DETAILED ACTION
Applicant's response, filed 11 May 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-20 are currently pending.
Claims 1-20 are rejected.
Priority
This application is a 371 of PCT/US2021/013267, filed 13 January 2021, which claims benefit of U.S provisional application no. 62/960,476, filed 13 January 2020. The instant application has the effective filing date of 13 January 2020.
Drawings
The objection to the drawings is withdrawn, in view of proper submission of corrected, replacement drawings.
The drawings, submitted 11 May 2026, are accepted by the examiner.
Claim Rejections - 35 USC § 101
The rejection to claims 1-20 is maintained.
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 1-20 are rejected under U.S.C 101 because the claimed invention is directed to an abstract idea without significantly more, as detailed in the analysis below.
Eligibility Step 1: Subject matter eligibility evaluation in accordance with MPEP § 2106:
Claims 1-7 are directed to a statutory category (method).
Claims 8-14 are directed to a statutory category (system).
Claims 15-20 are directed to a statutory category (machine).
Therefore, in accordance with MPEP § 2106.03, claims 1-20 have patent eligible subject matter.
[Eligibility Step 1: YES]
Eligibility Step 2A: This step determines whether a claim is directed to a judicial exception in accordance with MPEP § 2106.
Eligibility Step 2A -- Prong One: Limitations are analyzed to determine if the claims recite any concepts that could equate to a judicial exception (i.e. abstract idea, law of nature, or natural phenomenon).
Recitations of Judicial Exceptions:
Claim 1:
determining genetic information; (mental process)
determining, based on the genetic information, overlapping mate pairs, wherein the overlapping mate pairs are associated with a sequence and a quality score; (mental process)
determining, based on the overlapping mate pairs, at least one of a plurality of nucleotide combinations, wherein the at least one of the plurality of nucleotide combinations is associated with the sequence and the quality score; (mental process)
Amended limitation: determining, based on the at least one of the plurality of nucleotide combinations, an error rate associated with one or more tiles of a flowcell of a sequencing device wherein an outlier tile of the one or more outlier tiles is a tile associated with an error rate that satisfies a threshold (mental process, mathematical concept)
Amended limitation: suppressing one or more errors by removing data associated with the one or more outlier tiles (mental process)
Claims 2 and 9: further comprising determining a source of an error. (mental process)
Claims 3 and 16: wherein determining the source of the error comprises identifying a device associated with an error profile. (mental process)
Claim 10: wherein, to determine the source of error, the computing device is further configured to determine a device associated with an error profile. (mental process)
Claims 4 and 11: The method of claim 2, wherein determining the source of an error comprises determining at least one nucleotide combination associated with an error profile. (mental process)
Claims 8 and 15:
determine genetic information; (mental process)
determine, based on the genetic information, overlapping mate pairs, wherein the overlapping mate pairs are associated with a sequence and a quality score; (mental process)
determine, based on the overlapping mate pairs, at least one of a plurality of nucleotide combinations; (mental process)
determining, based on the at least one of the plurality of nucleotide combinations, an error rate. (mental process, mathematical concept)
Claim 18: to determine the source of the error further cause the apparatus to identify a nucleotide combination associated with an error profile. (mental process)
As genetic information could be determined by looking at a dataset, identifying and determining secondary data based on the observables equate to analysis techniques that require no more than mere observations of data that can be completed with only the human mind and pen/paper. As such, limitations that recite these processes fall under the mental process grouping of abstract ideas.
Furthermore, determining an error rate can equate to performing a mathematical calculation on a set of information to derive secondary data. Equations that recite such techniques fall under the mathematical concepts grouping of abstract ideas.
As such claims 1-4, 8-11, and 15-18 appear to recite judicial exceptions (abstract ideas).
[Eligibility Step 2A – Prong One: YES]
Eligibility Step 2A – Prong Two: A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. If the claim contains no additional claim elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)). This step analyzes limitations that are considered additional elements to determine if they integrate the judicial exceptions into practical application.
Eligibility Step 2B: Claim elements are probed for inventive concept equating to significantly more than the judicial exception (MPEP 2106.04(II)).
