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 .
Election/Restrictions
Applicant’s election of claims 1-11 and 13 in the reply filed on 06/25/2026 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)).
Claim Rejections - 35 USC § 101
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 1-11 and 13 are rejected under 35 USC 101 because the claimed invention is directed to an abstract idea without significantly more. The claims will be analyzed below according to MPEP 2106.
Inquiry 1: Is the claim directed to a statutory category of invention (process, machine, manufacture, or composition of matter)?
Claims 1-11 and 13 are directed to a process.
Inquiry 2A Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, claim 1 recites, in a first sequence, “measuring concentration of the measurement object from the first result based on a relationship between the anisotropy and a dispensing amount of the fluorescent reagent dispensed in the dispensing step” and, in a second sequence, “measuring the concentration of the measurement object from the second result based on the relationship between the anisotropy”. Both of these recitations refer to utilizing the mathematical relationship between fluorescent anisotropy and concentration to calculate the concentration of a measurement object. This is a mathematical calculation that is categorized as an abstract idea. See MPEP 2106.04(a)(2).
Claims 2-11 and 13 are dependent upon claim 1 and therefore recite by reference the mathematical calculation of claim 1.
Inquiry 2A Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
No, they do not.
Regarding claim 1, the “dispensing step” and “measuring step” are both considered to be the insignificant extra-solution activity of mere data-gathering, which is not sufficient in amounting to a practical application. See MPEP 2106.05(g). Furthermore, nothing occurs after the mathematical calculations of claim 1, so there is no practical application of such.
Claims 2, 4, 8, and 9 are directed to the insignificant extra-solution activity of mere data gathering that precedes the judicial exceptions; this does not integrate the judicial exception into a practical application. MPEP 2106.05(g).
Claims 3, 5, 6, 7, 10, 11, and 13 are directed to the judicial exceptions, but they amount to mere instructions to generally apply the judicial exceptions. MPEP 2106.05(f).
Inquiry 2B: Does the claim recite additional limitations that amount to significantly more than the judicial exception?
Regarding claim 1, the “dispensing step” and “measuring step” are both interpreted to be the insignificant extra-solution activity of mere data-gathering, which does not amount to significantly more than the judicial exceptions. See MPEP 2106.05(g). Furthermore, nothing occurs after the mathematical calculations of claim 1, so there is no practical application of such.
Claims 2, 4, 8, and 9 are directed to the insignificant extra-solution activity of mere data gathering that precedes the judicial exceptions; this does not amount to significantly more than the judicial exceptions. MPEP 2106.05(g).
Claims 3, 5, 6, 7, 10, 11, and 13 are directed to the judicial exceptions, but they amount to mere instructions to generally apply the judicial exceptions and do not amount to significantly more. MPEP 2106.05(f).
Furthermore, the subject matter of claims 1-11 and 13 are well-understood, routine, and conventional in the arts before the effective filing date of the instant application. Fukuyama (JP2021173731A) (references to Fukuyama in this office action are made using the Machine Translated version of the Description that is provided) teaches a method of dispensing and measuring analytes using fluorescent reagents and performing multiple measurements to measure/calculate the concentration of the analyte using the mathematical relationship between fluorescent anisotropy and concentration; Fukuyama also teaches the construction of several calibration curve (which shows saturation of anisotropy) using the measurement method, and teaches the use of predetermined values to guide the measurement method (see Examples 1-5 and Comparative examples 1-2 of Fukuyama, [47]-[57]). Colston et al. (US20220008928A1) teaches a method of performing a fluorescent anisotropy measurement method using a program on a computer-readable medium (see abstract, [184], [205], and [824] of Colston). See MPEP 2106.05(d).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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) 1-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fukuyama et al (US20210341488A1).
Regarding claim 1, Fukuyama teaches A measuring method comprising (see Examples 1-5 and Comparative Examples 1-2 of Fukuyama):
a dispensing step of dispensing fluorescent reagent into a measurement object ([80]) (The fluorescent labeling substance solution 8 μL… 30 μL of the rabbit IgG solution… were mixed to obtain 7-level 300 μL samples for preparing a standard curve) (Examiner interprets the “rabbit IgG solution” to be a measurement object);
a measuring step of irradiating light onto a reaction solution in which the measurement object and the fluorescent reagent are mixed, and of measuring anisotropy of fluorescent light emitted from the reaction solution ([82]) (the fluorescence polarization of the sample for standard curve preparation and the sample for measurement was measured with…);
a first sequence for acquiring a first result about the anisotropy by performing the dispensing step and the measuring step and for measuring concentration of the measurement object from the first result based on a relationship between the anisotropy and a dispensing amount of the fluorescent reagent dispensed in the dispensing step ([76] and [81] and [83]) (To quantify rabbit IgG and 30 μL of rabbit IgG solutions respectively containing 13 nM and 120 nM rabbit IgG were separately prepared, and 8 μL of the fluorescent labeling substance… were mixed to prepare a sample for measurement and In FIG. 8, black circles represent a standard curve, and black squares are the measurement results of the samples containing 1.3 nM (nanomol/L) and 12 nM (nanomol/L) of IgG) (Examiner points out that the two measurement samples/results are calculated based on a standard curve fit shown in figure 8, which is related to the dispensing amount of fluorescent reagent, concentration of IgG, measured anisotropy of the sample, and other factors);
I Fukuyama does not clearly describe a second sequence for acquiring a second result about the anisotropy by performing the dispensing step and the measuring step one or more times after the first sequence and for measuring the concentration of the measurement object from the second result based on the relationship between the anisotropy and the dispensing amount of the fluorescent reagent dispensed in the dispensing step.
