DETAILED ACTION
Applicant's response, filed 17 February 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/22/2025, 2/3/2026, and 5/1/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Status
Claims 110-121 and 126-130 are pending.
Claims 122-125 are cancelled.
Claims 110-121 and 126-130 are rejected.
Priority
Acknowledgment is made of applicant’s claim for priority. Application is a CON of application No. 17/179,279, which claims benefit of U.S. Provisional Application 62/978,130 filed on 2/18/2020. As such, the effective filing date of claims 110-130 is 2/18/2020.
Specification
Response to Amendment
In response to applicant’s amendments to the specification, previous objections to the specification regarding trade names and missing reference numbers is withdrawn.
Drawings
Response to Amendment
In response to applicant’s amendments to the drawings and specification, previous objections to the drawings for missing reference numbers is withdrawn.
Claim Rejections - 35 USC § 101
Response to Amendment
In response to applicant’s amendments to the claims, previous rejections under 35 U.S.C. 101 have been reviewed, updated, and provided below.
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 110-121, and 126-130 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method, system, and CRM for validating copy number variation status of a subject using a liquid biopsy assay. The judicial exception is not integrated into a practical application because while claims 110-121, and 126-130 attempt to integrated the exception into a practical application, said application is either generically recited computer elements that do not add a meaningful limitation to the abstract idea or it is insignificant extra solution activity and merely implementing the abstract idea on a computer. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the computer elements only store and retrieve information in memory as well as perform basic calculations that are known to be well-understood, routine and conventional computer functions as recognized by the decisions listed in MPEP § 2106.05(d).
Framework with which to Analyze Subject Matter Eligibility:
Step 1: Are the claims directed to a category of stator subject matter (a process, machine, manufacture, or composition of matter)? [see MPEP § 2106.03]
Claims are directed to statutory subject matter, specifically a method (Claims 110-121 and 126-128), a system (Claim 129), and a CRM (Claim 130).
Step 2A Prong One: Do the claims recite a judicially recognized exception, i.e., an abstract idea, a law of nature, or a natural phenomenon? [see MPEP § 2106.04(a)]
The claims herein recite abstract ideas, specifically mental processes and mathematical
concepts.
With respect to the Step 2A Prong One evaluation, the instant claims are found herein
to recite abstract ideas that fall into the grouping of mental processes and mathematical
concepts.
Claim 110: Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the copy number variation status being validated when one or more conditions/thresholds are satisfied, the measure of central tendency failing to satisfy thresholds when the measure is less than the measure threshold, are all processes of matching, deriving, or calculating information that can be done with pen and paper or within the human mind and are therefore, abstract ideas, specifically mental processes. Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the conditions comprising a requirement that the measure of central tendency satisfies one or measures of central-tendency plus deviation bin-level thresholds derived from a measure of central tendency corresponding to the plurality of bind and a measure of dispersion across the bin-level values, the measure of central tendency plus deviation bin-level threshold is a sum of a measure of central tendency of the bin-level values and a measure of central tendency of a plurality of absolute dispersions determined using a comparison, the measure of central tendency plus deviation bin-level threshold is the measure of central tendency of the bin-level values minus the measure of central tendency of a plurality of absolute dispersions determined using a comparison, and the measure of central tendency of the bin-level values minus the measure of central tendency of the plurality of absolute dispersions multiplied by a factor k, are verbal articulations of mathematical processes and therefore abstract ideas, specifically mathematical concepts.
Claim 111: The segment level measure of dispersion being a confidence interval, a standard deviation, a standard error, a variance, or a range is merely a verbal articulation of a mathematical process, and is therefore a mathematical concept.
Claim 112: The segment level measure of dispersion being a confidence interval, and determining each measure via bootstrapping bin-values are merely verbal articulations of mathematical processes and therefore mathematical concepts.