Additional elements within the claimed invention include:
Claim 8: A system comprising:
a sequencing device configured to:
a computing device configured to:
Claim 15: An apparatus comprising:
one or more processors; and
memory storing processor executable instructions that, when executed by the one or more processors, cause the apparatus to:
Claim 18: The apparatus of claim 15, wherein the processor executable instructions that, when executed by the one or more processors, cause the apparatus
These limitations represent generic computer or sequencing components that generate, transmit, and/or receive data necessary to complete the steps of the claimed invention. As such, the components when viewed separately or in the context of the whole, merely act as tools to execute the judicial exceptions, but do not integrate them into practical application, per Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016).
[Eligibility Step 2A – Prong Two: YES]
The claimed invention is drawn to a method of processing and analyzing sequencing data. This technique, as claimed, was found well-understood, routine, and conventional by the courts, in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014), which recognized nucleic acid sequencing; and Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, which recognized the analysis of DNA to provide sequence information.
[Eligibility Step 2B: NO]
Additional Elements that may be categorized differently include:
Claim 5, 12, 19: The method of claim 1, wherein the genetic information comprises at least one DNA sequence.
Claim 6, 13, 20: wherein the sequence comprises at least one base pair.
Claim 7, 14: The method of claim 1, wherein the quality score comprises a read value.
These limitations specify the format and length of data gathered or analysis technique to be performed. Selecting a particular data source or type of data to be manipulated is classified as an insignificant extra-solution activity and does not integrate the judicial exceptions of the claimed invention, when evaluated separately or as a whole, into practical application per MPEP 2106.05(g) and Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1354-55, 119 USPQ2d 1739, 1742 (Fed. Cir. 2016).
[Eligibility Step 2A – Prong Two: YES]
Considering the types of data (DNA sequence) and techniques (read-associated value) are also well-understood, routine, and conventional within the art, per Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, the elements are further found to lack inventive concept.
[Eligibility Step 2B: NO]
Additional elements that may be categorized differently include:
Claim 8:
transmit genetic information
receive genetic information;
These limitations complete necessary data gathering activities for the claimed invention and do not place necessary limits on or integrate the abstract ideas into practical application per MPEP 2106.05(f) and Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016).
[Eligibility Step 2A – Prong Two: YES]
Such data gathering activities that use a computer to transmit and receive data are further classified as insignificant extra-solution activities and considered well-understood, routine, and conventional per buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014).
[Eligibility Step 2B: NO]
As such claims 1-20 are directed to judicial exceptions and rejected under 35 U.S.C 101, in accordance with Alice/Mayo, MPEP 2143 evaluation.
Response to Arguments
Applicant argues the claims do not recite a mental process because determining an error rate associated with one or more flow cell tiles reads on analyzing millions of sequencing reads, associated with quality scores of which sequencing flow cells can contain hundreds of tiles each (page 3, para. 2); and that such technique cannot reasonably be performed in the human mind (pages 2-3).
Examiner responds the claims merely require determining an error rate with one or more tiles and therefore can reasonably be performed in the human mind because it is not limited to an embodiment that analyzes millions of sequencing reads per Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016).
Furthermore, the limitation is also cited to read on mathematical calculations which does not limit the error rate calculations to be performed in the human mind and/or with pen and paper.
As such, the claims are still directed to judicial exceptions in the form of abstract ideas (mental processes and mathematical concepts).
Applicant argues the cited judicial exceptions are integrated into practical application through the amended limitations of “determining one or more outlier tiles from the one or more tiles, wherein an outlier tile of the one or more outlier tiles is a tile associated with an error rate that satisfies a threshold" and "suppressing one or more errors by removing data associated with the one or more outlier tiles” (page 3, para. 3).
Examiner responds the amended limitations appear to merely link the use of the judicial exception to a particular technological environment of erroneous sequencing data but are still directed to mental processes and mathematical concepts commensurate in scope with collecting, analyzing, and comparing information per Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016); Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011); and calculating the difference between local and average data values, In re Abele, 684 F.2d 902, 903, 214 USPQ 682, 683-84 (CCPA 1982).
Applicant argues the invention provides an improvement to technology through the suppression of sequencing errors at the hardware-component level of a sequencing device (page 5, para. 2) via the amended limitations of “determining an error rate”… “associated with one or more tiles of a flow cell of a sequencing device”(page 6, para. 3); identifying specific tiles that are producing an unacceptable level of errors (page 6, para. 4); and removing the data they produced to yield measurable results (page 6, para. 5); in a manner where conventional error analysis cannot provide the granularity needed to suppress hardware-introduced errors (page 6, para. 2).
