DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 3, 18-50, 52-54, and 56 are canceled.
Claims 4-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-2, 15-17, 51, and 55 are pending and are examined on the merits.
Priority
The instant application is the National Stage entry of PCT/US2020/014011, International Filing Date: 01/17/2020, which claims priority to US Provisional Application 62793722, filed 01/17/2019. At this point in examination, all claims have been interpreted as being accorded this priority date.
Withdrawn Rejections/Objections
Rejections and/or objections not reiterated from previous office actions are hereby
withdrawn in view of the amendments filed 06/07/2024.
All rejections of claims 3 and 54 are hereby withdrawn; their cancelation moots the
rejections.
The objection to the Specification in the office action filed 11/06/2025 has been withdrawn in view of amendments received 02/06/2026 since Applicant previously submitted the references listed in the specification in a proper information disclosure statement.
The 35 U.S.C. 102(a)(2) rejections to claims 1, 51, and 54-55 in the office action filed 11/06/2025 has been withdrawn in view of amendments received 02/06/2026 specifically by adding limitations of claims 3 and 54 to claim 1.
The double patenting rejection to claims 1, 15-17, 51, and 54-55, the abandonment of reference Application 16/631,976 moot the rejection.
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2 15-17, 51 and 55 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea 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 (claim(s) 1-2, 15-17, 51, and 55 being representative) is directed to a method. 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.
Claims 1-2, 15-17, 51, 55 recite the following steps which fall under the mathematical concepts, mental processes, and/or certain methods of organizing human activity groupings of abstract ideas:
Claim 1 recites determining a global cancer pathway transcript (CPT) expression profile for the sample based on the RNA expression data for one or more cancer-related pathways; the limitation determining an expression profile is considered a mathematical calculation, as discloses in instant specification para. 77 “expression profiling of 212 genes from 12 cancer-related profiles were generated using a machine learning model … the machine learning model can optionally be t-distributed stochastic neighbor embedding (t-SNE)”. As such, said limitation falls into mathematical concepts groupings of abstract ideas. Also, said limitation given the plain meaning of “determining” encompasses mental observations or evaluations, e.g., mental determination of a profile based on known data. See MPEP 2106.04(a)(2), subsection III.
Claim 1 further recites providing a diagnosis, prognosis, or treatment recommendation based on the global CPT expression profile; the limitation providing a diagnosis, prognosis, or a recommendation, given the plain meaning of “providing” encompasses mental observation, evaluation, judgment, and opinion (See MPEP 2106.04(a)(2), subsection III.) since human mind is capable of providing a diagnosis, prognosis, or a recommendation based on the result of an analysis. As such, said limitation falls into mental processes groupings of abstract ideas.
Claim 1 further recites determining respective global CPT expression profiles for the tumors in the database based on the respective RNA expression data; the limitation determining an expression profile falls into mathematical concepts as well as mental processes of abstract ideas (see above).
Claim 1 further recites identifying recurring patterns of CPT expression among the tumors in the database; the limitation “identifying”, given the plain meaning of “identifying” encompasses mental observation, evaluation, judgment, and opinion (See MPEP 2106.04(a)(2), subsection III.) since human mind is capable of identifying patterns in a dataset. As such, said limitation falls into mental processes of abstract ideas.
Claim 1 further recites comparing the recurring patterns of CPT expression with the respective clinical parameters; the limitation comparing is considered a mathematical calculation, as disclosed in instant specification para. 86 “each t-E cluster were compared using Mantel-Haenszel (log-rank) methods”, as such said limitation falls into mathematical concepts groupings of abstract ideas. Said limitation also given the plain meaning of “comparing” encompasses observations, observation, evaluation, judgment, and opinion. See MPEP 2106.04(a)(2), subsection III. e.g., observing and evaluating patterns. As such, said limitation falls into mental processes groupings of abstract ideas.
Claim 55 recites applying a machine learning model that analyzes linear and non-linear relationships among the respective relative expression for each of the plurality of CPTs; the limitation applying a machine learning model/mathematical algorithm is considered mathematical calculation, as disclosed in instant specification para. 9 “the machine learning model can be t-distributed stochastic neighbor embedding (t-SNE)”, see also para. 85. As such said limitation falls into mathematical concepts groupings of abstract ideas.
