DETAILED ACTION
Applicant’s response filed 10/16/2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied.
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 2, 4-5, 7-8, 10, 13-16, 18-19, 21-22, 24-25, 27, 30-35, 37-39, 41-42, 44, 48-60, 62, 65-67, and 73-131 are cancelled by Applicant.
Claims 1, 3, 6, 9, 11-12, 17, 20, 23, 26, 28-29, 36, 40, 43, 45-47, 61, 63-64 and 68-72 are currently pending.
Claims 20, 23, 26, 36, 45-46, 63-64 and 72 are withdrawn, as discussed in the Restriction and Election section of the Office Action filed 02/12/2024.
Claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are herein under examination.
Claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are rejected.
Priority
The instant application claims domestic benefit to U.S. Provisional Application No. 62/941,012 filed 11/27/2019. The claim to the benefit of priority for claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 is acknowledged. The effective filing date for these claims is 11/27/2019.
Withdrawn Rejections
35 USC 112(b)
The rejection claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 under 35 USC 112(b) is withdrawn in view of Applicant’s claim amendments.
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, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon without significantly more.
Any newly recited portions herein have been necessitated by claim amendment.
Step 2A, Prong 1:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomena (Step 2A, Prong 1). In the instant application, claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-69 recite a method, claim 70 recites a system, and claim 71 recites a computer-readable medium. The instant claims recite the following limitations that equate to one or more categories of judicial exception:
Claims 1, 70 and 71 recite “(A) determining . . . from a first plurality of sequence reads . . . the first plurality of sequence reads comprising hundreds of thousands of sequence reads of a first plurality of nucleic acid molecules in a first biological sample obtained from the test subject at a first test time point, a first genotypic data construct for the test subject, the first genotypic data construct comprising values for a plurality of genotypic characteristics based on the first plurality of sequence reads.” The broadest reasonable interpretation (BRI) of determining a first genotypic construct is that a human could practically identify a nucleotide variation as it would merely requiring comparing sequences. This claim therefore equates to a mental process. Claims 1, 70 and 71 recite “(B) inputting the first genotypic data construct into a model for the disease condition, thereby generating a first model score set for the disease condition, wherein the model is a machine-learning classification model that is trained on time time-series genotypic construct data”. These limitations equate to a mental process because a human could practically input data into an unspecified machine learning classification model such as a logistic regression to then produce an output. A human could also with pen and paper train a logistic regression merely by using the output to manually alter the parameters of the logistic regression. These limitations also equate to a mathematical concept because inputting data into an unspecified machine learning model that generates values is the verbal equivalent of a function that performs a calculation because the model could be a logistic regression, which performs calculations. Claims 1, 70 and 71 recite “(C) determining, from a second plurality of sequence reads . . . the second plurality of sequence reads comprising hundreds of thousands of sequence reads of a second plurality of nucleic acid molecules in a second biological sample obtained from the test subject at a second test time point, a second genotypic data construct for the test subject, the second genotypic data construct comprising values for the plurality of genotypic characteristics based on the second plurality of sequence reads; (D) inputting the second genotypic data construct into the model, thereby generating a second model score set for the disease condition.” For the reasons stated above in Steps (A), Step (C) is a mental process. For the reasons stated above in Step (B), Step (D) is a mental process and a mathematical function/calculation. Claims 1, 70 and 71 recite “(E) determining a test delta score set based on a difference between the first and second model score set”. The BRI of determining the difference between two values is performing a calculation between two numbers, which can be practically performed by a human and is considered a mental process. This limitation also equates to a mathematical calculation since determining a difference between two numbers is a verbal equivalent for performing a calculation and since delta scores are calculated. Claims 1, 70 and 71 recite “(F) refining an ability . . . to correctly identify a true positive and true negative by adjusting one or more aspects of the test delta score set to account for one or more biological factors of the test subject that affect a magnitude of the test delta score set.” These limitations equate to mental process because a human could practically with pen and paper adjust a value by using, for example, a covariate that thereby affects the newly calculated value. This limitation also equates to a mathematical concept because the BRI of this limitation includes performing a calculation using numerical values to output more numerical values. Claims 1, 70 and 71 recite “wherein the adjusting comprises: utilizing an amount of time between a respective first time point and a respective second time point for each respective reference subject in a plurality of reference subjects as a first covariate in calculating a distribution of reference delta score sets” The BRI is that a human could practically could perform calculations using covariates, which makes this a mental process. This limitation also equates to a