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 09/09/2026 has been entered. Claims 1-13 remain pending in the application. Claim 10 is withdrawn. Applicant’s amendments to the claims have overcome each and every 112(b) rejections previously set forth in the Non-Final Office Action mailed 09/09/2026.
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 1-9 and 11-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Claim 1 recites the limitations “determining, from the acquired image, a biological sample criterion”, “determination, from the acquired holographic image, of a value of a distribution parameter…”, and “comparing the value…with at least one threshold value…”.
In accordance with MPEP 2106, the claims are found to recite statutory subject matter (Step 1: YES) and are analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A: Prong 1).
In the instant application, the limitations of “determining, from the acquired image, a biological sample criterion”, “determination, from the acquired holographic image, of a value of a distribution parameter…”, and “comparing the value…with at least one threshold value…” covers performance of a limitation in the mind, i.e. mental process or mathematical calculation. Other than an analysis instrument, if the claim limitations, under its broadest reasonable interpretation, covers performance of the limitations in the mind but for the recitation of generic computer components (e.g. analysis instrument), then the claim limitations fall within the “Mental Processes” grouping of abstract ideas (MPEP 2106.05(f)). Accordingly, the claims recite abstract ideas (Step 2A: Prong 1: Yes).
This judicial exception is not integrated into a practical application because the claims do not recite any additional elements that reflects an improvement to technology or applies or uses the judicial exception in some other meaningful way (Step 2A, Prong 2: No). The preceding steps and limitations are used for data gathering in the abstract idea; wherein, data gathering to be used in the abstract idea is insignificant extra-solution activity, and not a particular practical application. Additionally, the step of “issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range” is insignificant extra-solution activity. See MPEP 2106.05(g). Additionally, if the value of the distribution parameter is inside the compliance range, no additional steps are performed, therefore there is no application of the abstract idea. Therefore, the claimed limitations do not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. Thus, the claims are directed to an abstract idea that is not integrated into a practical application (Step 2A, Prong 2: No).
The claims 1-9 and 11-13 do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Claim 1 and dependent claims 2-9 and 11-13 further recite limitations, however these limitations generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)), which alone or in combination do not amount to significantly more. Further, while claim 1 recites an analysis instrument and holographic imager, those elements are broad and the claim does not include particular elements of a machine or apparatus (see MPEP 2106.05(b)(I)). Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). The claims are not patent eligible.
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 1-5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Masutani et al. (US 20210073979 A1; effectively filed 10/06/2017) in view of Neugebauer et al. (US 20190162655 A1) and Fisher et al. (US 20030020907 A1).
Regarding claim 1, Masutani teaches a method for analyzing a biological sample by means of an analysis instrument (abstract and Figs. 3,6 teaches a method for analyzing cells using an image-processing device), wherein, after the biological sample has been placed in an analysis receptacle in a field-of-view of a holographic imager (paragraphs [0021]-[0022] teaches biological samples placed in a well plate, i.e. analysis receptacle, is placed on a stage of a microscope for imaging, i.e. in a field of view; paragraph [0034] teaches the microscope device has functions of a holographic microscope, i.e. holographic imager), the receptacle comprising at least one reagent intended to interact with biological agents present in the biological sample (paragraphs [0037] and [0042] teach fluorescent proteins or chemical reagents for staining or dying cells for imaging; therefore, the well plate with the samples are interpreted as including reagents intended to react with cells in the sample), the method comprises the following steps carried out in a repeated manner for a plurality of measurement times during a measurement period (Fig. 6 and paragraphs [0093]-[0095] teaches steps of imaging and determining number of cells is repeated, therefore is repeated for a plurality of measurement times during a period):
- acquiring an image of the biological sample (Fig. 6, step S520),
- determining, from the acquired image, a biological sample analysis criterion (Fig. 6 and paragraph [0093] teach determining number of cells from the image, i.e. biological sample analysis criterion),
wherein, the method further comprises:
- an acquisition of an image of the biological sample by the holographic imager (Fig. 6 and paragraph [0097], step S560 teaches capturing a main image), and
- a determination, from the acquired image, of a value of a distribution parameter representative of the quantitative spatial distribution of biological agents in the field-of-view (Fig. 6, step S570 teaches analysis of the main image; paragraph [0063] teaches determination of quantities, i.e. value of a distribution parameter, of cells imaged in the main captured image), the biological sample analysis criterion from which the analysis results are obtained being a value of the distribution parameter representative of the quantitative spatial distribution of biological agents (Fig. 6 and paragraph [0093] teach determining quantity or number of cells from the image, i.e. biological sample analysis criterion), and
the method also comprising, for at least one measurement time within a first half of the measurement period, an initial compliance check for the biological sample (Fig. 6 and paragraphs [0094]-[0096] teaches step S550 of determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit, wherein step S550 is interpreted as within a first half of a measurement period from the start to end of the method of Fig. 6), comprising comparing the value of the distribution parameter with at least one threshold value defining a limit of a compliance range (Fig. 6 and paragraphs [0094]-[0096] teaches determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit, therefore the number is implied to be compared to a threshold value, i.e. imaging condition, that defines a limit of a compliance range, in order to determine whether to proceed to step S555 or S560).
