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
The Amendment filed 12/29/2025 has been entered. Claims 29 and 31-52 remain pending in the application. Claims 42-48 are withdrawn. Applicant’s amendments to the drawings and claims have overcome each and every objection and 112(b) rejections previously set forth in the Non-Final Office Action mailed 08/28/2025.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 51-52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 51, claim 51 recites “wherein the associated incubation time for said sample is different than each of the incubation times correlated to the at least two sets of reference data.” While the specification discusses the sets of reference data comprises at least two sets of reference data having different incubation time attribute representing incubation time that differs (page 12, lines 26-28; page 13, lines 5-10; page 17, lines 29-30), the disclosure fails to describe “wherein the associated incubation time for said sample is different than each of the incubation times correlated to the at least two sets of reference data”. Therefore, the claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 52 is rejected by virtue of its dependency on claim 51.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 51-52 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 51, claim 51 recites “each of the incubation times correlated to the at least two sets of reference data”. There is insufficient antecedent basis for “the incubation times” in the claim. Claim 29 establishes “an incubation time” and “correlating the data representing the associated incubation time for said sample to said at least two sets of reference data”. It is unclear which “incubation times” is being referred to that is correlated to the at least two sets of reference data. It appears that only “data representing the associated incubation time” is correlated to “the at least two sets of reference data”. Claim 52 is rejected by virtue of its dependency on claim 51.
Regarding claim 52, claim 52 recites “wherein one of the at least two sets of reference data is correlated to an incubation time that is less than the associated incubation time for said sample, and another of the at least two sets of reference data is correlated to an incubation time that is greater than the associated incubation time for said sample.” It is unclear if the limitations of claim 52 is referring to the programmed steps of the computer system. Is the computer system further programed to perform the correlating steps of claim 52 (e.g. “is correlated…”)? It is suggested to recite the computer system further programmed to include the steps of claim 52.
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.
Claims 29, 32-38, 40-41, and 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia et al. (Cornaggia, C., et al., "Novel Assay Procedures for the Measurement of α-Amylase in Weather-damaged Wheat, Journal of the Science of Food and Agriculture, 2016, Vol. 96, Iss. 2, pp. 404-412 (published online February 27, 2015); cited in the IDS filed 04/11/2023) in view of Makiuchi et al. (US 5047351 A; cited in the IDS filed 04/11/2023) and Kappe et al. (US 4055752 A).
Regarding claim 29, Cornaggia a system (abstract teaches an assay comprising reagents, substrate, and enzyme) for determining activity of a target enzyme in a sample (abstract teaches specific assay of amylase activity), the system comprises
a substrate (pages 405-406, section “Preparation of reagents containing colorimetric/fluorometric substrates and ancillary enzymes for a-amylase assays”, teaches Amylase HR, Amylase SD, Substrate III, and Substrate IV) for the target enzyme (pages 405-406, section “Preparation of reagents containing colorimetric/fluorometric substrates and ancillary enzymes for a-amylase assays”, therefore, the reagents containing colorimetric/fluorometric substrates are for a-amylase, i.e. target enzyme),
an incubator (page 406, section “Calculation of enzyme/substrate reaction kinetics” teaches enzyme activity assays were performed with incubation of tubes, i.e. incubator; page 407, section “Standard extraction and assay procedures” teaches assays were performed, which included incubation in tubes, i.e. incubator) for incubating said sample with said substrate (page 406, section “Calculation of enzyme/substrate reaction kinetics” teaches enzyme activity assays were performed with incubation of tubes with a-amylace and a substrate; page 407, section “Standard extraction and assay procedures” teaches assays were performed with the reagents/substrates in the tubes),
an optical reader (page 406, section “Calculation of enzyme/substrate reaction kinetics” and page 407, section “Standard extraction and assay procedures” teaches measurements absorbances were measured; page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, i.e. optical reader) for determining a signal parameter associated to enzymatic actions of said target enzyme of said substrate (interpreted as an intended use, see MPEP 2114; page 406, section “Calculation of enzyme/substrate reaction kinetics” and page 407, section “Standard extraction and assay procedures” teaches absorbances were measured, wherein absorbances are interpreted as a parameter associated to enzymatic actions as claimed; page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, which is structurally capable of being used for determining a parameter as claimed)
wherein the target enzyme is a degrading or digestion enzyme capable of degrading or digesting the substrate (pages 405-406, section “Preparation of reagents containing colorimetric/fluorometric substrates and ancillary enzymes for a-amylase assays”, therefore, the reagents containing colorimetric/fluorometric substrates are for a-amylase, i.e. target enzyme),
wherein the substrate is selected from the group comprising a dyed substrate, a chromogenic substrate, and a chromophore labelled substrate (Fig. 2 shows colorimetric/fluorometric substrates comprising a chromogenic element, i.e. chromogenic substrate).
