DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Apr 23 2026 has been entered.
Applicant’s response, filed Apr 23 2026, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Claims 1-8 and 10-19 are pending.
Claim 9 is canceled.
Claims 17-19 are newly added.
Claim 19 is objected to.
Claims 1-8 and 10-19 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/JP2020/030151, filed Aug 6 2020, is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to App. No. JP2019-152592, filed Aug 23 2019. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Should the applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d), a certified English translation of the foreign priority application must be submitted. Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Accordingly, each of claims 1-16 are afforded the effective filing date of Aug 23 2019.
Claim Objections
The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
The claims are objected to because of the following informalities. The instant objection is newly stated and is necessitated by claim amendment.
Claim 19 includes an “and” at the end of the third limitation which should be deleted.
Claim Rejections- 35 USC § 112
35 USC § 112(b)
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.
Claims 14 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. The instant rejection is newly stated and is necessitated by claim amendment.
Claim 14 is dependent from claim 9, which has been cancelled. The metes and bounds of claim 14 are unclear because it is not clear which claim it should depend from. For compact examination, it is assumed that claim 14 is intended to depend from claim 10 instead of claim 9. The rejection may be overcome by clarifying the dependency of the claim.
Claim 14 recites “The display method”. However, there is insufficient antecedent basis for this limitation because there is no previous recitation of a display method. The claim should be amended to be directed to the statutory class from which the claim is intended to depend, as discussed in the above 35 USC 112(b) rejection.
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 1-8 and 10-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. The rejection is newly stated and is based on claim amendment.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, claims 1-8 and 10-19 are directed to a device and a system i.e., a process, machine, or manufacture within the above 101 categories; [Step 1: YES for claims 1-16; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claims 1 and 10-11: process the multidimensional analysis target data (claims 1 and 10)/plurality of fluorescent intensities (claim 11) to determine gate subsets of the plurality of particles which are respectively included in respective segments of the plurality of gates;
perform clustering on the multidimensional analysis target data (claims 1 and 10)/plurality of fluorescent intensities (claim 11) to obtain a plurality of clusters based on the plurality of attributes of the analysis target (claims 1 and 10)/plurality of fluorescent intensities (claim 11); and
based on the user input, process the first cluster and the gate subsets to determine a correspondence relationship between the first cluster and the first gate.
Independent claim 19: perform clustering on the multidimensional analysis target data to obtain a plurality of clusters based on the plurality of attributes of the analysis target; and
based on the user input, process the multidimensional analysis target data corresponding to the first cluster to determine a correspondence relationship between the first cluster and a first gate.
Dependent claims 2-5, 8, and 17-18 recite further steps that limit the judicial exceptions in dependent claim 2 and, as such, also are directed to those abstract ideas. For example, claim 2 further limits determining; claim 3 further limits the data being analyzed to being from a plurality of cells and calculating the matching degree using a confusion matrix; claim 4 further limits the data being analyzed to intensities corresponding to a plurality of fluorescent dyes detected from the plurality of cells labeled with the plurality of fluorescent dyes; claim 5 further limits calculating a matching degree with a cluster for all the gates; claim 8 further limits calculating a matching degree for combinations of all the clusters and all the gates; claim 17 further limits the determined correspondence relationship; and claim 18 further limits processing the first cluster and the gate subsets to determine a correspondence relationship.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually calculate a matching degree and display that information. Without further detail as to the methodology involved in “processing”, “performing”, and “calculating”, under the BRI, one may simply, for example, use pen and paper to process multidimensional analysis target data/fluorescence intensities to identify subsets of gates in a plurality of gates already obtained, perform clustering on the multidimensional analysis target data/fluorescence intensities to obtain clusters, and determine a correspondence relationship between the subset of gates and a cluster of the clusters by calculating matching degrees between the gates and the cluster.
The steps of performing clustering and calculating a matching degree recited in the dependent claims requires a mathematical technique as the only supported embodiments, as the claims describe the mathematical process of clustering numerical data and calculating numerical data to determine a matching degree in words.