Masutani fails to teach: obtaining analysis results from the biological sample analysis criterion at the end of the measurement period; wherein, the method further comprises, for a plurality of measurement times during the measurement period within a first half and a second half of the measurement period; the acquisition of a holographic image of the biological sample by the holographic imager; the determination, from the acquired holographic image, of a value of a distribution parameter representative of the quantitative spatial distribution of biological agents in the field-of-view, the determination of the value of the distribution parameter comprising the determination, for each of a plurality of zones of the holographic image, of the presence or absence of biological agents in the zone, and the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range.
Masutani teaches a holographic microscope (paragraph [0034]). Masutani teaches observation of number of cells at a first time and a second time (paragraph [0038]). Masutani teaches imaging a plurality of number of times (paragraph [0131]). Masutani teaches presence/absence of a cell may be set as conditions for selecting imaging positions of an image (paragraph [0057]). Masutani teaches selecting a plurality of imaging areas and determining if the imaging areas satisfy imaging conditions in order to select an imaging position for analysis (paragraph [0061]).
Neugebauer teaches methods for determination of a microbial pathogen and its anti-infective resistance (abstract), including optical detection performed by holographic detection (paragraphs [0013],[0115]). Neugebauer teaches using holographic approaches, averaged data can be captured on the image section and the characteristics of the individual microbes can also be determined by data evaluation (paragraph [0126]). Neugebauer teaches optical detection of a sample at at least two time points during cultivation of a sample (paragraph [0023]). Neugebauer teaches an indicator of the resistance of the microbial pathogen to the anti-infective agent is an unchanged cell growth of the microbial pathogen compared to negative control data (paragraph [0110]). Neugebauer teaches cell growth, i.e. analysis result, can be determined by observing cell number over time (paragraph [0111]).
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 method of Masutani to incorporate the teachings of a holographic microscope, observing number of cells at different times, and presence/absence of cells as conditions for selecting images of Masutani (paragraphs [0034],[0038],[0057],[0131]) and the teachings of analysis of a sample of cells based on holographic detection and observing number of cells over time of Neugebauer (paragraphs [0013], [0023],[0110],[0111],[0115],[0126]) to provide: obtaining analysis results from the biological sample analysis criterion at the end of the measurement period (e.g. cell growth); wherein, the method further comprises, for a plurality of measurement times during the measurement period within a first half and a second half of the measurement period; the acquisition of a holographic image of the biological sample by the holographic imager; the determination, from the acquired holographic image, of a value of a distribution parameter representative of the quantitative spatial distribution of biological agents in the field-of-view, the determination of the value of the distribution parameter comprising the determination, for each of a plurality of zones of the holographic image, of the presence or absence of biological agents in the zone. Doing so would have a reasonable expectation of successfully improving image analysis and characterization of a sample over the measurement period and ensuring the areas of the holographic image contains desired biological agents to be analyzed.
Modified Masutani fails to teach: the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range.
Masutani teaches checking if imaging conditions are satisfied within a first half of a measurement period (Fig. 6, step S550 and paragraph [0094]), wherein a determination unit determines whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit and the distribution of the cells calculated by the cell distribution calculating unit (paragraph [0094]).
Fisher teaches methods for controlling concentration in a composition (abstract). Fisher teaches a check standard stage is typically run after a calibration stage and before a sample measurement stage to verify the measurement instrument is accurately determining concentration and is properly calibrated; wherein if the measured concentration and/or standard deviation are not within the predefined range limits, this indicates that the instrument is not in calibration and a sample failure alarm, for example, a visual and/or aural alarm, activates (paragraph [0031]).
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 method of modified Masutani to incorporate the teachings of checking if imaging conditions are satisfied of Masutani (paragraph [0094]) and the teachings of activating an alarm if measured conditions such as measured concentration are not within predefined range limits of Fisher (paragraph [0031]) to provide: the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range. Doing so would have a reasonable expectation of successfully improving notification to a user to indicate whether or not the biological sample meets desired conditions for image analysis, therefore preventing inaccurate or undesired analysis of a sample.
