DETAILED ACTION
Applicant’s response, filed 23 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.
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 .
Election/Restrictions
The restriction requirement between Groups I and III and Groups II and III was still deemed proper and was therefore made FINAL as set forth in the Office action mailed 24 April 2026.
Response to Arguments
Applicant's arguments filed 23 July 2026 regarding claim 26 having unity of invention with the non-withdrawn claims have been fully considered but they are not persuasive.
Applicant remarks that Molpario does not disclose the biomarker combination defined by amended claim 1, and none of the cited reference teach the relationship between the biomarker combination in claim 1 and urogenital system tumors, and therefore the biomarker combination is a special technical feature and claim 26 should be rejoined (Applicant’s remarks at pg. 31, para. 5 to pg. 32, para. 3).
This argument is not persuasive. First, the relationship between the biomarker combination and urogenital system tumors is not a shared technical feature, because claim 26 does not recite any such relationship. Claim 26 is merely a combination of biomarkers. Furthermore, Molparia (previously cited; cited in IDS filed 05 Nov. 2021) discloses downloading whole genome copy number variation data (i.e. including all positions on all chromosomes) (pg. 13, para. 3), which is considered to be a biomarker combination that includes the combination of biomarkers according to claim 1, and thus is not a special technical feature. The biomarkers of claim 26 are not closed to unrecited elements, and thus the copy number variation data of the whole genome reads on the claimed combination.
Status of Claims
Claims 8-9, 11, 15, 17, 20, 22, 22-25, and 29-30 are cancelled.
Claims 1-7, 10, 12-14, 16, 18-19, 21, and 26-28 are pending.
Claim 26 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 19 March 2026.
Claims 1-7, 10, 12-14, 16, 18-19, 21, and 27-28 are rejected.
Claims 1 and 6 are objected to.
Priority
Applicant’s claim for the benefit of a prior-filed application, PCT/CN2020/087830 filed 29 April 2020, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority to App. No. CN201910374094.1, filed 07 May 2019, under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Accordingly, the effective filing date of the claimed invention is 07 May 2019.
Drawings
The objection to the drawings in the Office action mailed 24 April 2026 has been withdrawn in view of the replacement drawings filed 23 July 2026.
The replacement drawings filed 23 July 2026 are accepted.
Specification
The objection to the abstract of the disclosure in the Office action mailed 24 April 2026 has been withdrawn in view of the replacement abstract filed 23 July 2026.
Claim Objections
The objection to claims 5 and 16 in the Office action mailed 24 April 2026 has been withdrawn in view of the claim amendments filed 23 July 2026.
Claims 1 and 6 are objected to because of the following informalities. This objection is newly recited and necessitated by claim amendment.
Claim 1 recites “determining category or categories…”, which is missing an article and should recite “determining a category or categories”…”.
Claim 1 recites “dividing genome of the target sample…”, which is missing an article and should recite “dividing a genome…”.
Claim 1 recite “wherein: A represents actual number of reads…B represents theoretical number of reads”, which are missing articles “an” and ”a” before “actual number of reads” and “theoretical number of reads”, respectively;
Claim 1 recites “wherein the copy number variation data…is calculated according to the following method: dividing…, wherein: A represents….; B represents…; the ratio A/B represents…”. To increase readability, the substeps (including the wherein clauses) for calculating according to the following method should be further indented. Furthermore, there should be an “and” after the penultimate wherein clause to recite “…B represents…; and the ratio A/B represents…”.
Claim 6 recites “i)…votes, category…” which is missing an article and should recite “a category corresponding to the group…”.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites “wherein the copy number variation data of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label is obtained by calculation from sequencing data of a cfDNA in a urine sample”. Claim 1 previously recites “calculating a similarity degree between the target cfDNA copy number variation data and cfDNA copy number variation data of each category label”. However, claim 1 does not recite a step of calculating cfDNA copy number variation data of each category label. Therefore, the wherein clause is interpreted to define the process in which the cfDNA copy number variation data of each category label was previously obtained. See MPEP 2113. In the alternate embodiment, the wherein clause further limits the calculating step of the copy number variation data of cfDNA in the target sample to be calculated from already generated sequencing data of a cfDNA in a urine sample. However, the claim does not require an active step of sequencing cfDNA in a urine sample.
