DETAILED ACTION
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 .
Status of the Claims
Claims 1-2, 4-9, 12-13, 15-20, 23-24, and 26-31 are pending and examined herein.
Claims 3, 10-11, 14, 21-22, 25, and 32-33 are canceled.
Priority
As detailed on the 25 January 2022 filing receipt, the application claims priority as early as 15 January 2021. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
An information disclosure statement (IDS) was filed on 03 February 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Withdrawn Objections and/or Rejections
The objections to the disclosure are withdrawn in view of correction of typographical errors.
The objection to the claims are withdrawn in view of correction of typographical errors.
The rejection under 35 USC 112(b) is withdrawn in view of amended formatting clarifying the required elements nested within other elements of the claims.
The rejection under 35 USC 103 is withdrawn. The previously applied art, including Newman (US 2020/0176080; previously cited on the 04 May 2022 IDS form) and Meng (IEEE Journal of Biomedical and Health Informatics 23(5): 2091-2098, 2019; previously cited on the 23 September 2025 PTO-892 form) do not teach the required limitation that the feature vectors for uncommon cells’ expression patterns is bootstrapped from known variations to produce noise, thereby producing a simulated population of the uncommon cells. Newman teaches bootstrapping the vectors for all samples (pg. 33, col. 1, paragraph [249]) and Meng teaches adding noise to morphology the least common type of cell (pg. 2093, col. 1, Section B), but bootstrapping expression profiles of uncommon cell types is not taught or fairly suggested and thus the claims are considered free of the prior art.
The following rejections and/or objections constitute the complete set of rejections and/or objections applied to the instant claims.
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 1-2, 4-9, 12-13, 15-20, 23-24, and 26-31 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of sensing and classifying cells.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
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 (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a computer system (claims 1-2 and 4-9), a method (claims 12-13 and
15-20), and a non-transitory computer-readable medium (claims 23-24 and 26-31), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
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 (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
The recited limitation to “generate.. a feature vector representing gene expression values” (claims 1, 12, and 23) is interpreted as a mathematical concept, where a feature vector is disclosed as an array, list, or vector of features (pg. 8, paragraph [25]), interpreted as having a numerical form. Generating such a vector is also interpreted as a step practically performed by the human mind and thus a mental process.
The recite limitation to “process the feature vector… to generate an output that specifies a cell type for the individual cell” is interpreted as a mathematical process by which the numerical input is processed to generate a classification value (pg. 9, paragraph [29]), where inputting a number and outputting a number is interpreted as a mathematical process.
The recited limitation to “determine at least some of the cell types as uncommon” is interpreted as a decision or data evaluation step regarding the data. The human mind is practically equipped to perform identifications and classifications based on data and thus this step is considered a mental process.
The recited limitation to generate bootstrap vectors by generating noise and applying the noise is interpreted as mathematical steps as bootstrapping is a mathematical resampling process and the noise is disclosed as mathematical with statistical profiles (pg. 2, paragraph [4]).
The recited limitation to generate a cell-corpus by aggregating the bootstrap vectors and feature vectors is interpreted as a mental step of collecting the generated data, or as a mathematical step of joining them in a mathematical construct, and where the data is abstract.
Dependent claims 5, 16, and 27 recite a root node of the decision-tree has a child for
immune cells and a child for non-immune cells, interpreted as directed to data interpretation and thus a mental process.
Dependent claim 7, 18, and 29 recite steps of identifying a cell as having high entropy, disassociating it from the generated cell type, and classifying it as a novel type, all of which the human mind is practically equipped to perform and thus is a mental process.
Dependent claims 8, 19, and 30 recite steps of identifying a cell as having high entropy and disassociating it from the generated cell type, which the human mind is practically equipped to perform and thus is a mental process.
Dependent claims 9, 20, and 31 recites calculating Shannon entropy, which is a verbal description of a mathematical concept. It is noted that a mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation (MPEP 2106.04(a)(2)).
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Claims 1, 12, and 23 recite additional elements that are not abstract ideas: "a cell sampler,” “a sample receiver,” “sensors,” “sense… physical phenomena of biological cells,” “transmit… sensor-data,” a “processing apparatus” comprising one or more processors and memory, to “receive… the sensor-data,” “using one or more neural network classifiers,” and to “update the neural network classifier parameter values by training the classifiers on an updated corpus.” Additional elements recited in the independent claims also include a computer or processors (claims 1, 12, and 23) and “a computer-readable medium” (claim 23).
Dependent claims 4, 15, and 26 recite the neural network classifiers include classifiers arranged in a hierarchical decision-tree and each node has an ensemble of neural network classifiers configured to vote on classification.
Dependent claims 6, 17, and 28 recite one or more neural network classifies were pre-trained on the initial-corpus of training data.
Claims 2, 8, 13, 19, 24, and 30 recite at least “storing… cell-corpuses to a data repository.”
