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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/19/2025 has been entered.
Office Action Overview
Claim Status
Canceled:
1-44, 48, 50-53, 59-60, 62, 71, and 77-78
Pending:
45-47, 49, 54-58, 61, 63-70, and 72-76
Withdrawn:
none
Examined:
45-47, 49, 54-58, 61, 63-70, and 72-76
Independent:
45
Amended:
45, 63, 65, 66
New:
none
Allowable:
none
Objected to:
none
Rejections applied
Abbreviations
X
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
102, 103
JE
Judicial Exception
X
101 JE(s)
112/a
35 USC 112(a) and similarly for 112/b, etc.
101 Other
N:N
page:line
Double Patenting
MM/DD/YYYY
date format
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, U.S. Provisional Application No. 62/726,922, filed 04 September 2018, and U.S Provisional Application No. 62/810,625, filed 26 February 2019, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claims 45 and 74 both recite the limitation “using a beta-binomial distribution”. This limitation is not supported by the disclosures of U.S. Provisional Application No. 62/726,922, filed 04 September 2018, and U.S Provisional Application No. 62/810,625, filed 26 February 2019. All dependent claims ultimately depend from independent claim 45; accordingly, claims 46-47, 49, 54-58, 61, 63-70, and 72-76 are not entitled to the benefit of the prior application. Pending claims 45-47, 49, 54-58, 61, 63-70, and 72-76 are being examined with an effective filing date of 04 September 2019.
Withdrawal/Revision of Objections/Rejections
In view of the amendment and remarks received 09/19/2025:
• The 112(a) rejection of claim 45-47, 49, 54-58, 61, 63-70, and 72-76 is withdrawn.
• The 101 rejection of claims 45-47, 49, 54-58, 61, 63-70, and 72-76 is maintained with revision.
Note about canceled claims listed in remarks
Regarding claims 77 and 78, it is acknowledged that the Applicant's remarks at (p.1, paragraph 1) disclose claims 77 and 78 as canceled, however, claims 77 and 78 are not listed as canceled (nor are they included) in the amended claim document. One of the requirements for effectively amending claims in a national phase application is a complete listing of all claims ever presented, including the text of all pending and withdrawn claims. The status of every claim in such listing must be indicated after its claim number by one of the following identifiers in a parenthetical expression: (Original), (Currently Amended), (Canceled), (Withdrawn), (Previously Presented), (New), and (Not Entered). (See MPEP 1893.01(a)(4). With compact prosecution in mind, the pending claims will be examined with the expectation that Applicant will include claims 77 and 78, with proper status indicator of "Canceled" as appropriate, on all future claim sets.
Regarding claim 65, it is acknowledged that claim 65 is listed as both canceled and amended in the remarks; however, because claim 65 is listed as an amended claim in the amended claim document, then claim 65 will be examined as a pending, amended claim.
Claim Interpretation
The term “mutant allele fraction (MAF)” is recited in claim 45, 58, 59, 65, and 72. Regarding the definition of “MAF” in Specification paragraph [00040], which recites “ ’MAF’ refers to the fraction of nucleic acid molecules harboring an allelic alteration or mutation”, the term is being interpreted to be used interchangeably with the term “variant allele fraction (VAF)”.
The term “single nucleotide variant (SNV)”, recited in claim 56, is being interpreted to include “single nucleotide polymorphisms (SNPs)”. No definition was given for SNV in the Specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 61 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 61 is dependent on claim 60, which is now canceled. There is a lack of clarity as to which claim it is that claim 61 should depend from. For compact examination, it is assumed that claim 61 should depend from claim 45.
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 45-47, 49, 54-58, 61, 63-70, and 72-76 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 details the following framework to analyze Subject Matter Eligibility:
• Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? (see MPEP § 2106.03)
• 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)). Note, the MPEP at 2106.04(a)(2) & 2106.04(b) further explains that abstract ideas and laws of nature are defined as:
• mathematical concepts, (mathematical formulas or equations, mathematical
relationships and mathematical calculations);
• certain methods of organizing human activity (fundamental economic practices
or principles, managing personal behavior or relationships or interactions between
people); and/or
• mental processes (procedures for observing, evaluating, analyzing/ judging and
organizing information).