Cornaggia fails to teach: a computer system wherein the computer system is storing at least two sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme involving said substrate as a function of enzyme activity and correlated to an incubation time represented by an incubation time attribute, wherein said at least two sets of reference data have different incubation time attributes representing different incubation times, wherein the computer system is configured for receiving data representing a determined parameter for a sample and receiving data representing an associated incubation time for said sample and wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, correlating the data representing the determined parameter to the data representing the best fit standard curve and determine data representing the target enzyme activity, and transmitting said data representing the target enzyme activity to a display.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at different reaction times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches Michaelis–Menten curves for this enzyme on substrates I–IV at various concentrations in the presence of fixed amounts of the required ancillary enzyme are shown in Fig. 3 (page 409, left column, second paragraph).
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches calibration curves for respective reaction times are obtained (column 2, lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67).
Since Makiuchi teaches optical analysis of an analyte including calibration or standardization of data by measuring at different reaction times, similar to Cornaggia, 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 the system of Cornaggia to incorporate Makiuchi’s teachings of selecting an appropriate calibration curve corresponding with respective reaction times of an analysis reaction, wherein multiple calibration curves for different reaction times are obtained and memorized in a computer for calculations (abstract; column 2, lines 1-13; column 5, lines 21-53; column 6, lines 20-22) and Cornaggia’s teachings of Michaelis–Menten curves are calculated into a graph (page 409, left column, second paragraph), standardization of a-amylase activity by incubating mixtures of starch and a-amylase at different times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”), and obtaining measurement values at different reaction times and conversion using a standard curve (page 405, left column, last 3 lines - right column, first 4 lines; page 406, section, “Standardisation of a-amylase activity…”) to provide: a computer system wherein the computer system is storing at least two sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme of said substrate as a function of enzyme activity and correlated to an incubation time represented by an incubation time attribute, wherein said at least two sets of reference data have different incubation time attributes representing different incubation times; wherein the computer system is configured for receiving data representing a determined parameter for a sample and receiving data representing an associated incubation time for said sample, wherein the computer system is programmed for transmitting said data representing the target enzyme activity to a display. Doing so would have a reasonable expectation of successfully improving accuracy and analysis time of correlations between the said signal parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to multiple reference or standard data of enzyme activity at different incubation times. Additionally, doing so would have a reasonable expectation of successfully improving desired data input to the computer system and outputting a result to a display for proper computational analysis by a user.
Modified Cornaggia fails to teach: wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, and correlating the data representing the determined parameter to the data representing the best fit standard curve and determine data representing the target enzyme activity.
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding, i.e. correlating, to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches calibration curves for respective reaction times are obtained (column 2,lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67). Makiuchi teaches optical density corresponds to the amount of color substance produced (column 1, lines 37-39).
Kappe teaches enzyme activity for a given sample is automatically determined at a succession of points in time and involving a plurality of measurements at each time (abstract). Kappe teaches measurement points are obtained, mean value and standard deviation are calculated, and a regression curve, i.e. best fit standard curve, is drawn through the measurement points to allow for enzyme activity to be determined from the slope of thereof at a predetermined time (column 3, lines 1-15). Kappe teaches the new method precludes random measurement errors that may occur (column 3, lines 16-24).