Regarding claim 2, modified Masutani fails to teach: wherein the threshold value is a bottom threshold value corresponding to a bottom limit of the compliance range, and if the value of the distribution parameter is lower than the bottom threshold value, the analysis instrument issues a biological sample non-compliance alert and/or the threshold value is a top threshold value corresponding to a top limit of the compliance range, and if the value of the distribution parameter is higher than the top threshold value, the analysis instrument issues a biological sample non-compliance alert.
Masutani teaches checking if imaging conditions are satisfied within a first half of a measurement period (Fig. 6, step S550 and paragraph [0094]), wherein a determination unit determines whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit and the distribution of the cells calculated by the cell distribution calculating unit (paragraph [0094]). Masutani teaches the number of cells as the imaging conditions is in the range of 100 to 500 (paragraph [0061]).
Fisher teaches methods for controlling concentration in a composition (abstract). Fisher teaches a check standard stage is typically run after a calibration stage and before a sample measurement stage to verify the measurement instrument is accurately determining concentration and is properly calibrated; wherein if the measured concentration and/or standard deviation are not within the predefined range limits, this indicates that the instrument is not in calibration and a sample failure alarm, for example, a visual and/or aural alarm, activates (paragraph [0031]).
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 method of modified Masutani to incorporate the teachings of checking if imaging conditions, such as if a number of cells are within a range, are satisfied of Masutani (paragraphs [0061],[0094]) and the teachings of activating an alarm if measured conditions such as measured concentration are not within predefined range limits of Fisher (paragraph [0031]) to provide: wherein the threshold value is a bottom threshold value corresponding to a bottom limit of the compliance range, and if the value of the distribution parameter is lower than the bottom threshold value, the analysis instrument issues a biological sample non-compliance alert and/or the threshold value is a top threshold value corresponding to a top limit of the compliance range, and if the value of the distribution parameter is higher than the top threshold value, the analysis instrument issues a biological sample non-compliance alert. Doing so would have a reasonable expectation of successfully improving notification to a user to indicate whether or not the biological sample have conditions that are within desired ranges for image analysis, therefore preventing inaccurate or undesired analysis of a sample.
Regarding claim 3, modified Masutani fails to teach: wherein the biological sample initial compliance check is carried out for at least one measurement time within the first quarter of the measurement period.
Masutani teaches checking if imaging conditions are satisfied within a first half of a measurement period (Fig. 6, step S550 and paragraph [0094]), wherein a determination unit determines whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit and the distribution of the cells calculated by the cell distribution calculating unit (paragraph [0094]).
Neugebauer teaches optical detection can take place at the beginning of cultivations and intervals of not more than 15 or 5 minutes (paragraph [0036]). Neugebauer teaches tracking growth of bacteria every 15 minutes via imaging (paragraph [0172]).
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 biological sample initial compliance check of modified Masutani to incorporate the teachings of checking if imaging are conditions are satisfied of Masutani (paragraph [0094]; Fig. 6) and the teachings of optical detecting at the beginning of cultivations at intervals of not more than 15 or minutes (paragraphs [0036],[0172]) to provide: wherein the biological sample initial compliance check is carried out for at least one measurement time within the first quarter of the measurement period. Doing so would have a reasonable expectation of successfully ensuring the biological sample meets desired conditions prior to continuing the method, therefore preventing inaccurate or undesired analysis of a sample.
Regarding claim 4, modified Masutani fails to teach wherein the biological sample initial compliance check is carried out for at least one measurement time within the first hour of the measurement period, or within the first 30 minutes of the measurement period.
Masutani teaches checking if imaging conditions are satisfied within a first half of a measurement period (Fig. 6, step S550 and paragraph [0094]), wherein a determination unit determines whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit and the distribution of the cells calculated by the cell distribution calculating unit (paragraph [0094]).
Neugebauer teaches optical detection can take place at the beginning of cultivations and intervals of not more than 15 or 5 minutes (paragraph [0036]). Neugebauer teaches tracking growth of bacteria every 15 minutes via imaging (paragraph [0172]).
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 biological sample initial compliance check of modified Masutani to incorporate the teachings of checking if imaging are conditions are satisfied of Masutani (paragraph [0094]; Fig. 6) and the teachings of optical detecting at the beginning of cultivations at intervals of not more than 15 or minutes (paragraphs [0036],[0172]) to provide: wherein the biological sample initial compliance check is carried out for at least one measurement time within the first hour of the measurement period, or within the first 30 minutes of the measurement period. Doing so would have a reasonable expectation of successfully ensuring the biological sample meets desired conditions prior to continuing the method, therefore preventing inaccurate or undesired analysis of a sample.