• laws of nature and natural phenomena are naturally occurring principles/ relations that
are naturally occurring or that do not have markedly different characteristics compared to
what occurs in nature.
• 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))
• Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? (see MPEP § 2106.05)
Regarding Step 1: Yes, the claims 45-47, 49, 54-58, 61, 63-70, and 72-76 are directed to a system, and therefore to a category of statutory subject matter. (See MPEP § 2106.03).
Regarding Step 2A, Prong One: The claims are found to recite mental processes and mathematical concepts and as follows:
Independent claim 45 recites mental processes of: considering the sequence reads of cell free DNA from a subject sample; aligning the sequence reads (also considered a mathematical concept); identifying a germline variant(s) set present at a mutant allele fraction (MAF) in the sample, wherein individual germline variants in the set of germline variants have corresponding MAF values; using a beta-binomial distribution and detecting less than 2 germline single nucleotide polymorphisms (SNPs) below 15% mutant allele fraction (MAF) (also considered a mathematical concept); determining a quantitative measure of the set of germline variants that are among a plurality of discrete ranges of MAF values (also considered a mathematical concept); detecting the presence or absence of allelic imbalance in the sample based on a predetermined criterion; filtering the set of germline variants based on at least the quantitative measure (also considered a mathematical concept); and (amended portion): considering the information contained in the generated report on the presence or absence of allelic imbalance and/or contamination of the sample; and: considering the quantitative measure of (d) comprises a number of the set of germline variants that are among the plurality of discrete ranges of MAF values; considering the predetermined criterion comprises the quantitative measure of (d) being greater than a predetermined germline variant threshold; selecting the one or more quantitative measures indicative of the CNV s or the diploid genes from the group consisting of a maximum CNV level across the sample, a minimum CNV level across the sample, a fraction of diploid genes, and a copy number mean; and selecting the predetermined one or more criteria from the group consisting of: a maximum CNV level across the sample of greater than a predetermined maximum CNV threshold, a minimum CNV level across the sample of less than a predetermined minimum CNV threshold, a fraction of diploid genes of less than a predetermined fraction diploid threshold, and a copy number mean in the same germline variant having an absolute value greater than a predetermined copy number mean threshold (also considered mathematical concepts).
Claim 46 recites a mental process of: detecting, from the plurality of aligned sequence reads, one or more quantitative measures indicative of copy number variations (CNVs) or diploid genes. Claim 54 recites a mental process of: detecting a presence or absence of contamination or a second genome in the sample when the absence of the allelic imbalance is detected in the sample. Claim 55 recites a mental process of: considering the set of germline variants comprises at least about 1,000 distinct germline variants. Claim 56 recites a mental process of: considering the set of germline variants comprises genetic variants selected from the group consisting of a single nucleotide variant (SNV), an insertion or deletion (indel), and a fusion. Claim 57 recites a mental process of: considering the germline variants found in COSMIC, The Cancer Genome Atlas (TCGA), or the Exome Aggregation Consortium (ExAC). Claim 58 recites a mental process of: considering the plurality of discrete ranges of MAF values comprises a first range of about 3% to about 40% and a second range of about 60% to about 97%. Claim 61 recites a mental process of: considering the predetermined germline variant threshold is about 21. Claims 63 and 64 recite a mental process of: considering, respectively, the two and the three or more quantitative measures indicative of the CNVs or the diploid genes are selected from the group consisting of a maximum CNV level across the sample, a minimum CNV level across the sample, a fraction of diploid genes, and a copy number mean. Claim 65 recites a mental process of: considering the same germline variant has an MAF of less than about 3%. Claim 66 recites a mental process of: considering the predetermined criterion comprises one or more thresholds selected from the group consisting of: a maximum CNV threshold of about 0.22, a minimum CNV threshold of about -0.14, a fraction