Therefore, claims 1, 10-11 and 19 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claims 1 and 10-11: obtain… a plurality of fluorescent intensities (claim 11)/multidimensional analysis target data (claims 1 and 10) about an analysis target comprising a plurality of particles and having plurality of attributes;
receive information identifying a plurality of gates obtained by gate analysis of the analysis target based on the plurality of attributes, respective gates of the plurality of gates bounding respective segments of the multidimensional analysis target data;
receive a user input indicating a first cluster of the plurality of clusters, the user input representing a request to determine a first gate of the plurality of gates corresponding to the first cluster; and
cause (only in claim 10) display, on a display device, an indication of the first gate; and the correspondence relationship.
Independent claim 19: obtain multidimensional analysis target data about an analysis target comprising a plurality of particles and having plurality of attributes;
receive a user input indicating a first cluster of the plurality of clusters; and
display, on a display device, an indication of the first gate; and the correspondence relationship.
The dependent claims recite further limitations of the additional elements as follows. Claim 2 further limits displaying the correspondence relationship; claims 5-8 and 13-16 further limit displaying information about the gates.
It is noted that the independent claims 1, 10-11, and 19 and those claims dependent therefrom recite devices or systems which do not include a display device as part of the device or system. Therefore, the limitations in each of these claims directed to “display” or “cause display” on a display device are interpreted to merely recite instructions output by the one or more processors for display of the recited information, but do not require the actual display of that information.
The claims also include non-abstract computing and data gathering elements. For example, independent claim 1 includes an information processing device comprising one or more processors; independent claim 10 includes a storage device storing a program that, when executed by a computer, is configured to cause the computer to perform method steps; independent claim 11 includes an information processing system comprising a measurement device including a measurement unit that irradiates a measurement target with light, the measurement target comprising a plurality of particles; detects fluorescence emitted from the measurement target; and measures a fluorescence intensity; and an information processing device including one or more processors configured to perform method steps; and independent claim 19 includes an information processing device comprising: one or more processors configured to perform method steps. Dependent claim 12 further limits the measurement device to a flow cytometer.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps and non-abstract measurement devices directed to data gathering elements, such as “obtaining” or “receiving” data or a user input and the measurement device in claims 11-12, and to data outputting, such as instructions for displaying or causing to display on a display device, perform functions of collecting and outputting the data needed to carry out the judicial exceptions. Data gathering and outputting does not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to additional non-abstract computing elements do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)).
The specification discloses that the technical problem addressed by the invention is that it is difficult for a user to cause two analysis results to correspond to each other at [0005], but does not provide a clear explanation for how the additional elements provide any improvements. Therefore, the additional elements do not clearly improve the functioning of a computer, or comprise an improvement to any other technical field. Further, the additional elements do not clearly affect a particular treatment; they do not clearly require or set forth a particular machine; they do not clearly effect a transformation of matter; nor do they clearly provide a nonconventional or unconventional step (MPEP2106.04(d)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the specification as published discloses that samples may be labeled with a fluorescent dye by a known method and is not limited beyond what is known [0041; 0043], that known photodetectors may be used [0049]. The prior art review to Adan et al. (Critical Reviews in Biotechnology, 37(2):163-176; newly cited) discloses that flow cytometers are measurement devices for measuring fluorescence intensity of cells, as in claims 11-12, which are well known in the art. The entire review is relevant. Further, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)). As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
The computer-related elements or the general purpose computer recited in the claims do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (Alice Corp., 573 U.S. at 225-26, 110 USPQ2d at 1984; see MPEP 2106.05(A)). The specification as published also notes that computer processors and systems, as example, are commercially available or widely used at [0121-0128]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Response to Applicant Arguments
At p. 12-13, Applicant submits that the pending claims recite an improvement to multidimensional cluster-and-gate analysis technology at Step 2A, Prong 2. Applicant submits that it is difficult for a user to assess correspondence between gating and cluster analysis of a sample, which the present application addresses. Applicant submits that the improvement is reflected in the amended claims because the claims recite the limitations directed to processing the data to determine gate subsets, performing clustering, determining a correspondence between gates and clusters, and displaying the correspondence. Applicant submits that these limitation are conceivably able to be performed in the human mind or with pen and paper, except in its most simplistic form (Synopsys, Inc. v. Mentor Graphics Corp., 839 F. 3D 1138, 1148 (Fed. Circ. 2016)), and are therefore patent eligible as they do not recite abstract ideas.
