DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
The amended claim set received 25 November 2025 has been entered into the application.
Claim 2 has been amended.
Claims 1, 3, 5-8, 9, 12-16, 20, 23, 25-27, 29-37, 41-45, 47-49, and 51 are canceled.
Claim(s) 2, 4, 10-11, 17-19, 21-22, 24, 28, 38, 40, 46, 50, and 52 are pending.
Priority
Application 17/108, 980 is a continuation of PCT/US2019/035871 filed 06 June 2019 which claims priority to U.S Provisional Application filed 06 June 2018.
35 USC § 112(b)
The rejection of claim 2 under 35 U.S.C. 112(b) in the Office Action mailed 01 August 2025 is withdrawn in view of the arguments received 25 November 2025.
The rejection of claim 2, 4, 10-11, 17-19, 21-22, 24, 28, 38, 40, 46, and 50 under 35 U.S.C. 112(b) in the Office Action mailed 01 August 2025 is withdrawn in view of the arguments received 25 November 2025.
Claim Rejections - 35 USC § 101
The instant rejection is maintained for reason for record in the Office Action mailed 01 August 2025 and modified in view of the amendments filed 25 November 2025
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 2, 4, 10-11, 17-19, 21-22, 24, 28, 38, 40, 46, 50, and 52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Following the flowchart of the MPEP 2106.
Step I - Process, Machine, Manufacture or Composition
Claims 2, 4, 10-11, 17-19, 21-22, 24, 28, 38, 40, 46, 50, and 52 are drawn to a method, so a process.
2A Prong I - Identification of an Abstract Idea
Claim 2 recites:
processing, by a computer, the first plurality of sequencing reads to generate a first sample fingerprint comprising a coverage of the first plurality of nucleic acid molecules at each of a plurality of genetic loci based on the first plurality of sequencing reads
This step can be performed in the human mind by organizing information (i.e., coverage of nucleic acids) to generate a first sample fingerprint and is therefore an abstract idea.
wherein the plurality of genetic loci comprises autosomal single nucleotide polymorphisms (SNPs)
This step describes the genetic loci as comprising autosomal single nucleotide polymorphisms (SNPs).
wherein the processing comprises aligning the first plurality of sequencing reads to a reference genome
This step encompasses performing mathematical/statistical computations for aligning first plurality of sequence reads to a reference genome. For example, aligning nucleic acid data to a reference genome encompasses dynamic programming, graph theory, probability, and statistics to identify similarities and evolutionary relationships between DNA sequences. For example, aligning encompasses matrix mathematics (e.g., scoring matrices), match/mismatch scoring systems, and scoring matrix generation. As such, this process converts biological sequences into mathematical objects (strings) and uses numerical scoring systems to calculate the optimal alignment.
processing, by a computer, the second plurality of sequencing reads to generate a second sample fingerprint comprising a coverage of the second plurality of nucleic acid molecules at each of the plurality of genetic loci based on the second plurality of sequencing reads.
This step can be performed in the human mind by organizing information (i.e., coverage of nucleic acids) to generate a second sample fingerprint and is therefore an abstract idea.
wherein the processing comprises aligning the second plurality of sequencing reads to the reference genome
This step encompasses performing mathematical/statistical computations for aligning sequence reads to a reference genome similar to the previous step of aligning the first plurality of sequence reads to a reference genome above and therefore reads on abstract ideas.
performing a pairwise comparison between the first sample fingerprint generated from the first biological sample and the second sample fingerprint generated from the second biological sample to determine whether a sample match or a sample mismatch is present between the first and second biological samples from the subject
This step can be performed in the human mind by observing, comparing, and evaluating a pairwise comparison between sample fingerprints data to determine whether a sample match or mismatch is present between samples and is therefore an abstract idea. This step encompasses performing a pairwise comparison between the first sample fingerprint and the second sample fingerprint which encompasses mathematical/statistical computations for calculating a pairwise comparison between sample fingerprints and is therefore an abstract idea. For example, pairwise sequence comparison uses dynamic programming, substitution matrices, and alignment algorithms to quantify the similarity between two sequences. Here, the goal of performing pairwise comparisons is to calculate an optimal score by maximizing matches and minimizing penalties for mismatches, insertions, and deletions (gaps), using formulas to find the minimum edit distance. Thus, pairwise comparisons read on abstract ideas/mathematical concepts. Here, the term” performing” is interpreted as an alternative to term for “calculating”. See MPEP 2106.04(a)(2)(I)(C).
wherein performing the pairwise comparison comprises generating a quantitative measure of genotype similarity
This step can be performed in human mind by following instruction to generate a quantitative measure of genotype similarity and is therefore an abstract idea. This step encompasses performing pairwise comparison which encompasses mathematical/statistical computations for generating a quantitative measure of genotype similarity (i.e., numerical values representing genotype similarity) and is therefore an abstract idea.
identifying the sample mismatch when the difference between the first sample fingerprint and the second sample fingerprint exceeds a predetermined threshold.