Additionally, claims 1-2, 15-17, 51 and 55 recite a correlation between tumor sample RNA and survivability of the subject for cancer, and as such, falls into judicial exception of Laws of nature and natural phenomena. See MPEP 2106(b) I.
The identified claims recite a law of nature, a natural phenomenon (product of nature) or fall into one or more of the groups of abstract ideas of mathematical concepts, mental processes, and/or certain methods of organizing human activity for the reasons set forth above. See MPEP 2106.04 (a)(2) III and MPEP 2106.04 (b) I. Therefore, claims are directed to one or more judicial exception(s) and require further analysis in Prong Two. [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.
The additional elements of claims 1-2, 15-17, 51 and 55 include the following.
Claim 1 recites receiving RNA expression data for a sample of tumor from the subject; using a computing device.
Claim 51 recites receiving the sample of tumor; extracting RNA from the sample; isolating a plurality of CPTs from the extracted RNA; and obtaining the RNA expression data from the isolated CPTs.
Claim 54 recites receiving respective RNA expression data and respective clinical information for each of a plurality of tumors from a database.
The additional element of a computing device amount to generic computer component and/or processes. There are no limitations that indicate that the computing device require anything other than generic computing systems. 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).
Furthermore, the additional elements of receiving sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data amount to nothing more than gathering the data necessary to perform the abstract idea. Steps of receiving sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data are performed in order to gather data for the mathematical and/or mental analysis steps, and is a necessary precursor for the recited exception. Said step do not pose meaningful limitations on the scope of the claims: they would be performed in exactly the same manner if the samples were analyzed using a different abstract idea, or none at all.
The courts have found the limitations that amount to necessary data gathering and outputting are insignificant extra-solution activity that do not integrate a recited judicial exception into a practical application in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and O/P Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (see MPEP 2106.05(g)).
Therefore, these additional elements amount to general-purpose computer and/or insignificant extra-solution activity, which is not sufficient to integrate the recited judicial exception into a practical application. See MPEP 2106.05(g). Thus, claims 1-2,15-17,51 and 55 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. An inventive concept cannot be furnished by an abstract idea itself. 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.
The additional elements of claims 1-2, 15-17, 51 and 55 include the following.
Claim 1 recites receiving RNA expression data for a sample of tumor from the subject; using a computing device.
Claim 51 recites receiving the sample of tumor; extracting RNA from the sample; isolating a plurality of CPTs from the extracted RNA; and obtaining the RNA expression data from the isolated CPTs.
Claim 54 recites receiving respective RNA expression data and respective clinical information for each of a plurality of tumors from a database.
The additional element of a computing device amount to conventional 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); TU 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 receiving sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data amount to nothing more than gathering the data necessary to perform the abstract idea. said additional elements are activities incidental to the primary process or product (all uses of the judicial exception require such data gathering or data output) that are merely a nominal or tangential addition to the claim and they amount to necessary data gathering and outputting. These additional elements are considered insignificant extra-solution activities. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept. See MPEP 2106.05(g)(3).
Furthermore, additional elements of receiving tumor sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data amount to well-understood, routine, and conventional methods cancer diagnosis. This position is supported by Engqvist et al. (Transcriptomic and genomic profiling of early-stage ovarian carcinomas associated with histotype and overall survival, Oncotarget, 2018, Vol. 9, (No. 80), pp: 35162-35180). Engqvist teaches extracting RNA from tumor samples, sequencing and aligning reads, determining differentially expressed transcripts of the tumor samples in the study and control cohort, and cancer pathway analysis to identify cancer-related biological functions associated with the identified genetic variants, differentially expressed genes and fusion transcripts (pg. 35174-35176). Engqvist further teaches analyzing clinical data of patients with cancer in Table 1.
Therefore, the additional element is not sufficient to amount to significantly more than the judicial exception.
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 without significantly more.
