DETAILED ACTION
Applicant's response, filed 06/24/2026, 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. Herein, "the previous Office action" refers to the Non-Final rejection of 02/24/2026
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 1-2, 4-5, 7-9, 13-16, 18-19, 21-23, 26, 28-29, 32, 34-35, and 40 are currently pending and under exam herein.
Claims 3, 6, 10-12, 17, 20, 24-25, 27, 30-31, 33, 36-39, and 41-67 were previously cancelled.
Claims 1-2, 4-5, 7-9, 13-16, 18-19, 21-23, 26, 28-29, 32, 34-35, and 40 are rejected.
Priority
The previously discussed claim for the benefit of priority assigned an effective filing date of 14 September 2018. In future actions, the effective filing date of one or more claims may change, due to amendments to the claims, or further analysis of the disclosure(s) of the priority application(s).
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 1-2, 4-5, 7-9, 13-16, 18-19, 21-23, 26, 28-29, 32, 34-35, and 40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Any newly applied rejection/portion is necessitated by instant application amendment.
The instant rejection reflects the framework as outlined in the MPEP at 2106.04:
Framework with which to Evaluate Subject Matter Eligibility:
(1) Are the claims directed to a process, machine, manufacture, or composition of matter;
(2A) Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
(2B) If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
With respect to step (1): yes, the claims are directed to a method, a computer-readable medium, and a system for detecting copy number variation (CNV) in genetic sequences, therefore the answer is "yes".
With respect to step (2A)(1), the claims recite an abstract idea. To determine if the claims recite any concepts that equate to an abstract idea, law of nature, or natural phenomenon, MPEP at 2106.03 teaches abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships, and mathematical calculations), certain methods of organizing human activity, and mental processes (including procedures for collecting, observing, evaluating, and organizing information (see MPEP 2106.04(a)(2)). In the instant application, the claims recite the following limitations that equate to an abstract idea with mental steps and mathematical concepts.
With respect to the instant claims, under the step (2A)(1) evaluation, the claims are found herein to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for obtaining, analyzing, and organizing information) and mathematical concepts (in particular mathematical relationships and formulas).
The claims directing to abstract ideas are as follows:
Mental processes:
Claims 1, 15, and 28 recite determining a read depth for the genetic sequence… separating the genetic sequence into a plurality of bins, each bin of the plurality of bins comprising a plurality of base pairs of the genetic sequence, wherein a read depth of a first bin of the plurality of bins is determined using the read depth determined for the genetic sequence;…determining a CNV status for the first bin of the plurality of bins… identifying two or more bins to be merged to create a merged bin and an associated merged CNV status, wherein: the merged CNV status is determined based at least in part on the CNV statuses of each of the two or more bins; merging the two or more bins to create the merged bin by determining the merged CNV status is a same CNV status as the CNV status of at least one of the two or more bins; determining a number of base pairs in the two or more bins over which the merged CNV status and the CNV status of the at least one of the two or more bins are the same; and merging the at least two bins when the merged CNV status is a same CNV status as CNV status of the at least one of the two or more bins over a threshold number of base pairs in the two or more bins; and identifying the at least one CNV in the genetic sequence based on the determined CNV statuses.
Claim 4 and 18 recite aligning the genetic sequence with a reference genome to generate genetic sequence alignment data
Claim 5, 19, and 32 recite identifying at least one unique genetic region … within the at least one autosomal chromosome comprises: determining that each 25 k-mer of the at least one unique genetic region appears only once within the genetic sequence; and determining that the at least one unique genetic region comprises greater than 20,000 base pairs.
Claims 7, 21, and 34 recite comparing the read depth of the at least one autosomal chromosome to the read depth of the genetic sequence; and determining whether the genetic sequence comprises an aneuploidy based on the compared read depths.
Mathematical concepts:
Claim 1 recites converting the read depth of the first bin to a percentile; and converting the percentile to a CNV status by providing the percentile as input to a Hidden Markov Model with a Poisson distribution of read depth, wherein the CNV status is indicative of whether the first bin includes at least one duplicated or deleted CNV in at least a subset of the plurality of base pairs of the genetic sequence in the first bin;
Claim 4 and 18 recite wherein: dividing the genetic sequence into the plurality of bins comprises dividing the genetic sequence alignment data into the plurality of bins.
Claim 5, 19, and 32 recite calculating a read depth for the at least one unique genetic region
Claims 7, 21, and 34 recite calculating a read depth of the at least one autosomal chromosome based on a read depth of the at least one unique genetic region
Claims 8, 22, and 35 recite wherein the two or more bins comprise adjacent pluralities of base pairs associated with the two or more bins.
Claims 9 and 23 recite wherein converting the read depth to a percentile comprises: dividing the read depth of each bin of the plurality of bins by the number of base pairs in the plurality of base pairs and multiplying by the read depth of the genetic sequence.