Regarding claim 5, modified Masutani further teaches wherein the distribution parameter is derived from a number of biological agents appearing in the holographic image (Masutani, paragraph [0063] teaches determination of quantities of cells, i.e. number of biological agents, imaged in the main captured image; see above claim 1, modified Masutani teaches the image is the holographic image).
Regarding claim 8, modified Masutani fails to teach wherein the holographic image is a hologram or an image reconstructed from a hologram.
Masutani teaches the microscope device has functions of a holographic microscope (paragraph [0034]).
Neugebauer teaches methods for determination of a microbial pathogen and its anti-infective resistance (abstract), including optical detection performed by holographic detection (paragraphs [0013],[0115]). Neugebauer teaches using holographic approaches, averaged data can be captured on the image section and the characteristics of the individual microbes can also be determined by data evaluation (paragraph [0126]). Neugebauer teaches optical detection of a sample at at least two time points during cultivation of a sample (paragraph [0023]). Neugebauer teaches an indicator of the resistance of the microbial pathogen to the anti-infective agent is an unchanged cell growth of the microbial pathogen compared to negative control data (paragraph [0110]). Neugebauer teaches cell growth, i.e. analysis result, can be determined by observing cell number over time (paragraph [0111]).
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 method of Masutani to incorporate the teachings of a holographic microscope of Masutani (paragraphs [0034]) and the teachings of analysis of a sample of cells based on holographic detection and observing number of cells over time (paragraphs [0013], [0023],[0110],[0111],[0115],[0126]) to provide: wherein the holographic image is a hologram or an image reconstructed from a hologram. Doing so would have a reasonable expectation of successfully improving image analysis and characterization of a sample over the measurement period and ensuring the areas of the holographic image contains desired biological agents to be analyzed.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Masutani in view of Neugebauer and Fisher as applied to claim 1 above, and further in view of Nakatomi et al. (US 20210142474 A1; effectively filed 06/07/2018).
Regarding claim 6, modified Masutani fails to teach: wherein a zone of the holographic image is between 5 and 20 times larger than a typical size of the biological agents of the biological sample.
Masutani teaches selecting a plurality of imaging areas and determining if the imaging areas satisfy imaging conditions in order to select an imaging position for analysis (paragraph [0061]). Masutani teaches eight image areas (paragraph [0074]).
Nakatomi teaches an imaging processing device including a cell analyzer that analyzes an image of cells cultured within a culture container (abstract). Nakatomi teaches dividing an image into a plurality of regions (paragraphs [0092]-[0094]), wherein the size of the regions are set in accordance with the size of each cell in the image (paragraph [0093]). Nakatomi teaches calculating a number of cell divisions within each region (paragraph [0094]).
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 a zone of the holographic image of modified Masutani to incorporate the teachings of a plurality of imaging areas of Masutani (paragraphs [0061],[0071]) and the teachings of size of regions of an image are set according to size of each cell in an image of Nakatomi (paragraphs [0092]-[0094]) to provide: wherein a zone of the holographic image is between 5 and 20 times larger than a typical size of the biological agents of the biological sample through routine experimentation. Doing so would have a reasonable expectation of successfully ensuring the size of the zones encompass desired biological agents at an optimal size for quantification and analysis. See MPEP 2144.05 (II).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Masutani in view of Neugebauer and Fisher as applied to claim 1 above, and further in view of Hammond et al. (US 20150118708 A1).
Regarding claim 7, modified Masutani fails to teach wherein the presence or absence of biological agents in a zone is determined by comparing a value of level of grey of the zone with a threshold, or by comparing a pattern of the zone with reference patterns of a database.
Hammond teaches a method for detecting bacteria and determining the concentration thereof in a liquid sample (abstract). Hammond teaches differentiating bacteria from non-bacteria in a sample (paragraph [0114]), wherein a straight forward measurement can be made by thresholding the image and identifying the objects from the background (e.g., turning each pixel into a grayscale value and then choosing any pixel above a certain threshold value to be white while all other pixels are black); and counting all of the individual white areas (each connected white pixel will be considered as one element) will yield the object count (paragraph [0114]).
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 method of modified Masutani to incorporate the teachings of detecting the presence of bacteria and counting bacteria by thresholding an image and comparing to a threshold value of Hammond (paragraph [0114]) to provide: wherein the presence or absence of biological agents in a zone is determined by comparing a value of level of grey of the zone with a threshold, or by comparing a pattern of the zone with reference patterns of a database. Doing so would have a reasonable expectation of successfully improve differentiation and detection of the biological agents in the zone for analysis of the desired biological agents.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Masutani in view of Neugebauer and Fisher as applied to claim 1 above, and further in view of Ozcan et al. (US 20190137932 A1).
