DETAILED ACTION
Applicant's response, filed 20 July 2026, has been fully considered. 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 .
Claim Status
Claims 8 and 17 are cancelled.
Claims 1-7, 9-16, and 18-19 are pending.
Claims 1-7, 9-16, and 18-19 are rejected.
Priority
This application claims foreign priority to application no. 202141044464, filed in India 09/30/2021. The instant application has the effective filing date of 30 September 2021.
Information Disclosure Statement
No information disclosure statement (IDS) has been filed in the instant application. Applicants are reminded of their duty to disclose all information known to them to be material to patentability as defined in 37 C.F.R. 1.56.
Drawings
The drawings, submitted on 09/30/2022, are accepted by the examiner.
Claim Rejections - 35 USC § 112
Applicants’ arguments, see page 1, para. 2-5, are considered and are persuasive.
The rejections to claims 1-7, 9-16, and 18-19 under 35 U.S.C. 112(b) are withdrawn, in view of the claim amendments.
The rejection to claims 8 and 17 are withdrawn, in view of claim cancellations.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The following rejection is newly recited and necessitated by amendment.
Claims 1-7, 9-16, and 18-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for the following reasons.
The independent claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The independent claims recite to “measuring using a testing machine…” wherein it is not reasonably described how a processor is configured to perform actions on such machine.
Claim Rejections - 35 USC § 101
The rejections to claims 1-7, 9-16, and 18-19, under U.S.C 101, are maintained.
The rejections to claims 8 and 17, under U.S.C 101, are withdrawn, in view of claim cancellations.
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 1-7, 9-16, and 18-19 are rejected under U.S.C 101 because the claimed invention is directed to abstract ideas and laws of nature without significantly more, as detailed in the analysis below.
Eligibility Step 1: Subject matter eligibility evaluation in accordance with MPEP § 2106:
Claims 1-7 and 9 are directed to a statutory category (system).
Claim 10-16 and 18 are directed to a statutory category (method).
Claim 19 is directed to a statutory category (product).
Therefore, in accordance with MPEP § 2106.03 all claims have patent eligible subject matter.
[Eligibility Step 1: YES]
Eligibility Step 2A: This step determines whether a claim is directed to a judicial exception in accordance with MPEP § 2106.
Eligibility Step 2A -- Prong One: Limitations are analyzed to determine if the claims recite any concepts that could equate to a judicial exception (i.e. abstract idea, law of nature, or natural phenomenon). Possible judicial exceptions are explored below.
Recitations of Judicial Exceptions:
Claims 1, 10, and 19: generate, a sensing matrix with a plurality of rows (m) and a plurality of columns (n) based on at least one input from a user device, indicating a number of pools and a number of the plurality of the biological samples to be tested wherein the plurality of biological samples are combined or grouped based on the sensing matrix to generate a plurality of pools; (mathematical concept, mental process)
mitigate numerical inaccuracies inherent in floating-point representations of dynamic-range biological signals by transforming a noisy linear inverse problem into a noisy nonlinear inverse problem, including constructing a nonlinear equation by applying log and exp functions to variables of the sensing matrix and the noisy output data: (mathematical concept, mental process)
generate a probabilistic graphical model based on a non-linear equation for detecting and quantifying the plurality of molecules in the plurality of biological samples, wherein the sensing matrix and quantitative measures of molecules are converted as conditional statements in the probabilistic graphical model (mathematical concept, mental process)
recover individual sample results for the plurality of molecules in the plurality of biological samples from a single-round combinatorial pooling assay, by providing the noisy output data from each pool to the probabilistic graphical model and identifying and quantifying the presence of the plurality of molecules in the plurality of biological samples by executing a non-linear solver inference for the probabilistic graphical model along with the noisy output data (mathematical concept, mental process)
Claims 2 and 11: wherein the processor is configured to detect a condition of interest based on the identified and quantified molecules in the plurality of biological samples, wherein the condition of interest comprises at least one of an infectious disease, cancer, a genetic disease, an inflammation condition, a metabolic syndrome, cardiac disease, or diabetes. (mathematical concept, natural correlation)