The cell sampler, comprising a receiver and sensors, is interpreted as required for collecting data for sorting and classifying the cells based on physical phenomena. The physical phenomena data is transmitted and received to perform the classification steps and generating the corpus. Thus, these elements are interpreted as related to insignificant extra-solution activity (MPEP 2106.05(g)). Similarly, the accessing step is a require step gathering the data to generate the bootstrap vectors for the uncommon cell types, and thus also insignificant extra-solution activity.
The memory, processor, and computer-readable medium are presented without details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Furthermore, using the neural network is considered to be mere instructions to apply the abstract idea because it is done by a computer step (MPEP 2106.05(f)). Additionally, using neural network classifiers indicates a field of use or technological environment in which the judicial exception is performed which limits the processing step determining a cell type to a particular technological environment (neural networks) and thus fails to add an inventive concept to the claims. See MPEP 2106.05(h).
Dependent claims 2, 8, 13, 19, 24, and 30 recite storing data. Storing the corpuses is interpreted as occurring after the classification steps and does not materially change the classification, and thus is interpreted as insignificant extra-solution activity (MPEP 2106.05(g)).
Therefore, the elements in addition to the abstract ideas are not interpreted as integrating the abstract ideas into a practical application. [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Claims 1, 12, and 23 recite additional elements that are not abstract ideas: "a cell sampler,” “a sample receiver,” “sensors,” “sense… physical phenomena of biological cells,” “transmit… sensor-data,” a “processing apparatus” comprising one or more processors and memory, to “receive… the sensor-data,” “using one or more neural network classifiers,” and to “update the neural network classifier parameter values by training the classifiers on an updated corpus.” Additional elements recited in the independent claims also include a computer or processors (claims 1, 12, and 23) and “a computer-readable medium” (claim 23).
Dependent claims 4, 15, and 26 recite the neural network classifiers include classifiers arranged in a hierarchical decision-tree and each node has an ensemble of neural network classifiers configured to vote on classification.
Dependent claims 6, 17, and 28 recite one or more neural network classifies were pre-trained on the initial-corpus of training data.
Claims 2, 8, 13, 19, 24, and 30 recite at least “storing… cell-corpuses to a data repository.”
The claims recite a device which receives and sample and senses, using sensors, physical phenomena of cells. A physical phenomenon is interpreted as reading on a level of a biomarker, which is a conventional activity in the life sciences (Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017) (MPEP 2106.05(d)).
Liu (bioRvix 002758: 27 pgs., 2020; newly cited) teaches the neural network classifier using a decision tree arrangement as “leveraging the ability of DNNs to learn complex structure” (pg. 19, last paragraph) and adapting the “well-known decision tree algorithm” wherein entropy is also calculated (pg. 20, “Hierarchical Cell Type Assignment.” Liu teaches training DNN classifiers (pg. 20, first paragraph) and multiple training sets to teach the classifiers (pg. 17, first paragraph).
The claims recite a generic computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer is a conventional computer function (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93; MPEP 2106.05(d)). Transmitting and accessing data is conventional (buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014); MPEP 2106.05(d)).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 17 December 2025 Applicant Remarks
Applicant remarks state processing the feature vector and updating the parameter values cannot be performed by the human mind as they recite a neural network (pg. 14, last paragraph to pg. 15, first paragraph). At Step 2A Prong One, it is determined whether the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c)). These steps are here considered to be mathematical steps implemented by a computer in the form of a neural network. As abstract ideas are recited, the analysis in the 101 framework continues.
Applicant remarks state “the present claims provide an improvement in the technological field of machine learning-based single-cell analysis, e.g., by enabling neural network classifiers to accurately identify uncommon and rare biological cell types from sensor-derived gene-expression data, even when only a small number of training examples of such rare cell types are available” and “this improves the functioning of the claimed computer-implemented system” (pg. 14, last paragraph). This argument is not persuasive. At Step 2A Prong Two, it is determined if the judicial exceptions are integrated into a practical application by an additional element (MPEP 2106.04(d)). Here, the additional elements are interpreted as sensors for data collection and computer elements, including neural network classifiers, for data analysis. That is, the improvement lies in data analysis and not functioning of a computer.
Applicant remarks assert the data collecting steps of training based on rare data types provides the improvement (pg. 14, last paragraph). However, the data is considered to be gathered using conventional techniques such as single cell RNA sequencing and then bootstrapped – a mathematical concept – to be used in the neural network. Applicant remarks state the improvement is derived from enabling bootstrap vectors generated by statistical models (pg. 16, first paragraph), where bootstrapping is a mathematical concept used to generate the data. Therefore, the improvement appears to stem from abstract steps.
Applicant remarks state the claims recite a particular solution to improving the classifier function analogous to the 101 eligible decision in Ex Parte Desjardins (pg. 16, second paragraph). Ex Parte Desjardins is directed to improvement of a computer while the instant claims are directed to improvement to the abstract idea of cell classification. Therefore, the two are not considered to be analogous.
Conclusion
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 Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685