Response to Arguments
Applicant's arguments filed 02/06/2026 have been fully considered but they are not persuasive. Applicant states:
Claim 1 has been amended to require creating a control by identifying recurring patterns of CPT relative expression. The claimed identification of relative expression is a specific real- world (technological) application that distinguishes useful data from background data. Nevertheless, Applicant has also amended claim 1 to recite that the identifying of recurring patterns of CPT relative expression is performed by a computing device. Amended claim 1 therefore recites physical components that are performing the functions of the method recited in claim 1. As such, the invention recited in claim 1 cannot be directed to a mental process as the functionality is being performed by physical components to achieve the result of creating a control by identifying recurring patterns of CPT relative expression. The complexity of the operations is such that they cannot be performed in the human mind.
It is respectfully submitted that these are not persuasive. The Applicant remarks are directed to Step 2A Prong One of 101 analysis, specifically that whether the claims recite a judicial exception.
As stated above, the steps of b) determining, c) providing, e) determining, f) identifying, and g) comparing recite abstract ideas (i.e., mental and mathematical concepts) that merely uses a general-purpose computer as a tool to perform the process and therefore not subject matter eligible. See MPEP 2106.05(f).
With regards to Applicant referring to complexity of operation, Examiner submits that there is not a threshold at which point performing mental and/or mathematical processes graduates from what can be performed by the mind to not performable by the human mind. While this may take a long time, the use of a physical aid, such as a pen-and-paper or computer, may accelerate this process, and this does not negate the mental and/or mathematical nature of the limitation. Applicant will further note that complexity of operations does not equate to eligibility. The fact remains that the steps are directed to operations that are mental and/or mathematical as above.
Applicant further states:
Creating a control by determining the patterns of relative expression of cancer pathway transcripts reliably predicted survival in 30 cancer types, proving of predictive value in 91.4% of all cancers examined. See specification, page 26, paragraph 106. This is an extremely significant improvement in the field of cancer detection and prognosis.
It is respectfully submitted that this is not persuasive. The Applicant remarks are directed to Step 2A Prong Two of 101 analysis, specifically whether the additional elements integrate the recited judicial exception into a practical application of the exception.
The additional element of a computing device amounts to general purpose computer to perform the abstract ideas and do not integrate the judicial exception into a practical application. Furthermore, the additional elements of receiving sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data amount to nothing more than gathering the data necessary to perform the abstract idea and don not integrate the judicial exceptions into a practical application.
Determining patterns and predicting, as noted by the Applicant above, ae abstract ideas. Taken as a whole, the instant claims are directed to diagnosing and monitoring cancer through series of mental and mathematical calculation. It is important to note, the judicial exception alone cannot provide the improvement (See MPEP 2106.04(d) III). The improvement must 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. See MPEP § 2106.04(d) (discussing Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 1299, 1303-04, 125 USPQ2d 1282, 1285-87 (Fed. Cir. 2018)).
Applicant further states:
The Engqvist et al. reference (Transcriptomic and genomic profiling of early-stage
ovarian carcinomas associated with histotype and overall survival, Oncotarget, 2018, Vol. 9 (No. 80) pp. 35162-35180) does not teach determining the relative expression patterns of cancer pathway transcripts. Therefore, the Engqvist et al. reference fails to establish that the additional elements of the amended claims are not significantly more than the judicial exception.
It is respectfully submitted that these are not persuasive. The Applicant remarks are directed to Step 2B of 101 analyses, specifically evaluating additional elements to determine whether they amount to an inventive concept by considering them both individually and in combination to ensure that they amount to significantly more than the judicial exception itself.
As stated above, additional element of a computing device amounts to general purpose computer to perform the abstract ideas and do not integrate the judicial exception into a practical application. Furthermore, the additional elements of receiving sample, extracting RNA, isolating CPTs from extracted sample data, and receiving RNA and clinical data amount to nothing more than gathering the data necessary to perform the abstract idea and don not integrate the judicial exceptions into a practical application. See MPEP 2106.05(g)(3).
