concentration of the generated hydrogen peroxide includes using a standard solution containing fructosyllysine (<< Method for measuring activity of enzyme acting on glycated amino acid >> <Composition of reaction solution>…1.0 mM α-carbobenzoxy-ε-D-fructosyl-L-lysine or fructosyl valine; para.[0026]) to perform measurement calibration (para. [0027]).
Regarding claim 21, Modified Takatsuma discloses the claimed invention as discussed above in claim 14. Takatsuma discloses in the first reaction, a mixture solution of the solution does not contain a protein denaturing agent (<R-1> 10mM Tris buffer pH7.258mM 4-AA (manufactured by Wako Pure Chemical Industries, Ltd.) 15U/ml POD (manufactured by Sigma) 10mg/ml Alkaline protease (manufactured by Nagase & Co., 3000PU/) ml)1% CHAPSO0.4mM AlCl310mM EDTA0.001675% BCP0.5% Tween20; para.[0058]) and the pH is adjusted to a range of 4.5 to 7.5 (After stirring, the mixture is allowed to stand at room temperature for 1 minute or longer…and BCP at pH 4.5 to 7.5 (Figure 3). is there. Para. [0050]). The ranges cited overlapped with the claimed range of 7.0 to 8.5. It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to have selected the overlapping portion of the ranges disclosed by Takatsuma because selection of overlapping portion of ranges has been held to be a prima facie case of obviousness. See MPEP § 2144.05.I.
Response to Arguments
Applicant's arguments filed 05/07/26 have been fully considered but they are not persuasive. The remark is directed to newly amended limitation “in a state where the color indicator is present”. Furthermore, applicant argues that the detection of the second reaction is done via colorimetric using a second dye (para. 1, page 8). Examiner has acknowledged the difference and newly amended limitation and addresses the concern in the newly modified rejection of claim 1 above.
In summary, Takatsuma/Kouzuma discloses the procedure is set up and optimized so both reactions can be done within one reaction vessel. Takatsuma/Kouzuma teaches the color indicator of the albumin quantification should not affect the signal for detection of glycated protein with the right experimental condition such as pH and amount of stop reagent added for the first reaction. Therefore, Examiner believes that one of ordinary skill in the art would have still expected same interferent-free behavior from the first indicator with another form of detection other than by colorimetric. For the reason mapped out in the newly amended claim 1, the rejection is respectfully maintained.
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 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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/M.H./ Examiner, Art Unit 1758
/MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758
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