It is respectfully submitted that this is not persuasive. Applicant alleges that processing the data to determine gate subsets, performing clustering, and determining a correspondence between gates and clusters represents an improvement. However, those steps pointed to by Applicant that provide the supposed improvement (i.e., making it easier for a user to assess correspondence between gating and cluster analysis) in the instant claims are steps that are, themselves, the judicial exceptions and cannot therefore be a practical application of the judicial exception. The courts have made clear that a judicial exception is not eligible subject matter (Bilski, 561 U.S. at 601, 95 USPQ2d at 1005-06 (quoting Chakrabarty, 447 U.S. at 309, 206 USPQ at 197 (1980)) if there are no additional claim elements besides the judicial exception, or if the additional claim elements merely recite another judicial exception that is insufficient to integrate the judicial exception into a practical application. See, e.g., RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017) ("Adding one abstract idea (math) to another abstract idea (encoding and decoding) does not render the claim non-abstract"); Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) (eligibility "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself."). For a claim reciting a judicial exception to be eligible, it is the additional elements (if any) in the claim that must "transform the nature of the claim" into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981, either at Prong Two or in Step 2B. If there are no additional elements in the claim, then it cannot be eligible. It is submitted here that the instant claims do not include any additional elements that provide for a practical application. Rather, the “additional element” in the instant claims (see exemplary claim 1) includes only the step of obtaining or receiving data and instructions to display the correspondence. As set forth above, said steps operate in the claim as data gathering and outputting steps and do not integrate any of the recited judicial exceptions into a practical application, nor do the claims as a whole include any inventive concept beyond well-understood, routine and conventional steps.
It is further noted that the claims do not actually require the display of the data, as discussed in the above rejection. Because the claims are directed to a system and devices but do not include a display device as part of the system and device, steps for “one or more processors configured to… display, on a display device” are interpreted merely as instructions produced by the processor to instruct the display on a display device, where the display is not part of the scope of the claims. Therefore, Applicant’s arguments that the improvement is reflected in the claims are not convincing. It is noted that even if the display were encompassed by the scope of the claims, the display would either be considered as a judicial exception, as set forth in previous Office Actions, or would merely recite data outputting that does not provide a practical application. It is not apparent that making it easier for a user to see correspondence between gating and clustering strategies is an improvement because it is not agreed that multidimensional cluster-and-gate analysis technology is a technological field that can be improved at Step 2A, Prong 2.
Applicant’s arguments regarding the claims not reciting an abstract idea are not convincing. Applicant has not provided any arguments for why the above indicated steps could not be performed mentally or with the aid of pen and paper. That the data is multidimensional data in some of the claims does not provide a reasonable explanation for why a person would not be able to select a subset of gates from a previously provided list of gates, or perform a clustering process on multidimensional data that is inherently numerical. Additionally, even if the claims were considered to not recite a mental process, Applicant has provided no arguments for why the claims do not recite mathematical techniques. The processes of clustering and calculating similarities using matrices are considered to recite inherently mathematical processes.
The instant claims are not analogous to those at issue in Synopsys because the claims are not directed to translating a functional description of a logic circuit into a hardware component description of the logic circuit. It is additionally noted that the courts found that the claims at issue in Synopsys did recite mental processes (see MPEP 2106.04(a)(2)).
Claim Rejections - 35 USC § 102
The outstanding rejections from the previous Office Action are withdrawn in view of the amendments submitted herein. As submitted by Applicant at p. 9-12, Chen et al. (US 2017/0371886) does not explicitly teach “receiving a user input indicating a first cluster”.
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.