Furthermore, in response to appellant stating that Engqvist does not teach determining the relative expression patterns of cancer pathway transcripts, Examiner submits that the "‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1315, 120 USPQ2d 1353, 1358 (Fed. Cir. 2016) (quoting Diamond v. Diehr, 450 U.S. at 188–89, 209 USPQ at 9). See also Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) ("a claim for a new abstract idea is still an abstract idea. The search for a § 101 inventive concept is thus distinct from demonstrating § 102 novelty."). In addition, the search for an inventive concept is different from an obviousness analysis under 35 U.S.C. 103. See, e.g., BASCOM Global Internet v. AT&T Mobility LLC, 827 F.3d 1341, 1350, 119 USPQ2d 1236, 1242 (Fed. Cir. 2016). See MPEP 2106.05 I.
Additionally, Engqvist (pg. 35163, col. 2, last para.) discloses pathway analysis performed using genes corresponding to the potential deleterious variations, revealed an association with a number of cancer-related pathways.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 15-17, 51, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Kennedy et al. (US 20160068915 A1) as applied to claims 1, 51 and 54-55 above, and further in view of Ma et al. (Overexpression of E2F1 Promotes Tumor Malignancy and Correlates with TNM Stages in Clear Cell Renal Cell Carcinoma, PLoS One. 2013 Sep 4;8(9): e73436).
Regarding claim 1, Kennedy discloses kits, compositions, and methods relating to the classification of samples that can be used for diagnosing and/or treating a subject suspected of having a disease such as cancer (abstract) [0004]; reading on limitations of a method for diagnosing, monitoring the progress of, and/or providing a prognosis of a cancer in a subject.
Kennedy further discloses obtaining a biological sample from said subject; assaying an expression level of one or more gene expression products in the biological sample (claim 1 and 27) where the gene expression product is RNA, mRNA, rRNA, tRNA, or miRNA [0026]; reading on limitations of receiving RNA expression data for a sample of tumor.
Kennedy further discloses that gene expression profiling can comprise the measurement of the activity or expression of a plurality of genes at once, to create a global picture of cellular function [0174]. Kennedy further discloses determination of the underlying genetic, metabolic, or signaling pathways responsible for the resulting pathology where the signaling pathways is indicative of cancer [0160] [0247]; reading on limitations of determining a global cancer pathway transcript (CPT) expression profile for the sample based on the RNA expression data for one or more cancer-related pathways.
Kennedy further discloses classifying the biological sample as containing or not containing cancer and/or a specific tissue type based upon the comparison of the one or more clinical classifiers to yield a classification of the biological sample; and diagnosing and/or treating the subject based upon the classification [0014]. Kennedy further discloses comparing gene expression product levels (e.g., profile) from a biological sample with a biomarker panel and/or a classification panel; and characterizing the biological sample (e.g., as cancerous, suspicious, or benign; as male or female; as mutant or wild-type; etc.) based on the comparison [0098] and that the number and/or type can further be compared to a control sample or a sample considered normal [0166]. Kennedy further discloses application of various inhibitors of the aberrantly activated or dysregulated pathway, or drugs known to inhibit the activity of the pathway can then be tested against the tumor cell line for growth inhibition. Molecular profiling can also be used to monitor the effect of these inhibitors on for example down-stream targets of the implicated pathway [0255]. Kennedy further discloses that driver mutations can be causally implicated in oncogenesis or tumor survival. Such mutations can be positively selected during carcinogenesis and can show a recurrent pattern within or across tumor types… the biological samples may be further classified as having an aggressive prognosis or not having an aggressive prognosis [0269] and that a diagnostic result can indicate a certain molecular pathway is involved in the cancer disease or condition, or a certain grade or stage of a particular cancer disease or condition [0234]. Kennedy further discloses possible outcomes of the classifier, where a true negative (e.g., definitive benign) has occurred when both the prediction outcome and the actual value are n (where “n” is a negative classifier output, such as benign, or absence of a particular disease tissue) [0239]; reading on limitations of providing a diagnosis, prognosis, or treatment recommendation based on the global CPT expression profile; wherein a change in one or more cancer pathway transcripts relative to a control indicates an increase in survivability of the subject for the cancer.