Regarding claim 9, modified Masutani fails to teach wherein the analysis receptacle has at least two opposite transparent faces, and the holographic imager is configured so that the field-of-view extends over a field depth of at least 100 um between the two opposite transparent faces of the analysis receptacle.
Ozcan teaches imaging a sample contained on a sample holder (abstract). Ozcan teaches a microscope that uses holographic imaging to produce high-resolution images, wherein a sample is contained on an optically transparent substrate to be holographically imaged (paragraph [0008]). Ozcan teaches an optically transparent sample holder holds a sample along an optical path (paragraph [0012]). Ozcan teaches the holographic microscope has an enhanced depth of field which spans several hundreds microns, and the holograms over a large sample area can thus be easily focused by autofocusing and digital back-propagation algorithms (paragraph [0088]).
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 analysis receptacle and holographic imager of modified Masutani to incorporate the teachings of transparent substrates for samples and holographic microscopes with enhanced depth of fields of several hundreds microns of Ozcan (paragraphs [0008],[0012],[0088]) to provide: wherein the analysis receptacle has at least two opposite transparent faces, and the holographic imager is configured so that the field-of-view extends over a field depth of at least 100 um between the two opposite transparent faces of the analysis receptacle. Doing so would have a reasonable expectation of successfully improving the resolution of images of the biological agents and allowing for improved focusing of the biological agents over a large sample area as taught by Ozcan (paragraph [0088]).
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Masutani in view of Neugebauer and Fisher as applied to claim 1 above, and further in view of Toi et al. (US 20040208795 A1).
Regarding claim 11, modified Masutani fails to teach: wherein the issuing of the biological sample non-compliance alert comprises the analysis instrument arresting the remainder of the analysis of the biological sample.
Fisher teaches methods for controlling concentration in a composition (abstract). Fisher teaches a check standard stage is typically run after a calibration stage and before a sample measurement stage to verify the measurement instrument is accurately determining concentration and is properly calibrated; wherein if the measured concentration and/or standard deviation are not within the predefined range limits, this indicates that the instrument is not in calibration and a sample failure alarm, for example, a visual and/or aural alarm, activates (paragraph [0031]).
Toi teaches an automated liquid handling system for drug metabolic experiments (abstract; [0002]). Toi teaches the system includes procedure checks (paragraphs [0046],[0064]), wherein if intended check results are not obtained, then a control device displays an alarm to draw the operator's attention and stops the operation (paragraph [0064]). Toi teaches the control sequence may be set in advance so that the abnormally processed process number and the contents of abnormality are displayed after all the processes are complete (paragraph [0069]).
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 method of modified Masutani to incorporate Fisher’s teachings of verifying the measurement instrument (paragraph [0031]) and Toi’s teachings of procedure checks and stopping operation if intended check results are not obtained (paragraphs [0064]) to provide: wherein the issuing of the biological sample non-compliance alert comprises the analysis instrument arresting the remainder of the analysis of the biological sample. Doing so would have a reasonable expectation of successfully improving control and stopping of the analysis instrument, therefore preventing inaccurate or undesired analysis of a sample and allowing for an operator to check the instrument.
Regarding claim 12, modified Masutani fails to teach: wherein the analysis instrument comprises an electroacoustic transducer and a display screen, and the issuing of the biological sample non-compliance alert comprises issuing a sound intended for an operator and displaying on the display screen a message warning the operator of the non- compliance and indicating the value of the distribution parameter.
Fisher teaches methods for controlling concentration in a composition (abstract). Fisher teaches a check standard stage is typically run after a calibration stage and before a sample measurement stage to verify the measurement instrument is accurately determining concentration and is properly calibrated; wherein if the measured concentration and/or standard deviation are not within the predefined range limits, this indicates that the instrument is not in calibration and a sample failure alarm, for example, a visual and/or aural alarm, activates (paragraph [0031]).
Toi teaches an automated liquid handling system for drug metabolic experiments (abstract; [0002]). Toi teaches the system includes procedure checks (paragraphs [0046],[0064]), wherein if intended check results are not obtained, then a control device displays an alarm to draw the operator's attention and stops the operation (paragraph [0064]). Toi teaches the control sequence may be set in advance so that the abnormally processed process number and the contents of abnormality are displayed after all the processes are complete (paragraph [0069]).
