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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/22/2026 has been entered.
Claim Status
Claims 1-4 and 6-20 are pending and under examination.
Claims 1-4 and 6-20 are rejected.
Claim 5 is canceled.
Claim 1 is independent.
Claims 19 and 20 are new.
Office Action Overview
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
X
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed in the 06/10/2025 filing receipt, this application is a continuation application of U.S. Patent Application No. 16/678,060, filed 11/08/2019, which is a continuation of application PCT/US2018/033038, filed 05/16/2018, which claims the benefit of priority to Provisional Application No. 62/507,127, filed 05/16/2017. The pending claims are each afforded the benefit of priority to Provisional Application No. 62/507,127, filed 05/16/2017.
Withdrawal/Revision of Objections and/or Rejections
In view of the amendment and remarks received 01/22/2026:
• The claim objections are withdrawn.
• The 112(a) rejections are withdrawn.
• The 112(b) rejections are withdrawn. New 112(b) rejections are applied below.
• The 101 rejection is maintained with revision.
• The Non-Statutory Double Patenting rejecting is maintained and revised to include additional reference applications.
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 4, and 8-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate.
In claim 3, the connection is unclear between the singular "the allele frequency" and the plural variants in "the set of genetic variants," in the recitation "wherein the measure of variability comprises standard deviation or variance of the allele frequency of the set of genetic variants." It is not clear if the allele frequency refers to one variant of the set, or to all variants, in the set of genetic variants. Additionally, "the allele frequency of the set of genetic variants" lacks antecedent basis. Possibly amending claim 3 to recite "... of the allele frequency of each of the plurality of genetic variants in the set of genetic variants" might help overcome both the clarity and lack of antecedent basis issues of the rejection.
In claim 8 steps (i) and (ii), the connection between the recited numbers of "genes selected from the list consisting of" and the actual number of genes listed is not clear. Specifically, step (i) recites "at least a portion of each of at least 5,..., at least 40, ...or 97 of the genes selected from a list consisting of AKT1, ...and ERBB2 (exons 19 &20)", however, the list only lists 37 gene names, such that it is not clear in what way the selecting of at least 40, at least 45, ... up to at least 97 genes would occur. Similarly, in step (ii), the list recites only 77 names of genes, but recites the selecting at least 80,..., or 115 of the genes selected from a list consisting of" (and recites names of only 77 genes). Possibly amending to delete the numbers which exceed the actual number of named genes in both steps (i) and (ii) might help to overcome the rejection.
In a related rejection, claim 8 step (iii) lacks clarity in reciting "at least 20" when only 20 genes are named on the list in step (iii). It is not clear in what way more than 20 genes could be selected from a list with only 20 gene names. Possibly amending step (iii) to recite "or 20" instead of "or at least 20," may help overcome the rejection of step (iii).
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 1-4 and 6-20 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)
Step 1:
Claims 1-4 and 6-20 are directed to a 101 process, here a method, which falls under a category of statutory subject matter. (See MPEP § 2106.03).
Step 2A, Prong One:
The claims recite judicial exceptions in the form of abstract ideas as follows:
Claim 1 recites mental processes and mathematical concepts of:
• allocating a read budget
• determining allele frequency
• determining a measure of variability of the allele frequency
• determining an allele frequency threshold for classification of the variant of interest
• classifying the selected genomic region as being unaffected by copy number variation
• classifying the variant of interest as germline origin or as somatic origin based respectively on the allele frequency of the variant being greater or being less than the allele frequency threshold.