This step can be performed in the human mind by observing and evaluating if the differences between the first sample fingerprint and the second sample fingerprint exceed a predetermined threshold to identify the sample mismatch and therefore is an abstract idea. This step encompasses utilizing mathematical concepts of equalities and inequalities to determine if the first and second sample fingerprints exceed a predetermined threshold (i.e., a range of numerical values) and is therefore an abstract idea.
excluding the second biological sample from further laboratory or clinical analysis based on the identified sample mismatch.
This step can be performed in the human mind by observing and evaluating identified sample mismatches to exclude the second biological sample from further laboratory or clinical analysis (i.e., assaying) and is therefore an abstract idea. Furthermore, the step of excluding the second biological sample from further assaying based on identified sample mismatches reads on making a decision to not perform an assay on the second sample because the step does not include any particular physical transformations or real-world steps, and is therefore a further abstract idea/mental process.
wherein the first plurality of nucleic acid molecules and the second plurality of nucleic acid molecules comprise cell-free DNA (cfDNA) or solid tumor DNA
This step describes the first plurality of nucleic acid molecules and the second plurality of nucleic acid molecules as from cell-free DNA (cfDNA) or solid tumor DNA.
wherein the autosomal single nucleotide polymorphisms comprise simple single nucleotide polymorphisms and that do not any have no insertions or deletions.
This step describes the autosomal single nucleotide polymorphisms as a simple single nucleotide polymorphism and does not contain a single polymorphism from an insertions or deletions mutations.
Claims 4, 11, 22, 24, 28, 38, 40, 46, 50, and 52 are further drawn to limitations that describe the abstract ideas of claim 2 and are therefore also abstract ideas.
2A Prong II - Consideration of Practical Application
Claim 2 does not recite any additional element which integrates the recited judicial exception into a practical application. Here, in the instant case, the claims merely set forth a method of nucleic acid sequence data analysis by generating nucleic acid sample fingerprint(s) to identify matches and mismatches between the sample fingerprints. As such, practicing the claims merely results in identifying sample matches and mismatches between a first and second sample fingerprint. Such a result only produces information and does not provide for a practical application in the physical-world realm of physical things and acts, i.e., the claims do not utilize the data generated by the judicial exception to affect any type of change. See MPEP 2106.04(a)(2)(A)(iv). Therefore, the claims do not utilize the obtained samples, sequenced nucleic acids, generated sample fingerprints, performed pairwise comparison, and the identified sample mismatches, and the abstract ideas to construct a practical application such as treating a subject, transformation of matter, or improving upon an existing technology.
This judicial exception is not integrated into a practical application because the claims do not meet any of the following criteria:
an additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
2B Analysis - Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea.
The recited additional element of obtaining a first sample and second sample of claim 1 does not add more than the recited judicial exception because obtaining a biological sample to obtain nucleic acids and/or nucleic acid data that is subsequently analyzed by the abstract ideas is deemed a well-known and conventional extra-solution activity. See MPEP 2106.05(g).
The recited additional element of using computer element of claims 2 and 46 does not add more than the recited judicial exception because using computer processes, components, and equipment to process and store abstract ideas is deemed well-known and conventional. See MPEP 2106.05(b) and 2106.05(d)(II).
The recited additional element of sequencing of claims 2 and 10 does not add more than the recited judicial exception because sequencing to obtain/provide nucleic acid data that is subsequently analyzed by the abstract idea is deemed well-known and conventional. See MPEPE 2106.05(d)(II)(ii, v, vii).
The recited additional element of enriching nucleic acids claims 17-19 and 21 does not add more than the recited judicial exception because enriching nucleic acid by amplification to obtain nucleic acid data that is subsequently analyzed by the abstract idea is deemed well-known and conventional. See MPEPE 2106.05(d)(II)(vii). To provide evidence of conventionality of using selective amplification, Vos et al. (Vos) teach selective amplification for DNA fingerprinting [abstract] (Nucleic acids research, 1995-11, Vol.23 (21), p.4407-4414) (Cited in the Office Action mailed 01 August 2025). To provide evidence of conventionality of using universal amplification, Faulkner et al. (Faulkner) et al. teach universal amplification was performed on 35 paired specimens of malignant ovarian germ cell tumors [abstract] (Gynecologic oncology, 2000-05, Vol.77 (2), p.283-288) (Cited in the Office Action mailed 01 August 2025). To provide evidence of conventionality of enrichment by selectively isolating, Zhu et al. (Zhu) teach the processes can be broken down into four steps of CTC enrichment, isolation, genome or transcriptome amplification, and sequencing and data analysis [pages 406-407 bottom right col to upper left col] (Cell biology and toxicology, 2018, Vol.34 (5), p.405-415, Cited in the Office Action mailed 11 September 2024).
