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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/22/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner with the exception of "International Search Report / Written Opinion for PCT/IB2022/058848 file on 09-19-2022, pages." because a copy of this reference has not been filed.
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.
Claim(s) 1-5, 7-8, 10, 27-31, 33-34, 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nugent (US 20210223163 A1) in view of Mizutani (US 20200057880 A1).
Regarding claim 1, Nugent discloses a method of evaluating a fluidic substance having particles ([0187] means for detection of analytes (i.e. particles) in a fluid), the method comprising:
capturing, via an image capture device, a reference image of at least a portion of a container that is in an empty state ([0581]-[0582] an image of a container (e.g. cuvette, pipette tip) that is full of air (i.e. in an empty state); [0193] camera for capturing images; [0571] the image of the tip filled with air is used as a reference image);
determining, via a processor , a reference value of at least a portion of the reference image ([0571], [0581] measuring a reference value (e.g. absorbance) of the blank container in the reference image; [0746] image analysis performed by a processor);
aspirating an aspirated volume of the fluidic substance into the container ([0526] aspirating a specified volume of fluid into a container (e.g. pipette tip));
capturing, via the image capture device , a test image of the container containing the aspirated volume of the fluidic substance (Fig. 61, Fig. 62, [0526]-[0527] capturing images of the container (e.g. pipette tip) containing the aspirated fluid volume);
determining, via the processor, a test value of at least a portion of the test image ([0532], [0547]-[0548] measuring test values (e.g. absorbance, optical density) of the fluid in the container in the test image);
calibrating, via the processor, a universal calibration curve relating particle concentration and value based on the reference value and the test value to generate a calibrated universal calibration curve ([0571] subtracting the reference value (e.g. absorbance of empty container) from the test value (e.g. absorbance of container containing sample) to determine absorbance of the fluid in the container (i.e. calibrating to generate a universal curve); [0546]-[0548] calculate particle concentration in the fluid based on absorbance (i.e. relating particle concentration and measured image value); Fig. 79, [0537]-[0538] displaying normalized curve relating concentration to signal (i.e. calibrated universal calibration curve)); and
determining, via the processor , a particle concentration in the fluidic substance based on the test value and the calibrated universal calibration curve ([0920] using a standard curve (i.e. universal calibration curve) to determine particle concentration based on measured signal (i.e. test value)).
Nugent fails to disclose the reference value being a grayscale value, the test value being a grayscale value, and the calibration curve relating particle concentration and grayscale value.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the reference value being a grayscale value and the test value being a grayscale value ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both reference and test values can be present)), and the calibration curve relating particle concentration and grayscale value (Fig. 75, [0821], [0835] calibration curve relating particle concentration and grayscale value is output).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use grayscale values as the reference and test values and generate a calibration curve that relates particle concentration to grayscale value, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 2, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses further comprising determining, via the processor, one or more empty regions of interest in the reference image of the container, wherein the reference value is an average value of the one or more empty regions of interest ([0581] an image including a region of interest including a blank (e.g. air) inside a pipette tip (i.e. empty container); [0571], [0581] determining a reference value based on the empty region of interest).
Nugent fails to disclose the reference value being a grayscale value.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the reference value being a grayscale value ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both reference and test values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use a grayscale as the reference value, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 3, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses wherein calibrating the universal calibration curve further comprises utilizing the reference value and the test value to adjust an output of the universal calibration curve ([0571] subtracting the reference value (e.g. absorbance of empty container) from the test value (e.g. absorbance of container containing sample) to determine absorbance of the fluid in the container (i.e. calibrating to generate a universal curve);).
Nugent fails to disclose the reference and test values being grayscale values.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the reference value being a grayscale value and the test value being a grayscale value ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both reference and test values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use grayscale values as the reference and test values, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 4, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses further comprising determining, via the processor , one or more test regions of interest in the test image of the container , wherein the test value is an average value of the one or more test regions of interest ([0524], Fig. 62, [0545] multiple regions of interest of the container image are indicated and their values averaged, the values corresponding to absorbance of the fluid (i.e. test value)).
Nugent fails to disclose the test value being a grayscale value.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the test value being a grayscale value ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both reference and test values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use a grayscale as the test value, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 5, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses wherein determining the particle concentration further comprises converting the test value to the particle concentration by applying the calibrated universal calibration curve ([0532]-[0533], [0537]-[0538] utilizing normalized (i.e. with applied calibrated calibration curve) signals such as absorbance of the fluid samples (i.e. test value) to determine particle concentration).
