DETAILED ACTION
Notice of 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 .
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 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.
Withdrawal of Objections and Rejections
Applicant's response, filed 03/17/2026, has been fully considered.
In view of the amendment and remarks from 03/17/2026, the objection to claims and the rejection of the following claims are withdrawn:
claims 1-15 under 35 USC § 112(b).
The following rejections and/or objections are either maintained or newly applied for claims 1-20. They constitute the complete set applied to the instant application. Herein, "the previous Office action" refers to the Non-Final Rejection of 12/18/2025.
Status of the Claims
Claims 1-20 are pending.
Claims 1-20 are rejected.
Priority
This US Application 17/780,037 (05/26/2022) is a 371 of PCT/EP2020/083444 (11/26/2020) and claims priority from US Application No. 62/940,444 (11/26/2019) as reflected in the filing receipt mailed on 09/16/2022. The claims to the benefit of priority are acknowledged; and the effective filing date of claims 1-20 is 11/26/2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/17/2026 was considered by the examiner.
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 1-20 are rejected under 35 USC § 101 because the claimed inventions are directed to one or more Judicial Exceptions (JEs) without significantly more. Regarding JEs, "Claims directed to nothing more than abstract ideas..., natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 §I). Abstract ideas include mathematical concepts and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). Any newly recited portions are necessitated by claim amendment.
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 1-9 and 19-20) and a system (claims 10-18); each of which falls within one of the categories of statutory subject matter.
[Step 1: claims 1-20: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mathematical concepts (in particular mathematical relationships and formulas) and mental processes (in particular procedures for observing, analyzing and organizing information) as well as a law of nature or a natural phenomenon are as follows.
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• " determining a splice status for the one or more of the plurality of variant, the splice status comprising an indication of whether a variant has an effect on splicing of a gene" (independent claims 1, 10 and 19);
• " determining a variant-based expression regulation status, the variant- based expression regulation status comprising an indication of whether the variant has an effect on expression of a gene" (independent claims 1, 10 and 19);
• "determining a gene-based expression regulation status, the gene- based expression regulation status comprising an indication of whether the variant has a functional impact on a target gene in a pathway" (independent claims 1, 10 and 19);
• "determining a gene-based copy number variant (CNV) and epigenetic impact status, the gene-based CNV and epigenetic impact status comprising an indication of whether the CNV and/or epigenetic impact has an impact on expression of one or more of the plurality of genes in the genomic sample" (independent claims 1, 10 and 19);
• "adjusting, based on the gene-based CNV and epigenetic impact status, the variant-based expression regulation status and/or the gene-based expression regulation status" (independent claims 1, 10 and 19);
• "associating, in a database, the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status with one or more of a response to therapy, a diagnosis, or a prognosis of a patient to generate one or more associations" (independent claim 19);
• "executing a matching algorithm that identifies one or more matches between a patient genomic profile of a patient and the stored one or more associations, wherein identifying the one or more match comprises generating a response of the patient to therapy, a diagnosis, or a prognosis" (independent claim 19);
• "filtering/filter at least some of the plurality of variants or genes based at least on the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status associated with each respective variant and/or gene" (claims 2 and 11); and
• "ranking/rank at least some of the plurality of variants or genes" (claims 3 and 16).
Under the BRI, the recited limitations are mental processes because a human mind is sufficiently capable of evaluate/filter/rank a dataset and determine an indication of an effect on a certain function based on data; subsequently adjust the status found depending on the dataset; associate a status with a therapy; execute a match between a patient genomic profile and the associations made; and report the evaluations via a database or a table using pen and paper.
Dependent claims 4-9, 12-15, 17-18 and 20 recite further steps that limit the judicial exceptions in independent claims 1, 10 and 19 and, as such, also are directed to those abstract ideas. For example, dependent claims 4-7, 9, and 13-15, 17-18 recite further details about the "indication of an impact" performed by the variants; dependent claims 8 and 20 recite further details about the reporting step; and dependent claim 12 recites further details about the adjusting step.
Furthermore, the instant claims recite a natural correlation by correlating the measurement of an amount of a gene/variant naturally found in the body with the functional impact/effect of said gene/variant. (see MPEP 2106.04(b).I).
[Step 2A Prong One: claims 1-20: Yes ]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claims 1, 10 and 19 recite additional elements that are not abstract ideas:
• "obtaining genomic sample information for a plurality of genes, the genomic sample information comprising at least a plurality of variants identified in a genomic sample, gene expression information obtained from the genomic sample, copy number variation for one or more of the plurality of genes in the genomic sample, and epigenetic effects on one or more of the plurality of genes in the genomic sample" (independent claims 1 and 19)
• "genomic sample information for a plurality of genes, the genomic sample information comprising at least the plurality of variants identified in the genomic sample, gene expression information obtained from the genomic sample, copy number variation for one or more of the plurality of genes in the genomic sample, and epigenetic effects on one or more of the plurality of genes in the genomic sample" (independent claim 10); and
• "a user interface" (independent claim 10).
• "reporting at least the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status for each of the plurality of variants and/or the plurality of genes in the genomic sample" (independent claims 1 and 10);
• "reporting, via a clinical report generated relevant to the patient, the identified one or more identified matches, including the generated response of the patient to therapy, a diagnosis, or a prognosis" (independent claim 19);
Considerations under Step 2A, Prong Two
The recited limitations in claims 1, 10 and 19 are interpreted as requiring the use of a computer. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions or instructions to implement on a generic computer.
Further steps directed to additional non-abstract elements of a computing device/computer do not describe any specific computational steps by which the "computer parts" perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions.