Claim 16 recites “A method…comprising the following steps, comprising step (1), step (2), optionally step (3), and step (4):…”. Therefore, under the broadest reasonable interpretation of the claims, the method of claim 16 is interpreted to comprise steps (1), (2), and (4).
Claim 21 recites a “normal decision-making unit”, “renal caner decision-making unit”, a “urothelial cancer decision-making unit”, and a “prostate cancer decisions-making unit”. Claim 21 recites these units comprise “3 random forest binary classifiers” and include instructions executed by a processor. Accordingly, each decision-making unit is interpreted to correspond to instructions for 3 random forest binary classifiers stored in memory and executable by a processor. Thus claim 21 recites sufficient structure for the function of “decision-making” of the various units, and do not invoke 35 U.S.C. 112(f).
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
.
Claims 1-7, 10, 12-14, 16, 18-19, 21, and 27-28 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Any newly recited portion is necessitated by claim amendment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “cfDNA copy number variation data of each category label”. Given the claim does not previously recite any category labels, it is not clear what set of labels “each category label” is referring to. It is noted that later in the claim, categories including “renal cancer”, “normal”, etc. are recited in Tables 1-7. If Applicant intends for each category label to refer to these categories, the claim should be amended accordingly. For purpose of examination, the category labels will be interpreted to refer to any two or more disease categories recited in Tables 1-7.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “…wherein the copy number variation data of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label…is calculated according to the following methods: dividing [a] genome of the target sample…”. It is not clear if claim 1 intends for the copy number variation data of cfDNA in the target sample to be required to be performed according to the following methods, as suggested by the dividing step, or if claim 1 intends to encompass calculating the copy number variation data for the target sample or the copy number variation data for each category label, such that the sample being divided is not required to be the target sample. Clarification is requested on whether the claims intend to require using the “following methods” on the target sample or if this is an alternative embodiment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “the sequencing data” in lines 15-16. Claim 1 previously recites “wherein the copy number variation data of cfDNA in the target sample and/or the copy number variation data of each category label is obtained by calculating from a sequencing data of cfDNA…”.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “the ratio A/B represents the copy number variation”. Claim 1 previously recites “copy number variation data of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label”, which may include multiple copy number variations (e.g. in the various bins). As a result, it is unclear what copy number variation is being referenced. Furthermore, since claim 1 previously recites “calculating a ratio of A/B of each bin”, it is further unclear if claim 1 intends to require that a copy number variation is determined in each bin of the 5,000 to 500,000 bins, or if the ratio A/B is simply intended to represent copy number, which may include a copy number variation. For purpose of examination, the limitation is interpreted to mean that the determined A/B ratios correspond to the copy number variation data of the cfDNA in the target sample and/or the cfDNA copy number variation data of each category label.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “extracting the ratio A/B for each biomarker in a biomarker combination”. There is insufficient antecedent basis for “the ratio A/B for each biomarker in a biomarker combination”, given claim 1 previously only determined an A/B ratio for each bin and each bin has an equal length. As a result, it is further unclear if (1) each ratio A/B corresponds to a bin (e.g. of a set length), (2) if each ratio A/B corresponds to a specific biomarker (which have varying lengths as recited in the Tables), (3) if each ratio A/B corresponds to a specific combination of biomarkers, and/or (3) if the biomarkers or biomarker combinations are supposed to correspond to the bins. It is further noted the recited biomarker combinations do not include 5,000 to 500,000 biomarkers (and are only required to be over 50 biomarkers), and thus the bins do not appear to correspond to the biomarkers, raising confusion on what regions of the genome each ratio is intended to correspond to. Clarification is requested. A review of Applicant’s specification at para. [0187]-[0188] discloses ratios of A/B corresponding to the groups of biomarkers are used for classification. Therefore, for purposes of applying prior art, the claims are interpreted to mean A/B ratios are determined for each of the bins and the chromosomal region of each biomarker of the biomarker combination (any one to seven of the recited groups).