diploid threshold of about 0.7, and a copy number mean threshold of about 10. Claim 67 recites a mental process of: detecting the presence of the contamination or the second genome in the sample with a positive predictive value (PPV) of at least about 60%. Claim 68 recites a mental process of: detecting the absence of the contamination or the second genome in the sample with a negative predictive value (NPV) of at least about 90%. Claim 69 recites a mental process of: detecting the presence of the contamination or the second genome in the sample with a sensitivity of at least about 90%. Claim 70 recites a mental process of: detecting the absence of the contamination or the second genome in the sample with a specificity of at least about 35%. Claim 72 recites a mental process of: identifying (i) no germline variants having an MAF less than about 3% or (ii) germline variants having an MAF less than about 3% and a copy number mean in the same germline variant having an absolute value greater than about 10. Claim 73 recites a mental process of: considering the quantitative measure does not comprise use of tissue sample measurements. Claim 74 recites mathematical concepts of: using a beta-binomial distribution; determining an estimate of μbin and ρ from the beta binomial distribution as listed in step (i); and calculating a two-tailed p-value from the equation listed in step (ii) (also considered to be mental processes). Claims 75 and 76 respectively recite mental processes of considering the sample comprises “at least 2xl010 polynucleotide molecules” and “at least 6xl010 polynucleotide molecules.”
To summarize Step 2A Prong One, the claims recite abstract ideas, characterized as mental processes and mathematical concepts. Considering the broadest reasonable interpretation (BRI) of the claims, there are mental processes and mathematical concepts recited in independent claim 45 (e.g., for aligning reads to a reference sequence; identifying a germline variant(s) at an MAF, detecting less than 2 germline SNPs below 15% MAF, using beta-binomial distribution; determining a quantitative measure of the set of germline variants; detecting the presence or absence of allelic imbalance; filtering the set of germline variants, etc.). Under the BRI of the claims, these steps encompass mental observations or evaluations or calculations that can be practically performed in the human mind, as the claims do not limit the size of the reference sequence, etc. The aligning of reads recited in claims 45 is considered a mental process, as merely repeating a mental process a large number of times does not change the fact that it can be done mentally. The mathematical concepts recited in claims 45 and 74, for using a beta-binomial distribution, are discussed in Specification para. [000125], which points to the incorporated by reference application PCT/US2018/052087, filed September 20, 2018; this PCT app. discloses the specific math concepts at paragraph [011]. Further, under the BRI of the claims, the mathematical concepts encompass processes that can be performed mentally, or with pen and paper. While the recited mental processes and mathematical concepts (e.g., considering and aligning of sequence reads, detecting allelic imbalance based on a criterion, using beta-binomial distributions, etc.) may take considerable time and effort, and although a general-purpose computer can perform these calculations and determinations at a rate and accuracy that can far exceed the mental performance of a skilled artisan, the nature of the activity is essentially the same, and therefore constitutes an abstract idea. In this case, regardless of the volume of sequence reads, and although the read analysis could be performed on a computer, the activity still represents an abstract idea. Therefore, the claims recite elements that constitute a judicial exception in the form of an abstract idea. (Step 2A, Prong One: Yes.)
Regarding Step 2A, Prong Two: 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. 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. The Step 2A, Prong Two analysis is performed in order to determine if the abstract idea is integrated into a practical application [see MPEP § 2106.04(d) and (d)(I)] by analyzing the additional elements of the claim, alone or in combination, for the following considerations:
• an improvement to technology [see MPEP 2106.04(d) & (d)(1); and 2106.05(a)]
• a particular therapy/prophylaxis [see MPEP 2106.04(d) & (d)(2); and 2106.05(e)]
• a particular machine [see MPEP 2106.04(d) and 2106.05(b)]
• a particular transformation [see MPEP 2106.04(d) and 2106.05(c)]
• or for applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment [see MPEP 2106.04(d) and 2106.05(e)].