mathematical calculation since a distribution is calculated. Claims 1, 70 and 71 recites “adjusting the test delta score set based on a second covariate representing a difference in time between the first test time point and the second test time point for the test subject.” The BRI is that a human could adjust a delta score based on a covariate as it merely requires performing calculations, thus making this limitation a mental process. This limitation also equates to a mathematical relationship since the values of the delta score are being manipulated based upon the covariate. Claims 1, 70 and 71 recite “(G) evaluating, subsequent to adjusting the one or more aspects of the test delta score set, the test delta score set against a plurality of reference delta score sets, thereby determining whether the test subject has the disease condition and a stage of the disease condition, wherein each reference delta score set in the plurality of reference delta scores sets is for a respective reference subject in a plurality of reference subjects.” The BRI of evaluating and determining is that a human could practically look at delta scores and decide whether or not a subject has a delta score similar to reference delta scores associated with a disease condition, which makes this limitation a mental process. Claims 1, 70 and 71 recite “(H) identifying, responsive to determining that the test subject has the disease condition, a treatment corresponding to the stage of the disease condition”. The BRI of this limitation includes evaluating data and making a determination, both of which can be practically performed by the human mind. Moreover, Steps (A) – (F) recite a natural phenomenon because these steps correlate genetic variations with the likelihood that a disease is present in a patient.
Claim 3 recites “the first model score set comprises a probability that the test subject has the disease condition at the first test time point, the second model score set comprises of a probability that the test subject has the disease at the second test time point.” These limitations are included in the mathematical function/calculation in claim 1 of generating a first/second model score set for the disease condition since these limitations merely attempt to limit what data is associated with the model scores but does not change the fact that the model scores are part of the judicial exception. This limitation also equates to a mathematical relationship since probabilities are merely a calculation of the likelihood of an event to occur. Claim 3 recites “evaluating (G) comprises comparing the test delta score set to the distribution of the reference delta score sets, wherein each reference delta score set in the plurality of reference delta score sets is for a respective reference subject in the plurality of reference subject based on a difference between: (i) a first probability that the respective reference subject has the disease condition provided by the model using a respective first reference genotypic data construct comprising values for the plurality of genotypic features, taken using a respective first biological sample acquired at a respective first time point from the respective reference subject, and (ii) a second probability that the respective reference subject has the disease condition provided by the model using a respective second genotypic data construct comprising values for the plurality of genotypic features, taken using a respective second biological sample acquired from the respective reference subject at a respective second time point occurring after the respective first time point, and wherein the respective training subject is free of the disease condition during at least the respective first and second time points.” The BRI of comparing is that a human could practically compare delta scores to other delta scores, thereby making this limitation a mental process. These limitations also equate to a mathematical relationship since probabilities are merely a calculation of the likelihood of an event to occur.
Claim 6 recites “wherein the evaluating (G) comprises: determining a measure of central tendency of the distribution and a measure of spread of the distribution.” The BRI here is that a human could practically perform the calculations necessary to determine central tendency and spread of a distribution, which makes this limitation a mental process. This limitation also equates to a mathematical function/calculation since central tendency and spread of distribution are calculated. Claim 6 recites “determining a significance of the test delta score set using the measure of central tendency of the distribution and the measure of spread of the distribution.” The BRI is that a human could practically perform the calculations necessary to determine statistical significance of delta scores, thus making this limitation a mental process. This is also a mathematical function/calculation since central tendency and spread of distribution are calculated.
Claim 9 recites “the measure of central tendency of the distribution is the mean of the distribution, the measure of spread of the distribution is the standard deviation of the distribution, and the determining the significance of the test delta score set using the measure of central tendency of the distribution and the measure of spread of the distribution comprises determining a number of standard deviations the test delta score set is from the mean of the distribution.” The BRI of these limitations is that a human could practically perform the calculations using pen and paper, which makes these limitations a mental process. These limitations are also a mathematical function/calculation since each one requires a calculation be made using an equation. Additionally, these limitations are included in the judicial exception of claim 6 since these limitations merely attempt to alter what type of equation is used for the calculations in claim 6 but do not change the fact that claim 6 is a judicial exception.