Examiner responds the highlighted limitations have been identified as abstract ideas; and MPEP 2106.05 (a) recites that it is important to note, the judicial exception alone cannot provide the improvement. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II.
Furthermore, conventional error analysis can suppress hardware-introduced error, as evidenced by Zhou et al. (Molecular Ecology; Vol. 23; 2014), which reviews pathologies of prevention, diagnosis, and treatment of high-throughput sequencing data; and teaches: tools such as BIGPRE (Zhangetal.2011), HTQC (Yangetal.2013b) and SOLEXAQA (Coxetal.2010), can perform tile-based quality assessment, which helps to identify problems that affect specific regions, known as tiles, on a flowcell (page 3, column 1); and remove low-complexity reads likely representing sequencing artefacts via other tools (page 7, column 2).
As such, the limitations do not represent an improvement to technology in line with the requirements set forth by MPEP 2106.05 (a).
Claim Rejections - 35 USC § 102
Applicant’s argument, that the cited art does not anticipate the amended limitations (pages 9-12), has been fully considered and is persuasive.
The rejection to claims 1-20 is withdrawn, in view of claim amendments.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The following rejections are newly recited and necessitated by amendments.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Chen-Harris et al. (IDS; filed on 11/11/2022; NPL; cite no. 1; 2013, previously cited) in view of Fantini et al. (Plos One; Vol. 12: 5; 2017; newly cited).
Claims 1, 8, and 15 are directed to methods, systems, and machines that obtain genetic information. The genetic information includes overlapping mate pairs, associated with a sequence, quality score, and at least one combination of nucleotides. The methods use this information to generate an error rate, associated with at least one tile of a flowcell within a sequencing device; determine at least one tile as an outlier according to its error rate satisfying a threshold; and suppressing at least one error by removing data associated with the outlier tile.
Claim 8 is further directed to a system with a sequencing device that obtains and transmits genetic information to a computing device, that receives it.
Claim 15 is further directed to a machine capable of executing the method/system described.
Chen-Harris et al. describes a method of modeling sequencing data errors via overlapping read pairs (ORPs).
Chen-Harris et al. teaches carrying out Illumina paired-end sequencing to generate overlapping read pairs (page 2, column 2); and using mismatched read pairs, defined as incongruent nucleotides (page 11, column 1), to calculate mismatch rates (page 11, column 1) and examine them, in association with quality scores from the sequencers (page 8, column 1).
Chen-Harris et al. further teaches estimating sequencing errors from mismatch rates in the ORP (page 8, column 1) and calculating error rates as a ratio between the total number of candidate base calls differing from the consensus nucleotides summed across the genome and the total number of base calls made across the genome (page 10, column 2).
Regarding claim 8, Chen-Harris et al. teaches that the sequencing of three natural samples and the two control plasmids, was carried out using an Illumina Genome Analyzer II (page 10, column 1), and table 1 summarizes the output generated in the sequencing run (page 10, column 1). Therefore, a computing device received genetic information obtained and transmitted by a sequencing device.
Regarding claim 15, Chen-Harris et al. teaches results that demonstrate a practical sequencing and computational analytic approach to studying viral evolution with an unprecedented level of genetic resolution (page 2, column 2). Therefore, the results of the method and system described are executable by a computer (machine).
Chen-Harris et al. further teaches identifying a high variation in error rates between sequencers (page 2, column 1); and an empirical guideline for the selection of Q-score threshold, to distinguish PCR error rates from sequencing error rates (page 4, column 1-2).
Therefore, Chen-Harris et al. teaches determining sequencing device associated error rates.
Claims 2, 9, and 16 are directed to finding a source of error.
Chen-Harris et al. teaches a method that demonstrates how PCR amplification can become the dominant source of error over the sequencer’s error, even when using a high fidelity polymerase (page 2, column 1).
Claims 3, 10, and 17 are directed to finding a device associated with information about an error.
Chen-Harris et al. teaches that the number of erroneous matching ORPs was relatively constant with respect to Q-scores, which suggests that they were dominated by PCR errors and not sequencing errors (page 4, column 2). Chen-Harris et al. further teaches comparing error rates between two different sequencers (page 10, column 1) and identifying a high variation in error rates between them (page 2, column 1). Chen-Harris et al. further teaches the difference can be attributed to the Q-score calibration of the two instruments (page 3, column 2), underscoring the utility of using ORP to recover an empirical sequencing error rate and minimize technical artifacts introduced by the sequencer (page 4, column 1).