The claims recite the following additional elements:
Additional elements of data gathering, inputting, and outputting steps: Claim 45 recites the additional element of obtaining data and generating a report. Claim 49 recites the additional element of communicating the report to a third party. Data gathering and outputting steps are additional elements which perform functions of inputting, collecting, and outputting the data needed to carry out the abstract idea. These steps are considered insignificant extra-solution activity, and are not sufficient to integrate an abstract idea into a practical application as they do not impose any meaningful limitation on the abstract idea or how it is performed, nor do they provide an improvement to technology [see MPEP § 2106.04(d)(I)].
Additional elements of computer components and a sequencer: Claim 45 recites a system, a controller, computer readable media, non-transitory computer-executable instructions, and a processor. Claim 47 recites the additional element of a sequencer. Claims 49, 54, and 67-70 also recite the additional elements of non-transitory computer-executable instructions and a processor. The claims require only generic computer components and a generic sequencer, which do not improve computer technology or sequencing technology, and do not integrate the recited judicial exception into a practical application (see MPEP§2106.04(d)(1) and MPEP§2106.05(f)).
The claims have been further analyzed with respect to Step 2A, Prong Two, and no additional elements have been found, alone or in combination, that would integrate the judicial exception into a practical application. (Step 2A, Prong Two: No).
Regarding Step 2B: Because the additional claim elements do not integrate the abstract ideas 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. An inventive concept is furnished by an element or combination of elements that is recited in the claim in addition to the judicial exception, and is sufficient to ensure that the claim, as a whole, amounts to significantly more than the judicial exception itself (see MPEP § 2106.05).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are well-understood, routine, and conventional. Those additional elements are as follows:
Additional elements of data gathering, inputting, and outputting steps: Additional elements of obtaining data and generating a report (claim 45), and communicating the report to a third party (claim 49), do not cause the claims to rise to the level of significantly more than the judicial exception. The courts have recognized receiving or transmitting data over a network; storing and retrieving information in memory; analyzing DNA to provide sequence information or detect allelic variants; and amplifying and sequencing nucleic acid sequences, [see MPEP§2106.05(d)(II)], as well-understood, routine, conventional activity when they are claimed in a merely generic manner (e.g., at a high level of generality) or as extra-solution activity. Thus, the data gathering steps are shown to be routine, well-understood, and conventional, and do not provide an inventive concept needed to amount to significantly more than the judicial exception.
Additional elements of computer components and a sequencer: Claims 45, 47, 49, 54, and 67-70 recite the additional elements of a system, a controller, computer readable media, non-transitory computer-executable instructions, a processor, and a sequencer. These are conventional computer components/sequencer, which are additionally shown to be conventional by the following references:
Shendure et al., (Nature biotechnology, vol. 30(11), pages 1084-1094 (2012)), presents a review on next generation sequencing (NGS), and lists sequencing instruments in table 2, p.1087.
Shu et al. shows sequencing using Illumina MiSeq or HiSeq4000 NGS platforms (Illumina) (p.9) and computational analysis of sequencing data using a customized bioinformatic pipeline (p.2; p.4, fig.2; and throughout document).
Therefore, the additional elements of computer components and a sequencer do not cause the claims to rise to the level of significantly more than the judicial exception as they do not provide an inventive concept.
Further regarding the conventionality of additional elements, the MPEP at 2106.05(b) and 2106.05(d) presents several points relevant to conventional computers and data gathering steps in regard to Step 2A Prong 2 and Step 2B, including:
• A general purpose computer that applies a judicial exception, such as an abstract idea, by use of conventional computer functions, does not qualify as a particular machine (see 2106.05(b)(I)), as in the case of claims 45, 47, 49, 54, and 67-70, which are interpreted to recite conventional computer components/sequencer.