A. Claims 1-2, 10-12, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2017/0371886; previously cited) in view of Meehan et al. (US 2015/0293992; newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Claim 1 discloses an information processing device comprising one or more processors. Claim 10 discloses a storage device storing a program that, when executed by a computer, is configured to cause the computer to perform method steps. Claim 11 discloses an information processing system comprising: a measurement device including a measurement unit that irradiates a measurement target with light, the measurement target comprising a plurality of particles, detects fluorescence emitted from the measurement target, and measures a fluorescence intensity; and an information processing device including one or more processors configured to perform method steps. Claim 12, which depends on claim 11, discloses that the measurement device is a flow cytometer. Claim 19 discloses an information processing device comprising one or more processors configured to perform method steps.
The prior art to Chen discloses a method for identifying clusters in a dataset (abstract) by analyzing cytometry data with the aid of a computer (title). Chen teaches a computer system (i.e., an information processing device, as in claims 1 and 11) configured to perform the disclosed method, where the computer system includes a processor, an output interface [0076] which may include a display for display the visualization of the clusters (i.e., a display control unit) [0079], and processes implemented as modules that are executable on the computer system [0031; 0077]. As Chen teaches flow cytometry, it is considered that Chen fairly teaches “a measurement device including a measurement unit that irradiates a measurement target with light, detects fluorescence emitted from the measurement target, and measures a fluorescence intensity” as recited in claim 11, because claim 12 limits such a device to a flow cytometer. It is therefore considered that a flow cytometer inherently that irradiates a measurement target with light, detects fluorescence emitted from the measurement target, and measures a fluorescence intensity.
The method steps of claims 1, 10-11, and 19 include:
obtaining multidimensional analysis target data (claims 1, 10, and 19)/fluorescence intensities (claim 11) about an analysis target comprising a plurality of particles and having plurality of attributes;
Chen teaches that their method is used to analyze cytometry data [0034; 0038], which reads on obtaining multidimensional analysis target data/fluorescence intensities as instantly claimed. Chen teaches analyzing different cell populations according to 8 different markers (i.e., analysis target having a plurality of attributes) [0061].
receiving information identifying a plurality of gates obtained by gate analysis of the analysis target based on the plurality of attributes, respective gates of the plurality of gates bounding respective segments of the multidimensional analysis target data (claims 1 and 10)/fluorescence intensities (claim 11);
Chen teaches manually gating different cell populations according to 8 different markers (i.e., analysis target having a plurality of attributes) in two datasets [0061].
processing the multidimensional analysis target data (claims 1 and 10)/fluorescence intensities (claim 11) to determine gate subsets of the plurality of particles which are respectively included in respective segments of the plurality of gates;
Chen teaches examining specific gates from the manually gated dataset [0061-0063], which reads on determining gate subsets as instantly claimed.
performing clustering on the multidimensional analysis target data(claims 1, 10, and 19)/fluorescence intensities (claim 11) to obtain a plurality of clusters based on the plurality of attributes of the analysis target;
Chen teaches applying several dimensionality reduction methods, including t-SNE, on the two datasets which were manually gated [0061].
receiving a user input indicating a first cluster of the plurality of clusters (claim 19), the user input representing a request to determine a first gate of the plurality of gates corresponding to the first cluster (claims 1 and 10-11);
based on the user input, processing the first cluster and the gate subsets to determine a correspondence relationship between the first cluster and the first gate; and
Chen teaches an interactive user interface of a web application that that generates an interactive visualization of the analysis results, including the cell subpopulations, where users may explore the relationship of the cell subsets to explore the expression patterns mapped on the dimensionality reduced data (i.e., clusters) (FIG. 9; [0056; 0060]). Chen teaches calculating the precision, recall, and F-measures of the clusters produced by the various clustering algorithms and the manually determined gates (i.e., correspondence relationship) [0066]. As Chen teaches calculating these features between each of the clusters and the gates, it is considered that Chen fairly teaches a first cluster and a first gate as instantly claimed.
Chen does not explicitly teach “receiving a user input indicating a first cluster”. See below for teachings by Meehan regarding this limitation.
displaying, on a display device: an indication of the first gate; and the correspondence relationship.