Earlier in the disclosure, Fukuyama teaches of collecting all data in triplicate ([63]) (All data were measured 3 times). It is commonly understood in the art of biochemical assays that preparing samples and collecting data in triplicate improves the statistical accuracy of the data that is collected.
It would have been obvious for a person having ordinary skill in the art before the effective filing date of the invention to duplicate the first sequence of Fukuyama by repeating the first sequence so that a total number of dispensing steps and measuring steps is 3 because doing so would improve the accuracy of the data that is collected with a reasonable expectation of success (see [63] and Example 4 of Fukuyama). See also MPEP 2144.04.
Regarding claim 2, Fukuyama teaches the measuring method according to claim 1 as rejected above. Fukuyama teaches the use of predetermined values, where a first result (fluorescence polarization value) is smaller than a first predetermined value ([37]) (FIG. 1 indicates that the total mass region that can be measured by fluorescence polarization differs depending on the fluorescence life of a fluorescent dye and that concentration of a target substance can be quantified when the fluorescence polarization is within a predetermined range (a range of about 0.05 to 0.35 in FIG. 1)). Examiner is interpreting “0.35” to be a first predetermined value, which corresponds to the upper limit of the sigmoidal relationship between fluorescence anisotropy and the amount of the target substance and fluorescent labeling substance. Examiner is also interpreting figure 1 to show instances where the anisotropy result is below said predetermined value. See Figure 1:
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Fukuyama teaches that, in Example 4, the fluorescence anisotropy shows a similar sigmoidal relationship between anisotropy and the amount of IgG; see figure 8 (dotted lines indicate maximum and minimum anisotropy values, the maximum anisotropy value being ~0.13 polarization):
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It would have been obvious to a person having ordinary skill in the art before the effective filing date of the instant application to combine the method of Fukuyama as described above for claim 1 with a first predetermined value corresponding to the upper limit of quantification for the fluorescence anisotropy as suggested by Fukuyama earlier in the disclosure (see [37], [76], [81], [83], and Figures 1 and 8 of Fukuyama). The combination of these teachings would have yielded the predictable result of defining the maximum fluorescent anisotropy value and obtaining measurement results below the predetermined threshold value with a reasonable expectation of success.
Regarding claim 3, Fukuyama teaches the measuring method according to claim 2 as rejected above, wherein the first sequence measures the concentration of the measurement object based on a first calibration curve indicating a relationship between the concentration of the measurement object and the anisotropy ([76] and [81] and [83]) (To quantify rabbit IgG and 30 μL of rabbit IgG solutions respectively containing 13 nM and 120 nM rabbit IgG were separately prepared, and 8 μL of the fluorescent labeling substance… were mixed to prepare a sample for measurement and In FIG. 8, black circles represent a standard curve, and black squares are the measurement results of the samples containing 1.3 nM (nanomol/L) and 12 nM (nanomol/L) of IgG) See Figure 8, which shows the standard curve (circles are standard curve samples) and the measurement values (squares are ‘measurement samples’) that are below the predetermined value of ~0.13 polarization:
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Regarding claim 4, Fukuyama teaches the measuring method according to claim 2 as rejected above, wherein the measuring method performs the second sequence in a case where the first result is equal to or larger than the first predetermined value. See annotated Figure 8 which shows the first result is equal to or larger than the first predetermined value (~0.13 polarization):
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Note that the “result” is the anisotropy value (~0.13) of the sample that is pointed to above; it is roughly equal to the predetermined value (~0.13).
Regarding claim 5, Fukuyama teaches the measuring method according to claim 1 as rejected above. Fukuyama teaches wherein the second sequence repeats the dispensing step and the measuring step as rejected above.
Fukuyama does not clearly teach within a single embodiment “until an anisotropy value becomes smaller than a predetermined value.”