Claims 4, 11, and 18 are directed to finding at least one combination of nucleotides that are associated with an error.
Regarding claims 4, 11, and 18, Chen-Harris et al. teaches that at a given locus, any polymorphisms in the ORPs that deviated from the known consensus nucleotide are taken as errors introduced either through PCR amplification or sequencing (page 5, column 1).
Claims 5, 12, and 19 are directed to the genetic information obtained including at least one DNA sequence.
Regarding claims 5, 12, and 19, Chen-Harris et. al teaches that library preparation yielded a target DNA fragment that was 142bp long (page 2, column 2).
Claims 7 and 14 are directed to the quality scores including a read value.
Regarding claims 7 and 14, Chen-Harris et al. teaches that the Q-score (quality score) of 2 is a ‘read segment control indictor’ in the FASTQ format that tags specific final portion of the read as unreliable and unfit for downstream analyses (page 4, figure 3) and that Q=2 reads comprised a disproportionally large fraction of mismatched read pairs is consistent with the fact that mismatched ORPs result from error during sequencing (page 4, figure 3).
Claims 6, 13, and 20 are directed to the sequence having at least one base pair.
Chen-Harris et al. teaches that the paired end reads had an average overlap of 88bp (page 2, column 2) and at every base, all overlapping read pairs were separated into two categories: matching and non-matching base pairs (page 11, column 1).
Chen-Harris et al. does not explicitly teach determining an error rate associated with a tile of a flow cell of a sequencing device; determining at least one tile as an outlier according to its error rate satisfying a threshold; nor suppressing at least one error by removing data associated with the outlier tile (claims 1, 8, and 15).
Fantini et al. describes an assessment of antibody library diversity through next generation sequencing and technical error compensation.
Fantini et al. teaches comparing Phi-X reads to the reference sequence, to get a real measure of error rates per tile and per cycle (page 6, column 1); and that sequencing errors need to be identified and removed (page 15, column 1).
Fantini et al. shows a scatter plot of the correlation of Q-score and log2(% Mismatches) in Phi-x control spike-in library, where each point represents the mean value from a single flow cell tile at a given sequencing read number; and the Q score in the first 40 reads fails to be predictive of mismatch rate (page 7; fig. 2).
Fantini et al. teaches since it is crucial to have good quality sequencing data, the reads underwent a very strict quality trimming process (page 9, column 1), where only the reads which had a median Phred score of at least 32 (base call accuracy > 99.937%) survived the filter; and a higher trimming survival count was obtained for the hVH nanobody library, due to both the shorter length and the overlap of the two reads (page 10, column 1).
Fantini et al. teaches the DEAL software tool minimizes confusion between real base sequence variants from the background technical noise of technical misreading by taking into account both Phred derived error rate (Q-score) and Phi-X derived error rate (page 8, column 1); and ignoring error prone bases (page 8, column 1); by using the default parameters: i) unreliable flag set when either error threshold for the Phi-X in the position was over 1% or quality in position is less than Phred 32 or ii) seed position was located in the CDR3 of both VH and VL fragment (page 10, column 1).
Fantini et al. further teaches flagging uncertain base read positions as unreliable, by checking both for a low Phred quality score associated to the base considered and for a high error rate in the sequencing cycles, that is retrieved from the error rate of control phage DNA (Phi-X); in which the two flagging descriptors (Phred quality and cycle quality) relate to two different checkpoints; and if one or both the quality checks are not passed, the base is considered unreliable (page 9, column 1).
Therefore Chen-Harris et al. and Fantini et al. teach methods of identifying sequencing errors by taking into account overlapping read pairs, mismatch rates, and Phred Q-scores. Fantini et al. further teaches determining tile specific sequencing errors, outliers, and removing the erroneous data. Therefore, it would be obvious to one of ordinary skill in the art combine the method of Chen-Harris et al. with the method of Fantini et al. in order to result in an improved technical error identification and removal system with a reasonable expectation of success.
Response to Arguments
Applicant’s arguments, that the cited art does not anticipate the amended limitations (page 12, para. 4), has been fully considered and are now moot, based on further consideration of the prior art.
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.
No claims are currently allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Milana Thompson whose telephone number is (571)272-8740. The examiner can normally be reached Monday - Friday, 9:00-6:00 ET.
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/M.K.T./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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