• Integral use of a machine to achieve performance of a method may integrate the recited judicial exception into a practical application or provide significantly more, in contrast to where the machine is merely an object on which the method operates, which does not integrate the exception into a practical application or provide significantly more (see 2106.05(b)(II). In the instant claims, the recited conventional computer components/sequencer are used in are used in sequence data analysis to determine allelic imbalance and generate a report; as such, the conventional computer components and experimental system act only as a tool to perform the steps of data analysis, and do not integrate the exception into a practical application or provide significantly more.
• Use of a machine that contributes only nominally or insignificantly to the execution of the claimed method (e.g., in a data gathering step or in a field-of-use limitation) would not integrate a judicial exception or provide significantly more (see 2106.05(b)(III). The conventional computer components/sequencer of the claims do not impose meaningful limitations on the claims.
• The courts have recognized “receiving or transmitting data over a network”, “performing repetitive calculations”, and “storing and retrieving information in memory”, as well-understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)(II)). The obtaining and outputting of data in the claims is recited in a generic manner.
All the limitations of claims 45-47, 49, 54-58, 61, 63-70, and 72-76 have been analyzed with respect to Step 2B, and none of these claims provide a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception, and thus do not transform the judicial exception into a patent eligible application of the exceptions. Step2B: NO. Therefore, claims 45-47, 49, 54-58, 61, 63-70, and 72-76, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as reciting non-patent eligible subject matter.
Response to Applicant Arguments - 35 USC § 101
The Applicant's arguments filed 09/19/2025 have been fully and respectfully considered but they are not persuasive.
Regarding Step 2A Prong One:
The Applicant asserts, at p.11-13 of Applicant's remarks (bold emphasis added):
• Claim 1 requires "aligning the plurality of sequence reads to a reference sequence…". These steps necessarily involve next-generation sequencing data…which is not information that can be apprehended or manipulated in the human mind. Claim 1 further requires "identifying one or more germline variant …using a beta-binomial distribution". These recitations require the calculation of complex statistical distributions across large volumes of sequencing data. They are not processes that can be "performed in the human mind or with pen and paper,"… (p.11)
• While these limitations involve data analysis, they do not recite any mathematical equation or formula. Rather, they describe operations applied to biological sequencing data. The "mutant allele fraction (MAF)" is a biological measurement... Likewise, a "quantitative measure" is not presented as a formula or calculation in the claim, but as a contextual characteristic of the mapped data… Accordingly, Claim 1 does not fall within the mathematical concepts grouping of abstract ideas. It does not recite any mathematical relationship, formula, or calculation in the abstract, but instead claims a bioinformatics workflow that processes next-generation sequencing data to classify a genomic region. (p.13)
Referring to 101 analysis as organized in MPEP 2106, Applicant's remarks are understood to address Step 2A, Prong Two, 1st consideration explanation of improvement over the previous state of the technology field (MPEP 2106.04). The Step 2A Prong One arguments are not yet persuasive because: When considering the broadest reasonable interpretation (BRI) of the claims, at least the steps of aligning of sequence reads, identifying germline variants, and using a beta-binomial distribution are recited in a way which would not preclude analysis by mental process. Regarding mathematical concepts, the aligning of sequence reads includes use of algorithms (discussed at Specification [000118]), and mathematical concepts are explicitly recited in the beta-binomial distribution used in identifying germline variants. While the mathematical processes and mental steps of aligning reads, identifying variants, and using a beta-binomial distribution may take considerable time and effort, and although a general-purpose computer can perform these calculations and determinations at a rate and accuracy that can far exceed the mental performance of a skilled artisan, the nature of the activity is essentially the same, and therefore constitutes an abstract idea.
Regarding Step 2A Prong Two:
The Applicant asserts, at p.14-16 of Applicant's remarks (bold emphasis added):
• Independent claim 1 recites a specific sequence of computer-implemented steps that improve the functioning of a classifier by conditioning variant calls on a computed measure of statistical probability distribution, quantitative measure and filtering criterion (p.14).