Claims 4 and 13: wherein the nonlinear equation comprises v = f(A g(u)), wherein the, (a) A is the sensing matrix with the plurality of rows (m) and the plurality of columns (n); (b) u is a column vector of dimension n, wherein the n indicates a number of the plurality of biological samples to be tested, wherein detection of the column vector (u) enables to detect the presence or absence of the plurality of molecules in the plurality of biological samples and quantify the plurality of molecules if the molecules are present in the plurality of biological samples; (c) v is a vector of dimension m, wherein v is considered as the output data from each pool and v' is considered as the noisy output data of the output data from each pool; (d) g is a nonlinear vector-valued function of n variables; (e) f is a nonlinear vector-valued function of m variables. (mathematical concept)
Claims 5 and 14: wherein executing non-linear solver comprises systemically specifying prior and regulatory conditions for the probabilistic graphical model. (mathematical concept)
Claims 6 and 15: convert a noisy linear inverse problem into a noisy nonlinear inverse problem when there are multiples orders of nonzero entries in the sensing matrix; and construct the nonlinear equation v = log (A
e
u
) by considering f and g as log and exp functions instead of considering f and g as identity functions, wherein the nonzero entries indicate that each sample in the plurality of columns (n) of the sensing matrix (A) represents at least one biological signal. (mathematical concept)
Claims 7 and 16: perform a plurality of iterations to create the sensing matrix for obtaining compression in pooling by (i) creating a first sensing matrix based on a size of the assay, (ii) subsequently creating a second sensing matrix based on the first sensing matrix, and (iii) thereafter creating a subsequent sensing matrix based on the second sensing matrix or a previous sensing matrix, wherein a size of the second sensing matrix or a number of pools of the second sensing matrix is smaller than a number of pools of the first sensing matrix. (mathematical concept, mental process)
Claims 9 and 18: wherein the at least input comprises at least one of a name of the assay, and a size of the assay, wherein the size of the assay indicates a total number of biological samples to be tested and a number of biological samples estimated as positive out of the total number of biological samples. (mathematical concept)
Step 2A- Prong One Analysis:
Decoding, generating matrices, and vectorizing data represent transformations and organizations of data using mathematical formulas and calculations. Claims that recite such techniques fall under the mathematical concept grouping of abstract ideas.
Grouping and making determinations of data requiring nothing more than the human mind and pen/paper fall under the mental process grouping of abstract ideas.
Detecting a condition based on the analysis of biological molecules in a sample fall under the natural correlation/law of nature grouping of judicial exceptions (see Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017)).
Therefore, the claims are found to recite judicial exceptions.
[Eligibility Step 2A – Prong One: YES]
Eligibility Step 2A – Prong Two: A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. If the claim contains no additional claim elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)). Additional elements are recited, categorized, and analyzed below.
Data Gathering Elements:
Claims 1, 10, and 19: measure, using a testing machine, a noisy output data after completing the assay in each pool, wherein the noisy output data is an output data with noise from each pool;
Claims 3 and 12: wherein the testing machine is a polymerase chain reaction (PCR) machine, a high-performance liquid chromatography (HPLC), microarray screens, a next generation sequencing (NGS) device, a mass spectrometry, a nuclear magnetic resonance (NMR) spectroscopy, or a Raman spectroscopy.
Computer Components:
Claims 1 and 19: a memory that stores a set of instructions; a processor that is configured to execute the set of instructions for performing one or more operations, the processor is configured
Step 2A – Prong Two Analysis:
The data gathering limitations represent insignificant extra-solution activities that do not integrate the judicial exceptions into practical application per MPEP 2106.05(g).
Generic computer components and implementations provide mere instructions to implement the abstract ideas per Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
When evaluated separately or in the context of a whole claimed invention, the limitations do not integrate the judicial exceptions into practical application.
[Eligibility Step 2A – Prong Two: NO]
Eligibility Step 2B: Claim elements are probed for inventive concept equating to significantly more than the judicial exception (MPEP 2106.04(II)).