Claim 11 recites “wherein the evaluating (G) comprises inputting the test delta score into a classifier trained against the plurality of reference delta score sets.” The BRI of inputting data into a classifier is that a human could practically input data to perform the calculation of a classifier such as a linear regression, which makes this a mental process. This also equates to a mathematical function/calculation since the specification states that the classifier may be a linear regression [147], which is an equation that calculates values. Claim 11 recites “wherein each reference delta score set in the plurality of reference delta score sets is for a respective reference subject in the plurality of reference subject based on a difference between: (i) a first probability that the respective reference subject has the disease condition provided by the model using a respective first reference genotypic data construct comprising values for the plurality of genotypic features, taken using a respective first biological sample acquired at a respective first time point from the respective reference subject, and (ii) a second probability that the respective reference subject has the disease condition provided by the model using a respective second genotypic data construct comprising values for the plurality of genotypic features, taken using a respective second biological sample acquired from the respective reference subject at a respective second time point occurring after the respective first time point, and wherein the respective training subject is free of the disease condition during at least the respective first and second time points.” These limitations are included in the judicial exception of inputting the test delta score into a classifier since they merely attempt to limit what the reference delta score sets comprise but do not change the fact that inputting the test delta score into a classifier is a judicial exception. These limitations also equate to a mathematical relationship since probabilities are merely a calculation of the likelihood of an event to occur.
Claim 12 recites “wherein the classifier is further trained against, for each respective training subject in at least a subset of the plurality of reference subjects, a determination of whether the respective subject had the disease condition at a respective third time point occurring after the respective second time point.” The BRI of training a classifier based upon a determination, which is recited at such a high level of generality, is that a human could performing the calculations of a linear regression (i.e. a classifier) by using the given data of the limitation, which makes this limitation a mental process. This limitation also equates to a mathematical function/calculation since the specification states that a classifier can be a linear regression, which merely requires performing calculations to train itself.
Claim 17 recites “further comprising normalizing, wherein: each respective reference delta score set in the plurality of reference delta scores sets is normalized for an amount of time between the respective first time point and the respective second time point for the respective subject; the test delta score set is normalized for an amount of time between the first test time point and the second test time point.” The BRI of normalizing data, which is recited at such a high level of generality, is that a human could perform the steps of a normalization process as it would merely require performing calculations, which makes these limitations a mental process. These limitations are also a mathematical calculation/relationship since the BRI of normalizing includes performing calculations and/or manipulating data.
Claim 28 recites “wherein the disease condition is a cancer condition.” This limitation is included in the judicial exception of claim 1 as it merely limits the type of disease but does not change the fact that the disease condition is part of the judicial exception in claim 1. This claim also equates to a natural phenomenon since the instant invention aims to correlate genetic variations with the likelihood that a disease is present in a patient.
Claim 29 recites “wherein the disease condition is a type of disease condition in a set of disease conditions and the model provides a probability or likelihood for each disease condition in the set conditions.” These limitations are included in the judicial exception of claim 1 since they attempt to limit the type of disease and the output of the model but do not change the fact that claim 1 is a judicial exception. Additionally, the model providing a probability equates to a mathematical relationship since probabilities represent the mathematical likelihood of an event. This claim also equates to a natural phenomenon since the instant invention aims to correlate genetic variations with the likelihood that a disease is present in a patient.
Claim 40 recites “wherein the first biological sample obtained from the test subject and the second biological sample obtained from the test subject are both blood samples.” This limitation is included in the judicial exception of claim 1 since it merely limits where the biological samples are derived but does not change the fact that claim 1 is a judicial exception.
Claim 43 recites “wherein the first plurality of nucleic acid molecules and the second plurality of nucleic acid molecules are cell-free DNA molecules.” This limitation is included in the judicial exception of claim 1 since it merely limits where the nucleic acid molecules are derived but does not change the fact that claim 1 is a judicial exception.
Claim 47 recites “the plurality of genotypic characteristics for the first genotypic data structure comprises a first plurality of bin values, each respective bin value in the first plurality of bin values representing a corresponding bin in a plurality of bins, each respective bin value in the first plurality of bin values is representative of a number of unique nucleic acid fragments with a predetermined methylation pattern identified using sequence reads in the first plurality of sequence reads that map to the corresponding bin in the plurality of bins, the plurality of genotypic characteristics for the second genotypic data structure comprises a second plurality of bin values, each respective bin value in the second plurality of bin values representing a corresponding bin in the plurality of bins, each respective bin value in the second plurality of bin values is representative of a number of unique nucleic acid fragments with a predetermined methylation pattern identified using sequence reads in the second plurality of sequence reads that map to the corresponding bin in the plurality of bins, and each bin in the plurality of bins represents a non-overlapping region of a reference genome of a species of the test subject.” All the limitations of claim 47 are included in the judicial exception of claim 1 since these limitations merely attempt to limit what type of data comprises genotypic characteristics but do not change the fact that the genotypic characteristics in claim 1 are part of the judicial exception.
