DETAILED ACTION
Applicant’s response filed 20 July 2026 has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 20 July 2026 has been entered.
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 Claims
Claims 2-10, 14-15, 19, 22-26, 28-29, 31-34, 42-45, and 48 are cancelled.
Claims 1, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are pending.
Claims 1, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are rejected.
Claim Interpretation
Claim 1 recites “(C) determining…a set of sequence features for the cancer subject consisting of mRNA abundance values of a plurality of genes…”. When the phrase "consists of" appears in a clause of the body of a claim, rather than immediately following the preamble, there is an "exceptionally strong presumption that a claim term set off with ‘consisting of’ is closed to unrecited elements." See MPEP 2111.03 II. In the instant case, the “set of sequence features” is closed off to unrecited elements other than mRNA abundance values of at least 75 genes. However, the claims are open to using other sets of sequence features in the single model because the claims use the transitional phrase “comprising”.
Claim 1 recites “…(D) applying the set of sequence features to a single model…”, and claim 24, from which claim 1 depends, further limits the model to comprise an algorithm selected from a group including a boosted regression decision tree ensemble algorithm and a random forest decision tree ensemble algorithm. Accordingly, the single model of claim 1 can include a model comprising an ensemble of models or a model.
Claim 20 recites “k-mer hashing based pseudoalignment”. The term “pseudoalignment” is interpreted to mean read assignment to target sequences without any base-level sequence alignment, as understood by one of ordinary skill in the art. Therefore “k-mer hashing based pseudoalignment” is interpreted to mean assigning reads to target sequences using k-mer hashing, without any base-level sequence alignment.
Claim 27 recites “outputting a clinical report comprising:…when a pair of a respective cancer origin in the list of respective cancer origins and a gene in the list of respective genes matches with a respective targeted cancer therapy, in a plurality of targeted cancer therapies, a recommendation for treatment of the subject comprising administration of the respective targeted cancer therapy”. Accordingly, the limitation is interpreted to require outputting a clinical report that comprises a recommendation to administer the respective targeted cancer therapy, but does not require a step of administering the respective targeted cancer therapy.
Claim Rejections - 35 USC § 101
The rejection of claims 24-25 under 35 U.S.C. 101 in the Office action mailed 12 Nov. 2024 has been withdrawn in view of the cancellation of these claims received 20 July 2026.
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, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and law of nature without significantly more. This rejection is previously cited.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim 1 being representative) is directed to a method for determining a cancer type. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 1 recites the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
(C) determining, from the first plurality of sequence reads, a set of sequence features for the subject consisting of relative mRNA abundance values of a plurality of genes, wherein the plurality of genes is at least 75 genes and wherein the plurality of genes includes at least 30 genes selected from the group consisting of GPM6A, CDX1, SOX2, NAPSA, CDX2, MUC12, SLAMF7, HNF4A, ANXA10, TRPS1, GATA3, SLC34A2, NKX2-1, SLC22A31, ATP10B, STEAP2, CLDN3, SPATA6, NRCAM, USH1C, SOX17, TMPRSS2, MECOM, WT1, CDHR1, HOXA13, SOX10, SALL1, CPE, NPR1, CLRN3, THSD4, ARL14, SFTPB, COL17A1, KLHL14, EPS8L3, NXPE4, FOXA2, SYT11, SPDEF, GRHL2, GBP6, PAX8, ANO1, KRT7, HOXA9, TYR, DCT, LYPD1, MSLN, TP63, CDH1, ESR1, HNF1B, HOXA10, TJP3, NRG3, TMC5, PRLR, GATA2, DCDC2, INS, NDUFA4L2, TBX5, ABCC3, FOLH1, HISTlH3G, S100A1, PTHLH, ACER2, RBBP8NL, TACSTD2, C19orf77, PTPRZI, BHLHE41, FAM155A, MYCN, DDX3Y, FMN1, HISTlH3F, UPK3B, TRIM29, TXNDC5, BCAM, FAM83A, TCF21, MIA, RNF220, AFAP1, KRT5, SOX21, KANK2, GPM6B, Clorfl16, FOXF1, MEIS1, EFHD1, and XKRX; and
(D) applying the set of sequence features to a single model, thereby determining the primary origin of the cancer, wherein: the single model provides, for each respective cancer origin in a set of at least 60 cancer origins, responsive to application of the set of sequence features to the single model, a corresponding first indication of whether the respective cancer origin is the primary origin of the cancer afflicting the cancer subject, wherein the corresponding first indication is on a continuous scale and represents (i) a likelihood or a probability that the respective cancer origin is the primary origin of the cancer afflicting the cancer subject or (ii) a likelihood or a probability that the respective cancer origin is not the primary origin of the cancer afflicting the cancer subject, and the set of at least 60 cancer origins comprises leiomyosarcoma, liposarcoma, vascular sarcoma, osteosarcoma, ewing sarcoma, rhabdomyosarcoma, chondrosarcoma, synovial sarcoma, fibrous sarcoma, schwannoma, and carcinosarcoma.