Earlier in the disclosure, Fukuyama teaches of a first and second predetermined value ([37]) (FIG. 1 indicates that the total mass region that can be measured by fluorescence polarization differs depending on the fluorescence life of a fluorescent dye and that concentration of a target substance can be quantified when the fluorescence polarization is within a predetermined range (a range of about 0.05 to 0.35 in FIG. 1)). Examiner is interpreting “0.35” to be a first predetermined value, which corresponds to the upper limit of the sigmoidal relationship between fluorescence anisotropy and the amount of the target substance and fluorescent labeling substance; Examiner is interpreting “0.05” to be a second predetermined value, which corresponds to the lower limit of the sigmoidal relationship between fluorescence anisotropy and the amount of the target substance and fluorescent labelling substance. Examiner is also interpreting figure 1 to show instances where the anisotropy result is equal to, below, and above said predetermined values. See Figure 1:
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Fukuyama teaches that, in Example 4, the fluorescence anisotropy shows a similar sigmoidal relationship between anisotropy and the amount of IgG; see figure 8 (dotted lines indicate maximum and minimum anisotropy values, the maximum anisotropy value being ~0.13 polarization and the minimum anisotropy value being ~0.09):
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Note that for each instance of measurement shown above in figure 8, the dispensing step and measuring step is repeated ([80] and [81]) (The fluorescent labeling substance solution 8 μL… the rabbit IgG solution of each concentration, and 232 μL of PBS were mixed to obtain 7-level 300 μL samples for preparing a standard curve and rabbit IgG were separately prepared… 30 μL of the rabbit IgG solution, and 232 μL of PBS were mixed to prepare a sample for measurement). In figure 8, samples are collected at various concentrations of IgG: at the highest concentration of IgG (~100 nM IgG, corresponding to an anisotropy of ~0.13, which is the same as the maximum anisotropy value) until the samples are at their lowest IgG concentration and show minimal anisotropy (<1 nM IgG, corresponding to an anisotropy of <0.09, which is lower than the minimum anisotropy value of ~0.09).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the instant application to modify the method of Fukuyama as described above for claim 1 by using a predetermined value corresponding to the lower limit of quantification as suggested by Fukuyama earlier in the disclosure (see [37], [76], [81], [83], and Figures 1 and 8 of Fukuyama). The combination of these teachings would have yielded the predictable result of defining the minimum fluorescent anisotropy values and obtaining measurement results equal to, above, and below the predetermined values with a reasonable expectation of success.
Regarding claim 6, Modified Fukuyama teaches the measuring method according to claim 5 as rejected above. Modified Fukuyama teaches wherein the second sequence measures the concentration of the measurement object from the second result based on a second calibration curve indicating a relationship between the dispensing amount of the fluorescent reagent and the concentration of the measurement object; see claim 1 ‘duplication of parts’ rejection, which would duplicate at least the dispensing, measurements, results and calibration curves.
Regarding claim 7, Fukuyama teaches the measuring method according to claim 6, wherein the second sequence measures the concentration of the measurement object based on the second calibration curve, the second result, and the dispensing amount of the fluorescent reagent in the second sequence; see claim 1 ‘duplication of parts’ rejection, which would duplicate at least the dispensing, measurements, results and calibration curves.
Regarding claim 8, Fukuyama teaches the method of claim 1 as rejected above, wherein the dispensing amount of the fluorescent reagent dispensed in the dispensing step of the first sequence and the dispensing amount of the fluorescent reagent dispensed in the dispensing step of the second sequence are equal to each other. Examiner points out that the duplication of the dispensing, measurement etc. would use the same dispensing amount of the fluorescent reagent.