Claim 61 recites “wherein the model is trained on a cohort of subjects in which a first portion of the cohort has the disease condition and a second portion of the cohort is free of the disease condition.” The BRI is that a human could practically perform the operations of a model such as a linear regression, then change the parameters of the model to train it, which makes this limitation a mental process. This limitation also equates to a mathematical function/calculation since the instant specification states that the model may be a linear regression [147] that performs calculations.
Claim 68 recites “prior to evaluating (G): determining a plurality of baseline genotypic data constructs for the test subject, each respective baseline genotypic data construct in the plurality of baseline genotypic data constructs comprising values for the plurality of genotypic characteristics based on a corresponding baseline plurality of sequence reads . . . of a corresponding plurality of nucleic acid molecules in a corresponding baseline biological sample, in a plurality of baseline biological samples . . .” The BRI of determining baseline genotypic data constructs is a mental process as it merely requires a human to evaluate data, which can be practically performed. Claim 68 recites “using an amount of variance in values for one or more respective genotypic characteristic, in the plurality of genotypic characteristics, between respective baseline genotypic data constructs in the plurality of baseline genotypic constructs to calculate a baseline variance covariate specific to the test subject.” The BRI of using variance to calculate a baseline variance covariate merely requires a human to perform calculations, which can be practically performed and thus equates to a mental process. This limitation also equates to a mathematical calculation as it requires calculating a baseline variance covariate. Claim 68 recites “applying the baseline covariate to the distribution of the reference delta score sets, to normalize the distribution of the reference delta score sets against the baseline variability of the test subject.” The BRI is that a human could normalize data as it merely requires calculations which can be done using pen and paper, and thus equates to a mental process. This also equates to a mathematical calculation/relationship as the normalization of data requires calculations and manipulating data to correlate information.
Claim 69 recites “wherein a span between the first test time point and the second test time point is based upon the first model score set.” This limitation is included in the judicial exception of claim 1 since it merely limits the timeframe between the test points but does not change the fact that the test points are part of the judicial exception in claim 1.
These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), creating a formula for computing an alarm limit in Parker v. Flook, 437 U.S. 584, 585, 198 USPQ 193, 195 (1978) (B1=B0 (1.0–F) + PVL(F)), and correlating the presence of myeloperoxidase in a bodily sample (such as blood or plasma) to cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017) that the courts have identified as concepts that can be practically performed in the human mind, mathematical relationships/functions/calculations, or naturally occurring relations. Therefore, these limitations fall under the “Mental process”, “Mathematical concepts”, and “Natural Phenomena” groupings of abstract ideas, respectively.
As such, claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 recite an abstract idea and a natural phenomenon (Step 2A, Prong 1: Yes).
Step 2A, Prong 2:
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exception is not integrated into a practical application because the claims do not recite additional elements that reflect an improvement to technology (MPEP § 2106.04(d)(1)) nor do they provide some other meaningful limitation. Rather, the claims merely include instructions to implement an abstract idea on a computer (MPEP § 2106.05(f)) and to insignificant, extra-solution activity (MPEP § 2106.05(g)). The instant claims recite the following additional elements:
Claims 1, 70 and 71 recite “(A) . . . using one or more processors associated with a computer system . . . in electronic form . . .”, “(C) . . . in electronic form . . .” and “(F) . . . of the computer system . . .” These limitations equate to instructions to apply an abstract idea on a generic computer.
Claim 68 recites “. . . in electronic form . . .” and “. . . obtained from the test subject at a corresponding baseline test time point occurring before the second test time point” These limitations equate to instructions to apply an abstract idea on a generic computer.
Claim 70 recites “A non-transitory computer-readable storage medium having stored thereon program code instructions that, when executed by a processor, cause the processor to perform the method of claim 1.” This equates to instructions to apply an abstract idea on a generic computer.
Claim 71 recites “A computer system comprising: one or more processors; and a non-transitory computer-readable medium including computer-executable instructions that, when executed by the one or more processors, cause the processors to perform a method of claim 1.” This equates to instructions to apply an abstract idea on a generic computer.