Claim 2 further limits the selected genomic region and abstract ideas of claim 1. Claim 3 further limits the measure of variability and abstract ideas of claim 1. Claim 4 further limits the allele frequency threshold and abstract ideas of any of claim 1-3. Claim 6 further limits the measure of variability, allele frequency variability threshold, and abstract ideas of claim 1 by: considering the measure of variability is standard deviation and the variability threshold is a standard deviation threshold. Claim 7 further limits the classification of the selected genomic region and abstract ideas of claim 6. Claim 8 further limits the selected genomic region and abstract ideas of any preceding claim. Claim 11 further limits any preceding claim and recites abstract ideas of detecting and quantifying genetic variants. Claim 14 further limits the allele frequency threshold and abstract ideas of claim 1 by reciting the abstract idea of comparing allele frequency distributions. Claim 15 further limits the classification of the variant of interest and abstract ideas of claim 1 by reciting the abstract idea of designating the variant of interest as ambiguous when the measure of variability exceeds the allele frequency variability threshold. Claim 16 further limits the abstract ideas of claim 1 by: generating a report. Claim 17 further limits the determining the allele frequency threshold and abstract ideas of claim 1 by: applying statistical and/or probabilistic models to allele-frequency distributions of allele frequencies of the plurality of genetic variants of the plurality of genomic regions to generate a classification boundary for separating germline and somatic allele-frequency values. Claim 18 further limits the empirically derived allele frequency distributions and allele frequency threshold and abstract ideas of claim 1. Claim 19 further limits the abstract idea of allocating the read budget of claim 1. Claim 20 further limits the abstract idea of allocating of claim 20.
Step 2A Prong One Summary:
• The claims recite abstract ideas, characterized as mental processes and mathematical concepts. Considering the broadest reasonable interpretation (BRI) of the claims, the mental processes recited in independent claim 1 (e.g., allocating a read budget, determining allele frequency, determining a measure of variability, determining allele frequency threshold, classifying the selected genomic region as being unaffected by copy number variation, classifying the variant of interest as having germline or somatic origin, etc.) can be performed mentally because no limitations are recited which would prevent performance in the human mind or with pen and paper.
• "Allocating a/the read budget" of amended claim 1 and new claims 19 and 20 is characterized as a mental process of assigning (i.e., dividing) the number of to-be-obtained reads in a sample in order to provide greatest sensitivity and specificity for the regions (e.g., hotspot and genomic) in the sample, as discussed in Specification paragraphs [232-234]. Note, the actual sequencing of claim 11 is characterized as an additional process of data gathering at Step 2A Prong Two below, while the aspect of sequencing based on a "read budget" is shown as conventional below at Step 2B by the Illumina reference.
• Additionally, the limitations for determining allele frequency, determining a measure of variability (i.e., standard deviations, and standard deviation thresholds), determining allele frequency threshold, classifying the selected genomic region as being unaffected by copy number variation, classifying the variant of interest as having germline or somatic origin, etc. recite mathematical concepts such as discussed in Specification [76, 220, 260, 293]. Such analysis performed mentally, or with paper and pencil, may take considerable time and effort, and although a general-purpose computer can perform these calculations 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.
Therefore, the claims recite elements that constitute a judicial exception in the form of an abstract idea. (Step 2A, Prong One: Yes.)
Step 2A, Prong Two:
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). Here at Step 2A, Prong Two, any remaining steps and/or elements not identified as JEs are therefore in addition to the identified JE(s), and are considered additional elements. Because the claims have been interpreted as being directed to judicial exceptions (abstract ideas in this instance) then Step 2A, Prong Two provides that the claims be examined further to determine whether the judicial exception is integrated into a practical application [see 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.
MPEP § 2106.04(d)(I) lists the following five example considerations for evaluating whether a judicial exception is integrated into a practical application:
(1) An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a).
(2) Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2).
(3) Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
(4) Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c).
(5) 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, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
The claims recite additional elements as follows:
Additional elements of data gathering and outputting data (including samples and sequencing): Claim 1 recites additional elements of providing sequence reads based on the read budget. Claim 9 recites an additional element of isolating cfDNA molecules from a body fluid. Claim 10 recites an additional element of circulating tumor DNA. Claim 11-13 recite additional elements for: sequencing cfDNA; preparing a nucleic acid library, and the cfDNA molecule is barcoded. Data gathering 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, and as such do not integrate the recited judicial exception into a practical application. [see MPEP § 2106.04(d)(I)].
Additional elements of a computer and a computer system: The preamble of claim 1 recites an additional element of a computer. Claim 16 recites “a computer system”. The claims require only a generic computer, which does not improve computer technology, and does not integrate the recited judicial exception into a practical application (see MPEP § 2106.04(d)(1) and MPEP § 2106.05(f)).