The identified claim limitations falls the group of abstract ideas of mental processes for the following reasons. In this case, the step of determining mRNA abundance values for at least 75 genes from the first plurality of sequence reads involves analyzing and counting the number of reads that correspond to each of the 75 genes, including at least 30 genes from the recited group to determine abundance values, which can be practically performed in the mind or with pen and paper. Furthermore, applying the sequence features (e.g. the mRNA abundance values) to a single classification model can be performed mentally by inputting the values into a model (e.g. linear regression model) to calculate an output for each of 60 cancer types, including the recited sarcomas, which can be practically performed in the mind or with pen and paper. Therefore, these limitations recite a mental process. See MPEP 2106.04(a)(2) III.
Furthermore, the step of applying sequence features to a classification model further recites a mathematical concept. The broadest reasonable interpretation of applying sequence features to a single model to determine a cancer type includes inputting numerical values (e.g. the mRNA abundance values) into a logistic regression classifier, as described in Applicant’s specification at para. [0071], which requires performing addition of weighted variables, and thus, amounts a textual equivalent to performing mathematical calculations. Therefore, this limitation recites a mathematical calculation. See MPEP 2106.04(a)(2) I.
Last, the claim further recites the law of nature of a natural correlation between expression levels of at least 75 genes, including the recited genes, and the presence of various cancer types in a subject. See MPEP 2106.04(b) I.
Dependent claims 17-18, 20-21, 27, 35-38, 47, and 49-53 further recite an abstract idea and/or further limit the abstract idea of claim 1. Dependent claims 17 and 18 further limit the mental process of determining mRNA abundance values to be for at least 200 genes and from 75 to 500 genes, respectively. Dependent claim 20 further recites the mental process of determining the mRNA abundance values by k-mer hashing-based pseudoalignment to an exome reference construct. Dependent claim 21 further recites the mental process and mathematical concept of normalizing the mRNA abundance values relative to the total number of transcripts in the first plurality of sequence reads, which requires performing division. Dependent claim 27 further recites the mental process of identifying from the second plurality of sequence reads, a respective level of support for mutations responsive to targeted therapies in in each of a plurality of genes in the genome of the cancerous tissue. Dependent claims 35-36 further limit the mental process and mathematical concept of applying the model to the mRNA abundance features to comprise outputting a discrete-binary indication for each cancer type of whether the cancerous tissue is the respective cancer type. Dependent claims 37-38 further limit the mental process and mathematical concept of applying the model to the mRNA abundance features to output a discrete-binary indication for each cancer type of whether the cancerous tissue is not the respective cancer type. Dependent claim 47 further limits the mental process and mathematical concept of applying the model to determine the primary origin of the cancer is one of the recited cancer types. Dependent claim 49 further limits the mental process of determining abundance values for less than 7500 genes. Dependent claims 50-53 further limit the mental process and mathematical concept of applying the single model to determine an origin of the cancer detect the cancer at the recited precision, accuracy, and/or recall. Therefore, claims 1, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 recite an abstract idea and law of nature. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Claims 17-18, 20-21, 35-38, and 49-53 further recite an abstract idea, as discussed above, but do not recite any elements in addition to the recited judicial exception and thus are part of the judicial exception.
The additional elements of claims 1, 16, 27, and 39-41 include:
(A) sequencing a plurality of mRNA molecules from the cancerous tissue, thereby obtaining a first plurality of sequence reads of RNA from the cancerous tissue (claim 1);
wherein the first plurality of at least 10,000 sequence reads is at least 100,000 sequence reads (claim 16);
wherein the sequencing is RNA-seq (claim 40); and
wherein the RNA molecules from the cancerous tissue are from a solid tumor sample of the cancerous tissue (claim 41).
The additional element of claim 27 includes:
sequencing a plurality of DNA molecules from the cancerous tissue, thereby obtaining a second plurality of sequence reads of DNA from the cancerous tissue.
The above additional elements of sequencing a plurality of mRNA molecules from a solid tumor sample of the cancerous tissue using RNA-seq to product at least 10,000 sequence reads, as recited in claims 1, 16, and 39-41, and sequencing a plurality of DNA molecules from the cancerous tissue to obtain DNA sequence reads, as recited in claim 27, only serves to collect data for use by the abstract idea (e.g. as input into the model or for identifying a support for certain mutations that are responsive to targeted therapies). Therefore, the additional elements amount to insignificant extra-solution activity. See MPEP 2106.05(g).
The additional elements of claim 1 further include:
a computer system having one or more processors and memory; and
obtaining, in electronic format, one or more data structures that collectively comprise the first plurality of sequence reads.
The additional elements of claims 11-13 include:
outputting a clinical report comprising a ranked list of the respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood satisfying a threshold likelihood (i.e. data output) (claim 11);
wherein the ranked list of the respective cancer origins consists of the three respective cancer origins, in the set of at least 60 cancer origins, having the highest likelihood of being the primary origin (i.e. data output) (claim 12); and
wherein the clinical report comprises a list of excluded cancer origins comprising the respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood that does not satisfy the threshold (i.e. data output) (claim 13).