Regarding the above cited limitations in claims 1, 68 and 70-71 of processors associated with a computer system, in electronic form, a non-transitory computer-readable storage medium, and a computer system containing processors and non-transitory computer-readable medium, there are no limitations that these components require anything other than a generic computing system. Therefore, these limitations equate to mere instructions to implement an abstract idea on a generic computer, which the courts have established does not render an abstract idea eligible in Alice Corp. 573 U.S. at 223, 110 USPQ2d at 1983.
Regarding the above cited limitation in claim 68 of obtaining data, this limitation equates to insignificant, extra-solution activity of mere data gathering because it collects data to be used for the recited judicial exception in claims 1 and 68.
As such, claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are directed to an abstract idea and a and natural phenomenon (Step 2A, Prong 2: No).
Step 2B:
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). These claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these claims recite additional elements that equate to instructions to apply the recited exception in a generic way or in a generic computing environment (MPEP § 2106.05(f)) and to well-understood, routine and conventional (WURC) limitations (MPEP § 2106.05(d)). The instant claims recite the following additional elements:
Claims 1, 70 and 71 recite “(A) . . . using one or more processors associated with a computer system . . . in electronic form . . .”, “(C) . . . in electronic form . . .” and “(F) . . . of the computer system . . .” These limitations equate to instructions to apply an abstract idea on a generic computer.
Claim 68 recites “. . . in electronic form . . .” and “. . . obtained from the test subject at a corresponding baseline test time point occurring before the second test time point” These limitations equate to instructions to apply an abstract idea on a generic computer.
Claim 70 recites “A non-transitory computer-readable storage medium having stored thereon program code instructions that, when executed by a processor, cause the processor to perform the method of claim 1.” This equates to instructions to apply an abstract idea on a generic computer.
Claim 71 recites “A computer system comprising: one or more processors; and a non-transitory computer-readable medium including computer-executable instructions that, when executed by the one or more processors, cause the processors to perform a method of claim 1.” This equates to instructions to apply an abstract idea on a generic computer.
Regarding the above cited limitations in claims 1, 68 and 70-71, these limitations equate to instructions to implement an abstract idea on a generic computing environment, which the courts have established does not provide an inventive concept in Intellectual Ventures I LLC v. Capital One Bank (USA), 792 F.3d 1363, 1367, 115 USPQ2d 1636, 1639 (Fed. Cir. 2015). The limitation in claim 68 of obtaining data in electronic form equates to transmitting/receiving data over a network, which the courts have established as a WURC function of a genetic computer in buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014).
When these additional elements are considered individually and in combination, they all equate to WURC functions/components of a generic computer, and thus do not comprise an inventive concept that transforms the judicial exception into a patent-eligible application of the judicial exception itself (Step 2B: NO).
As such, claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are not patent-eligible.
Response to Arguments under 35 USC 101
Applicant's arguments filed 10/16/2025 have been fully considered but they are not persuasive.
Applicant argues that claim 1 does not recite a mental process because a human cannot practically perform its limitations (pg. 19, para. 2 – pg. 20, para. 2 of Applicant’s remarks). Applicant’s argument is not persuasive for the following reasons:
Claim 1 does not require collecting the sequences. Rather, it requires determining from them, as they are already collected. Claim 1 does not require use of all the hundreds of thousands of reads because it recites “the first genotypic data construct comprising values for a plurality of genotypic characteristics based on the first plurality of sequence reads”. The “based on” language indicates that not all reads are required to construct the genotypic construct. The BRI of “a machine-learning classification model that is trained on time-series genotypic construct data” includes a multinomial logistic regression, a linear model, or a linear regression as stated in specification para. [147]. A human is capable of performing calculations with any of these models given that the input is a genomic construct comprising at least two numerical values as required by the claim. The BRI of claim 1 step (f) includes calculating the delta score using a logistic regression with a covariate defined as time between the first and second time point, which a human could do. The BRI of claim 1 step (f) also includes comparing the adjusted delta score to a distribution of reference delta scores, wherein a human is capable of calculating a distribution to then compare a delta score against the distribution.
Applicant’s arguments regarding how the limitations discussed in the paragraph above require specialized computing resources and statistical models are acknowledged, but are not persuasive for the same reasons applied above – mostly because a human can perform them under their BRI (pg. 20, last sentence of para. 2 of Applicant’s remarks).