The recited additional element of laboratory or clinical analysis of claims 2 and assaying of claim 46 does not add more than the recited judicial exception because performing clinical/laboratory analysis and assaying a biological sample for obtaining/providing nucleic acid data that is subsequently analyzed by the abstract idea is deemed well-known and conventional. See MPEPE 2106.05(d)(II)(vii).
In conclusion and when viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 25 November 2025 have been fully considered but the rejection is maintained.
The Applicant states the amended claims are not directed to the judicial exception of an abstract idea. The Applicant points Step 2A Prong I of the 101 analysis and MPEP 2106.004(II)(A)(I) for guidance [remarks, page 7]. The Applicant states that using a computer to process sequencing reads cannot be performed in the human mind. The Applicant points to MPEP 2106.04(a)(2)(III)(A) for guidance. The Applicant states that generating a sample fingerprint using sequence coverage cannot be performed in the human mind. The Applicant states aligning cannot practically be performed in the human mind. The Applicant states both processing steps of claim 2 are specified as being performed on a computer which underscores the infeasibility of processing sequence reads and generating a sample fingerprint from sequence read coverages. [remarks, pages 8-9].
In response, with respect to using a computer for generating a sample and aligning sequence reads, this amounts to merely processing abstract ideas on a generic computer and in a computer environment and using a computer as a tool to perform mental processes. See MPEP 2106.04(a)(2)(III)(C)(1-3). Thus, the computer is tangential to the claimed method. Therefore, using a computer to generate sequencing coverage (i.e., sample fingerprint) and align sequence data does not preclude the method from being performed in the human mind and does not render the claimed method patent eligible. Additionally, with respect to processing sequencing read data, the argument is not persuasive because it is acknowledged that such computations (i.e., aligning sequence reads and sequence read coverage) performed mentally, or with paper and pencil, would take considerable time and effort, but that is, of course, the singular purpose of computers and computer networks, to perform large numbers of calculations, via algorithms, rapidly, and without error (assuming no error in user input). Although a general-purpose computer can perform calculations at a rate and accuracy that can far outstrip the mental performance of a skilled artisan, the nature of the activity is essentially the same, and constitutes an abstract idea. See SiRF Tech: "In order for the addition of a machine to impose a meaningful limit on the scope of a claim, it must play a significant part in permitting the claimed method to be performed, rather than function solely as an obvious mechanism for permitting a solution to be achieved more quickly, i.e., through the utilization of a computer for performing calculations" and Bancorp: "the fact that the required calculations could be performed more efficiently via a computer does not materially alter the patent eligibility of the claimed subject matter. … Using a computer to accelerate an ineligible mental process does not make that process patent-eligible".
The Applicant states excluding a biological sample from further laboratory or clinical analysis represents a non-mental process. The Applicant states excluding a sample from further laboratory analysis affects real world analysis change by foregoing further laboratory/clinical analysis which would constitute concrete, physical steps. [remarks, page 9 B].
In response, as noted in Step 2A Prong I of the 101 analysis, excluding a sample from further analysis reads on judging, observing, and evaluating identified sample mismatches to make decision whether to exclude the second sample from further clinical analysis. Moreover, excluding a sample a sample from further analysis excludes the sample from having laboratory/clinical tests (i.e., assaying) from being performed on said sample(s). Thus, excluding a sample from laboratory/clinical tests (i.e., assaying) does not contain any concrete physical steps because the sample is excluded from testing. Here, even if the sample was to be included in laboratory/clinical tests (i.e., assaying), laboratory/clinical tests (i.e., assaying) are extra-solution activities for gathering sequence read data for subsequent quantitative and qualitative analysis. See MPEP 2106.05(d)(II)(i-iii, v, vii).
The Applicant states aligning sequencing reads to a reference genome and performing pairwise comparisons between sample fingerprints does not recite mathematical calculations. The applicant points to MPEP 2106.04(a)(2)(I) for guidance. The Applicant states aligning sequence reads to a reference genome merely compares sequence reads between a sample and a reference genome. The Applicant states performing pairwise comparison between samples does not require mathematical/statistical calculation. [remarks, pages 9-10 C].
In response, and as noted in Step 2A Prong I of the 101 analyses above, aligning sequence reads encompasses performing mathematical/statistical computations. For example, aligning encompasses matrix mathematics (e.g., scoring matrices), match/mismatch scoring systems, and scoring matrix generation. As such, this process converts biological sequences into mathematical objects (strings) and uses numerical scoring systems to calculate the optimal alignment which reads on abstract ideas/mathematical concepts.