Claim 113: The segment-level measure of dispersion failing to satisfy a confidence threshold when a lower bound measure of dispersion is lower than the confidence threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 114: The segment-level measure of dispersion failing to satisfy a confidence threshold when an upper bound of the measure of dispersion is higher than the respective threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 115: A confidence threshold being a measure of central tendency of segment-level values corresponding to all other segments is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claim 116: Deriving bin-level values from a comparison of test read depth and central tendency is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 117: A condition that a measure of central tendency satisfies one or more bin-level thresholds is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claim 118: The measure of central tendency satisfying bin-level thresholds when the measure is greater than a bin-level amplification threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 119: The measure of central tendency satisfying bin-level thresholds when the measure is less than a bin-level deletion threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 120: Using circular binary segmentation to identify subsets of adjacent bins is a process of matching/comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 121: The measure of central tendency being a weighted mean is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claim 126: Conditions comprising a requirement that the segment-level value satisfies one or more segment-level thresholds is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claim 127: The segment-level value satisfying one or more segment-level thresholds when the segment-level value is greater than an amplification threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 128: The segment-level value satisfying one or more segment-level thresholds when the segment-level value is less than a segment-level amplification threshold is a process of comparing information which can be done with pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claim 129: Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the copy number variation status being validated when one or more conditions/thresholds are satisfied, are all processes of matching, deriving, or calculating information that can be done with pen and paper or within the human mind and are therefore, abstract ideas, specifically mental processes. Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the conditions comprising a requirement that the measure of central tendency satisfies one or measures of central-tendency plus deviation bin-level thresholds derived from a measure of central tendency corresponding to the plurality of bind and a measure of dispersion across the bin-level values, the measure of central tendency plus deviation bin-level threshold is a sum of a measure of central tendency of the bin-level values and a measure of central tendency of a plurality of absolute dispersions determined using a comparison, the measure of central tendency plus deviation bin-level threshold is the measure of central tendency of the bin-level values minus the measure of central tendency of a plurality of absolute dispersions determined using a comparison, and the measure of central tendency of the bin-level values minus the measure of central tendency of the plurality of absolute dispersions multiplied by a factor k, are verbal articulations of mathematical processes and therefore abstract ideas, specifically mathematical concepts.
Claim 130: Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the copy number variation status being validated when one or more conditions/thresholds are satisfied, are all processes of matching, deriving, or calculating information that can be done with pen and paper or within the human mind and are therefore, abstract ideas, specifically mental processes. Determining bin-level values corresponding to regions of the reference genome that cover a specific portion of the genome by performing a comparison between samples and a reference, determining segment-level values corresponding to regions of the reference genome via a measure of central tendency, determining segment-level measures of dispersion via the plurality of bin-level values and segment-level values, the conditions comprising a requirement that the measure of central tendency satisfies one or measures of central-tendency plus deviation bin-level thresholds derived from a measure of central tendency corresponding to the plurality of bind and a measure of dispersion across the bin-level values, the measure of central tendency plus deviation bin-level threshold is a sum of a measure of central tendency of the bin-level values and a measure of central tendency of a plurality of absolute dispersions determined using a comparison, the measure of central tendency plus deviation bin-level threshold is the measure of central tendency of the bin-level values minus the measure of central tendency of a plurality of absolute dispersions determined using a comparison, and the measure of central tendency of the bin-level values minus the measure of central tendency of the plurality of absolute dispersions multiplied by a factor k, are verbal articulations of mathematical processes and therefore abstract ideas, specifically mathematical concepts.
Step 2A Prong Two: If the claims recite a judicial exception under prong one, then is the judicial
exception integrated into a practical application? [see MPEP § 2106.04(d) and MPEP §
2106.05(a)-(c) & (e)-(h)]
Because the claims do recite judicial exceptions, direction under Step 2A Prong Two
provides that the claims must be examined further to determine whether they integrate
the abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract
elements:
Claim 110: A computer system, processors, memory and programs are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Aligning sequences is an insignificant extra solution activity, specifically mere data gathering [See § MPEP 2106.05(g)].
Claim 129: A computer system, processors, non-transitory computer readable medium, and instructions are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Aligning sequences is an insignificant extra solution activity, specifically mere data gathering [See § MPEP 2106.05(g)].
Claim 130: A non-transitory computer readable medium, program code instructions, and processors are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)]. Aligning sequences is an insignificant extra solution activity, specifically mere data gathering [See § MPEP 2106.05(g)].
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive
concept? [see MPEP § 2106.05]
Because the additional claim elements do not integrate the abstract idea into a practical
application, the claims are further examined under Step 2B, which evaluates whether
the additional elements, individually and in combination, amount to significantly more
than the judicial exception itself by providing an inventive concept.
The claims do not recite additional elements that are sufficient to amount to
significantly more than the judicial exception because the claims recite additional
elements that are generic, conventional or nonspecific. These additional elements
include:
The additional elements of a computer system, processors, memory, a non-transitory computer readable medium, and program code instructions, are generic and nonspecific elements of a computer that are well-understood, routine and conventional within the art and therefore do not improve the functioning of any computer or technology described therein (Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See § MPEP 2106.05(d)(II)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional element of aligning sequences is a well-understood, routine and conventional activity as described the MPEP (See Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546 and Arranging a hierarchy of groups, sorting information, eliminating less restrictive pricing information and determining the price, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1331, 115 USPQ2d 1681, 1699 (Fed. Cir. 2015)) [See § MPEP 2106.05(d)(II)].
Therefore, claims 110-130, when the limitations are considered individually and as a whole, are rejected
under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 2/17/2026 have been fully considered but they are not persuasive.
Applicant asserts on page 16 of the Remarks filed 2/17/2026 that the claims as described do not recite an abstract idea, rather the limitations are directed to limitations that cannot be practically performed within the human mind. First, examiner never asserted that the alignment of sequence reads as described is a mental process.