Further concerning the additional elements of a computer/ computer system of claims 1 and 16, the MPEP 2106.05(f) discusses limitations identified by the courts that do not integrate a judicial exception into a practical application. These limitations include: merely including instructions to implement an abstract idea on a computer or merely using a computer as a tool to perform an abstract idea, (as in a “computer-implemented method” of claim 1). See MPEP 2106.05(f).
Step 2A Prong Two summary: 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).
Step 2B:
Because the additional claim elements do not integrate the judicial exceptions (i.e., 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: The additional elements of providing sequence reads based on the read budget in claim 1; isolating cfDNA from a body fluid, and ctDNA of claims 9 and 10; and sequencing cfDNA, preparing a nucleic acid library, and barcoded cfDNA molecules, of claims 11-13, 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; determining the level of a biomarker in blood by any means; using polymerase chain reaction to amplify and detect DNA; detecting DNA or enzymes in a sample; 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. Additionally, the following reference shows isolating cfDNA from a body fluid, ctDNA, sequencing, barcoded samples, and preparation of libraries to be well understood, routine, and conventional:
Kamps, (International journal of molecular sciences, vol. 18(2):308, 57 pages (Jan.2017); cited on the Form PTO-892 mailed 07/01/2025) present a review on next generation sequencing (NGS) in oncology, and shows analysis of cell-free tumor DNA from patient plasma (p.30-31); sequencing (p.2-4, and entire document), library prep (p.3-5), and barcoding (p.3).
Illumina, ((2014) Considerations for Designing a Successful TruSeq® Targeted RNA Expression Experiment [Online]; 2 pages; accessed: 02/27/2026. Available at www.illumina.com/documents/products/technotes/technote_truseq_targ_rna_design.pdf ), shows sequencing with a read budget and discusses read budget with regard to read depth (p.1-2).
Therefore the additional elements of data gathering are shown to be routine, well-understood, and conventional in the art, and do not provide an inventive concept needed to amount to significantly more than the judicial exception.
Additional elements of a computer and computer system: The additional elements of a computer and computer system of claims 1 and 16 do not cause the claims to rise to the level of significantly more than the judicial exception; these are conventional computers, generically claimed and discussed at Specification [264-274]. The computer and computer system 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 claim 1 and 16, which are interpreted to recite conventional computers.
• 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 computer and computer system act only as a tool to perform the steps of data analysis or generating data, 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 computers in claim 1 and 16 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 providing of data in claim 1 is recited in a generic manner.
All limitations of claims 1-4 and 6-20 have been analyzed with respect to Step 2B, and none provides 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, the claims, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter.
Response to Applicant Arguments - 35 USC § 101
Applicant's arguments filed 01/22/2026 have been fully considered but they are not yet persuasive.
Regarding Step 2A Prong One arguments:
Applicant asserts, p. 9-14 of 20, that the claims do not recite a judicial exception, as follows:
Regarding abstract ideas of mental processes at Step 2A Prong One:
Applicant asserts the claims do not recite a mental process (p.9-12) as follows:
• "The amended claim does not recite a mental process because it requires machine-scale
sequencing, data allocation, and statistical analysis that no human could practically perform mentally or with pen and paper. The claim requires "allocating, using one or more processors, a read budget that specifies a target sequencing depth"...and that read budgets may range "between 100,000,000 reads and 100,000,000,000 reads. ...Human cognition is not equipped to allocate, track, or manage billions of sequencing reads across genomic regions... " (p.10, ¶ 3)
• "...providing, based on the read budget, a set of sequence reads of cfDNA molecules ... mapped to the selected genomic region of a reference genome.... These are algorithmic bioinformatics operations that cannot be performed mentally." (bridging p.10-11)
• "...steps require automated statistical computation over thousands of variants and millions of reads and cannot be carried out in the human mind." (p.11, ¶ 2)
• "Empirically deriving probability distributions from tens of thousands of data points is not something a human can practically do mentally." (p.11, ¶ 3)
• "The claim then requires classifying genomic regions and variants using explicit greater than and less-than threshold logic...These classification steps depend on prior computational analysis...cannot be performed by mental judgment alone." (p.11, ¶ 4)
•...the amended claim requires processor-executed operations on massive sequencing datasets, empirical statistical modeling, and threshold-based classification logic that cannot practically be performed in the human mind." (p.12, ¶ 2)
The arguments regarding mental processes at Step 2A Prong One are not persuasive because the claims and the abstract idea within are recited at a level of complexity such that there are embodiments which include performance of the steps mentally or with pen and paper. While the claims do not specifically recite any limitation similar to millions of reads or billions of reads, even if the claims recited as such, the claims would most likely still recite a mental process. This is because considering that the performance of the sequence data analysis mentally, or with paper and pencil, may take considerable time and effort, and although a general-purpose computer can perform the analysis 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. A claim that requires a computer may still recite a mental process [see MPEP 2106.04(a)(2)(III)(C)]. Additionally, limitations for sequencing and data gathering are additional elements, and not considered JEs.