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 method of modified Masutani to incorporate Fisher’s teachings of verifying the measurement instrument and providing visual and aural alarms (paragraph [0031]) and Toi’s teachings of procedure checks and stopping operation if intended check results are not obtained (paragraphs [0064]) and displaying contents of abnormality of processes (paragraph [0069]) to provide: wherein the analysis instrument comprises an electroacoustic transducer and a display screen, and the issuing of the biological sample non-compliance alert comprises issuing a sound intended for an operator and displaying on the display screen a message warning the operator of the non- compliance and indicating the value of the distribution parameter. Doing so would have a reasonable expectation of successfully improving notification to a user to indicate whether or not the biological sample meets desired conditions for image analysis, therefore preventing inaccurate or undesired analysis of a sample and allowing for an operator to check the instrument and contents of the abnormality (i.e. value of the distribution parameter).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Masutani in view of Neugebauer and Fisher as applied to claim 1 above, and further in view of Yamakawa et al. (US 20200096940 A1).
Regarding claim 13, Masutani further teaches wherein the holographic imager (paragraph [0034] teaches the microscope device has functions of a holographic microscope, i.e. holographic imager) comprises a light source arranged on one side of the analysis receptacle (paragraph [0035] teaches the microscope device images transmission light that has been transmitted through cells inside wells; therefore the holographic imager includes a light source on side of the analysis receptacle, i.e. wells) and configured to illuminate the analysis receptacle in the field-of-view (paragraph [0035] teaches the microscope device images transmission light that has been transmitted through cells inside wells; therefore the holographic imager is configured to illuminate the wells in the field-of-view), and a digital image sensor (Fig. 2, imaging unit 22; paragraph [0031] teaches the imaging unit includes a CCD, CMOS, or the like) arranged on an other side of the analysis receptacle (paragraph [0035] teaches the microscope device images transmission light that has been transmitted through cells inside wells; paragraph [0032] teaches the lens of the imaging unit receives light that has been transmitted through a cell; therefore, the imaging unit 22 is arranged an other side of the well while the light source is on one side of the well).
Modified Masutani fails to teach: the holographic imager configured to illuminate the analysis receptacle in the field-of-view with an illumination beam of coherent light; and wherein the acquisition of the holographic image comprises the digital image sensor acquiring a hologram formed by interference, on the digital image sensor, between a wave scattered by the biological agents present in the field-of-view and a reference wave of the illumination beam.
Yamakawa teaches a microscopic observation unit acquiring hologram data at each measurement position on a cell culture plate (abstract). Yamakawa teaches a digital holographic microscope, including: a) a light-source section configured to generate coherent output light; b) a detector section configured to obtain a hologram which is an interference pattern formed by reference wave and object wave when a sample containing a cell is illuminated with the output light of the light-source section (paragraphs [0014]-[0016]). Yamakawa teaches the light-source section (Fig. 2, element 11) on one side of a cell culture plate (13) and each image sensor (12) on another side of the cell culture plate (Fig. 2). Yamakawa teaches that by viewing this hologram image displayed on the display section during the execution of the measurement, the user can check for the presence of a foreign object other than the biological cells as well as the appropriateness of the measurement; and if the user considers that it is unnecessary to continue the measurement, the user can stop the measurement halfway to avoid the execution of the useless measurement (paragraph [0025]).
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 holographic imager of modified Masutani to incorporate Yamakawa’s teachings of holographic imaging with coherent light to obtain a hologram which is an interference pattern formed by reference wave and object wave (paragraphs [0014]-[0016]; Fig. 2) to provide: the holographic imager configured to illuminate the analysis receptacle in the field-of-view with an illumination beam of coherent light; and wherein the acquisition of the holographic image comprises the digital image sensor acquiring a hologram formed by interference, on the digital image sensor, between a wave scattered by the biological agents present in the field-of-view and a reference wave of the illumination beam. Doing so would have a reasonable expectation of successfully improving analysis of cells, which could allow for checking for foreign objects to stop measurement to avoid execution of useless measurement (Yamakawa, paragraph [0025]).
Response to Arguments
Applicant’s arguments, see page 6, filed 09/09/2026, with respect to the rejections under 35 U.S.C. 112(b) have been fully considered and are persuasive. The rejections under 35 U.S.C. 112(b) of 03/09/2026 have been withdrawn.
Applicant's arguments, see pages 6-9, filed 09/09/2026, with respect to the rejections under 35 U.S.C. 101, have been fully considered but they are not persuasive.
In response to applicant’s argument that the limitations of claims 1 are integrated into a practical application and the additional limitations are not insignificant extra-solution activities (Remarks, pages 7-8), the examiner disagrees. With respect to the argued limitation of “issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range” (Remarks, page 7), the limitation is insignificant extra-solution activity of providing an alert based on a result. See MPEP 2106.05(g).