The additional elements of claim 27 include:
obtaining, in electronic format, the second plurality of sequence reads (i.e. receiving data); and
outputting a report comprising: a list of respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood satisfying a threshold likelihood, a list of a respective genes, in the plurality of genes, for which mutations that are responsive to targeted therapies were validated based on the corresponding level of support identified from the second plurality of sequence reads, and when a pair of a respective cancer type in the list of respective cancer origins and a gene in the list of respective genes matches with a respective targeted cancer therapy, in a plurality of targeted cancer therapies, a recommendation for treatment of the subject comprising administration of the respective targeted cancer therapy (i.e. data output).
The additional elements of processors memory, data input, and data output are generic computer components and/or processes. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See MPEP 2106.05(f)(2). Furthermore, the additional elements of claims 12-13 only serve to further limit the type of data that is outputted, which does not integrate the recited judicial exception into a practical application.
The additional element of claims 30 and 46-47 include:
administering to the subject an anti-cancer agent selected from the group consisting of lenalidomid, pembrolizumab, trastuzumab, bevacizumab, rituximab, ibrutinib, human papillomavirus quadrivalent (types 6, 11, 16, and 18) vaccine, pertuzumab, pemetrexed, nilotinib, nilotinib, denosumab, abiraterone acetate, promacta, imatinib, everolimus, palbociclib, erlotinib, bortezomib, bortezomib (claim 30);
administering to the subject a respective therapy tailored for treatment of the primary origin of the caner afflicting the cancer subject determined by the single model (claim 46); and
administering to the cancer subject a respective therapy tailored for treatment of the leiomyosarcoma, liposarcoma, vascular sarcoma, osteosarcoma, ewing sarcoma, fibrous sarcoma, schwannoma, or carcinosarcoma (claim 47).
Regarding the administering step of claim 30, the administering step does not integrate the recited judicial exception into a practical application because the treatment is not particular. The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). See MPEP 2106.04(d)(2). Here, claim 1 involves using a model to determine the cancer origin, from among at least 60 cancer types, and while the various anti-cancer agents recited in claim 30 are specific to cancer, the treatment being administered does not depend on the determined origin cancer, and is instead merely instructions to “apply” the exception in a generic way (e.g. by administering an anti-cancer agent a subject with cancer regardless of the determined cancer type). Thus the treatment step does not integrate the recited judicial exception of determining the cancer origin to effect a particular treatment. Regarding the administering step of claims 46-47, the claims merely administer “a respective therapy tailored for treatment of [the determined cancer origin]”, which does not recite a particular treatment. Instead, this administering step is analogous to “administering a suitable medication to a patient”, as exemplified in MPEP 2106.04(d)(2), which is not sufficient to effect a particular treatment. Therefore, the additional elements of claims 30 and 46-47 do not integrate the recited judicial exception into the practical application of a particular treatment or prophylaxis for a disease or medical condition. See MPEP 2106.04(d).
Last, the claims do not improve the functioning of a computer or to any other technology. It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. While the claimed method may improve the time and cost to reach a cancer diagnosis, the improved time and cost is directly provided by the judicial exception of analyzing the sequencing data with a model, while the sequencing step simply serves to generate data for use by the judicial exception. As discussed above, the judicial exception alone cannot provide the improvement.
Therefore, the additionally recited elements amount to insignificant extra-solution activity and/or merely invoke computers as a tool to perform an existing process, and, as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
Claims 17-18, 20-21, 35-38, and 49-53 further recite an abstract idea, as discussed above, but do not recite any elements in addition to the recited judicial exception and thus are part of the judicial exception.
The additional elements of claims 1, 16, 27, and 39-41 include:
(A) sequencing a plurality of mRNA molecules from the cancerous tissue, thereby obtaining a first plurality of sequence reads of RNA from the cancerous tissue (claim 1);
wherein the first plurality of at least 10,000 sequence reads is at least 100,000 sequence reads (claim 16);
wherein the sequencing is RNA-seq (claim 40); and
wherein the RNA molecules from the cancerous tissue are from a solid tumor sample of the cancerous tissue (claim 41).
The additional element of claim 27 includes:
sequencing a plurality of DNA molecules from the cancerous tissue, thereby obtaining a second plurality of sequence reads of DNA from the cancerous tissue.
The above additional elements of sequencing a plurality of mRNA molecules from a solid tumor sample of the cancerous tissue using RNA-seq to product at least 10,000 sequence reads, as recited in claims 1, 16, and 39-41, and sequencing a plurality of DNA molecules from the cancerous tissue to obtain DNA sequence reads, as recited in claim 27, are well-understood, routine, and conventional. This position is supported by Applicant’s own specification at para. [00141]-[00142], which discloses that methods for performing mRNA sequencing to obtain the sequence reads, such as RNA-seq, and methods for performing next-generation sequencing are well known in the art. This position is further supported by Yoo et al. (Clinical multi-omics strategies for the effective cancer management, 2018, Journal of Proteomics, 188, pg. 97-106; previously cited). Yoo overviews multi-omics strategies for managing cancer, and discloses tumor tissue (i.e. cancerous tissue from a solid tumor) is routinely obtained from surgical specimens or biopsies and is routinely used in multi-omics approaches, including both RNA sequencing for gene expression and transcriptome analysis and DNA sequencing to analyze mutations (pg. 98, col. 2, para. 3; pg. 101, col. 2, para. 1 to pg. 102, col. 1, para. 2; Figure 2), and further discloses that multi-omics strategies have been utilized and facilitated the discovery of biomarkers for cancer treatment and assessment (pg. 103, col.1 , para. 4). Yoo further discloses computational techniques are essential for using -omics data, citing several computational methods for analyzing such data (pg. 103, col. 1, para. 3), demonstrating that the combination of gathering DNA and RNA omics data and computers are well-understood, routine, and conventional.