...
• The specification confirms this technical improvement. It explains that conventional approaches relied on manual human review, which are inherently inaccurate in the presence of multiple possible factual scenarios…Specification, ¶¶ 126 and 130. The specification also describes that describes that "By applying a method disclosed herein to distinguish between samples with allelic imbalance and samples with contamination, the overcalling rate of the cell-free DNA assay is reduced by 20%, while maintaining a perfect sensitivity of 100%." Specification, ¶ 136. …reducing errors inherent in human manual review as described (p.15).
...
•…the classifier's logic is re-architected so that classification does not proceed unless a probabilistic distribution, quantitative measure, and filtered criterion measure reliable classifies a sample. This is a meaningful technological limitation, not a mental step. …the claims are not directed to the abstract idea of "allelic imbalance" in the abstract, but to a new and useful bioinformatics technique that leverages those measures in a specific algorithmic sequence to improve classification. Accordingly, when read as a whole, …claim 1 integrates any alleged abstract idea into a practical application by reciting a specific, computer-implemented improvement to cfDNA variant classification technology (p.16).
Referring to 101 analysis as organized in MPEP 2106, Applicant's remarks are understood to address Step 2A, Prong Two, 1st consideration explanation of improvement over the previous state of the technology field (MPEP 2106.04(d) and (d)(1)).
The argument is not yet persuasive because it is not yet clear in what way the functioning of a computer is improved.
The argument is not yet persuasive because is not yet clear which assays are being compared in determining overcalling being reduced by 20%, nor is it known if all embodiments of the claim would result in a reduction in overcalling and perfect sensitivity, nor is not clear if the sensitivity distinguishes the instant claims from the previous state of the technology.
The argument is not yet persuasive because the improvement appears to be to the abstract idea, even when considering the claim as a whole. However, a detailed explanation of a technical improvement may help to overcome a 101 rejection, as discussed at Step 2A/2nd Prong, 1st consideration of the 101 analysis in MPEP 2106.04(d) and (d)(1). The explanation might include a concise statement of the improvement, including improvement over the previous state of the technology field; identification of the technology field; explanation of how the claims deliver the improvement and that reasonably all embodiments within the claim scope also will result in the asserted improvement, and extension of the explanation to persuasively demonstrate the nexus of integration of the judicial exceptions into a practical application.
Regarding Step 2B:
The Applicant asserts, p.16-18 of Applicant's remarks (bold emphasis added):
• Even if claim 1 were found to recite an abstract idea, the claim as a whole provides an inventive concept because it does not merely invoke conventional sequencing analysis or generic computation. Instead, it requires a specific, non-routine architecture that improves classification by imposing gating rules not practiced in the field (bridging p.16-17).
• This approach is not well-understood, routine, or conventional and presents clear
advantages and improvements. As described supra, the method not only eliminates the need for human manual review, but also entirely removes ambiguity that human manual review cannot achieve (p.17).
• …independent claim 1 recites significantly more than well understood, routine, and conventional activity. The recited combination of calculating probabilistic distributions, determining associated quantitative metrics across MAF ranges,
applying filtering criterion, provides an unconventional and effective improvement in cfDNA analysis, in both the classification and characterization of sample…
• …this ordered combination improves operation of a classifier by eliminating overlapping and ambiguity, while also conferring new advantageous capabilities such as sample characterization (e.g., loss of heterozygosity) (p.18).
The argument is not yet persuasive because the additional elements of data gathering, sequencing, and computer components/sequencers are conventional. Even when considering the claim as a whole, there is not an inventive concept furnished which provides significantly more than the judicial exception. Additionally, there is not yet an improvement shown at Step 2A Prong Two.
Conclusion
No claim is allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this action.
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/M.A.V./Examiner
Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner
Art Unit 1686