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 the computer system of modified Cornaggia to incorporate Makuchi’s teachings of selecting a calibration curve correlating to the reaction time from multiple calibration curves in order to analyze a reaction of an analyte via a computer (abstract; column 2, lines 1-13; column 6, lines 20-22; column 5, lines 54-67) and Kappe’s teachings of determining a regression curve from measurement points to allow for enzyme activity to be determined (column 3, lines 1-15; abstract) to provide: wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, and correlating the data representing the determined parameter to the data representing the best fit standard curve and determine data representing the target enzyme activity. Doing so would have a reasonable expectation of successfully determining enzyme activity with reduced measurement errors as taught by Kappe (column 3, lines 1-24) and improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at different incubation times.
Regarding claim 32, Cornaggia further teaches wherein the target enzyme is a hydrolase, a lyase, a ligase, a lipase, a protease, a cellulose or an amylase (abstract, amylase).
Regarding claim 33, Cornaggia further teaches wherein the substrate comprises a biopolymer comprising a polymer comprising biomolecules selected from polynucleotides, polypeptides, polysaccharides or any combinations thereof (page 406, section “Calculation of enzyme/substrate reaction kinetics” teaches soluble starch, i.e. polysaccharide; Fig. 1 teaches substrates I-IV comprising a maltoheptaose backbone of repeating units of monosaccharide units, i.e. polysaccharides), wherein the biopolymer optionally is crosslinked (interpreted as not required due to “optionally”).
Regarding claim 34, Cornaggia further teaches wherein the signal parameter is an optical parameter (page 407, section “Standard extraction and assay procedures” teaches measurement of absorbance and fluorescence).
Regarding claim 35, modified Cornaggia fails to teach: wherein the computer system is configured for receiving at least a portion of said data representing the associated incubating time for said sample from a user via a user interface or wherein the computer system is configured for receiving at least a portion of said data representing the associated incubation time for said sample from the optical reader.
Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches a computer receives optical measurement data from the photometric part (column 5, lines 44-49; Fig. 1), wherein the photometric head for light measurement is electrically coupled to the computer (Fig. 1).
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 the computer system of Cornaggia to incorporate the teachings of a computer receiving data from a reader of Makiuchi (column 5, lines 44-49; Fig. 1) and the teachings of a computer having calibration curves memorized in the computer of Makiuchi (column 6, lines 20-22) to provide: wherein the computer system is configured for receiving at least a portion of said data representing the associated incubating time for said sample from a user via a user interface or wherein the computer system is configured for receiving at least a portion of said data representing the associated incubation time for said sample from the optical reader. Doing so would have a reasonable expectation of successfully improving data input by a user or the reader to the computer system, thus allowing for proper calculations.
Regarding claim 36, modified Cornaggia fails to teach: wherein the computer system is configured for receiving said data representing the determined parameter for the sample from a user via at least one of a user interface and the optical reader.
Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches a computer receives optical measurement data from the photometric part (column 5, lines 44-49; Fig. 1), wherein the photometric head for light measurement is electrically coupled to the computer (Fig. 1).
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 the computer system of Cornaggia to incorporate the teachings of a computer receiving data from a reader of Makiuchi (column 5, lines 44-49; Fig. 1) and the teachings of a computer having calibration curves memorized in the computer of Makiuchi (column 6, lines 20-22) to provide: wherein the computer system is configured for receiving said data representing the determined parameter for the sample from a user via at least one of a user interface and the optical reader. Doing so would have a reasonable expectation of successfully improving data input by a user or the reader to the computer system, thus allowing for proper calculations.