The additional elements of claim 1 further include:
a computer system having one or more processors and memory; and
obtaining, in electronic format, one or more data structures that collectively comprise the first plurality of sequence reads.
The additional elements of claims 11-13 include:
outputting a clinical report comprising a ranked list of the respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood satisfying a threshold likelihood (i.e. data output) (claim 11);
wherein the ranked list of the respective cancer origins consists of the three respective cancer origins, in the set of at least 60 cancer origins, having the highest likelihood of being the primary origin (i.e. data output) (claim 12); and
wherein the clinical report comprises a list of excluded cancer origins comprising the respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood that does not satisfy the threshold (i.e. data output) (claim 13).
The additional elements of claim 27 include:
obtaining, in electronic format, the second plurality of sequence reads (i.e. receiving data); and
outputting a report comprising: a list of respective cancer origins, in the set of at least 60 cancer origins, that have a likelihood satisfying a threshold likelihood, a list of a respective genes, in the plurality of genes, for which mutations that are responsive to targeted therapies were validated based on the corresponding level of support identified from the second plurality of sequence reads, and when a pair of a respective cancer type in the list of respective cancer origins and a gene in the list of respective genes matches with a respective targeted cancer therapy, in a plurality of targeted cancer therapies, a recommendation for treatment of the subject comprising administration of the respective targeted cancer therapy (i.e. data output).
The additional elements of processors memory, data input, and data output are generic computer components and/or processes. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Furthermore, the additional elements of claims 12-13 only serve to further limit the type of data that is outputted. Therefore, the above additional elements, when considered alone and in combination, as discussed above in view of Yoo, are not sufficient to amount to significantly more than the recited judicial exception.
The additional element of claims 30 and 46-47 include:
administering to the subject an anti-cancer agent selected from the group consisting of lenalidomid, pembrolizumab, trastuzumab, bevacizumab, rituximab, ibrutinib, human papillomavirus quadrivalent (types 6, 11, 16, and 18) vaccine, pertuzumab, pemetrexed, nilotinib, nilotinib, denosumab, abiraterone acetate, promacta, imatinib, everolimus, palbociclib, erlotinib, bortezomib, bortezomib (claim 30);
administering to the subject a respective therapy tailored for treatment of the primary origin of the caner afflicting the cancer subject determined by the single model (claim 46); and
administering to the cancer subject a respective therapy tailored for treatment of the leiomyosarcoma, liposarcoma, vascular sarcoma, osteosarcoma, ewing sarcoma, fibrous sarcoma, schwannoma, or carcinosarcoma (claim 47).
Last, administering a subject with cancer an anti-cancer agent from the above recited group and administering to the subject a respective therapy tailored for treatment of the cancer type are well-understood, routine, and conventional. This position is supported by Yoo, which further discloses the impact of omics data on treatment decisions has been demonstrated in various cancers, including in cancer patients treated with bevacizumab and trastuzumab (i.e. a respective therapy tailored for treatment of the cancer type) (pg. 101, col. 2, para. 1; pg. 103, col. 1, para. 1). Similarly, Applicant’s own specification at para. [0005] discloses that genomic analysis tumors is becoming routine clinical practice to provide tailored patient treatments, such that administering a tailored treatment to a subject is conventional. Accordingly, the additional element of administering one of the anti-cancer agents or tailored therapy to a subject with cancer, in combination with analyzing omics data is well-understood, routine, and conventional.
Therefore, taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea and law of nature without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 20 July 2026 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks the claims improve the diagnosis and treatment of cancer, and incorporates by reference their previous arguments for brevity, and that when properly considered, amended claim 1 contains an inventive concept that is significantly more than the judicial exception (Applicant’s remarks at pg. 8, para. 4-5).
This argument is not persuasive for the same reasons previously discussed in the Examiner’s Answer mailed 19 May 2026, and in the Office action mailed 12 Nov. 2024.
Applicant remarks that step (D) of claim 1 does not recite a mathematical concept because the Office’s conclusion conflate a claim limitation that may be implemented using mathematics with a claim limitation that sets forth or describes mathematics (Applicant’s remarks at pg. 9, para. 1-2). Applicant further remarks the rejection relies only on the principles in MPEP 2106.04(a)(2) without considering the wealth of administrative guidance on the subject, and further remarks that the rejection selects a possible model and imports arithmetic used in a possible implementation of the model, which is improper and vitiates the line drawn between involving math and reciting math (Applicant’s remarks at pg. 9, para. 3 to pg. 10, para. 2).