Nugent fails to disclose the test value being a grayscale value.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the test value being a grayscale value ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both reference and test values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use a grayscale as the test value, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 7, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses further comprising conducting a plurality of trials to generate the universal calibration curve ([0590] calibration and normalization may be performed for each assay trial), wherein conducting each trial comprises, for each trial of the plurality of trials:
capturing, via the image capture device, a baseline image of at least a portion of a trial container that is in an empty state; determining, via the processor , a baseline value of at least a portion of the baseline image ([0590] calibration and normalization may be performed for each assay trial; [0581]-[0582] a image of a container (e.g. cuvette, pipette tip) that is full of air (i.e. in an empty state); [0193] camera for capturing images; [0571] the image of the tip filled with air is used as a reference image for normalizing/calibrating an assay; [0571], [0581] measuring a reference value (e.g. absorbance) of the blank container in the reference image; [0746] image analysis performed by a processor);
aspirating an aspirated volume of a trial fluidic substance comprising the particles into the trial container ; capturing, via the image capture device , a trial image of the trial container containing the aspirated volume of the trial fluidic substance ; determining, via the processor , a trial value of at least a portion of the trial image by using the baseline value as a reference ([0526] aspirating specified volumes of fluid into multiple containers (e.g. pipette tip); Fig. 61-62, [0526]-[0527] capturing images of the containers (e.g. pipette tip) containing the aspirated fluid volumes; [0532], [0547]-[0548] measuring test values (e.g. absorbance, optical density) of the fluid in the container in the test image; [0538] the measurements are taken for each assay; [0571] subtracting the reference value (e.g. absorbance of empty container) from the test value (e.g. absorbance of container containing sample) to determine absorbance of the fluid in the container);
determining, via a spectrophotometer , a trial particle concentration in the trial fluidic substance ; and recording, via the processor , the trial particle concentration corresponding to the trial value ([0537]-[0538] determine concentrations of a plurality of samples based on the test values (e.g. optical signals) and record the values into graph displays (see figs. 79, 80); [0753] a processor is involved in determining and analyzing the concentration values; [0547]-[0549] data collected via spectrophotometer).
Nugent fails to disclose the baseline and trial values being grayscale values.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the baseline and trial values being grayscale values ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both baseline and trial values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use grayscale values as the baseline and trial values, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 8, Nugent in view of Mizutani discloses the method of claim 7 as applied above. Nugent further discloses further comprising generating a plot between the trial values corresponding to the plurality of trials and the trial particle concentrations corresponding to the plurality of trials, wherein the universal calibration curve is generated from the plot (Fig. 79, [0532], [0537]-[0538] generating a plot relating trial values (e.g. normalized optical signals) and particle concentrations for a plurality of assays; Fig. 80, [0540] additional plot showing relationship between calculated trial results and expected/actual concentration values (i.e. generate calibration curve)).
Nugent fails to disclose the plot including trial values which are grayscale values.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the plot including trial values which are grayscale values (Fig. 75, [0821], [0835] calibration curve relating particle concentrations and grayscale values (i.e. test grayscale values) is output).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and generate a plot including trial values which are grayscale values, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 10, Nugent in view of Mizutani discloses the method of claim 1 as applied above. Nugent further discloses further comprising generating a flagging result based on the particle concentration in the fluidic substance , wherein the flagging result is indicative of a quality of the fluidic substance ([0745]-[0747] imaging is used to determine the concentration of a particle in a sample and whether the concentration falls within a certain range, the imaging may then be used to determine whether the sample falls within quality control requirements; [0027] an alert is provided if conditions do not fall within the desired range).
Regarding claim 27, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 1).
Regarding claim 28, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 2).
Regarding claim 29, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 3).
Regarding claim 30, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 4).
Regarding claim 31, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 5).
Regarding claim 33, Nugent in view of Mizutani discloses the system of claim 27 as applied above. Nugent further discloses wherein the system is further configured to conduct a plurality of trials to generate the universal calibration curve ([0590] calibration and normalization may be performed for each assay trial), and wherein, for each trial:
the system further comprises a trial container configured to contain an aspirated volume of a trial fluidic substance comprising the particles [0526] aspirating specified volumes of fluid containing particles into multiple containers (e.g. pipette tip);
the image capture device is further configured to capture a baseline image of at least a portion of the trial container in an empty state and a trial image of the trial container containing the aspirated volume of the trial fluidic substance ([0581]-[0582] a image of a container (e.g. cuvette, pipette tip) that is full of air (i.e. in an empty state); [0193] camera for capturing images; [0571] the image of the tip filled with air is used as a reference image for normalizing/calibrating an assay; [0746] image analysis performed by a processor; [0526]-[0527] capturing images of the containers (e.g. pipette tip) containing the aspirated fluid volumes); and the processor is further configured to:
determine a baseline value of at least a portion of the baseline image ; and determine a trial value of at least a portion of the trial image by using the baseline value as a reference ([0571], [0581] measuring a reference value (e.g. absorbance) of the blank container in the reference image; [0532], [0547]-[0548] measuring test values (e.g. absorbance, optical density) of the fluid in the container in the test image; [0538] the measurements are taken for each assay; [0571] subtracting the reference value (e.g. absorbance of empty container) from the test value (e.g. absorbance of container containing sample) to determine absorbance of the fluid in the container)).