Chen teaches displaying the gated populations (i.e., indication of the first gate), clusters, precision, recall, and F-measures (i.e., correspondence relationship) in Table 13. Chen also teaches displaying clusters of cells color coded by gated populations in FIG. 10-11 [0062-0063], which also teaches the above limitation. Chen teaches that the computer system includes an output interface [0076] which may include a display for display the visualization of the clusters (i.e., a display device) [0079].
Chen does not explicitly teach “receiving a user input indicating a first cluster”.
However, the prior art to Meehan discloses analyzing data using population clustering through density based merging (abstract) in the field of flow cytometry [0004]. Meehan teaches displaying to a user results of an automated clustering of data points using a subset of the parameters, the first clustering indicating one or more data clusters; registering an input from the user selecting a first selected cluster from which to generate children clusters; providing an interface allowing a user to optionally choose different parameters allowing for the children clusters; and displaying a hierarchy of clustering results [0014]. Meeahan teaches that an attribute of the present disclosure is the optional guidance of a clustering sequence by including at least one manual imposition of gating on the displayed clusters e.g., via a human operator drawing on a touch sensitive screen displaying clusters [0166]. It is therefore considered that Meehan teaches receiving a user input indicating a first cluster as instantly claimed, and also including the manual gating associated with that cluster in a display.
Regarding claims 1, 10-12, and 19, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Chen in view of Meehan because both references disclose methods for comparing clustering and manual gating of flow cytometry data. The motivation would have been to incorporate human insight/intuition with an automated gating process, as taught by Meehan [0166].
Regarding claim 2, Chen in view of Meehan teaches the information processing device of claim 1 as described above. Claim 2 further adds that the one or more processors determine the correspondence relationship by calculating a matching degree between the first gate and the first cluster, and that the display device displays the correspondence relationship by displaying the indication of the first gate such that the first gate corresponds to the first cluster on a basis of a matching degree.
Chen teaches calculating the precision, recall, and F-measures (i.e., a matching degree) of the various clustering algorithms and the manually determined gates in FIG. 13 (i.e., displaying the gate such that the gate corresponds to the cluster on a basis of a matching degree) [0066]. Chen also teaches overlaying manually determined gates [0065-0066] and clusters [0057] onto dimension reduction visualizations of the cytometry data by mapping (FIGs 9-11). Chen teaches displaying the gate such that the gate corresponds to the cluster on a basis of a matching degree calculated by the calculation unit in the table of FIG. 13 which shows the gated population, the clusters, and the F-measure.
Regarding claim 17, Chen in view of Meehan teaches the information processing device of claim 1 as described above. Claim 17 further adds that the correspondence relationship is a one-to-one relationship.
Chen teaches calculating the precision, recall, and F-measures of the clusters produced by the various clustering algorithms and the manually determined gates (i.e., correspondence relationship) [0066], which is considered to read on a one-to-one relationship between the cluster and the gate as instantly claimed.
Regarding claim 18, Chen in view of Meehan teaches the information processing device of claim 1 as described above. Claim 18 further adds that processing the first cluster and the gate subsets to determine a correspondence relationship between the first cluster and the first gate is based on an overlap between the first cluster and a gate subset of the first gate.
Chen teaches calculating and then displaying in a table the precision, recall, and F-measures (i.e., a matching degree) of the various clustering algorithms and the manually determined gates in FIG. 13, where only the clusters and the manually determined gates with the highest F-measures are displayed [0066], which is considered to read on an overlap between the first cluster and a gate subset and a gate subset of the first gate because Chen teaches determining relationships between the clusters and all the gates but only displaying a subset of that information.
B. Claims 3-6, 8, 13-16, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Chen in view of Meehan, as applied to claims 1-2 above, in view of Aghaeepour et al. (Nature Methods, 2013, 10(3):228-243; previously cited). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claim 3, Chen in view of Meehan teaches the information processing device of claims 1-2 as described above. Claim 3 further adds that the analysis target is a plurality of cells, and the one or more processors calculate the matching degree using a confusion matrix based on a number of cells included in the first gate and the number of cells included in the first cluster.