This argument is not persuasive. First, the guidance noted by Applicant clearly states “The MPEP (9th Edition, Rev. 01.2024), published in November 2024, includes the current examination guidance related to subject matter eligibility. Examiners should refer to MPEP sections 2103 to 2106.07 for guidance on 35 U.S.C. 101.” (see pg. 1 of the Kim Memorandum dated 04 Aug. 2025). Furthermore, 35 U.S.C. 101 guidance was considered. It is not clear if Applicant is suggesting reliance on the MPEP by the Examiner is improper, or if the MPEP is incorrect in view of the guidance, which is not the case.
MPEP 2106.05(a) states 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 calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. 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.
Claim 1, step (D) recites “(D) applying the set of sequence features to a single model, thereby determining the primary origin of the cancer, wherein: the single model provides….a corresponding first indication…wherein the corresponding first indication is on a continuous scale and represents (i) a likelihood or a probability that the respective cancer origin is the primary origin… or (ii) a likelihood or probability…”. In other words, the step calculates/determines a likelihood or probability using a set of sequence features applied to a model, which clearly is an act of calculating using mathematical methods (i.e. a model) to determine a number (i.e. a probability or likelihood), particularly when considering the broadest reasonable interpretation in light of the specification, which, for example discloses the model may be a logistic regression algorithm or a naïve bayes algorithm ([0393]). Furthermore, while Applicant alleges step (D) merely “involves math”, Applicant has not described in what way the limitation in step (D) that involves elements other than math.
Applicant alleges that importing arithmetic used in a possible implementation is improper and vitiates the line between involving and reciting math; however, the rejection is merely describing the broadest reasonable interpretation of the limitation of Step (D) in explaining why the limitation recites a mathematical calculation, in accordance with MPEP 2106.05(a). It is not improper to consider the broadest reasonable interpretation of the claim when determining a limitation recites a mathematical concept, as made clear by MPEP 2106.05(a).
Last, it is noted that even if step (D) was not considered a mathematical concept, step (D) also recites a mental process as set forth in the above rejection. That is, applying the sequence features (e.g. the mRNA abundance values) to a single classification model can be performed mentally by inputting the values into a model (e.g. multinomial logistic regression model) to calculate an output for each of 60 cancer types, including the recited sarcomas, which can be practically performed in the mind or with pen and paper. The human mind is practically able to perform weighted addition to calculate a likelihood. Therefore, regardless of whether step (D) recites a mathematical concept, the limitation would still recite an abstract idea under Step 2A, prong 1.
Applicant remarks that step (D) is analogous to example 39, which is a method of training a neural network, and furthermore, claim 2 of example 47 shows what is required to cross the line from involving mathematics to reciting mathematics by expressly requiring a training algorithm includes a backpropagation algorithm and a gradient descent algorithm (Applicant’s remarks at pg. 10, para. 3 to pg. 11, para. 4).
This argument is not persuasive. Example 39, incorporated into MPEP 2106.04(a)(1), is a method of training a neural network on a set of digital facial images. The instant claims, simply use/apply “a model” and do not even require the “model” is a machine learning model, let alone require training of a neural network on digital facial images. Simply applying a model to features to determine a likelihood or probability recites a mathematical concept for the reasons discussed above.
Regarding claim 2 of example 47, the claim recites “(c) training…the ANN based on the input data…, wherein the selected training algorithm includes a backpropagation algorithm and a gradient descent algorithm”. Therefore, claim 2 of example 47 similarly relates to step of training a neural network, and not simply applying a model to features to determine a likelihood/probability as recited in the instant claims. Following Applicant’s logic, at best, claim 2 of example 47 and example 39 demonstrate that while “training a neural network” may only involve math, training a neural network using a backpropagation algorithm and gradient descent algorithm recites math (i.e. a backpropagation algorithm and gradient descent algorithm). However, step (D) of the instant claims do not involve training a neural network, let alone even training a machine learning model, and furthermore do not even require the model is a machine learning model. Therefore, claim 1 does not fall on the Example 39 side of the line between reciting and involving math, contrary to Applicant’s assertion.
Last, step (D) of the instant claims is further dissimilar to claim 2 of Example 49, given the step also recites a mental process grouping of abstract idea, as discussed above.
Applicant remarks claim 1 does not recite a mathematical concept, mental process, or law of nature for the reasons set forth above and in previously submitted remarks (Applicant’s remarks at pg. 11, para. 5).
This argument is not persuasive for the reasons set forth above and in previous Office actions.