Regarding claim 9, Fukuyama teaches the measuring method according to claim 2, wherein the first predetermined value is set based on a value at which the anisotropy is saturated relative to the concentration of the measurement object. See Figure 8, where the upper dotted line shows the first predetermined value (~0.13 polarization) corresponding to saturated anisotropy:
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Regarding claim 10, Fukuyama teaches the measuring method according to claim 1, wherein the measuring method performs the second sequence in a case where the first result is equal to or larger than a first predetermined value, wherein the second sequence repeats the dispensing step and the measuring step, and wherein the second predetermined value is set to be equal to or smaller than the first predetermined value. Fukuyama teaches of a first and second predetermined value ([37]) (FIG. 1 indicates that the total mass region that can be measured by fluorescence polarization differs depending on the fluorescence life of a fluorescent dye and that concentration of a target substance can be quantified when the fluorescence polarization is within a predetermined range (a range of about 0.05 to 0.35 in FIG. 1)). Examiner is interpreting “0.35” to be a first predetermined value, which corresponds to the upper limit of the sigmoidal relationship between fluorescence anisotropy and the amount of the target substance and fluorescent labeling substance; Examiner is interpreting “0.05” to be a second predetermined value, which corresponds to the lower limit of the sigmoidal relationship between fluorescence anisotropy and the amount of the target substance and fluorescent labelling substance. Examiner is also interpreting figure 1 to show instances where the anisotropy result is equal to, below, and above said predetermined values. See Figure 1:
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Fukuyama teaches that, in Example 4, the fluorescence anisotropy shows a similar sigmoidal relationship between anisotropy and the amount of IgG; see figure 8 (dotted lines indicate maximum and minimum anisotropy values, the maximum anisotropy value being ~0.13 polarization and the minimum anisotropy value being ~0.09):
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Note that for each instance of measurement shown above in figure 8, the dispensing step and measuring step is repeated ([80] and [81]) (The fluorescent labeling substance solution 8 μL… the rabbit IgG solution of each concentration, and 232 μL of PBS were mixed to obtain 7-level 300 μL samples for preparing a standard curve and rabbit IgG were separately prepared… 30 μL of the rabbit IgG solution, and 232 μL of PBS were mixed to prepare a sample for measurement). In figure 8, samples are collected at various concentrations of IgG: at the highest concentration of IgG (~100 nM IgG, corresponding to an anisotropy of ~0.13, which is the same as the maximum anisotropy value) until the samples are at their lowest IgG concentration and show minimal anisotropy (<1 nM IgG, corresponding to an anisotropy of <0.09, which is lower than the minimum anisotropy value of ~0.09).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the instant application to modify the method of Fukuyama as described above for claim 1 by using a first predetermined value corresponding to the upper limit of quantification for the fluorescence anisotropy and a second predetermined value corresponding to the lower limit of quantification as suggested by Fukuyama earlier in the disclosure (see [37], [76], [81], [83], and Figures 1 and 8 of Fukuyama). The combination of these teachings would have yielded the predictable result of defining the maximum and minimum fluorescent anisotropy values and obtaining measurement results equal to, above, and below the predetermined values with a reasonable expectation of success.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fukuyama (US20210341488A1) as applied to claim 1 above, and further in view of Jameson et al. (Chemistry Reviews, Vol. 110, No. 5, 12 May 2010, pgs. 2685-2705).
Regarding claim 11, Fukuyama teaches the measuring method according to claim 1 as rejected above. Fukuyama teaches a first and second sequence as rejected above.
Fukuyama is silent to wherein the first sequence adjusts the dispensing amount of the fluorescent reagent so as to measure the concentration of the measurement object lower than that in the second sequence.
In the analogous art of Fluorescence Polarization/Anisotropy in Diagnostics and Imaging, Jameson teaches of adjusting the dispensing amount of the fluorescent reagent so as to measure the concentration of the measurement object lower than that in the second sequence (pg. 12 first paragraph) (a fluorescent, non-hydrolyzable GTP analog) was present and the concentration of the GTP-binding protein, dynamin, was varied by starting at high concentrations followed by dilution. The binding curve was fit to the anisotropy equation). Jameson teaches that this dilution process allows for more precise anisotropy measurements to be made, which allows for more accurate observations in relation to the anisotropy (pg. 12 first paragraph of Jameson) (A Kd of 8.3 micromolar was found… If one did not take into account the enhancement of the mant-GTPγS fluorescence upon binding one would erroneously determine a Kd near 2.5).
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fukuyama (US20210341488A1) as applied to claim 1 above, and further in view of Colston et al. (US20220008928A1).
Regarding claim 13, Fukuyama teaches the measuring method according to claim 1 as rejected above.
Fukuyama is silent to a non-transitory computer-readable storage medium storing a program that causes a computer to execute the measuring method according to claim 1.
In the analogous art of using fluorescent anisotropy to determine the concentration of an analyte (abstract and [824] of Colston), Colston teaches the use of a computer-readable storage medium storing a program that causes a computer to execute a measuring method ([184] and [205] of Colston) (The control electronics may be in communication with and/or may be programmed to control any other aspects of system and Controller also may contain a computer-readable medium… including instructions for performing any of the methods disclosed herein). Colston teaches that this is advantageous because it enables the tracking of reagent usage and other relevant data related to the measuring method ([184]) (The memory device may carry information about the cartridge, such as reagents pre-loaded to the cartridge, data about the loaded sample, aspects of sample processing).
It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to modify the measurement method of Fukuyama to include a non-transitory computer-readable storage medium storing a program that causes a computer to execute the measuring method according to claim 1 as suggested by Colston because it would lead to the tracking of reagent usage and other relevant data related to the measuring method with a reasonable expectation of success ([184] and [205] of Colston and Examples 1 and 4 of Fukuyama).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Roger et al. (WO2010060454A1) teaches a method and computer-mediated apparatus for measuring the fluorescent anisotropy of an analyte; Weissleder et al. (US20200408687A1) teaches a method of utilizing fluorescent anisotropy to detect and analyze various biological analytes such as nucleic acids and bacterial samples.
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/H.D.C./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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