Applicant appears to argue that the claims involve a mathematical concept but do not recite a mathematical concept, referring specifically to claim 1 steps (b) and (d). Applicant also makes reference to Subject Matter Eligibility Example 39 which recites “training the neural network in a first stage using the first training set”. Applicant references how the training step in Example 39 involves mathematical concepts but does not recite any mathematical relationships, calculations, formulas, or equations using words or mathematical symbols (pg. 20, last para. – pg. 21, para. 1 of Applicant’s remarks). Applicant’s argument is not persuasive for the following reasons:
Example 39 describes training a neural network on images whereas instant claim 1 steps (b) and (d) describe using a model, which may be a linear regression, that uses numerical values as input to output model score sets, which may be likelihoods or probabilities as described in instant claims 3 and 29. A linear regression is a mathematical function that performs calculations to output a numerical value.
Moreover, claim 1 recites other mathematical concepts. Step (E) recites “determining a test delta score set based on a difference between the first and second model score set” which includes subtracting values under its BRI. Step (F) explicitly recites “calculating a distribution of reference delta score sets” which is a recitation of a calculation.
Applicant’s comments regarding the August 2025 Memo regarding 101 are considered but are not persuasive for the same reasons given above in the first response to arguments in this section (pg. 21, last para. of Applicant’s remarks).
Applicant argues that claim 1 steps (A-D) and (F) do not recite a mental process or a mathematical concept (pg. 22, last para. – pg. 23, para. 1 of Applicant’s remarks). Applicant’s arguments are not persuasive for the following reasons:
As discussed in the responses above, claim 1 steps (A-D) and (F) do recite mental processes and mathematical concepts under their BRI. Briefly, steps (A) and (C) do not require use of all the hundreds of thousands of sequence reads in each of the first/second plurality of sequence reads to generate the genotypic constructs because the values for the plurality of genotypic characteristics are based on the first/second plurality of sequence reads, indicating that not all sequences are required. A human can generate the values by taking a few sequences and aligning them against a human genome to find variants. Steps (B) and (D) under their BRI require a linear regression to calculate probabilities or likelihoods using the numerical values of the genotypic constructs.
Applicant argues that the claims do not recite any formulas or mental operations but instead discloses data transformations, algorithmic evaluations, and model-driven classification techniques that are rooted in computational processes (pg. 23, last para. – pg. 24, para. 1 of Applicant’s remarks). Applicant’s arguments are not persuasive for the following reason:
Claim 1 step (E) recites a mental process and a mathematical concept because determining a delta score is a textual replacement for performing a calculation between two numbers (i.e., the difference between the first and second model score set, which may be probabilities or likelihoods). A human can perform subtraction. See MPEP 2106.04(a)(2) regarding textual replacements for mathematical formulas or equations.
Applicant argues that claim 1 contains a practical application of improved sensitivity and disease detection (pg. 24, para. 2 – 3 of Applicant’s remarks). Applicant discusses the limitations in the claims that confer the improvement (pg. 24, last para. – pg. 25, para. 2 of Applicant’s remarks). Applicant’s arguments are not persuasive for the following reasons:
Applicant appears to argue that the following limitations in claim 1 contain a practical application of improving the ability of a computer to detect and classify disease, enhance performance of the machine learning model, and enables earlier detection and improved outcomes: “the generation of delta score sets, the covariates-based adjustment of those scores, and their comparison against statistical distributions derived from a reference population” (pg. 25, para. 1 of Applicant’s remarks). These limitations that Applicant cites have been identified as reciting a judicial exception. Thus, the alleged improvement appears to be a result of the judicial exception itself. MPEP 2106.05(a) recites “It is important to note, the judicial exception alone cannot provide the improvement.”
Furthermore, MPEP 2106.05(a)(I) recites “In computer-related technologies, the examiner should determine whether the claim purports to improve computer capabilities or, instead, invokes computers merely as a tool. Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1336, 118 USPQ2d 1684, 1689 (Fed. Cir. 2016).” In the instant case, computer functionality is not improved. Rather, the computer is used as a tool to perform an improved abstract idea (i.e. the limitations described in the paragraph above).
Conclusion
No claims are allowed.
Claims 1, 3, 6, 9, 11-12, 17, 28-29, 40, 43, 47, 61 and 68-71 are free from the prior art for the same reasons discussed in the Conclusion section of the Office action mailed 05/07/2025.
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.
Inquiries
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/N.A.A./Examiner, Art Unit 1687
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685