Chen teaches methods of detecting cell sub-populations in a plurality of cells [0002]. Chen teaches calculating an F-measure (i.e., a matching degree) as described above [0066], but does not teach using a confusion matrix as instantly claimed.
However, the prior art to Aghaeepour discloses an analysis of flow cytometry data processing challenges to examine whether automated algorithms can reproduce expert manual gating (abstract). Aghaeepour teaches performing manual gating by experts for comparison against cell population membership defined by each automated algorithm (p. 229, col. 2, par. 2). Aghaeepour teaches calculating an F-measure between the results of each cell population program and the reference method of manual gating by the subject matter expert (i.e., matching degree) using a 2x2 contingency table to calculate F = (2 × Pr × Re)/(Pr + Re), with the true positive (TP) defined as the situation in which the positive assignment of the prediction algorithm matches a positive assignment of manual gating, false positive (FP) when the positive assignment of the prediction algorithm matches a negative assignment of manual gating, and false negative (FN) when the negative assignment of the prediction algorithm matches a positive assignment of manual gating (p. 239, col. 2, par. 2). As the instant specification as published discloses that “In the confusion matrix, the number of cells belonging to the gate for which the matching degree is calculated and belonging to the cluster for which the matching degree is calculated is represented by True Positive (TP). In addition, the number of cells belonging to the gate for which the matching degree is calculated and belonging to a cluster other than the cluster for which the matching degree is calculated is represented by False Negative (FN). In addition, the number of cells belonging to a gate other than the gate for which the matching degree is calculated and belonging to the cluster for which the matching degree is calculated is represented by False Positive (FP).” at [0071], it is considered that the contingency table of Aghaeepour reads on the confusion matrix as instantly claimed. Aghaeepour further teaches comparing manual-gate consensus and ensemble clustering results by displaying the manual gates and results of the clustering algorithms on the same graph (Figure 3a and c).
Regarding claim 4, Chen in view of Meehan teaches the information processing device of claims 1-2, and, in view of Aghaeepour, of claim 3, as described above. Claim 4 further adds that the plurality of attributes is intensities corresponding to a plurality of fluorescent dyes detected from the plurality of cells labeled with the plurality of fluorescent dyes.
Chen teaches analyzing cytometry data (title) of flow cytometry experiments [0033], where data are positive or negative for different biomarker signals like CD4, CD8, CD3, etc. [0061], but does not explicitly teach that the attributes is intensities corresponding to a plurality of fluorescent dyes detected from the plurality of cells labeled with the plurality of fluorescent dyes.
However, Aghaeepour teaches that flow cytometers provide high-dimensional quantitative measurement of light scatter and fluorescence emission properties of hundreds of thousands of individual cells in each analyzed sample (p. 228, col. 1, par. 1), which is considered to teach the instant limitation, or, alternatively, to provide evidence that the cytometry data of Chen fairly teaches the instant limitation.
Regarding claims 5-6, Chen in view of Meehan teaches the information processing device of claims 1-2 as described above. Claim 5 further adds that the one or more processors calculate a matching degree with the first cluster for all gates of the plurality of gates, and the display device displays the first gate by a display method from display methods of other gates. Claim 6 further adds the different display method is a different color.
Chen teaches that the software package may include a Graphical User Interface (GUI) that allows a user to customize their analysis to choose the preferred merging method, cluster method and visualization method [0059], which is considered to read on a reception unit that receives selection of a cluster as instantly claimed. Chen teaches plotting cells using the first two dimensions of the dimensionality-transformed data and color coding by gated populations [0062-0063]. Chen also teaches that each cluster identified by the subset detection module may be represented with a different color, that each cluster may represent one cell type, and that the color map may also display different shapes for points on the map belong to different input data files [0056], which is considered to read on a display method different from display methods of the other gates as instantly claimed. Chen teaches calculating and then displaying in a table the precision, recall, and F-measures (i.e., a matching degree) of the various clustering algorithms and the manually determined gates in FIG. 13, where only the clusters and the manually determined gates with the highest F-measures are displayed [0066]. Chen does not teach displaying the gate and the correspondence using a display method different from display methods of gates not having the highest matching degree.