Additionally, and as further noted in Step 2A Prong I of the 101 analyses above, pairwise comparisons of sequence data contain mathematical concepts. For example, pairwise sequence comparison uses dynamic programming, substitution matrices, and alignment algorithms to quantify the similarity between two sequences. As such, the goal of performing pairwise comparisons is to calculate an optimal score by maximizing matches and minimizing penalties for mismatches, insertions, and deletions (gaps), using formulas to find the minimum edit distance. Thus, pairwise comparisons read on abstract ideas/mathematical concepts.
The Applicant states the claims recite additional elements that integrate the recite judicial exception into a practical application. The Applicant states the claims specify how the data (i.e., pairwise comparisons and identified sample mismatches) is used to affect a real-world change. The Applicant points to claim 2 excluding step for clarification. The Applicant states the step affects a real-world change by excluding a physical sample from further laboratory/clinical analysis which involves concrete physical actions. The Applicant states this element meaningfully applies the judicial exception. [remarks, pages 10-11 II]. The Applicant points to the specification paragraphs [0002-0003 and 0061] for guidance. The Applicant states the claims recites a clear practical application because the claims recite identifying mismatches between longitudinal samples (i.e., samples taken at different times [0003]) and samples get mixed up resulting in inaccurate patient assessment. [remarks, page 10].
In response, claim 2 does not contain any additional elements that integrate the judicial exception (i.e., identified mismatches) into a practical application. Here, the claims are drawn to gathering and analyzing information (i.e., nucleic acid sequence data) using conventional techniques and methods (i.e., computer elements, sequencing) for detecting allelic variant in a sample for determining sample mismatches in longitudinal samples. See MPEP 2106.05(a)(II)(v), 2106.05(d)(I)(i-iii, v, viii), and 2106.05(g). Additionally, it is noted in Step 2A Prong I of the 101 analysis above, identifying mismatches reads on abstract ideas. Here, the identified mismatches (e.g., abstract idea) are not applied to any additional elements so as to as to result in a practical application or an improvement to technology.
The Applicant states the recited method results in improved maintenance of sample identify. The Applicant points to fig 4 and 5 for guidance. The Applicant states excluding a biological sample from further analysis improve the integrity and accuracy of sample taken at different time points. The Applicant states this represents a clear and practical application that affects a real-world change. [remarks, page 11].
In response, the argument is not persuasive because the claims do not integrate any additional elements with the judicial exception such that to construct a practical application. Moreover, the steps are not applied to any additional elements so as to result in a practical application or an improvement to technology. Novel or improved abstract idea steps alone are not deemed to be an improvement to technology. With respect to excluding a sample from further analysis, this step reads on abstract ideas. Moreover, excluding a sample from further analysis excludes the sample from having laboratory/clinical tests (i.e., assaying) from being performed on said sample(s). Thus, excluding a sample from laboratory/clinical tests (i.e., assaying) does not contain any concrete physical steps or integrate any additional elements such that to construct a practical application of the judicial exception.
The Applicant states the claims are not well understood, routine, and conventional [remarks, page 12]. The Applicant points to MPEP 2106.05(d)(I) for guidance. The Applicants states claim 2 represents unconventional and not well-understood methods. The Applicant states the method describes a new and improved way for identifying biological sample that has been mismatched by comparing sample fingerprints between sample. [remarks, page 12]. The Applicant states Examiner has not identified any references that describes processing sequence reads, performing pairwise procedures, and excluding a sample from further analysis. [remarks, page 13].
In response, and as noted in Step 2B of the 101 analyses above, claim 2 does not encompasses any additional element that add significantly more. Here, the claims are drawn to gathering and analyzing information (i.e., nucleic acid sequence data) using conventional techniques and methods (i.e., computer elements, sequencing, enriching, data gathering) for detecting allelic variants in a sample for determining sample mismatches in longitudinal samples. See MPEP 2106.05(a)(II)(v), 2106.05(d)(I)(i-iii, v, viii), and 2106.05(g). With respect to the additional of sequencing nucleic acids, sequencing is deemed routine and conventional an extra-solution activity. See MPEP 2106.05(a)(II)(ii) and 2106.05(d)(I)(viii). Furthermore, and with respect to performing pairwise comparisons and excluding samples and as noted about in Step 2A Prong I of the 101 analysis, these limitations were found to encompass abstract ideas. Therefore, with respect to Step B analysis, the claims, in any combination and as a whole, are not patent eligible.
Conclusion
Claims 2, 4, 10-11, 17-19, 21-22, 24, 28, 38, 40, 46, 50, and 52 are rejected.
No claims are allowed.
Finality
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.
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/J.C.P./ Examiner, Art Unit 1687
/Anna Skibinsky/
Primary Examiner, AU 1635