Applicant remarks that claim 1 is patent eligible at Step 2B because its additional elements provide an inventive concept (Applicant’s remarks at pg. 11, para. 6 to pg. 12, para. 2). Applicant remarks that the Office analyzes the sequencing step, computer components, data input and output, and treatment limitations largely in isolation and does not address the ordered combination, and that claim 1 requires the following ordered combination of sequencing, obtaining the sequence reads and determining a set of sequence features from the reads, applying the feature set to a single model, and using the single model to provide a continuous scale indication for each of 60 cancer-types, and the inventive concept resides in this arrangement and interaction and not in any one component in a vacuum (Applicant’s remarks at pg. 12, para. 3 to pg. 13, para. 2). Applicant remarks the Examiner assigns every limitation that distinguishes the claimed diagnostic architecture to the judicial exception and then asks whether the residual recitations of sequencing and a computer are conventional, but the question is, however, whether the additional elements in combination with any alleged judicial exception, provide an inventive concept (Applicant’s remarks at pg. 13, para. 4 to pg. 14, para. 1).
This argument is not persuasive. Under Step 2B, the additional elements of the claims are evaluated individually and in combination to determine whether the additional elements are well-understood, routine, and conventional. See MPEP 2106.05 I. B. and II. Therefore, the steps of claim 1 relating to determining a set of sequence features from the sequence reads, applying the feature set to a single model, and using the single model to provide a continuous scale indication for each of 60 cancer-types (corresponding to steps (C) and (D) of claim 1) are not evaluated under Step 2B, given these steps are part of the abstract idea. The additional elements of the claims in steps (A)-(C) are well-understood, routine, and conventional considered alone and in combination, for the reasons discussed in the above rejection, and further discussed below in more detail.
In other words, Applicant’s assertion that the question under step 2B regarding the inventive concept requires the consideration of the additional elements in combination with any alleged exception is not the case. Only the additional elements are evaluated.
Applicant further remarks that step (D) is not a mathematical concept and must be evaluated as an additional element under Step 2B, and step (D) applies a feature set to a model that generates indications of at least 60 cancer origins, which are not math, mental observations or naturally occurring relationships (Applicant’s remarks at pg. 13, para. 3).
This argument is not persuasive. Step (D) recites math for the reasons already discussed above. Furthermore, applying a model to mRNA abundance values of 75 genes encompasses inputting the abundance values into a multinomial logistic regression model, which requires performing mathematical calculations (e.g. multiplication, division, addition, subtraction) to determine a probability for each class, which can be practically performed in the mind aided with pen and paper.
Applicant remarks that the passages cited in the Office action discuss using RNA sequencing data in cancer-origin classification, which is not evidence that it was routine or conventional to use the claimed restricted gene set in a single model, and Yoo does not disclose the recited gene group, the claimed closed feature set, one model for providing indications, or the collection of cancer origins (Applicant’s remarks at pg. 14, para. 2-3).
This argument is not persuasive. As discussed above, the extraction of features for the recited claim set, the use of extracted features from the recited claim set in the single model, the model, and the predictions for the cancer origins are all part of the abstract idea and, therefore, are not evaluated under Step 2B. Further regarding the specifically recited claim set, claim 1 involves in step (C), determining from the sequence reads, mRNA abundance values of the specified gene set, which is part of the abstract idea as identified in the above rejection. Yoo does demonstrate the conventionality of sequencing RNA molecules from cancerous tissue to analyze the entire transcriptome, as discussed in the above rejection.
Applicant remarks the same is true of Erlander, O’Neill, Grewal, Kerr, and other tumor-origin references discussed by the Examiner, and more importantly, the Office finds the claims are “free of the prior art”, which is irreconcilable with a conclusory assertion that the same combination was widely prevalent or in common use (Applicant’s remarks at pg. 14, para. 4 to pg. 15, para. 3).
This argument is not persuasive. The only reference relied upon in the above 101 rejection is Yoo, and Erlander, O’Neill, Grewal, Kerr, and other tumor-origin references are not relied upon in the 101 rejection.
Furthermore, lack of novelty under 35 U.S.C. 102 or obviousness under 35 U.S.C. 103 of a claimed invention does not necessarily indicate that additional elements are well-understood, routine, conventional elements. See MPEP 2106.05 I. Therefore, simply because the claims were identified as free of the prior art does not guarantee eligibility.
Applicant asserts that the Office’s finding that the closest art does not make obvious the claimed combination is not irreconcilable with the conclusion that the same combination is widely prevalent. However, the Office did not find the claimed combination of the claim (including both additional elements and the judicial exception) are well-understood, routine, and conventional. As discussed above, only the additional elements are evaluated under Step 2B, and the combination of additional elements in the claim was identified as well-understood, routine, and conventional.
Applicant remarks the claimed arrangement supplies an inventive concept because the claims involve a specific arrangement of a patient specific expression feature set that is supplied to a model, that this meaningful confines any judicial exception and does not preempt the use of gene expression generally, and the Office’s own prior art findings confirm the arrangement was not a generic application already disclosed in the field (Applicant’s remarks at pg. 15, para. 4 to pg. 16, para. 2).
This argument is not persuasive. While preemption is the concern underlying the judicial exceptions, it is not a standalone test for determining eligibility. Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1052, 119 USPQ2d 1370, 1376 (Fed. Cir. 2016). Instead, questions of preemption are inherent in and resolved by the two-part framework from Alice Corp. and Mayo (the Alice/Mayo test referred to by the Office as Steps 2A and 2B). See MPEP 2106.04 I. Therefore, simply because the claims do not preempt all uses of gene expression does not guarantee eligibility.
