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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 30 July 2026 has been entered.
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 29 July 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, determining the frequency 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, and 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. Generating a distribution for a few points would also be calculable mentally.
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. Fitting a model may also be interpreted as relating points with pen and paper and thus a mental process.
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))?
Because the claims recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they recite elements in addition to the abstract ideas which integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(III)).
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.
Thus, the claims recite elements in addition to the abstract ideas which do not integrate the abstract ideas into a practical application, and must be examined further to determine whether elements in addition to the abstract ideas provide significantly more (MPEP 2106.05). [Step 2A Prong Two: Yes]
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 29 July 2026 Applicant Remarks
At Step 2A Prong One, applicant remarks state the claims do not recite mathematical concepts (pg. 10, second paragraph) and the instant recitations are analogous to Example 39 rather than Example 47 (pg. 11, second paragraph).
Regarding the step of determining a variant allele frequency, the applicant remarks state the claims do not recite any fraction calculation, ratio, or arithmetic operation (pg. 12, first paragraph). A variant allele frequency is defined in the specification as a fraction of reads corresponding to an allele related to the total number of sequence reads at a locus (pg. 34, paragraph [94]). Therefore, the claims recite determining said fraction. It is unclear how determining a fraction based on counts of a particular allele versus all alleles is anything other than a mathematical process.
Regarding generating an empirical distribution, applicant remarks state there is no specific formula, equation, named algorithm, or mathematical relationship expressed (pg. 12, first paragraph). Given its plain meaning, the claim recites a relationship between two sets of values: tumor DNA fraction values and determine variant allele frequencies. The resulting distribution made up of the two sets of values is a mathematical relationship.
Regarding fitting a model to the empirical distribution, applicant remarks state fitting a model to the empirical distribution does not recite any specific fitting algorithm, does not recite a formula or equation, and does not specify any mathematical relationship between variables (pg. 11, third paragraph). Fitting a model to numerical data, where a model, given its plain meaning, is a explanation of the relationships of the numerical data points to each other, is a mathematical concept. This interpretation is supported in light of the specification, where it is disclosed “a model, such as a probability density model... can then be fitted to the empirical distribution model” (pg. 34, paragraph [97]). The claim element also introduces copy number and tumor average ploidy as other numerical variables which affect the fitting. It is unclear how these numerical values affect the model is the model is also not a numerical construct. If a numerical relationship among the frequencies is not intended, then a mental process wherein the points are explained relative to one another may be applicable.
Regarding determining a fraction for the sample, applicant remarks state such a determination cannot be performed mentally (pg. 12, last paragraph), but given a relationship between tumor DNA fraction and variant allele frequency, as found in Fig. 4, it is unclear why the human mind is not practically equipped to interpret the data and make a selection based on said data. Applicant remarks point to specification paragraphs [75-76] for indicating the model is the product of “machine-executed operations” but executing the operations to determine a mathematical relationship is still math, which is supported by the indicated portion of the specification which discloses it is a “formula” (pg. 30, paragraph [76]).
Finally, analogy to Example 39 is not persuasive because Example 39 is directed to training a neural network based on facial images. The instant claims recite neither a neural network nor interpreting image data. Instead, the instant claims are analyzing numerical data, generating a distribution based on data, and fitting a model to the distribution, and thus are performing abstract steps based on numerical biological data.
At Step 2A Prong Two, applicant remarks state an alleged improvement is provided by (1) being directed to the technical field of tumor detection and monitoring and (2) presenting specific ways to solve a problem similar to McRO (pg. 13, last paragraph). Regarding the first point, applicant remarks further state the field includes determining ctDNA based on liquid biopsy samples and monitoring informs clinical decision-making (pg. 14, last paragraph). This point is not persuasive because the claims do not recite an element in addition to the abstract idea such as a liquid biopsy analysis. The claims begin with data, perform data analysis steps, and end with data. At Step 2A Prong Two, 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 by additional elements of the claim (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). Here, the elements in addition to the abstract ideas are receiving data and analyzing the data on a computer, which are insignificant extra-solution activity and applying the abstract ideas using a computer, respectively, and thus do not integrate the abstract ideas into a practical application. Regarding the second point, McRO uses rules to achieve a function in a computer that a computer could not previously achieve and could not exist whatsoever. That is, at Step 2A, 2nd prong, the improvement was deemed eligible as it improved a technology or computer functionality rather than being directed to abstract ideas (MPEP 2106.04(d)). In the instant application, the claims recite steps for determining a tumor fraction. The claims recited abstract steps and not related to improvement of technology or computer functionality. Therefore, the outcome of 101 eligibility differs between McRO and the instant application.
Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
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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/Robert J. Kallal/Examiner, Art Unit 1685
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