Regarding abstract ideas of mathematical concepts at Step 2A Prong One:
Applicant asserts the claims do not recite a mathematical concept (p.12-14) as follows:
• "...amended claim 1 does not recite any mathematical relationship, formula, or equation in the abstract. The claim does not include any equation, numerical formula, or mathematical expression... The claim does not recite any equation for variability,
any formula for standard deviation, or any mathematical relationship in the abstract. It merely requires determining a characteristic of the biological data" (p.13, ¶ 2).
• "(the claim)...describes the use of empirically derived biological data distributions to determine a threshold used in classification...The claim itself, however, does not recite the mathematical form of that distribution or any equation describing it" (p.13, ¶ 3).
• ",,,the claim operates on biological sequencing data and empirically derived thresholds but does not "set forth or describe any mathematical relationships, calculations, formulas, or equations," and therefore does not recite a mathematical concept" (p.14, ¶ 2).
The arguments regarding mathematical concepts at Step 2A Prong One are not persuasive because genetic sequence analysis inherently involves the use of mathematical concepts to represent and statistically process genetic sequence data. In the case of the instant claims, the limitations for determining allele frequency, determining a measure of variability (i.e., standard deviations, and standard deviation thresholds), determining allele frequency threshold, classifying the selected genomic region as being unaffected by copy number variation, classifying the variant of interest as having germline or somatic origin, etc. inherently recite mathematical concepts such as discussed in Specification [76, 220, 260, 293]. While there is no step specifically reciting “calculating’, these steps of "determining" (of allele frequency, a measure of variability, an allele frequency threshold, etc.) are considered mathematical calculations in that the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation [see MPEP 2106.04(a)(2)(I)(C)].
Regarding Step 2A Prong Two arguments:
Applicant asserts, p.14-18 of 20, that the claims integrate the alleged judicial exception into a practical application as follows:
• "...independent claim 1 integrates any alleged abstract idea into a practical application
by improving the technological process of cfDNA sequencing analysis and variant-origin classification." (p.15, ¶ 3)
• " As amended, claim 1 requires "allocating, using one or more processors, a read budget that specifies a target sequencing depth for a selected genomic region sufficient to generate empirical allele-frequency distributions and variability measures for classification." (p.15, ¶ 4)
• "The specification explains why this sequence of operations produces a technical improvement.. "no computer implemented process can differentiate germline variants from somatic mutations automatically," and that conventional systems instead "rely on the expertise of an individual human expert or a consortium of experts." ...copy number variation causes distortion of allele-frequency measurements, and that "a STDEV threshold can be used to separate high CNV from low CNV, increasing the
predictive power of the method." (p.16, ¶ 3)
• "... Independent claim 1...restructures the logic of cfDNA variant classification so that classification accuracy is improved through controlled sequencing depth and empirically derived stability gating, rather than indiscriminate application of statistical thresholds." (p.17, ¶ 3)
• "Here, the claim is not directed to allele frequency, standard deviation, or statistics in the abstract, but to a new and useful sequencing-data-driven technique that improves the accuracy of germline versus somatic variant calling." (p.17, ¶ 4)
The arguments regarding a practical application shown by an improvement to technology at Step 2A Prong Two are not yet persuasive because the claims are directed to a JE (mental processes and mathematical concepts) as Applicant has not yet provided sufficient detail of the improvement of the claimed method for sequence data analysis resulting in classification of the variant of interest as having germline or somatic origin based on the allele frequency respectively being greater or less than the allele frequency threshold. The claimed method shows an improvement to the abstract idea of data analysis, but it is important to note, that while the judicial exception alone cannot provide the improvement, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. See MPEP 2106.05(a), ¶6.