Dependent claim 2, and claims dependent therefrom, are indefinite for recitation of “the similarity degree”. Claim 1, from which claim 2 depends, recites “calculating a similarity degree between the target cfDNA copy number variation data and the cfDNA copy number variation data of each category label”, such that there is a similarity degree corresponding to each category label. As a result, it is not clear which similarity degree, “the similarity degree” is referring to.
Claim 6 is indefinite for recitation of “ii)…the category corresponding to the group with a highest prediction probability in the groups….”. Claim 5, from which claim 6 depends, recites groups each with multiple categories (i.e. normal, renal, urothelial, prostate cancer in Group 1). As a result, it is not clear which category corresponding to the group with the highest prediction probability is intended to be the category to which the target cfDNA belongs.
Claims 16 and 21, and claims dependent therefrom, recite and “classifying…according to the classification method according to claim 1” and “configured to execute the classification method according to claim 1…”, respectively, and thus are also indefinite for each of the reasons set forth above with respect to claim 1.
Response to Arguments
Applicant's arguments filed 23 July 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive.
Applicant remarks that with the amendments, the indefiniteness rejections of claim 1 have been obviated (Applicant’s remarks at pg. 23, para. 3 to pg. 25, para. 1).
This argument is not persuasive. Indefiniteness remains as set forth above.
Applicant remarks that with the amendments, the indefiniteness rejections of claim 6 have been obviated (Applicant’s remarks at pg. 26, para. 3-4).
This argument is not persuasive. Indefiniteness remains as set forth above.
Applicant remarks that the indefiniteness of claims 16 and 21 are obviated in view of the amendments to claim 1 (Applicant’s remarks at pg. 28, para. 3-4).
This argument is not persuasive for the reasons discussed above for claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claims 14-15, 17, 23, and 29 under 35 U.S.C. 112(d) in the Office action mailed 24 April 2026 has been withdrawn in view of claim amendments and cancelations received 23 July 2026.
Claim Rejections - 35 USC § 101
The rejection of claims 9, 15, 17, 23, and 29-30 under 35 U.S.C. 101 in the Office action mailed 24 April 2026 has been withdrawn in view of claim amendments and cancelations received 23 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 1-7, 10, 12-14, 16, 18-19, 21, and 27-28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
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 (claims 1, 16, and 21 being representative) is directed to a method and apparatus for cancer diagnosis. 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:
calculating a copy number variation data of cfDNA in a target sample;
calculating a similarity degree between the target cfDNA copy number variation data and the cfDNA copy number variation data of each category label; and
determining a category or categories to which the target cfDNA belongs according to the similarity degree between the target cfDNA copy number variation data and cfDNA copy number variation data of each category label by using a classifier model, wherein the copy number variation data of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label is obtained by calculation from sequencing data of a cfDNA in a urine sample;
wherein the copy number variation data of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label is calculated according to the following method:
dividing a genome of the target sample to be tested into 5,000 to 500,000 bins with equal lengths or equal theoretical simulation copy numbers; normalizing the sequencing data, and calculating a ratio A/B of each bin;
wherein: A represents an actual number of reads in a bin after GC content correction; B represents a theoretical number of reads in the bin, which is obtained by dividing the total number of reads measured in the sample by the total number of bins; and the ratio A/B represents the copy number variation of cfDNA in the target sample and/or the cfDNA copy number variation data of each category label”.
extracting the ratio A/B for each biomarker in a biomarker combination, wherein the biomarker combination comprises m biomarkers, and m represents a positive integer greater than or equal to 50; each biomarker in the biomarker combination is a DNA fragment, correspondingly having an initiate site of C±n1 and a termination site of D+n2 on a chromosome; wherein, the n1 and n2 are independently non-negative integers less than or equal to 60,000;
wherein, the chromosome, C and D are any one, any two, any three, any four, any five, any six or all seven groups selected from the group consisting of the following Groups (1) to (7) (including the recited Tables).