Step 2B Analysis:
The data gathering elements are further found to be well-understood, routine, and conventional per Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016) for using PCR; and Ghasemi et al. (Am J Nucl Med Mol Imaging; Vol. 6: 6; 2016) for utilizing the other testing machines as conventional systems biology tools for obtaining and analyzing samples within a precision medicine pipeline (pages 311, column 2; 313, column 1; and 320, table 2).
The computer components are further found to be well-understood, routine, and conventional per 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 for storing and retrieving information in memory and Alice Corp., 573 U.S. at 225, 110 USPQ2d at 1984 (MPEP 2106.05 (a)).
[Eligibility Step 2B: NO]
As such, claims 1-7, 9-16, and 18-19 are directed to judicial exceptions without significantly more and are rejected under 35 U.S.C 101.
Response to Arguments
Applicant argues the characterizing of particular claim elements, including generation of sensing matrices, probabilistic graphical modeling, nonlinear equations, and inference operations, as mathematical concepts, improperly focuses on individual claim elements in isolation rather than evaluating the claim as an ordered combination (page 2, para. 2).
Examiner responds MPEP 2106.04 states, “Step 2A is a two-prong inquiry, in which examiners determine in Prong One whether a claim recites a judicial exception.” As such, recitations of abstract ideas are highlighted at Step 2A- Prong One, in line with MPEP guidance, and the argument is not found persuasive.
Applicant argues the mathematical calculations are directed to a specialized computational architecture for improving the accuracy and reliability of molecular detection from noisy assay measurements (page 2, para. 1) (page 3, para. 1); and the “transformation of a noisy linear inverse problem into a noisy nonlinear inverse problem by constructing a nonlinear equation using log and exp transformation” provides a specific improvement in a computational processing of biological measurement data (page 3, para. 1-3) (page 4, para. 1-2) (page 5, para. 1-4) (page 7, para. 1-2) and the technical operation of a molecular diagnostic computing system (page 3, para. 4).
Examiner responds, MPEP 2106.05(a) states: It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II. As the imitations highlighted by the applicant are directed to abstract ideas, mostly in the form of mathematical concepts, the argument is not found persuasive.
Applicant argues Example 48 demonstrates that mathematical transformations applied to input data can satisfy eligibility requirements when the transformation is part of an ordered combination that improves a technical system; and signal transformation is not treated as an abstract idea because it enables improved processing of audio signals. Applicant further argues the example is analogous because in the claimed invention, the log/exp transformation is not the end result being claimed; rather, it is a technical processing operation that enables improved computational processing of noisy biological signals spanning; thus, the log/exp transformation is not an abstract idea but a technological improvement in how a diagnostic computer handles high-dynamic-range signals, just as the transformations in Example 48 improve how computers handle mixed audio signals (page 4, para. 4-5).
Examiner responds, Example 48 is directed to synthesizing audio signals, which is different from the purely mathematical processing of biological signal data presented within the instant claims. As such, the fact patterns of example 48 are not analogous to those of this case, and the argument is found not persuasive.
Applicant argues McRo evidences that the particular ordered rules associated with the claim elements lead to an improvement to technology and the functioning of a computer render the instant claims eligible at step 2A, prong 2 (page 6, para. 1).
Examiner responds that the fact patterns of McRo required the rules associated with the abstract ideas to realize the improvements to the computer and other additional elements, aligned with the fact that the improvement can be provided by the additional element(s) in combination with the recited judicial exception, but not the judicial exception alone. See MPEP § 2106.04(d) (discussing Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 1299, 1303-04, 125 USPQ2d 1282, 1285-87 (Fed. Cir. 2018)). Therefore, the argument is not found persuasive.
Applicant argues “the claimed combination of nonlinear inverse problem conversion, log/exp transformation of biological signal variables, probabilistic graphical model generation, conditional representation of sensing matrix and molecule measurements and non-linear solver inference for recovering molecular quantities,” as recited in amended claim 1 is not well-understood, routine, or conventional in the field (page 6, para. 2).
Examiner responds, MPEP 2106.05(d) states: “determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry.”
As the elements cited by applicant are directed to judicial exceptions, the argument that they are not well-understood, routine, and conventional does not render eligibility at Step 2B. As such, the argument is not persuasive.