Regarding claim 37, modified Cornaggia fails to teach: wherein the computer system is storing at least three sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme involving said substrate correlated to an incubation time and an incubation time attribute representing said incubation time, wherein said sets of reference data having different incubation time attribute representing different incubation time and wherein each set of reference data comprises at least two data pairs of enzyme activity value versus parameter value, each set of reference data comprises at least three data pairs.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 reaction times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches at least two data pairs of falling number values versus amylase activities (Fig. 6).
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches at least three calibration curves for respective reaction times are obtained (column 2,lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67).
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 the computer system of modified Cornaggia to incorporate the teachings of selecting an appropriate calibration curve corresponding with respective reaction times of an analysis reaction, wherein multiple calibration curves for at least three reaction times are obtained and memorized in a computer of Makiuchi (abstract; column 2, lines 1-13; column 5, lines 21-53; column 6, lines 20-22), the teachings of standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 different times to measure absorbance of Cornaggia (page 406, section, “Standardisation of a-amylase activity…”), and data versus amylase activities of Cornaggia (Fig. 6) to provide: wherein the computer system is storing at least three sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme involving said substrate correlated to an incubation time and an incubation time attribute representing said incubation time, wherein said sets of reference data having different incubation time attribute representing different incubation time and wherein each set of reference data comprises at least two data pairs of enzyme activity value versus parameter value, each set of reference data comprises at least three data pairs. Doing so would have a reasonable expectation of successfully improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at three different incubation times.
Regarding claim 38, modified Cornaggia fails to teach: wherein said at least two sets of reference data comprise at least two sets of reference data having different incubation time attribute representing incubation times that differ by at least 30 seconds.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 reaction times, i.e. 0, 3, 6, 9, and 12 minutes, to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches at least two data pairs of falling number values versus amylase activities (Fig. 6).
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 the computer system of modified Cornaggia to incorporate the teachings of standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 reaction times, i.e. 0, 3, 6, 9, and 12 minutes, to measure absorbance of Cornaggia (page 406, section, “Standardisation of a-amylase activity…”) to provide: wherein said at least two sets of reference data comprise at least two sets of reference data having different incubation time attribute representing incubation times that differ by at least 30 seconds. Doing so would have a reasonable expectation of successfully improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at desired different incubation times as desired by Cornaggia.
Regarding claim 40, Cornaggia further teaches wherein said selected substrate is a dyed and/or chromogenic substrate (Fig. 2 shows colorimetric/fluorometric substrates comprising a chromogenic element, i.e. chromogenic substrate).
While Cornaggia teaches various substrates (Fig. 1), Modified Cornaggia fails to teach: wherein said at least two sets of reference data represents a standard curve associated to a selected substrate.
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches calibration curves for respective reaction times are obtained (column 2,lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67).
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 the computer system of modified Cornaggia to incorporate the teachings of selecting the calibration curve corresponding to the reaction time of Makiuchi (column 2, lines 1-13) and the teachings of various substrates of Cornaggia (Fig. 1) to provide: wherein said at least two sets of reference data represents a standard curve associated to a selected substrate. Doing so would have a reasonable expectation of successfully improving calculation of desired enzyme activity based memorized calibration curves according to the appropriate substrate being used.
Regarding claim 41, Cornaggia further teaches wherein said optical reader (page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, i.e. optical reader) is configured for reading at least one wavelength absorbable by a dye of said substrate (page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, is structurally configured and capable of reading a wavelength of absorbable by a dye of a substrate at a later time; MPEP 2112.01(I)).