Claims 16 recites the same abstract idea as identified above for claim 1 by reciting “classifying the cfDNA fragments according to the classification method according to claim 1”.
Claim 21 recites the same abstract idea as identified above for claim 1 by reciting “execute the classification method according to claim 1…”.
Claim 21 further recites the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
any one, any two, any three, or all of four decision-making units selected from the group consisting of the following four decision-making units, wherein each decision-making unit comprises 3 random forest binary classifiers:
I. 'normal decision-making unit':
normal-vs-renal cancer, normal-vs-urothelial cancer, normal-vs-prostate cancer;
II. 'renal cancer decision-making unit':
renal cancer-vs-normal, renal cancer-vs-urothelial cancer, renal cancer-vs-prostate cancer;
III. 'urothelial cancer decision-making unit:
urothelial cancer-vs-normal, urothelial cancer-vs-renal cancer, urothelial cancer-vs-prostate cancer;
IV. "prostate cancer decision-making unit':
prostate cancer-vs-normal, prostate cancer-vs-renal cancer, prostate cancer-vs-urothelial cancer
The following limitations fall into the group of abstract ideas of mental processes for the following reasons. In this case, the step of calculating a copy number variation data of cfDNA comprising dividing a genome into 5,000 to 500,000 bins, normalizing sequencing data, calculating an A/B ratio of each bin, and extracting A/B ratios for biomarkers can be practically performed in the mind because it encompasses organizing positions in a genome into bins (e.g. positions 1-10,000, positions 10,001 to 20,000, etc.), dividing a count of reads in each bin a fixed value to obtain normalized data, performing division between values representing the actual reads and theoretical reads to obtain A/B ratios, and then identifying an A/B ratio of a bin on a chromosome that covers a given biomarker. The human mind is practically able to organize information, perform division, and analyze positions on a chromosome. Calculating a similarity degree between the target cfDNA copy number variation data and cfDNA copy number variation data of category labels encompasses comparing copy number variation data of the cfDNA to copy number data of a category label to determine a difference between the copy numbers in each sample. Determining the category to which the target cfDNA belongs according to the similarity degree using a classifier model encompasses performing a clustering analysis on the copy number data, which merely involves calculating distances between the target cfDNA and copy numbers of category labels to determine which cluster the target cfDNA belongs. Furthermore, the limitations relating to the combination of biomarkers defines the ratio being calculated, and thus is part of the mental process identified above.
The steps of calculating a copy number variation data including normalizing sequencing reads and calculating a ratio of A/B for each bin, calculating a similarity degree, determining the category to which the target cfDNA belongs using a classifier model, and various decision-making units comprising three random forest classifiers further recite a mathematical concept. Performing normalizing on a count of sequencing reads amounts to a textual equivalent to performing division or multiplication. Furthermore, calculating a ratio of A/B also clearly recites a mathematical calculation and further recites a mathematical relationship between actual counts and theoretical counts. Calculating a similarity degree and determining a category to which the target cfDNA belongs according to the similarity degree using a classifier model encompasses calculating a difference between copy numbers to determine a similarity and performing a mathematical analysis, such as a random forest model, clustering, or a linear regression (the classifier model) using the similarity degree to determine the category. Last, the random forest classifiers of each decision making unit recite a mathematical relationship between copy number variation data and a disease probability. Therefore, these limitations recite a mathematical concept. See MPEP 2106.04(a)(2) I.