Claims 13, 26, and 40 recite dividing the merged bin into a plurality of regions, each region comprising an equal number of base pairs; assigning a uniqueness value to each region; filtering out regions having a uniqueness value below a threshold value; and identifying the at least one CNV status based on one or more regions that remain following the filtering.
Hence, the claims explicitly recite elements that, individually and in combination, constitute abstract ideas.
With respect to step (2A), under the broadest reasonable interpretation (BRI), the instant claims recite “detecting copy number variation (CNV) in genetic sequences.” Instant claims 1, 15, and 28 are therefore directed to the judicial exceptions of abstract groupings, both mathematical (determining a read depth…a Hidden Markov Model (HMM) with a Poisson distribution… converting the read depth to a percentile…to a CNV status… by the number of base pairs… multiplying by the read depth… genetic sequences/merged bins) and mental processes (identifying the at least one CNV … aligning the genetic sequence … comparing the read depth…determining whether… determining the merged CNV status … determining a number of base …; and merging the at least two bins … merging the at least two bins…over a threshold number… identifying the at least one CNV …).
Because the claims do recite judicial exceptions, direction under step (2A)(2) provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application (MPEP 2106.04(d). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim is said to fail to integrate into a practical application (MPEP 2106.04(d).III).
With respect to the instant recitations, the claims recite the following additional elements considered for practical application:
Claims 1, 15, and 28 recite CRM … system…processor(s)
Claims 2, 16, and 29 recite partial genome sequence or a whole genome sequence (WGS).
Said steps that are “in addition” to the recited judicial exception in the instant claims represent those of mere instructions or field of use limitations (partial/whole genome sequence) to implement in the recited judicial exception and do not impart meaning to said recited judicial exception, such that is applied in a practical manner. Further with respect to the additional elements in the instant claims, these steps direct to mere data gathering and handling (genetic sequence data) to carry out the abstract idea without imposing any meaningful limitation on the abstract idea. Thereby these steps are insignificant extra-solutions activity steps and are insufficient to integrate an abstract idea into a practical application. (MPEP 2106.05(g).
Further steps herein directed to additional non-abstract elements of computer components (processor, non-transitory computer-readable medium, system) do not describe any specific computational steps by which the “computer parts” perform or carry out the abstract idea, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer. (see MPEP 2106.05(f)). None of the recited dependent claims recite additional elements which would integrate a judicial exception into a practical application.
As such, the claims are lastly evaluated using the step (2B) analysis, wherein it is determined that because the claims recite abstract ideas, and do not integrate that abstract ideas into a practical application, the claims also lack a specific inventive concept. The judicial exception alone cannot provide the inventive concept or the practical application and that the identification of whether the additional elements amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements of data gathering, instructions, and field of use limitations described above do not rise to the level of significantly more than the judicial exception. As directed in the Berkheimer memorandum of 19 April 2018 and set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant recitations, the claims recite the following additional elements considered for inventive concepts:
Claims 1, 15, and 28 recite CRM … system…processor(s)
Claims 2, 16, and 29 recite partial genome sequence or a whole genome sequence (WGS).
These additional elements do not contribute significantly more to well-known and conventional steps, which are routinely performed by a biochemist with ordinary skill in the art of as of the effective filing date, and in their own heads. The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity: detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017); analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546; and amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014).
Furthermore, the MPEP 2106.05(a) teaches applying the judicial exception with computers or devices to perform or automate an existing process, and constitute insignificant extra-solution activity, as recited: “Mere automation of manual processes, such as using a generic computer to process an application for financing a purchase, Credit Acceptance Corp. v. Westlake Services, 859 F.3d 1044, 1055, 123 USPQ2d 1100, 1108-09 (Fed. Cir. 2017) or speeding up a loan-application process by enabling borrowers to avoid physically going to or calling each lender and filling out a loan application, LendingTree, LLC v. Zillow, Inc., 656 Fed. App'x 991, 996-97 (Fed. Cir. 2016) (non-precedential).
With respect to the instant claims, the steps and additional elements involving mathematical applications and automated mental steps to handle and analyze genetic data in order to detect copy number variation (CNV) do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-2, 4-5, 7-9, 13-16, 18-19, 21-23, 26, 28-29, 32, 34-35, and 40 are not patent eligible.
Response to Remarks – 101
Applicant's remarks (p.13-14), filed 06/24/2026, have been fully considered and are not persuasive for the previously stated reasons in the 02/24/2026 Office Action, with additions necessitated by claim amendments. The Applicant asserts:
“Technical improvement to the computational systems used to perform CNV analysis and detection [Remarks p4-5]: “In particular, the specification describes the improvements provided by the claimed binning and merging process in reducing the signal-to-noise ratio of the read depth data being analyzed, while maintaining sensitivity to small CNVs within the genetic data (11 62-63). By analyzing the CNV statuses of the bins with respect to the underlying base pairs within the bins, the claimed system enables flexible adjustment of the bins to improve the balance between the SNR and sensitivity to small CNVs, thereby resulting in an improved bin data structures to be used in the CNV analysis and detection process (Id.). As a result, the claimed systems and techniques described in the present application improve the underlying computational system utilized for performing CNV analysis and detection by providing flexible data structures that improve efficiency and accuracy of the CNV detection system…claims reflect the improvement to the computational systems for CNV analysis and detection described in the specification. Independent claim 1, recites in part: … determining the merged CNV status is a same CNV status as the CNV status of at least one of the two or more bins; determining a number of base pairs in the two or more bins over which the merged CNV status and the CNV status of the at least one of the two or more bins are the same; and merging the at least two bins when the merged CNV status is a same CNV status as the CNV status of the at least one of the two or more bins over a threshold number of base pairs in the two or more bins; and identifying the at least one CNV in the genetic sequence based on the determined merged CNV status.”