Nugent fails to disclose the baseline and trial values being grayscale values.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the baseline and trial values being grayscale values ([0512] capturing a grayscale image; Fig. 73, [0821], [0826]-[0828] brightness values of the grayscale image (i.e. grayscale values) are determined and used to generate calibration data; Fig. 70, [0822]-[0823] calibration data includes multiple sample images with varied concentrations (i.e. varied grayscale values, such that both baseline and trial values can be present)).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and use grayscale values as the baseline and trial values, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 34, Nugent in view of Mizutani discloses the system of claim 27 as applied above. Nugent further discloses wherein the processor is further configured to:
for each trial, determine a trial particle concentration in the trial fluidic substance based on signals received from a spectrophotometer ; record the trial particle concentrations corresponding to the plurality of trials ([0537]-[0538] determine concentrations of a plurality of samples based on the test values (e.g. optical signals) and record the values into graph displays (see figs. 79, 80); [0753] a processor is involved in determining and analyzing the concentration values; [0547]-[0549] data collected via spectrophotometer);
generate a plot between the trial values corresponding to the plurality of trials and the trial particle concentrations corresponding to the plurality of trials; and generate the universal calibration curve from the plot (Fig. 79, [0532], [0537]-[0538] generating a plot relating trial values (e.g. normalized optical signals) and particle concentrations for a plurality of assays; Fig. 80, [0540] additional plot showing relationship between calculated trial results and expected/actual concentration values (i.e. generate calibration curve)).
Nugent fails to disclose the plot including trial values which are grayscale values.
Mizutani, in a related system from the same field of evaluating a fluidic substance including determining particle concentrations based on images (Abstract, [0006]-[0009]), discloses the plot including trial values which are grayscale values (Fig. 75, [0821], [0835] calibration curve relating particle concentrations and grayscale values (i.e. test grayscale values) is output).
It would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to combine Mizutani with Nugent and generate a plot including trial values which are grayscale values, as disclosed by Mizutani, as part of a method of evaluating a fluidic substance having particles including generating a calibrated universal calibration curve, as disclosed by Nugent, for the purpose of improving reliability and consistency of results when automatically evaluating fluidic samples, such as those used for clinical diagnosis, where high levels of precision and accuracy are required for appropriate and timely treatment of patients (See Mizutani: [0003], [0503], [0822], [0839]).
Regarding claim 36, Nugent in view of Mizutani discloses everything claimed as applied above (see rejection of claim 10).
Allowable Subject Matter
Claims 12-13, 38-39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 12, Nugent in view of Mizutani discloses the method of claim 10 as applied above. However, neither Nugent nor any obvious combination of the closest known prior art discloses wherein the flagging result comprises an error flag when a magnitude of a difference between an expected particle concentration and the particle concentration based on the test grayscale value and the calibrated universal calibration curve is greater than 20% of the expected particle concentration.
Similar reasoning applies to claim 38.
Regarding claim 12, Nugent in view of Mizutani discloses the method of claim 10 as applied above.
Mizutani discloses wherein the flagging result comprises (i) a pass or a fail (Fig. 43, [0701] a flag indicates whether a concentration of a particle in the fluid falls within (i.e. passes) or does not fall within (i.e. fails) a tolerance range).
However, neither Nugent nor any obvious combination of the closest known prior art discloses (ii) an error flag when a magnitude of a difference between an expected particle concentration and the particle concentration based on the test grayscale value and the calibrated universal calibration curve is greater than 10% of the expected particle concentration, or (iii) an error flag when a magnitude of a difference between the particle concentration and 0.01 mg/ml is greater than 10% of 0.01 mg/ml, or (iv) an error flag when the particle concentration is greater than 0.0115 mg/ml, or (v) an error flag when the particle concentration is less than 0.0085 mg/ml.
Similar reasoning applies to claim 39.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Shiba (US 20150330878 A1) discloses a sample analyzer to determine a concentration of an analyte and generate a calibration curve based on a plurality of trials.
Kato (US 20220065881 A1) discloses a method of setting a calibration curve based on a known sample and adjusting the curve according to additional trials, including using a flag to indicate usability of the curve.
Case (US 20230069577 A1) discloses using imaging to determine characteristics of a sample fluid in a container including particle concentrations and including detecting error conditions.
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/CAROLINE E. DEPALMA/Examiner, Art Unit 2675
/ANDREW M MOYER/Supervisory Patent Examiner, Art Unit 2675