Kennedy [0268] discloses biomarkers related to signaling pathways such as adherens pathway, focal adhesion pathway, and tight junction pathway, or other pathway, as evidenced by Wilde et al. (Wilde [0363] “Pathway over-representation analysis on both gene lists is enriched for cell-membrane, cell cycle phase, mitosis, and spindle pathways”). Kennedy further discloses that the one or more cancer-related pathways is Cell cycle providing a list of gene markers representing lymphoma signature biomarkers...CDC2 cell division cycle 2, G1 to S and G2 to M 4.38E-13 1.92 3936913 CDC45L CDC45 cell division cycle 45-like (S. cerevisiae) 8.74E-13 1.52 3720896 CDC6 cell division cycle 6 homolog (S. cerevisiae) 2.92E-11 2.18 3090697 CDCA2 cell division cycle associated 2 5.18E-15 1.63 2516023 CDCA7 cell division cycle associated 7") [0381]. Kennedy further discloses that the biomarker is E2F8 [0381] and that the cancer is renal carcinoma [0092].
Further regarding claims 1, Kennedy does not expressly disclose that the cancer is clear cell renal cancer and that the transcript is E2F1. Ma explores the function of E2F1 in clear cell renal carcinoma (claims 15-17) and found that Transcription factor E2F1 (claim 3) was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (abstarct) and that E2F1 exerted an enforced effect on cell cycle (claims 2-3) progression which may partly explain the proliferation effect of E2F1 on ccRCC cells (pg. 4, col. 2, subsection: E2F1 accelerated G1/S transition in cell cycle).
Kennedy further discloses obtaining a biological sample from said subject;
assaying an expression level of one or more gene expression products in the biological sample;
using one or more clinical statistics to compare the expression level to a reference expression level of a plurality of genes to generate a comparison of expression levels (claim 56) reading on limitations of a) receiving respective RNA expression data and respective clinical information for each of a plurality of tumors from a database; b) determining respective global CPT expression profiles for the tumors in the database based on the respective RNA expression data; c) identifying recurring patterns of CPT expression among the tumors in the database; and d) comparing the recurring patterns of CPT expression with the respective clinical parameters.
Regarding claims 2, 15, 16 and 17, Kennedy [0268] discloses biomarkers related to signaling pathways such as adherens pathway, focal adhesion pathway, and tight junction pathway, or other pathway, as evidenced by Wilde et al. (Wilde [0363] “Pathway over-representation analysis on both gene lists is enriched for cell-membrane, cell cycle phase, mitosis, and spindle pathways”). Kennedy further discloses that the one or more cancer-related pathways is Cell cycle providing a list of gene markers representing lymphoma signature biomarkers...CDC2 cell division cycle 2, G1 to S and G2 to M 4.38E-13 1.92 3936913 CDC45L CDC45 cell division cycle 45-like (S. cerevisiae) 8.74E-13 1.52 3720896 CDC6 cell division cycle 6 homolog (S. cerevisiae) 2.92E-11 2.18 3090697 CDCA2 cell division cycle associated 2 5.18E-15 1.63 2516023 CDCA7 cell division cycle associated 7") [0381]. Kennedy further discloses that the biomarker is E2F8 [0381] and that the cancer is renal carcinoma [0092].
Further regarding claims 2, 3, 15, 16 and 17, Kennedy does not expressly disclose that the cancer is clear cell renal cancer and that the transcript is E2F1. Ma explores the function of E2F1 in clear cell renal carcinoma (claims 15-17) and found that Transcription factor E2F1 (claim 3) was mainly distributed in cancer cell nucleus and mRNA expression significantly increased in cases of clear cell renal cell carcinoma (ccRCC) tissues compared with adjacent non-cancerous kidney tissues (abstarct) and that E2F1 exerted an enforced effect on cell cycle (claims 2-3) progression which may partly explain the proliferation effect of E2F1 on ccRCC cells (pg. 4, col. 2, subsection: E2F1 accelerated G1/S transition in cell cycle).
