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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 22 May 2026 has been entered.
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 10 April 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Claim Interpretation
Claim 23 recites a computer-readable medium tangibly storing instructions to be performed by processors. The device controller, cell sampler, and microfluidic structure are elements in addition to the abstract ideas which are not specifically associated with the processor. Therefore, the claims as recited read on instructions for controlling a device and receiving data from a device. Amending the preamble of the claim to recite physical coupling of the memory and processors to the device controller, microfluidic structure, and sensors would clarify this relationship.
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 recited 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, which is considered to be 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,” “a microfluidic structure,” “a device controller,” controlling the microfluidic structure to perform single-cell partitioning, measuring signals to characterize cells in the receiver, interpreted as performing single-cell RNA sequencing because single-cell RNA sequencing data is then transmitted to a processing apparatus, one or more processors and memory configured 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, sensors, microfluidic structure, and controller device, is interpreted as required for collecting data for sorting and classifying the cells based on RNA sequencing data.. The data are 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)).
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,” “a microfluidic structure,” “a device controller,” controlling the microfluidic structure to perform single-cell partitioning, measuring signals to characterize cells in the receiver, interpreted as performing single-cell RNA sequencing because single-cell RNA sequencing data is then transmitted to a processing apparatus, one or more processors and memory configured 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.”
Ko (Lab Chip 18: 395-405, 2018; newly cited) teaches a review of liquid biopsies, including microfluidics and single-cell RNA sequencing for measuring biomarkers (pg. 395, col. 2, second paragraph). Ko teaches neural networks as increasingly popular including training said algorithm (pg. 400, col. 1, paragraphs 3-4). Ko teaches ensemble for more accurate prediction (pg. 402, col. 1, second paragraph) and bootstrapping classification models (pg. 403, col. 1, first paragraph). Ko teaches iterative training (pg. 397, col. 2, second paragraph), which is interpreted as updating training. Finally, Ko teaches application of these concepts to classifying individual cells (pg. 397, col. 1, last 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 22 May 2026 Applicant Remarks
Applicant remarks state the claims as amended overcome the rejection under 35 USC 101. This argument is not persuasive.
At Step 2A Prong One, the claims are amended to recite more elements in addition to the abstract ideas, including a device controller, microfluidic structure to perform single-cell partitioning, and the sensor is amended to measure signals from single-cell RNA sequencing data (pg. 11, third paragraph) and thus is interpreted as a sequencer. It is agreed that these elements are not mathematical nor practically performed by the human mind, and so analysis continues.
At Step 2A Prong Two, it is determined if the judicial exception is integrated into a practical application by an additional element (MPEP 2106.04(d)). Applicant remarks state the 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 (pg. 12, second paragraph) and improvement of a computer-implemented system (pg. 12, third paragraph). At Step 2A Prong Two, the elements in addition to the abstract ideas are evaluated. Here, the elements in addition to the abstract ideas are, as asserted in the remarks, the cell sampler comprising the controller, microfluidic structure, and sensor for determining expression data, which is later analysis using neural networks and/or decision trees. Applicant remarks state these steps improve a computer system (pg. 12, third paragraph), but the improvement appears to be directed to the abstract idea of cell classification. The cell sampler and its components are directed to data collection, where the data is then used for cell classification, and thus is a data gathering step, which does not integrate the abstract idea into a practical application (MPEP 2106.05(g)). Similarly, 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 (MPEP 2106.05(h)). The claims are, as asserted in the remarks, directed to creating of training sets, which is an abstract idea, and the additional elements – a sensor for RNA sequencing, a microfluidic structure, and machine learning-based classification including neural networks or decisions trees – are known within the state of the art.
Regarding the decision of Ex Parte Desjardins, it is agreed the claims solve a technical problem of catastrophic forgetting, which is an improvement to the computer function (pg. 13, third paragraph). The improvement in the instant claims is directed to cell classification and not a computer system, and thus the analogy with Ex Parte Desjardins is not persuasive.
While Step 2B of 101 analysis is not specification discussed in the remarks, it is noted that the additional elements are taught together by Ko as described above, where RNA sequencing, a microfluidic structure, and machine learning-based classification including neural networks or decisions trees are reviewed. Therefore, the apparatus for data gathering and the neural network elements are conventional alone or in combination, and therefore do not provide significantly more (MPEP 2106.05).
Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
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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/Robert J. Kallal/Examiner, Art Unit 1685
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