Second, there is no corresponding limitation regarding the determinations of sequence ratios, read counts, comparison of bin counts to reference counts, measures of dispersion, similarity, etc., that makes it not performable by the human mind, rather applicant directs description of the methods to the use of probabilistic methods such as circular binary segmentation which is a mathematical concept. MPEP 2106.04(a)(2)(III) states - The courts do not distinguish between mental processes that are performed entirely in the human mind and mental processes that require a human to use a physical aid (e.g., pen and paper or a slide rule) to perform the claim limitation. See, e.g., Benson, 409 U.S. at 67, 65, 175 USPQ at 674-75, 674 (noting that the claimed "conversion of [binary-coded decimal] numerals to pure binary numerals can be done mentally," i.e., "as a person would do it by head and hand.")…The use of a physical aid (e.g., pencil and paper or a slide rule) to help perform a mental step (e.g., a mathematical calculation) does not negate the mental nature of the limitation, but simply accounts for variations in memory capacity from one person to another. For instance, in CyberSource, the court determined that the step of "constructing a map of credit card numbers" was a limitation that was able to be performed "by writing down a list of credit card transactions made from a particular IP address." In making this determination, the court looked to the specification, which explained that the claimed map was nothing more than a listing of several (e.g., four) credit card transactions. The court concluded that this step was able to be performed mentally with a pen and paper, and therefore, it qualified as a mental process. Additionally, just because the bins represent 25Mb of genome and 10,000 reads does not make the limitation a non-mental process as, the limitation states determining the bin level values is comparing the proportion of reads mapped to each bin from the sample to a proportion for reference samples, which is a mental process as it is merely 500 comparisons.
Furthermore, it is stated in MPEP 2106.04(a)(2)(I) - A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the "mathematical concepts" grouping. A mathematical calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. As such the claims, given their BRI recite both mental processes and mathematical concepts.
Applicant asserts on page 18 of the Remarks filed 2/17/2026 that the claims integrate the judicial exception into a practical application. More specifically applicant asserts that the claims integrate any alleged judicial exceptions into technical architecture that enables efficient identification of focal CNVs, specifically citing the Desjardins decision regarding improvements to machine learning models themselves. However, applicant claims the improvement is directed to the identification of focal CNVs, yet MPEP 2106.05(a) - 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)). Here the improvement is not directed to an improvement to the additional elements as in Desjardins, but rather the abstract idea or judicial exception itself “efficient identification of focal CNVs”. Furthermore any and all additional elements are, as previously described, well-understood, routine and conventional or generic computer elements.
Claim Rejections - 35 USC § 102
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections under 35 U.S.C. 102 for anticipation under the prior art have been withdrawn.
Response to Arguments
Applicant’s arguments, see page 22 of the Remarks, filed 2/17/2026, with respect to claims 110, 129, and 130 have been fully considered and are persuasive. The rejection of claims 110, 129, and 130 has been withdrawn as they now integrate limitations from claims 123-125, that were previously acknowledged as not taught within the prior art. More specifically, as previously stated: Claims 123-125 are directed to how the thresholds are computed for a central tendency-plus-deviation metric, and while prior art has shown the obviousness of combining the central tendency and the dispersion (deviation) a threshold value, specifically for the purposes of segment classification (but also in a broader scope), is not found in the art. Therefore, other rejections (101, 112, etc.) notwithstanding, claims 123-125 contain allowable subject matter.
Claim Rejections - 35 USC § 103
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections under 35 U.S.C. 103 for obviousness under the prior art have been withdrawn.
Response to Arguments
Applicant’s arguments, see pages 22-24 of the Remarks, filed 2/17/2026, with respect to claims 111-128 have been fully considered and are persuasive. The rejection of claims 111-128 has been withdrawn as they now integrate limitations from claims 123-125, that were previously acknowledged as not taught within the prior art. More specifically, as previously stated: Claims 123-125 are directed to how the thresholds are computed for a central tendency-plus-deviation metric, and while prior art has shown the obviousness of combining the central tendency and the dispersion (deviation) a threshold value, specifically for the purposes of segment classification (but also in a broader scope), is not found in the art. Therefore, other rejections (101, 112, etc.) notwithstanding, claims 123-125 contain allowable subject matter.
Double Patenting
Response to Amendment
In view of applicant’s amendments to the claims previous rejections under double patenting over US 11211144 B2 have been withdrawn.
Response to Arguments
Applicant’s arguments, see page 24 of the Remarks, filed 2/17/2026, with respect to the rejection of claims 110-130 under non-statutory double patenting have been fully considered and are persuasive. The rejection of claims 110-130 has been withdrawn in view of the filing and acceptance of the terminal disclaimer.
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 KEENAN NEIL ANDERSON-FEARS whose telephone number is (571)272-0108. The examiner can normally be reached M-Th, alternate F, 8-5.
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/K.N.A./Examiner, Art Unit 1687
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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