Regarding claim 51, Kennedy discloses molecular profiling, which includes detection, extraction, analysis, and quantification of protein or nucleic acid (RNA or DNA) from one or more biological samples from a subject [0123] [0167]. Kennedy further discloses application of various inhibitors of the aberrantly activated or dysregulated pathway, or drugs known to inhibit the activity of the pathway can then be tested against the tumor cell line for growth inhibition. Kennedy further discloses that molecular profiling can also be used to monitor the effect of these inhibitors on for example down-stream targets of the implicated pathway [0255] and that a diagnostic result can indicate a certain molecular pathway is involved in the cancer disease or condition, or a certain grade or stage of a particular cancer disease or condition [0234]; reading on limitations of receiving the sample of tumor; extracting RNA from the sample; isolating a plurality of CPTs from the extracted RNA; and obtaining the RNA expression data from the isolated CPTs.
Regarding claim 55, Kennedy discloses classifying the biological sample as containing or not containing said disease and/or a specific tissue type based upon said comparison of said one or more clinical classifiers, to yield a classification of said biological sample (claim 1) wherein the comparison is performed using a trained algorithm or an algorithm that comprises a linear support vector machine classifier (claim 3). Kennedy further discloses that the model analyzes linear and non-linear relationships [0060-0062] [0100-0101] [0234-0235], where the classification can be useful for characterizing, identifying, and/or diagnosing thyroid cancers can include various pathway biomarkers [0268]; reading on limitations of identifying recurring patterns of CPT expression among tumors in the database further comprises applying a machine learning model that analyzes linear and non-linear relationships among the respective relative expression for each of the plurality of CPTs.
Applying the KSR standard to Kennedy and Ma, Examiner concludes that the combination of Kennedy and Ma represents simple substitution of known element for another. Both Kennedy and Ma are directed to cancer transcript expression analysis. Kennedy disclosed a method to diagnose and/or treat a subject suspected of having cancer by receiving RNA expression of tumor sample and determining pathway expression profile for cancer-related pathways such as cell cycle pathway and E2f8 transcript. In the same field of research, Ma provided the cell cycle E2F1 transcript in clear cell renal cancer. Combining the pathway transcript and cancer of Ma with cancer diagnosis method of Kennedy would have allowed for assessing the effects of E2F1 in clear cell renal carcinoma. One ordinary skilled in the art before he effective filing data of the claimed invention would have had a reasonable expectation of success in substituting one transcript with another in most common subtype of renal carcinoma. This combination would have been expected to have provided a more meaningful assembly of dataset for a more comprehensive cancer diagnosis. Therefore, the invention would have been prima facie obvious to one of skill in the art before the effective filing date of the claimed invention, absent evidence to the contrary.
Response to Arguments
Applicant's arguments filed 02/06/2026 have been fully considered but they are not persuasive. Applicant states:
Kennedy et al. did not teach or suggest that that a cell cycle cancer pathway transcript expression profile associated with increased survivability comprises CDKN1A, CCND2, CDKN1B, CCND1, CDK4, CCND3, CDKN2C, CCNE1, CDK5, E2F3, CDK2, CDKN2A, RB1, E2F1, and CDKN2B. As noted in the Office Action, Kennedy instead lists CDC2, CDC45L, CDC6, CDCA2 and CDCA7 as associated with lymphoma and cell cycle. The Ma et al. reference only discloses E2F1 and fails to disclose any of CDKN1A, CCND2, CDKN1B, CCND1, CDK4, CCND3, CDKN2C, CCNE1, CDK5, E2F3, CDK2, CDKN2A, RB1, and CDKN2B. Accordingly, there is no simple substitution when considering the amended claims. Neither Kennedy et al. nor Ma et al., either alone or in combination, teach or suggest all the elements of the amended claims.
It is respectfully submitted that the above statement is not persuasive. Applicant in Response to Restriction Requirement filed 08/04/2025 elected cell cycle pathway and E2F1 transcript along with clear cell renal cancer (KIRC), and accordingly said elected combination was examined. Further it would have been obvious to replace the transcript of Kennedy with another transcript known to be involved in the cell cycle pathway, as disclosed by Ma, to lead to diagnosis/prognosis result, as disclosed by Kennedy, and the results were reasonably predictable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GHAZAL SABOUR whose telephone number is (703)756-1289. The examiner can normally be reached M-F 7:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs can be reached at (571) 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.S./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
Prosecution Insights