Applicant’s argument regarding the arrangement of the patient specific expression feature set being supplied to a model providing the inventive concept and not being disclosed in the field is not persuasive for the reasons already discussed above with respect to Step 2B. That is, these elements are part of the abstract idea and therefore, their conventionality is not evaluated under Step 2B.
Applicant’s remarks the specification identifies a problem in cancer-origin classification in distinguishing between closely related cancer types, and claim 1 addresses the problem through a particular feature selection and single model configuration that conventional systems did not evaluate together in the claimed manner (Applicant’s remarks at pg. 16, para. 3). Applicant remarks the claimed arrangement material changes the clinical diagnostic workflow, by replacing the serial and conditional architecture with a single RNA sequencing assay and one model that determines the primary origin, and the resulting reduction in diagnostic time is from eliminating successive rounds of different assays, thus reducing reagents, equipment, facility, and tissue-sample requirements (Applicant’s remarks at pg. 16, para. 4 to pg. 17, para. 3).
This argument is not persuasive. It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. Furthermore, if it is asserted that the invention improves upon conventional functioning of a computer, or upon conventional technology or technological processes, a technical explanation as to how to implement the invention should be present in the specification. An indication that the claimed invention provides an improvement can include a discussion in the specification that identifies a technical problem and explains the details of an unconventional technical solution expressed in the claim, or identifies technical improvements realized by the claim over the prior art. See MPEP 2106.05(a).
Here, Applicant’s alleged improvement is that sequencing RNA molecules from cancerous tissue of a subject and analyzing the sequencing data to make the diagnosis is an improvement over using immunohistochemical studies and using antibodies to make a diagnosis of particular cancers because it is faster and more cost-effective. However, as noted by Applicant’s own specification at para. [0005], genomic analysis of tumors is routine in clinical practice in providing tailored patient treatments and at para. [0008] discloses that cancer origin classification can be performed using RNA sequencing data, citing several studies that use RNA sequencing data to determine cancer origin. Similarly, each of Erlander (US 2015/0329921 A1; previously cited), O’Neill (WO 2017/019918 A1; previously cited), and Grewal (JAMA Network Open, 2019, 2(4), pg. 1-15 and Suppl; previously cited) (Cited in the previous 103 rejection) each disclose methods for diagnosing large numbers of cancers presenting as unknown primary origin using mRNA expression data, as previously discussed in the 103 rejection in the final rejection mailed 11 Jan. 2024. Yoo, cited in the 101 rejection above, similarly overviews multi-omics strategies for managing cancer, and discloses tumor tissue (i.e. cancerous tissue from a solid tumor) is routinely obtained from surgical specimens or biopsies and is routinely used in multi-omics approaches, including both RNA sequencing for gene expression and DNA sequencing to analyze mutations (pg. 98, col. 2, para. 3; pg. 101, col. 2, para. 1 to pg. 102, col. 1, para. 2; Figure 2), and that multi-omics strategies have been utilized and facilitated the discovery of biomarkers for cancer assessment (pg. 103, col.1 , para. 4).
In other words, the use of mRNA expression data from RNA sequencing in diagnosing different cancers of unknown origin (i.e. the alleged faster and cheaper diagnosis due to a single omics assay) does not clearly provide an unconventional technical solution expressed in the claim, or identify technical improvements realized by the claim over the prior art, as required by MPEP 2106.05(a). Appellant is merely describing the benefits of tumor of origin tests that are based on RNA sequencing data, which are already conventional in the field as noted above. While the claimed judicial exception of analyzing gene expression levels of a particular gene set to determine at least 60 cancer types, including leiomysarcoma, liposarcoma, and vascular sarcoma, may allow for a diagnosis to be made using the generated RNA sequencing data, the judicial exception alone cannot provide the improvement to technology, as discussed above. Nor can one patent "a novel and useful mathematical formula," Parker v. Flook, 437 U.S. 584, 585, 198 USPQ 193, 195 (1978).
Overall, the claims do not recite any additional elements that integrate the recited judicial exception into a practical application of an improvement to technology. Instead, the additional element of sequencing RNA molecules from the cancerous tissue only serves to collect the necessary data for the abstract idea, which amounts to insignificant extra-solution activity, and furthermore, generally links the use of the judicial exception(s) to a particular technological environment (e.g. RNA sequencing). See MPEP 2106.05(g) and MPEP 2106.04(d)(1).
Applicant remarks that the claimed advance was not merely the substitution of any known RNA tumor-origin test for conventional clinical texting, since several conventional expression assays or diagnostic procedures do not cover the same range and specificity of cancer prediction, and the claimed use of the restricted expression feature set and one model to evaluate 60 cancer origins provides the asserted reduction in time, cost, reagents, and tissue (Applicant’s remarks at pg. 17, para. 3).
This argument is not persuasive. As discussed above, it is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. Furthermore, it is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. See MPEP 2106.05(a).