With the claimed invention, an explanation of improvement is a reasonable path to take in asserting integration into a practical application, however, more detail is needed to successfully assert and explain the improvement provided. As Applicant asserts an improvement in accuracy, it might be helpful to provide data regarding the quality of the improvement, e.g., statistical analysis showing accuracy, ROC curve, etc., as accuracy is asserted as a factor in improvement. Further, as Applicant asserts an improvement over conventional methods which use human experts to classify germline vs. somatic variants, it might be helpful to provide data of improvement over conventional methods, including data over methods which rely on human experts or consortiums. This data need not be extensive, but the improvement should be clear. It is further noted the data used in showing the improvement need not be disclosed in the specification, nor need it have been available at the instant critical date, but it should convey the quality of data such that the improvement is clear so as to integrate the judicial exceptions into a practical application at Step 2A Prong Two. Importantly, the explanation of improvement should persuasively demonstrate the nexus of integration of the judicial exceptions with a practical application.
Regarding Step 2B arguments:
Applicant asserts, p.18-19 of 20, that the claim recites elements that amount to significantly more as follows:
• "independent claim 1 does not merely invoke generic computation or conventional
sequencing analysis. Instead, the claim recites a specific, non-routine architecture that governs whether and when variant classification may occur... and...permits classification of the variant of interest using explicit greater-than and less-than comparisons to the allele frequency threshold." (p.18, ¶ 4)
• "This ordered combination goes beyond conventional thresholding or post hoc analysis... no computer implemented process can differentiate germline variants from somatic mutations automatically..." (p.18, ¶ 5)
• "...the disclosure introduces a control strategy in which "a STDEV threshold can be used to separate high CNV from low CNV, increasing the predictive power of the method..." (p.19, ¶ 1)
• "The claim's inventive concept lies in this gating logic, which changes how classification is executed." (p.19, ¶ 2)
• "The combination of allocating a read budget, determining variability, inferring copy number stability, and conditionally permitting or suppressing classification provides an inventive concept that improves cfDNA variant analysis and therefore renders the claim patent eligible." (p.19, ¶ 5)
The arguments (regarding significantly more at Step 2B) are not persuasive because the sequence data analysis steps represent abstract ideas, while the identified additional elements of data gathering, sequencing (including sequencing with respect to using read budgets), and a conventional computer are conventional and do not provide significantly more needed to result in an inventive concept, even when considering each claim as a whole.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Instant claims 1-4 and 6-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over one or more claims in reference applications: 16/678,060, 19/170,971, 19/170,982, 19/170,988, and 19/440,954 in view of Illumina, ((2014) Considerations for Designing a Successful TruSeq® Targeted RNA Expression Experiment [Online]; 2 pages; accessed: 02/27/2026. Available at: www.illumina.com/documents/products/technotes/technote_truseq_targ_rna_design.pdf ).
Although the reference claims are not identical to the instant claims, in a BRI they also are not patentably distinct from the instant claims: either (i) because the instant claims recite obviously equivalent or broader limitations in comparison to the reference claims or (ii) because the instant claims recite limitations which are obvious over the cited art. It is not clear that the instant claims recite limitations which are narrower than limitations in the reference claims.
Each reference application recites method and/or system claims for classifying or identifying a genetic variant or locus as somatic or germline in cell-free DNA. Although the instant application recites limitations using a read budget, this narrowing versus the reference claims is now interpreted as obvious, such that the instant invention would have been prima facie obvious in view of the cited art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/M.A.V./Examiner, Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686