Regarding claim 49, Cornaggia teaches a system (abstract teaches an assay comprising reagents, substrate, and enzyme) for determining activity of a target enzyme in a sample (abstract teaches specific assay of amylase activity), the system comprises
a substrate (pages 405-406, section “Preparation of reagents containing colorimetric/fluorometric substrates and ancillary enzymes for a-amylase assays”, teaches Amylase HR, Amylase SD, Substrate III, and Substrate IV) for the target enzyme (pages 405-406, section “Preparation of reagents containing colorimetric/fluorometric substrates and ancillary enzymes for a-amylase assays”, therefore, the reagents containing colorimetric/fluorometric substrates are for a-amylase, i.e. target enzyme),
an incubator (page 406, section “Calculation of enzyme/substrate reaction kinetics” teaches enzyme activity assays were performed with incubation of tubes, i.e. incubator; page 407, section “Standard extraction and assay procedures” teaches assays were performed, which included incubation in tubes, i.e. incubator) for incubating said sample with said substrate (page 406, section “Calculation of enzyme/substrate reaction kinetics” teaches enzyme activity assays were performed with incubation of tubes with a-amylace and a substrate; page 407, section “Standard extraction and assay procedures” teaches assays were performed with the reagents/substrates in the tubes),
an optical reader (page 406, section “Calculation of enzyme/substrate reaction kinetics” and page 407, section “Standard extraction and assay procedures” teaches measurements absorbances were measured; page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, i.e. optical reader) for determining a signal parameter associated to enzymatic actions of said target enzyme of said substrate (interpreted as an intended use, see MPEP 2114; page 406, section “Calculation of enzyme/substrate reaction kinetics” and page 407, section “Standard extraction and assay procedures” teaches absorbances were measured, wherein absorbances are interpreted as a parameter associated to enzymatic actions as claimed; page 405, left column teaches a Bruker Avance 400 NMR Spectrometer, which is structurally capable of being used for determining a parameter as claimed),
wherein the substrate is selected from the group comprising a dyed substrate, a chromogenic substrate, and a chromophore labelled substrate (Fig. 2 shows colorimetric/fluorometric substrates comprising a chromogenic element, i.e. chromogenic substrate).
Cornaggia fails to teach: a computer system wherein the computer system is storing at least two sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme of said substrate as a function of enzyme activity and correlated to an incubation time represented by an incubation time attribute, wherein said at least two sets of reference data having different incubation time attributes representing different incubation times wherein the computer system is configured for receiving data representing a determined parameter for a sample and receiving data representing an associated incubation time for said sample and wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, correlating the data representing the determined parameter to the data representing the best fit standard curve and determining data representing the target enzyme activity, and transmitting said data representing the target enzyme activity to a display.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at different reaction times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches Michaelis–Menten curves for this enzyme on substrates I–IV at various concentrations in the presence of fixed amounts of the required ancillary enzyme are shown in Fig. 3 (page 409, left column, second paragraph).
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches calibration curves for respective reaction times are obtained (column 2, lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67).
Since Makiuchi teaches optical analysis of an analyte including calibration or standardization of data by measuring at different reaction times, similar to Cornaggia, 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 the system of Cornaggia to incorporate Makiuchi’s teachings of selecting an appropriate calibration curve corresponding with respective reaction times of an analysis reaction, wherein multiple calibration curves for different reaction times are obtained and memorized in a computer for calculations (abstract; column 2, lines 1-13; column 5, lines 21-53; column 6, lines 20-22) and Cornaggia’s teachings of Michaelis–Menten curves are calculated into a graph (page 409, left column, second paragraph), standardization of a-amylase activity by incubating mixtures of starch and a-amylase at different times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”), and obtaining measurement values at different reaction times and conversion using a standard curve (page 405, left column, last 3 lines - right column, first 4 lines; page 406, section, “Standardisation of a-amylase activity…”) to provide: a computer system wherein the computer system is storing at least two sets of reference data, each set of reference data comprises data representing a standard curve for said signal parameter associated to said enzymatic actions of said target enzyme of said substrate as a function of enzyme activity and correlated to an incubation time represented by an incubation time attribute, wherein said at least two sets of reference data having different incubation time attributes representing different incubation times, wherein the computer system is configured for receiving data representing a determined parameter for a sample and receiving data representing an associated incubation time for said sample and transmitting said data representing the target enzyme activity to a display. Doing so would have a reasonable expectation of successfully improving accuracy and analysis time of correlations between the said signal parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to multiple reference or standard data of enzyme activity at different incubation times. Additionally, doing so would have a reasonable expectation of successfully improving desired data input to the computer system and outputting a result to a display for proper computational analysis by a user.