Dependent claims 2-7, 10, 12-14, and 27-28 further recite an abstract idea and/or are part of the abstract idea of claims 1, 16, and 21. Dependent claim 2 further recites the mathematical concept of determining a correlation degree between the copy number variation data of each category label and a tumor according to the similarity degree by using a random forest model, and then further limits the mental process and mathematical concept of determining the category of claim 1 to be according to the correlation degree. Dependent claim 3 further recites the mental process of sorting cfDNA copy number data according to the correlation degree to form a vector sequence, and the mathematical concept of inputting the vector sequence into the random forest model and determining the correlation degree. Dependent claim 4 further limits the mathematical concept of the correlation degree of claim 3 to correspond to a tumor selected from prostate cancer, urothelial cancer, and renal cancer. Dependent claim 5 further limits the mathematical concept of claim 3 of applying the random forest model to be three random forest classifiers from the recited group. Dependent claim 6 further recites the mental process of voting on each group and assigning a category with the highest number of votes as a final category. Dependent claims 7 and 10 further limits the mental process and mathematical concept of determining copy number variation data to be calculated from a sequencing data of cfDNA from a morning urine or morning urine supernatant. Dependent claims 12-13 further limit the mental process and mathematical calculations of calculating a ratio A/B for the m biomarkers to be performed for a particular number of biomarkers of a certain length. Dependent claim 14 defines the process in which each biomarker in the biomarker combination was previously derived from a human urine or human urine supernatant, and thus is part of the abstract idea of extracting A/B ratios for each biomarker of claim 1. Claim 27 recites the process in which the urogenital system tumor was previously diagnosed, and thus is part of the mental process and mathematical concept of determining the correlation degree for the tumor of claim 3. Dependent claim 28 further limits the mental process and mathematical concept of claim 4.
Last, the claims further recite a law of nature of a natural correlation between copy number variations of specific regions of a chromosome (biomarkers) and the presence of a urogenital system tumor, analogous to the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone, Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018). See MPEP 2106.04(b).
Therefore, claims 1-7, 10, 12-14, 16, 18-19, 21, and 27-28 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 1-7, 10, 12-14, 21, and 27-28 do not recite any elements in addition to the judicial exception and thus are part of the judicial exception.
The additional elements of claim 16 include:
(1) collecting a urine sample and extracting cfDNA;
(2) screening to obtain cfDNA fragments of 90 to 300 bp or cfDNA fragments of 100 to 300 bp;
(3) (optionally) using the obtained cfDNA fragments to construct a whole genome library; and
The additional elements of dependent claims 18-19 include:
wherein the urine sample is a morning urine or a morning urine supernatant;
wherein in step (2) the screening is a screening by magnetic beads;
The additional elements of claim 21 include:
a memory…wherein, the memory stores a program instruction to be executed; and
a processor.
First, the additional elements of claims 16 and 18-19 of collecting a morning urine and screening cfDNA fragments using magnetic beads is not sufficient to integrate the recited judicial exception because they only serve to collect the necessary data for the abstract idea. Therefore, the additional elements amount to insignificant extra-solution activity. See MPEP 2106.05(g).
The additional elements of a memory and processor of claim 21 are generic computer components used to carry out the abstract idea. 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).
Therefore, the additionally recited elements amount to insignificant extra-solution activity and/or merely invoke computers as a tool, and as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1-7, 10, 12-14, 16, 18-19, 21, and 27-28 are directed to an abstract idea and law of nature. [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 for the following reasons:
Claims 1-7, 10, 12-14, 21, and 27-28 do not recite any elements in addition to the judicial exception and thus are part of the judicial exception. The additional elements are outlined above under Step 2A, prong 2.