Applicant argues because the amended claim 1 is directed to a “computer-implemented process for improved processing of noisy machine-generated assay outputs and recovering quantitative molecular information through a specialized computational framework,” (page 7, para. 3) and the natural phenomenon is allegedly merely an input to the claimed technological process (page 7, para. 4), claim 1 is not directed to a natural phenomenon or correlation.
Examiner responds, claim 2 was cited as being directed to judicial exceptions including natural correlations; the cited judicial exceptions are not integrated into practical application; nor is the improvement to a technological field realized within the additional elements; nor is the natural correlation recited in the instant claims as input rather than an active detecting step. As such, the argument is not persuasive.
Claim Rejections - 35 USC § 103
Applicant argues Mourad et al. in view of Yi et al. do not teach the limitations of amended claim 1 (page 8-9).
Examiner responds, this argument is found persuasive and the rejections to claims 1-7, 9-16, and 18-19 are withdrawn, in view of claim amendments.
The rejection to claims 8 and 17 are withdrawn, in view of claim cancellations.
Conclusion
Independent claims 1, 10, and 19 appear to be free of the prior art. For clarity of the record, the closest prior art is recited below:
Claims 1, 10, and 19 are directed to systems, methods, and products that utilize input data to compute a sensing matrix with rows (m) and columns (n) indicating a number of pools and a number of biological samples to be tested; pool biological samples, based on the sensing matrix; and measure noisy output data from each pool, after an assay is performed on them.
Mourad et al. (IEE/ACM Trans on Comp Biol and Bioinformatics; Vol. 10: 6; 2013; previously cited) describes pooling system designs for noisy high-throughput protein-protein interaction experiments using compressed sensing.
Mourad et al. teaches using input parameters (1479, column 1), row number m, column number n, and column weight w, to generate binary sparse matrices (page 1483, column 1); pooling design algorithms that lay out how individual proteins are grouped together for testing (page 1478, column 2); and specifying the number of compounds n that are to be pooled (page 1479, column 1).
Mourad et al. further teaches checking whether the decoder solution is consistent with the pooling test outcomes from the noisy high-throughput experiments (page 1479, column 1); comparing the decoded Interpool and l1 -norm results using the experimental pooling data provided in [31], which represents the noisy measurement vector within the CS framework described in Section 2 (page 1484, column 2); and considering the random error rate for the assays (page 1482, column 1).
Yi et al. (arXiv:2004.05759v1; 2020; previously cited) describes high throughput testing of COVID-19 viruses via compressed sensing; and teaches collecting n samples of n persons (page 4, column 1) and using m to represent the number of pooling measurements (page 9, fig. 12).
Claims 1, 10, and 19 are further directed to mitigating numerical inaccuracies inherent in floating-point representations of dynamic-range biological signals by transforming a noisy linear inverse problem into a noisy nonlinear inverse problem, including constructing a nonlinear equation by applying log and exp functions to variables of the sensing matrix and the noisy output data; recovering individual sample results for the plurality of molecules in the plurality of biological samples, from a single-round combinatorial pooling assay, by providing the noisy output data from each pool to the probabilistic graphical model and identifying and quantifying the presence of the plurality of molecules in the plurality of biological samples by executing an non-linear solver inference for the probabilistic graphical model along with the noisy output data
Donoho et al. (Appl Comp Harm Analy; Vol. 2; 1995; newly cited) describes nonlinear solution of linear inverse problems by wavelet-vaguelette decomposition. Donoho et al. teaches solving ill-posed linear inverse problems by nonlinearly shrinking the WVD coefficients of the noisy, indirect data (page 1, column 1) and that such linear inverse problems arise in scientific settings ranging from medical imaging to physical chemistry (page 1, column 1).
The prior art does not teach nor suggest generating a probabilistic graphical model based on the non-linear equation, where the sensing matrix and quantitative measures of molecules are converted as conditional statements in the model (independent claims 1, 10, and 19). As such, the rejection under U.S.C. 103 is withdrawn.
No claims are currently allowed.
THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Milana Thompson whose telephone number is (571)272-8740. The examiner can normally be reached Monday - Friday, 9:00-6:00 ET.
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/M.K.T./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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