Modified Cornaggia fails to teach: wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, correlating the data representing the determined parameter to the data representing the best fit standard curve and determining data representing the target enzyme activity.
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding, i.e. correlating, to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches calibration curves for respective reaction times are obtained (column 2,lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67). Makiuchi teaches optical density corresponds to the amount of color substance produced (column 1, lines 37-39).
Kappe teaches enzyme activity for a given sample is automatically determined at a succession of points in time and involving a plurality of measurements at each time (abstract). Kappe teaches measurement points are obtained, mean value and standard deviation are calculated, and a regression curve, i.e. best fit standard curve, is drawn through the measurement points to allow for enzyme activity to be determined from the slope of thereof at a predetermined time (column 3, lines 1-15). Kappe teaches the new method precludes random measurement errors that may occur (column 3, lines 16-24).
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 the computer system of modified Cornaggia to incorporate Makuchi’s teachings of selecting a calibration curve correlating to the reaction time from multiple calibration curves in order to analyze a reaction of an analyte via a computer (abstract; column 2, lines 1-13; column 6, lines 20-22; column 5, lines 54-67) and Kappe’s teachings of determining a regression curve from measurement points to allow for enzyme activity to be determined (column 3, lines 1-15; abstract) to provide: wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, correlating the data representing the determined parameter to the data representing the best fit standard curve and determining data representing the target enzyme activity. Doing so would have a reasonable expectation of successfully determining enzyme activity with reduced measurement errors as taught by Kappe (column 3, lines 1-24) and improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at different incubation times.
Regarding claim 50, modified Cornaggia fails to teach the system of claim 29, wherein the standard curves are linear, or substantially linear.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines) wherein the standard curve is linear (see Supplemental Information of Cornaggia; section 2.1, Fig. S1), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at different reaction times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches Michaelis–Menten curves for this enzyme on substrates I–IV at various concentrations in the presence of fixed amounts of the required ancillary enzyme are shown in Fig. 3 (page 409, left column, second paragraph).
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 the standard curves of modified Cornaggia to incorporate the teachings of linear standard curves for calculating concentrations of Cornaggia (page 405, left column, last 3 lines - right column, first 4 lines; Supplemental Information of Cornaggia; section 2.1, Fig. S1) to provide: the system of claim 29, wherein the standard curves are linear, or substantially linear. Doing so would have a reasonable expectation of successfully allowing for calculation of concentrations of at target enzyme.
Regarding claim 51, modified Cornaggia fails to teach: the system of claim 29, wherein the associated incubation time for said sample is different than each of the incubation times correlated to the at least two sets of reference data.
Cornaggia teaches biochemical assays were performed in duplicate and the average value taken, fluorescence values were obtained, and relative fluorescent units can be converted to 4-methylumbelliferone concentration using the standard curve (page 405, left column, last 3 lines - right column, first 4 lines), and standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 reaction times to measure absorbance (page 406, section, “Standardisation of a-amylase activity…”). Cornaggia teaches at least two data pairs of falling number values versus amylase activities (Fig. 6).
Makiuchi teaches a method for shortening analysis time without adversely affecting the accuracy in the colorimetric analysis of an analyte (abstract), which includes selecting the calibration curve corresponding to the reaction time (column 2, lines 1-13). Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22). Makiuchi teaches analytical accuracy of analytes can be lowered depending on the reaction time (column 1, lines 45-57). Makiuchi teaches at least three calibration curves for respective reaction times are obtained (column 2,lines 41-43; Fig. 6). Makiuchi teaches the analyzer to determine the relationship between optical density and reaction time (column 5, lines 54-67).