However, Aghaeepour displays the manual gates and results of the clustering algorithms on the same graph colored by the F-measure (Figure 3a and c), where the different colors read on different display methods as instantly claimed.
Regarding claim 8, Chen in view of Meehan teaches the information processing device of claims 1-2 as described above. Claim 8 further adds that the one or more processors calculate a matching degree for combinations of all clusters and all gates, and the display device displays the respective gates using a display color of a respective cluster having a highest matching degree.
Chen teaches calculating the precision, recall and F-measure of each clustering method using the manually gated populations of cells [0065-0066], which is considered to read on calculating a matching degree for combinations of the clusters and the gates as instantly claimed. Chen teaches displaying the results with the highest F-measure for each cluster and gated population combination in FIG. 13. Chen does not teach a display color of a cluster having a highest matching degree.
However, Aghaeepour teaches a display color of a cluster having a highest matching degree in Figure 3a and c where the gates and clusters are colored by F-measure.
Regarding claims 13-16, Chen in view of Meehan teaches the information processing device according to claim 1, the display method of claim 9, the storage device of claim 10, and the information processing system of claim 11 as described above. Claims 13-16 further add displaying one or more lines constituting the first gate or displaying a name of the first gate, which Chen does not teach.
However, Aghaeepour displays the gates defined by lines (Figure 3a and c).
Regarding claims 3-6, 8, and 13-16, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Chen in view of Meehan and Aghaeepour because each reference discloses methods for analyzing cytometry data by comparing manual and automated gating methods. The prior art to Chen and Aghaeepour each teach methods for calculating the same type of F-measure to determine the performance of various methods in comparison to a ground truth dataset. Therefore, it would have been obvious to one of ordinary skill in the art to substitute the methods of calculating the F-measures. The substitution of the method of calculating the F-measure using the confusion matrix/contingency table, as taught by Aghaeepour, for the method of calculating the F-measure as taught by Chen in the method and system of Chen thus is no more than the simple substitution of one known element for another. Further, the motivation to display the gates, the clusters, and their correspondence according to the method of Aghaeepour would have been to demonstrate the practical utility of ensemble clustering of automated algorithm results through a visual example, as taught by Aghaeepour (p. 232, col. 2, par. 3).
C. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Chen in view of Meehan, as applied to claims 1-2 above, in view of Aghaeepour, as applied to claims 5-6 above, and in further view of Gondois-Rey et al. (Cytometry, 2016, 89A:480-490; newly cited). The instant rejection is newly stated and is necessitated by claim amendment.
Regarding claim 7, Chen in view of Meehan teaches the information processing device of claims 1-2 and, in further view of Agheeapour, claims 5-6 as described above. Claim 7 further adds that the display device displays a parent gate of the first gate in a color different from a color of the first gate.
Chen teaches that each cluster identified by the subset detection module may be represented with a different color, that each cluster may represent one cell type, and that the color map may also display different shapes for points on the map belong to different input data files [0056]. Chen does not teach displaying a parent gate.
However, the prior art to Gondois-Rey discloses a comparison of unsupervised computation tools of multi-stained samples to manual gating (abstract). Gondois-Rey teaches hierarchical gating strategies of different populations of cells, where the gates on the left of the figures are considered parent gates and those further to the right are subpopulations (Figure 1A, C, and D). Gondois-Rey displays the parent gate and subpopulation gates with different colors (red and black).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Chen in view of Meehan and Aghaeepour with Gondois-Rey because each reference discloses methods for analyzing cytometry data by comparing manual and automated gating methods. The motivation to display parent gates and gates of subpopulations would have been to visualize either fluorochrome intercontaminations or targeted population characteristics, as taught by Gondois-Rey (p. 484, col. 1, par. 1).
Response to Applicant Arguments
With respect to Applicant’s arguments under 35 USC 103, the arguments have been fully considered but are moot in view of the new grounds of rejection set forth above as necessitated by claim amendment herein.
Conclusion
No claims are allowed.
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/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685
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