In response to applicant’s argument that the method continues to operate to obtain analysis results, and therefore reflects an application of the abstract idea as a whole (Remarks, page 7, last paragraph – page 8 first paragraph), the examiner disagrees. As claimed, the analysis instrument issues an alert if the value is outside the compliance range. Therefore, if the value of the distribution parameter is inside the compliance range, no additional steps other than the abstract ideas are performed, therefore there is no application of the abstract idea.
In response to applicant’s argument that the holographic imager is not a generic computer, but a specific apparatus that makes the claimed measurement possible and therefore is an improvement to the analysis instrument and not merely an application of a mental process on a generic computer (Remarks, page 8), the examiner disagrees. While the claim recites the holographic imager, those elements are broad and the claim does not include particular elements of a machine or apparatus (see MPEP 2106.05(b)(I)). As evidenced in at least Masutani et al. (US 20210073979 A1; effectively filed 10/06/2017), holographic imagers (paragraph [0034] teaches the microscope device has functions of a holographic microscope) are well-understood, routine, and conventional in the art. The limitations of the holographic imager generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)).
In response to applicant’s argument that the references do not satisfy the requirement for well-understood, routine and conventional activities (Remarks, pages 8-9), the examiner agrees. However, the limitations of claim 1 and dependent claims 2-9 and 11-13 generally link the judicial exception to a particular field of use (MPEP 2106.05(h)) and are used for data gathering, wherein data gathering to be used in the abstract idea is an insignificant extra-solution activity, and not a practical application (see MPEP 2106.05(g)), which alone or in combination do not amount to significantly more. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). The claims are not patent eligible.
Applicant's arguments, see pages 9-12, filed 09/09/2026, 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 Masutani and Fisher fails to teach “an initial compliance check for the biological sample, comprising comparing the value of the distribution parameter with at least one threshold value defining a limit of compliance range, the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range” (Remarks, pages 10-12), the examiner disagrees.
Specifically, in response to applicant’s argument that Masutani does not teach a compliance check of a biological sample since Masutani teaches an image-selection criterion to select an appropriate field of view (Remarks, page 10, last paragraph – page 11, first paragraph), the examiner disagrees. Masutani teaches: the method also comprising, for at least one measurement time within a first half of the measurement period, an initial compliance check for the biological sample (Fig. 6 and paragraphs [0094]-[0096] teaches step S550 of determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit, wherein step S550 is interpreted as within a first half of a measurement period from the start to end of the method of Fig. 6), comprising comparing the value of the distribution parameter with at least one threshold value defining a limit of a compliance range (Fig. 6 and paragraphs [0094]-[0096] teaches determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit, therefore the number is implied to be compared to a threshold value, i.e. imaging condition, that defines a limit of a compliance range, in order to determine whether to proceed to step S555 or S560). The BRI of “an initial compliance check” includes Masutani’s teachings of step S550 of determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit (Fig. 6 and paragraphs [0094]-[0096]); and therefore Masutani’s teachings read on an “initial compliance check” since there is a check or determination whether conditions are satisfied.
In response to applicant’s argument that the combination of Fisher and Masutani would change the principle of operation of the prior art (Remarks, page 11), 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, it would have been obvious to one of ordinary skill in the art to have modified the method of modified Masutani to incorporate the teachings of checking if imaging conditions are satisfied of Masutani (paragraph [0094]) and the teachings of activating an alarm if measured conditions such as measured concentration are not within predefined range limits of Fisher (paragraph [0031]) to provide: the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range. Doing so would have a reasonable expectation of successfully improving notification to a user to indicate whether or not the biological sample meets desired conditions for image analysis, therefore preventing inaccurate or undesired analysis of a sample. Furthermore, doing so would not change the principle of operation of Masutani’s determination if imaging conditions is satisfied. Rather, the combination would provide improved notification to a user to indicate whether or not the biological sample meets desired conditions for image analysis, therefore preventing inaccurate or undesired analysis of a sample. Additionally, the modification does not prevent or remove additional potential steps, such as Masutani’s re-imaging response. Note that re-imaging is not claimed.
In response to applicant’s argument that Masutani fails to teach: “for at least one measurement time within a first half of the measurement period, an initial compliance check for the biological sample” (Remarks, page 11), the examiner disagrees. Masutani teaches the method also comprising, for at least one measurement time within a first half of the measurement period, an initial compliance check for the biological sample (Fig. 6 and paragraphs [0094]-[0096] teaches step S550 of determining whether or not imaging conditions are satisfied for each pre-captured image on the basis of the number of cells calculated by the cell number calculating unit, wherein step S550 is interpreted as within a first half of a measurement period from the start to end of the method of Fig. 6). The BRI of “within a first half of a measurement period” includes Masutani’s step S550 since is within a first half of a measurement period from the start to end of the method of Fig. 6. The examiner agrees that Masutani fails to teach “obtaining analysis results from the biological sample analysis criterion at the end of the measurement period; wherein, the method further comprises, for a plurality of measurement times during the measurement period within a first half and a second half of the measurement period” (Remarks, page 11), however Masutani in view of Neugebauer are used to arrive at the claimed limitations.