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 the computer system of modified Cornaggia to incorporate the teachings of selecting an appropriate calibration curve corresponding with respective reaction times of an analysis reaction, wherein multiple calibration curves for at least three reaction times are obtained and memorized in a computer of Makiuchi (abstract; column 2, lines 1-13; column 5, lines 21-53; column 6, lines 20-22), the teachings of standardization of a-amylase activity by incubating mixtures of starch and a-amylase at 5 different times to measure absorbance of Cornaggia (page 406, section, “Standardisation of a-amylase activity…”), and data versus amylase activities of Cornaggia (Fig. 6) to provide: the system of claim 29, wherein the associated incubation time for said sample is different than each of the incubation times correlated to the at least two sets of reference data. Doing so would have a reasonable expectation of successfully improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at various different incubation times.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia in view of Makiuchi and Kappe as applied to claim 29 above, and further in view of Niu et al. (US 20090005387 A1).
Regarding claim 31, while Kappe teaches a regression curve is obtained (abstract), modified Cornaggia fails to teach wherein the best fit standard curve is a calculated best fit standard curve obtained by performing a regression between two or more of said sets of reference data stored on a memory of said computer system.
Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22).
Niu teaches analysis of samples using a spectrometer (paragraph [0594]). Niu teaches a best-fit for calibration standards was calculated by weighted linear regression based on analyte/internal standard peak-area ratios for two replicates of eight calibration standards in order to calculate sample concentrations (paragraph [0594]).
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 the computer system of modified Cornaggia to incorporate the teachings of calibration curves memorized in a computer of Makiuchi (column 6, lines 20-22) and the teachings of a best-fit for calibration standards was calculated by regression based on at least two sets of data from standards (paragraph [0594]) to provide: wherein the best fit standard curve is a calculated best fit standard curve obtained by performing a regression between two or more of said sets of reference data stored on a memory of said computer system. Doing so would have a reasonable expectation of successfully improve calculation of enzyme activity by forming a best fit from two or more data sets of reference or calibration standards.
Claim 39 is rejected under 35 U.S.C. 103 as being unpatentable over Cornaggia in view of Makiuchi and Kappe as applied to claim 29 above, and further in view of Hooker et al. (US 20020046418 A1).
Regarding claim 39, Cornaggia further teaches wherein the system is configured for obtaining the sample by liquid extraction of a biological solid material, comprising a grain material (interpreted as a functional limitation of the system, see MPEP 2114; page 406, section “Extraction and purification of a-amylase from ground wheat” teaches obtaining amylase from extraction of wheat with a buffer, i.e. liquid extraction) and wherein the system further comprises
an extraction container (page 406, section “Extraction and purification of a-amylase from ground wheat” teaches a suspension of ground wheat sample and buffer was mixed and incubated, which implies the presence of a container to hold the suspension, i.e. extraction container),
an extraction buffer for extracting the preselected target enzyme (page 406, section “Extraction and purification of a-amylase from ground wheat” teaches a buffer for extraction of a-amylase).
While Cornaggia teaches centrifugation and applying the sample to a column of Sephadex G-25 to collect a-amylase (page 406, section “Extraction and purification of a-amylase from ground wheat”), modified Cornaggia fails to teach: a sample container.
Hooker teaches a system for production of protein in plants (abstract). Hooker teaches products of particular interest includes amylase (paragraph [0062]). Hooker teaches plants include wheat (paragraphs [0086],[0093]). Hooker teaches enzyme extraction includes a microcentrifuge tube and extraction medium (paragraphs [0130],[0138]).
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 the system of modified Cornaggia to incorporate the teachings of enzyme extraction using includes a microcentrifuge tube of Hooker (paragraphs [0130],[0138]) and the teachings of centrifugation and applying the sample to a column of Sephadex G-25 to collect a-amylase of Cornaggia (page 406, section “Extraction and purification of a-amylase from ground wheat) to provide: a sample container. Doing so would have a reasonable expectation of successfully filtering or centrifuging the sample for proper collection of the target enzyme in the sample.