The additional elements of claims 16 and 18-19 of collecting a morning urine or morning urine supernatant, extracting cfDNA, and screening cfDNA fragments using magnetic beads to obtain fragments of 90 to 300 bp or of 100 to 300 bp are well-understood, routine, and conventional. This position is supported by Lin et al. (Emerging Utility of Urinary Cell-free Nucleic Acid Biomarkers for Prostate, Bladder, and Renal Cancers, 2017, European Urology Focus, 3 , pg. 265-272; previously cited) and Ralla et al. (Nucleic acid-based biomarkers in body fluids of patients with urologic malignancies, 2014, Crit Rev Clin Lab Sci, 51(4), pg. 200-231; previously cited). Lin reviews the current status of urinary cell-free nucleic acid in genitourinary (GU) caners (Abstract), and discloses that urine has been found to be a comparable bodily fluid source for detecting cfDNA, citing numerous studies (pg. 266, col. 1, para. 2-3). Lin reviews numerous studies that have analyzed cfDNA in urine supernatant or whole urine (pg. 266, col. 2, para. 5 to pg. 267, col. 1, para. 1), and that urine collection comprises using first-void morning samples (pg. 268, col. 2, para. 1). Lin further discloses that cfDNA isolation (i.e. extraction) requires recovery of ~150 base pair sizes because it is the urinary subfraction enriched for tumor-derived DNA (i.e. screening for fragments from 90 to 300 base pairs) (pg. 268, col. 2, para. 3). Similar to Lin, Ralla reviews nucleic acid biomarkers in bodily fluids, including blood and urine, and their application in diagnosing urologic malignancies (Abstract), and discloses there are numerous isolation procedures for cell-free DNA published by several companies as commercial ready to use kits, including extraction with organic solvents, isolation by selective binding properties on silica-gel material, and the use magnetic beads (pg. 205, col. 1, para. 3). Thus even considered in combination, these additional elements are well-understood, routine, and conventional
The additional elements of a memory and processor of claim 21 are conventional computer components used to carry out the abstract idea. 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).
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 natural correlation 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 23 July 2026 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks that that in the claimed method a urine sample is obtained, followed by extracting the cfDNA from the urine sample, sequencing the cfDNA and obtaining sequencing data, calculating cfDNA copy number variation of cfDNA using the sequencing data and so on, and further remarks that the specification discloses that there is not tumor marker with good sensitivity and specificity that can be used for early diagnosis and postoperative follow-up of renal cancer and instead, imaging, fine needle aspiration, and core biopsy can assist in monitoring (Applicant’s remarks at pg. 30, para. 1 to pg. 31, para. 1). Applicant further remarks that the claimed method is truly noninvasive because urine collection is noninvasive and causes no pain in patients, and by detecting the cfDNA copy number variation in the urine supernatant, the diagnosis and classification of urogenital system tumors can be completed at one time, and therefore, the claim elements apply and judicial exception to the particular technological environment of the diagnosis of urogenital system tumors by enhancing compliance and comfort in a non-invasive manner (Applicant’s remarks at pg. 31, 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, or 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).
First, the argument is not commensurate with the scope of claim 1, which does not require any additional elements of obtaining a urine sample, extracting the cfDNA from the urine sample, and sequencing the cfDNA. Claim 1 does not recite any additional elements under Step 2A, Prong 2 and Step 2B above, and therefore, does not recite any additional elements that provide the alleged improvement.
Furthermore, it is acknowledged that claim 16 does require collecting a urine sample, extracting cfDNA, screening to obtain cfDNA fragments of a certain length, and then using these cfDNA fragments according to the method of claim 1. Claim 16 similarly does not require any sequencing of cfDNA fragments. However, the steps of collecting a morning urine, extracting cfDNA, and screening cfDNA fragments using magnetic beads only serve to collect the necessary data for the abstract idea, which amounts to insignificant extra-solution activity. See MPEP 2106.05(g). Applicant alleges these additional elements provide an improvement because they are non-invasive. However, in view of Lin and Ralla, discussed in the above rejection, the analysis of cfDNA in diagnosing urologic malignancies is already well-understood, routine, and conventional before the effective filing date of the claimed invention (see Step 2B above). As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional. Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978).
Therefore, it is not apparent that the alleged improvement is provided by one or more additional elements. Instead, any improvement in diagnosis and classification appears to provided solely by the analysis of copy number variation data for particular biomarker combinations to classify a category type, which is an improvement in the abstract idea rather than a technology.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAITLYN L MINCHELLA whose telephone number is (571)272-6485. The examiner can normally be reached 7:00 - 4:00 M-Th.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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