In response to applicant’s argument that Fisher fails to cure these deficiencies of Masutani and does not teach a non-compliance alert for a sample of unknown content (Remarks, pages 11-12), the examiner disagrees. The examiner notes that Fisher is not used to arrive at the claimed limitation of “obtaining analysis results from the biological sample analysis criterion at the end of the measurement period; wherein, the method further comprises, for a plurality of measurement times during the measurement period within a first half and a second half of the measurement period”, rather Fisher is used in combination with Masutani to provide: the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range. 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, Masutani provides teachings of checking if imaging conditions are satisfied (paragraph [0094]) and Fisher provides teachings and motivation of: activating an alarm if measured conditions such as measured concentration are not within predefined range limits (paragraph [0031]). It would have been obvious to one of ordinary skill in the art to have modified the method of modified Masutani to incorporate the teachings of checking if imaging conditions are satisfied of Masutani (paragraph [0094]) and the teachings of activating an alarm if measured conditions such as measured concentration are not within predefined range limits of Fisher (paragraph [0031]) to provide: the analysis instrument issuing a biological sample non-compliance alert if the value of the distribution parameter is outside the compliance range. Doing so would have a reasonable expectation of successfully improving notification to a user to indicate whether or not the biological sample meets desired conditions for image analysis, therefore preventing inaccurate or undesired analysis of a sample. Therefore, 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 to have provided an alarm trigged by a check standard as claimed.
In response to applicant’s argument that Neugebauer does not supply the initial compliance check or the non-compliance alert (Remarks, page 12), the examiner note that Neugebauer is used to arrive at the claimed limitations of “obtaining analysis results from the biological sample analysis criterion at the end of the measurement period (e.g. cell growth); wherein, the method further comprises, for a plurality of measurement times during the measurement period within a first half and a second half of the measurement period; the acquisition of a holographic image of the biological sample by the holographic imager; the determination, from the acquired holographic image, of a value of a distribution parameter representative of the quantitative spatial distribution of biological agents in the field-of-view, the determination of the value of the distribution parameter comprising the determination, for each of a plurality of zones of the holographic image, of the presence or absence of biological agents in the zone” and is not used to teach the initial compliance check or the non-compliance alert.
In response to applicant’s arguments regarding claims 2-9 (Remarks, page, 12), the examiner disagrees for the same reasons as discussed above regarding claim 1.
Additionally, the examiner acknowledges applicant’s notes regarding the Masutani with respect to claim 2 (Remarks, page 12) and Nakatomi with respect to claim 6 (Remarks, page 12), however, applicant does not provide arguments regarding the rejections of claim 2 or 6 under 35 U.S.C. 103 and therefore are not persuasive.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Oxborough (US 20190242825 A1) teaches a cell counting device (abstract). Oxborough teaches determining a cell density, and if the estimated cell density exceeds the threshold, at step S1018 an action is performed. The action may be indicating that the sample 1 is not compliant with the IMO D2 Standard (10 μm to 50 μm) and the US Coast Guard Discharge Standard (10 μm to 50 μm), using the display 60, an indicator light or an audible alarm either on the cell counting device 2 or on an external computing device (paragraph [0169]).
Thompson et al. (US 20040023223 A1) teaches a method and assay for chemical arrays (abstract; [0001]). Thompson teaches when the error exceeds a predetermined limit, any deposition (including further cycles) can be halted or an operator alert activated, or an automated or manual performance check or adjustment of one or more apparatus components performed (for example, in response to the operator alert) (paragraph [0055]).
Perree et al. (US 20140141462 A1) teaches a computer system for determining effectiveness of anti-cancer drugs (abstract). Perree teaches an alarm sends a notification to a recipient upon detection of an anomaly in optical density data being stored to the database; for example, if an assay is running, the alarm system will check the database at some predetermined time interval, perhaps 20 minutes; and if an expected reading is not recorded in the database, the alarm system notifies the lab manager or other appropriate personnel by telephone or electronic communication to advise of a problem (paragraph [0074]).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maris Kessel can be reached at (571) 270-7698. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HENRY H NGUYEN/Primary Examiner, Art Unit 1758