Prior Art
Regarding claim 52, the closest prior art of modified Cornaggia (see above rejection of claim 51 under 35 U.S.C. 103) fails to teach: the system of claim 51, wherein one of the at least two sets of reference data is correlated to an incubation time that is less than the associated incubation time for said sample, and another of the at least two sets of reference data is correlated to an incubation time that is greater than the associated incubation time for said sample. None of the prior art teaches or fairly suggests, alone or in combination, all of the limitations of claim 52.
Response to Arguments
Applicant’s arguments, see pages 10-11 and 14, filed 12/29/2025, with respect to the drawing objections, claim objections, rejections under 35 U.S.C. 112(b), and double patenting rejections have been fully considered and are persuasive in view of the amendments. The drawing objections, claim objections, rejections under 35 U.S.C. 112(b), and double patenting rejections of 08/28/2025 have been withdrawn.
Applicant's arguments, see pages 11-14, filed 12/29/2025, with respect to the rejections under 35 U.S.C. 103, have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “the best fit standard curve is determined based on the standard curves of the reference data…the best fit standard curve can be determined for incubation times that are not equivalent to the incubation times of any reference data sets”, Remarks, page 12, last paragraph) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Regarding the best fit standard curve, claim 29 recites “determining data representing a best fit standard curve correlated to said associated incubation time for said sample” .
In response to applicant’s arguments that the combination fails to teach: correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said incubation time for said sample (Remarks, pages 12-14), the examiner disagrees. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Makiuchi teaches preparation of calibration curves at each reaction time using an analyzer comprising a computer (column 5, lines 21-53), wherein all calibration curves are memorized in the computer and all calculations are carried out in the computer (column 6, lines 20-22); and selecting the calibration curve corresponding, i.e. correlating, to the reaction time (column 2, lines 1-13). Therefore, data representing the reaction time of a sample is correlated to at least two sets of reference data since the reaction time of a sample is compared with multiple calibration curves in order to select the proper calibration curve. Kappe teaches measurement points are obtained, mean value and standard deviation are calculated, and a regression curve, i.e. best fit standard curve, is drawn through the measurement points to allow for enzyme activity to be determined from the slope of thereof at a predetermined time (column 3, lines 1-15).
It would have been obvious to one of ordinary skill in the art to have modified the computer system of modified Cornaggia to incorporate Makuchi’s teachings of selecting a calibration curve correlating to the reaction time from multiple calibration curves in order to analyze a reaction of an analyte via a computer (abstract; column 2, lines 1-13; column 6, lines 20-22; column 5, lines 54-67) and Kappe’s teachings of determining a regression curve from measurement points to allow for enzyme activity to be determined (column 3, lines 1-15; abstract) to provide: wherein the computer system is programmed for correlating the data representing the associated incubation time for said sample to said at least two sets of reference data and determining data representing a best fit standard curve correlated to said associated incubation time for said sample, correlating the data representing the determined parameter to the data representing the best fit standard curve and determining data representing the target enzyme activity. Doing so would have a reasonable expectation of successfully determining enzyme activity with reduced measurement errors as taught by Kappe (column 3, lines 1-24) and improving accuracy and analysis time of correlations between the said parameter and enzyme activity as discussed by Makiuchi (column 1,lines 45-57) and to improve comparison of data to reference or standard data of enzyme activity at different incubation times. I.e. one of ordinary skill in the art would have correlated/compared the incubation time of the sample with at least two sets of reference data in order to select/determine the set of reference that that includes/represents a best fit standard curve that is correlated to the incubation time of the sample to improve accuracy and analysis time of correlations between the said parameter and enzyme activity. It is suggested to further incorporate additional limitation to further define the “correlating” step, “best fit standard curve”, and the “at least two sets of reference data”.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HENRY H NGUYEN whose telephone number is (571)272-2338. The examiner can normally be reached M-F 7:30A-5:00P.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758