DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-15, 17-29, and 31 are pending and examined herein.
Claims 16 and 30 are canceled.
Priority
As detailed on the 04 February 2025 filing receipt, the application claims priority as early as 15 July 2022. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 25 February 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
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 1-15, 17-29, and 31 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of "determining a tumor DNA fraction."
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to methods (claims 1-15, 17-20, 23-29, and 31), a computer system (claim 21), and a non-transitory computer-readable medium (claim 22), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts are interpreted as being recited in the claims. A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the "mathematical concepts" grouping. A mathematical relationship may be expressed in words and there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation (MPEP 2106.04(a)(2)).
The claims recite "determining… a variant allele frequency" based on sequence read data (claims 1 and 21-23). The specification defines a variant allele frequency, or a variant allele fraction, as the fraction of reads corresponding to a particular allele relative to the total number of sequence reads for a genomic locus (pg. 34, paragraph [95]). That is, counting a particular allele to form the numerator of a fraction and all alleles as the denominator of the fraction. Counting can arguably be performed mentally or as a mathematical function, a using the numbers to form a fraction is considered a mathematical concept.
The claims recite “generating… an empirical distribution of tumor DNA fraction values based on determined VAF" (claims 1 and 21-23). An empirical distribution is considered to be all such tumor DNA fraction values, calculated as described above, which is then considered to be a synthesis of multiple such abstract steps. The two numerical variables – ctDNA fraction and VAF – are then related to form the distribution, as found in Fig. 4, where relating the two numerical variables is interpreted as a mathematical concept.
The claims recite "fitting… a model to the empirical distribution" (claims 1 and 21-23). Fitting a model is a verbal description of a mathematical concept, which, given its broadest reasonable interpretation in light of the specification, which discloses the model may be a non-parametric probability density model (pg. 35, paragraph [97]) and thus a mathematical relationship.
Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, are interpreted as being recited in the claims. Using the model to determine a tumor DNA fraction (claims 1 and 21-23) is a mental process, as the human mind is practically equipped to interpret and evaluate data.
Claims 2 and 24 recite determining a confidence interval, which is a mathematical concept and disclosed mathematically in the specification (pg. 42, paragraph [115]).
Claims 3 and 25 recite additional information about the variants, which is abstract.
Claims 4 and 26 recite calculating fraction values, which is a mathematical concept.
Claims 5-15, 18, 27-29, and 31 recite additional information about the calculations or the data being calculated.
Claim 19 recites additional information about the sample, and does not require the active step of extracting a sample, and thus regards data.
Claim 20 recite diagnosing or confirming a diagnosis, which is a mental step based on data evaluation.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
The claims recite the following elements in addition to the abstract ideas: "receiving... sequence read data” (claims 1 and 21-23), a system with "processors" and "memory" (claim 21), and a "non-transitory computer-readable storage medium" executed by "processors" (claim 22).
The elements reciting computer components – processors and memory – are interpreted as amounting to a generic computer performing the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
The remaining additional element of receiving sequence read data is interpreted as data collecting steps to perform the abstract idea of calculating the tumor fraction. That is, in the input of the sequence read data is required to perform the recited abstract steps and thus is considered insignificant extra-solution activity. Insignificant extra-solution activity does not integrate the abstract ideas into a practical application (MPEP 2106.05(g)).
None of the dependent claims recite any additional non-abstract elements; they are all directed
to further aspects of the information being analyzed, the manner in which that analysis is performed, or
the mathematical operations performed on the information. [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
The claims recite the following elements in addition to the abstract ideas: "receiving... sequence read data” (claims 1 and 21-23), a system with "processors" and "memory" (claim 21), and a "non-transitory computer-readable storage medium" executed by "processors" (claim 22).
The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
The courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 25 February 2026 Applicant Remarks
Applicant remarks state the claims do not recite mathematical concepts but merely involve them, and support for the previous interpretation was improperly imported from the specification (pg. 11-12). These remarks are interpreted as directed to Step 2A Prong One of the 101 analysis. It is noted that the claims, including determination of what is an abstract idea such as a mathematical calculation, are given their broadest reasonable interpretation in light of the specification, and a mathematical relationship may be expressed in words and there is no particular word or set of words that indicate a claim recites a mathematical calculation (MPEP 2106.04(a)(2)). The claims are thus interpreted as reciting mathematical concepts because determining a variant allele frequency, generating a distribution, and fitting a model are all verbal descriptions of mathematical concepts which are consistent with the specification.
For instance, as found in the Definitions section of the specification, where definitions in the specification control interpretation of the term as it appears in the claim (MPEP 2111.01 (IV)(A)), a variant allele frequency, or a variant allele fraction is defined as the fraction of reads corresponding to a particular allele relative to the total number of sequence reads for a genomic locus (pg. 34, paragraph [95]). That is, counting a particular allele to form the numerator of a fraction and all alleles as the denominator of the fraction. It is unclear how at least generating a fraction can be interpreted as other than a mathematical concept. Similarly, steps of generating a distribution and fitting a model, while not explicitly mathematical equations, are interpreted as verbal descriptions of math as it is unclear what, for example, fitting a model could mean except as a mathematical function.
The MPEP puts forth an example regarding reciting versus involving a judicial exception, whether a machine operating in accordance with F=ma is the former and a teeter-totter and description of its constituent elements is the latter (MPEP 2106.04(II)(A)(1)). While a mathematical equation similar to Newton’s second law of motion is not recited, the only elements which are clearly not abstract are receiving data and computer elements (considered analogous to the teeter-totter components) whereas the steps that enable the instant claims of determining a frequency, generating a distribution, and fitting a model are all verbal descriptions of mathematical processes. Therefore, they are interpreted as mathematical concepts.
At Step 2A Prong Two of 101 analysis, it is determined whether the judicial exceptions are integrated into a practical application by an additional element(s) (MPEP 2106.04(d)). Applicant remarks assert the claimed method improves the technical field of tumor detection and nucleic acid analysis as the claims recite a specific computational process for determining tumor DNA fraction in cfDNA samples independent of determining a tumor aneuploidy value for the cfDNA sample (pg. 13, first paragraph). First, it is unclear whether tumor detection and nucleic acid analysis is a technical field. Second, the additional elements must integrate the abstract ideas into a practical application. While it is true that Enfish, LLC v. Microsoft Corp., 822 F. 3d 1327, 1339 (Fed. Cir. 2016) and McRO, Inc. v. Bandai Namco Games Am. Inc., 837 F.3d 1299, 1315 (Fed. Cir. 2016) are related to improvements to a computer technology, here, the elements in addition to the abstract ideas are receiving data and a general purpose computer. Instructions to implement the abstract ideas using a computer do not integrate them into a practical application (MPEP 2106.05(f)). Applicant remarks state the determinations are more reliable based on modeling of historical patient data (pg. 14, second paragraph), but this is data processing and thus abstract. Wet lab steps collecting the data were removed in this iteration of the claims and thus more of the claims are abstract.
Finally, it is asserted that the improvements result in computational efficiency (pg. 14, last paragraph). The computer as claimed herein is not specifically implemented or changed by operation of said steps. Rather, the computer functions as a tool to perform said steps and any computer is considered capable of performing said tasks.
Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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