However, this is not persuasive because improving CNV analysis and detection is an improvement to computation, which is the judicial exception (JE) of abstract mathematical idea, not to improving a system or system architecture or sequencer or processor. Instant claim amendments of determining… determining… merging…over thresholds…identifying are mental and mathematical concepts for data handling optimization or an intended use of genetic data, ultimately, to optimize signal to noise in CNV data with better math. Any improvement or non-routine step or nonconventional element cannot be found in the judicial exceptions alone. (Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016).”
The examiner acknowledges Applicant’s arguments which set forth that the claims lead to an improvement in CNV analysis and detection. According to the guidance set forth in MPEP 2106, this is an improvement to the judicial exception itself, and is not reflected back into a specific technological environment or practically applied process. An improvement in the judicial exception itself is not an improvement in the technology. For example, in In re Board of Trustees of Leland Stanford Junior University, 989 F.3d 1367, 1370, 1373 (Fed. Cir. 2021) (Stanford I), Applicant argued that the claimed process was an improvement over prior processes because it ‘‘yields a greater number of haplotype phase predictions,’’ but the Court found it was not ‘‘an improved technological process’’ and instead was an improved ‘‘mathematical process.’’ The court explained that such claims were directed to an abstract idea because they describe ‘‘mathematically calculating alleles’ haplotype phase,’’ like the ‘‘mathematical algorithms for performing calculations’’ in prior cases. Notably, the Federal Circuit found that the claims did not reflect an improvement to a technological process, which would render the claims eligible (FR89 no.137, p58137, 7/17/2024).
Here, Applicant has provided an improved mathematical process of bin read depth/merging calculation based on regions of interest, HMM, and k-mer uniqueness filtering of sequence/CNV data in the improved mathematical process for data normalization and noise suppression. The additional elements of CRM … system…processor(s)…partial/whole genome sequencing are well understood, routine, and conventional, and ultimately, do not add significantly more for any practical integration or any inventive concept.
Response to Remarks – 35 USC §102/103
Applicants remarks have been fully considered, and the outstanding rejection, is hereby withdrawn, in further view of 06/24/2026 instant application amendments, regarding independent claims 1, 15, and 28 under 35 U.S.C. § 103 as being unpatentable over Guan (02/24/2026 PTO 892), in view of Yoon (02/24/2026 PTO 892).
Applicant's assertion that Guan in view of Yoon does not disclose reducing signal noise specifically as recited: wherein the CNV status is indicative of whether the first bin includes at least one duplicated or deleted CNV in at least a subset of the plurality of base pairs of the genetic sequence in the first bin… merging the two or more bins to create the merged bin by determining the merged CNV status is a same CNV status as the CNV status of at least one of the two or more bins; determining a number of base pairs in the two or more bins over which the merged CNV status and the CNV status of the at least one of the two or more bins are the same; and merging the at least two bins when the merged CNV status is a same CNV status as the CNV status…
Therefore, the rejection of claims 1-2, 4-5, 7-9, 13-16, 18-19, 21-23, 26, 28-29, 32, 34-35, and 40 is withdrawn.
It is noted that independent claims 1, 15, and 28 appear free from the prior art as the prior art does not teach nor fairly suggest merging bins based on the CNV statuses of the bins and the relative size of the bins by base pair analysis of the pre-merge CNV statuses, intervening sequences, and the merged CNV status during its merging determination, so CNV status of a bin is identified based on a small proportion of base pairs within the bin itself. The closest prior art is:
Guan et al. is directed to reads binned by predetermined window conditions/thresholds for determining a gene copy number variation CNV according to the hidden Markov model/HMM (Guan in claim 1 and [0014:- 0015; 0049]).
Yoon et al. is directed to Poisson distribution of read coverage (read depth) [Yoon at p.1589], to detect CNVs by estimating the coverage or read depth in nonoverlapping intervals (discretized bins) across an individual genome, merging bins of CNV data according to thresholds [p.1588 para 4], then using a CNV-calling algorithm to detect events. Deviations from Poisson distributions contributes to detection of CNV duplications or deletions, and further, to assessments of sequencing data quality. [p.1587 para 3].
Conclusion
No claims are allowed.
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.
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/VR/
Examiner
Art Unit 1685
/MARY K ZEMAN/Primary Examiner, Art Unit 1686
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