Applicant states the improvement is being provided by the restricted feature set (i.e. step (C) determining, from the first plurality of sequence reads, a set of sequence features…of mRNA abundance values), and their input into the single model (step (D)), both which are part of the abstract idea. As discussed above, an improvement in the abstract idea is not an improvement to technology. The alleged improvement compared to conventional assays using sequencing of tumor samples is being provided solely by the extraction of the identified gene set and the use of the claimed single model, which are part of the abstract idea. The alleged improvement in specificity and range is not being provided by an additional element, and instead the claims are relying on conventional sequencing of RNA to generate the data for use by the abstract idea as discussed in the above rejection.
Applicant remarks that the previous evidence regarding the commercial embodiment of the claimed method and its favorable reception was not a routine implementation of conventional RNA sequences, and the RNA dismisses that evidence on the ground that the ability to distinguish 60 cancer origins is attributable to the abstract idea, but step (D) does not recite a judicial exception and thus it properly represents an inventive concept (Applicant’s remarks at pg. 17, para. 5 to pg. 19 para. 2).
This argument is not persuasive because step (D) is part of the abstract idea. Furthermore, the arguments regarding the favorable reception of the commercial embodiment are not persuasive for the reasons already discussed in the Examiner’s answer mailed 19 May 2026 (see pg. 10, para. 2 to pg. 11, para. 2).
Applicant remarks that the Examiner repeatedly states that a judicial exception alone cannot provide the improvement, but here the inventive concept is supplied by the additional elements and their interaction with the exception, including a physical RNA sequencing assay performed on the cancerous tissue, the generation of the expression feature set, and the application of the feature set on the model (Applicant’s remarks at pg. 19, para. 3). Applicant further remarks that characterizing sequencing as “data gathering” at Step 2A does not end the inquiry, and MPEP 2106.05 requires any limitation treated as extra-solution activity be reevaluated at step 2B, and further remarks even if RNA sequencing was conventional by itself, the rejection must still establish that using the resulting reads to generate the claimed feature set and applying the feature set to a model was conventional as an ordered combination (Applicant’s remarks at pg. 19, para. 4).
This argument is not persuasive. The additional element of “sequencing…” as claimed only interacts with the judicial exception in order to collect the necessary data for use by the abstract idea, which is insignificant extra-solution activity. The alleged improvement in classification is provided by an improved analysis of such sequencing data, rather than any particular way of generating sequencing data, as explained above. Therefore, the sequencing additional element does not provide integration under Step 2A, Prong 2.
Furthermore, while the sequencing step is reevaluated under step 2B for conventionality, the abstract idea (i.e. generating the claimed feature set and applying the feature set to a model) are not evaluated under Step 2B for the reasons already discussed above. Therefore, contrary to Applicant’s assertion, the rejection is not required to establish that the combination of the additional elements and the abstract idea (i.e. sequencing, generating the claimed feature set, and applying the feature set to the model) are well-understood, routine, and conventional.
Applicant remarks the generic computer components do not defeat the inventive concept because Applicant does not rely on the processors and memory alone, and further remarks the computer receives the sequence reads, generates the feature set, and operates the single model, and thus participate in the claimed architecture rather than being simply appended after the fact to a mental process (Applicant’s remarks at pg. 20, para. 1).
This argument is not persuasive. The generic computer components do not defeat the inventive concept because there is no inventive concept in the claims for the reasons already discussed above.
Furthermore, MPEP 2106.05(a) states in computer-related technologies, the examiner should determine whether the claim purports to improve computer capabilities or, instead, invokes computers merely as a tool. Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1336, 118 USPQ2d 1684, 1689 (Fed. Cir. 2016). In the instant case, the computer is merely used as a tool to carry out the abstract idea (as also explained by Applicant), and therefore, the computer does not provide any improvement or inventive concept.
Applicant’s remarks that the Office Action’s single sentence that the elements fail “even when viewed as a combination” does not provide the analysis or factual support required, and the cited evidence does not show the claimed combination was widely prevalent or in common use, and to the contrary the Office found the closest reference do not render obvious the combination (Applicant’s remarks at pg. 20, para. 2). Applicant remarks that therefore, claim 1 is eligible at step 2B even if the claim is directed to a judicial exception at Step 2A (Applicant’s remarks at pg. 20, para. 3).
This argument is not persuasive. First, the statement “even when viewed as a combination” in the conclusion of the step 2B analysis is not the only explanation regarding a combination of additional elements. The combination of additional elements is addressed throughout the body of the analysis under Step 2B. Furthermore, the combination of additional elements and the abstract idea is not evaluated under Step 2B, as already explained above.
Applicant remarks that claims 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are patent eligible for the same reasons discussed for claim 1 (Applicant’s remarks at pg. 20, para. 3).
This argument is not persuasive for the same reasons discussed above for claim 1.
Double Patenting
The terminal disclaimer filed 04 Nov. 2024 over U.S. App. No. 17/982,399 and U.S. Patent No. 11,527,323 B2 has been approved on 04 Nov. 2024.
Conclusion
No claims are allowed.
Claims 1, 11-13, 16-18, 20-21, 27, 30, 35-41, 46-47, and 49-53 are free of the prior art for the reasons discussed in the Office action mailed 12 Nov. 2024.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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