Limitations of claims 1-20 are considered to perform the claimed abstract idea with a computer, which is not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and merely performing the mental process in a computer environment do not negate the fact that something that can be carried out in the human mind. See MPEP 2106.04(a)(2).III.C.
The recited "obtaining genomic sample information" and the related claims 2-3 read on data gathering activities or the type of data being gathered; not amounting to a practical application. The type of data or how the data is organized does not change that it is mere data gathering or conventional computer receiving means. Said "obtaining genomic sample information" is utilized to gather data to be used by the judicial exceptions (i.e. determinations listed as mental steps above). Said "genomic sample information for a plurality of genes" is interpreted as data gathered that has been stored.
Claims directed to "reporting" information are interpreted as data outputting and as such insignificant extra-solution activity.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)).
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
[Step 2A Prong Two: claims 1-20: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during examination that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
Claims 1, 10 and 19 recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Further, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versa ta Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(Il)(i)).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
The instant claims constitute insignificant extra solution activity, and when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(g)). Hence, these elements, when considered individually, are insufficient to constitute inventive concepts that would render the claims significantly more than an abstract idea (see MPEP 2106.05(d)).
[Step 2B: claims 1-20: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For the reasons above, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept not clearly anything significantly more.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 03/17/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 13 para. 3
Here, Applicant asserts that the claims as a whole are not directed to the abstract ideas of a mental process. Rather, the claims are directed to a specific workflow and improvement in characterizing a functional impact of a plurality of variants identified from a genomic sample. The rejection's Step 2A, Prong One characterization as "mental processes" is inapposite. The claims require obtaining and processing genomic sample information that includes multiple heterogeneous -omic modalities (gene expression, CNV, and epigenetic effects) and generating multiple computed statuses, followed by an adjustment operation that changes the computed statuses based on CNV/epigenetic impact. The Detailed Description explains that the system operates on sequencing-derived expression data (including gene/transcript/exon expression and splicing data) (i][0034]-[0035]), leverages external databases such as sQTL/eQTL resources (i][0042], iJ[0052]), and, critically, performs a defined adjustment mechanism by comparing stored regulation entries to the gene-based CNV/epigenetic impact status and removing entries before recomputing the adjusted statuses (i][0087]-[0092]). This is not an "observation/evaluation" practically performable in the human mind; it is a computer-implemented, rule-based modification of stored multi-omic regulation data structures at genomic scale (i][00122]).
The argued processing sample information (i.e. determining and adjusting statuses based on data evaluation) have been identified as a judicial exception (i.e. mental processes) as supported by (MPEP 2106.04(a)(2)(III)) which states that concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions constitutes mental processes. This conclusion is also supported by the Applicant's arguments above regarding "a defined adjustment mechanism by comparing stored regulation entries to the gene-based CNV/epigenetic impact status and removing entries before recomputing the adjusted statuses" which discloses steps such as compare and remove entries, which can be performed in the human mind. The argued steps relating to obtaining sample information have not been identified as a mental process but instead it has been identified as an additional element that reads on receiving data. Therefore, the identification of mental processes in this instant application is coherent with the instructions found in the MPEP. Furthermore, limitations considered as using a computer to perform a judicial exception are not sufficient to integrate an abstract idea into a practical application (see MPEP 2106.05(f)); since steps that can be performed mentally and performing the mental process in a computer environment, in an automatic manner, do not negate the fact that something that can be carried out in the human mind, and are merely instructions to apply the judicial exceptions to a computer. See MPEP 2106.04(a)(2).III.C.
Applicant asserts starting in pg. 14 para. 3
Applicant affirms the conclusion above that the claims are not directed to a judicial exception, and respectfully asserts that the claims do indeed incorporate any judicial exception into a practical application. Even assuming, arguendo, that the claims are directed to an abstract idea, the elements of the independent claims integrate the exception into a practical application. Here, the claims integrate any alleged exception into a practical application in a technical field (i.e., computational genomics) by correcting expression-regulation inferences to account for CNV and epigenetic confounders. The specification explains the technical need to consider the combined impact of CNV and epigenetic factors in clinical applications (i][008 l]) and that the framework enables identifying causal variants/genes by systematically combining multi-layer evidence (i][00116]-[00118]). This is a technology-rooted improvement in how multi-omic functional impact is computed and reported, akin to rule-based, computer-implemented improvements found eligible in Enfish and McRO. Accordingly, Applicant respectfully asserts that that the claims are directed to patent eligible subject matter under the Alice framework. Applicant respectfully requests that the rejection of the pending claims under 35 U.S C. 101 be withdrawn
Regarding the argued improvement to a technical field by correcting expression-regulation inferences to account for CNV and epigenetic confounders at Step 2A Prong 2, it is respectfully submitted that this is not persuasive because the argument is not commensurate with the scope of the claims. The computing and reporting of multi-omic functional impact have been identified as judicial elements as described above. Regarding improvement to technology, the improvement cannot be in the judicial exception itself. Rather, the improvement is provided by the additional elements either on their own or in combination with the judicial exception. If the improvement is not realized in the additional elements then the improvement is in the judicial exception itself, which is not considered an improvement to technology. As it appears in the claims, there is no indication of an technology-rooted improvement that flows from an additional element.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 1-20 are rejected under 35 U.S.C. 103(a) as being unpatentable over Kagohara ("Epigenetic regulation of gene expression in cancer: techniques, resources and analysis" Briefings in functional genomics 17(1):49-63 (2018)) in view of Li ("RNA splicing is a primary link between genetic variation and disease." Science 352.6285:600-604 (2016)) in view of Geistlinger ("Widespread modulation of gene expression by copy number variation in skeletal muscle." Scientific reports 8(1):1399 (2018)); as cited on the 12/18/2025 Form PTO-892. Any newly recited portions are necessitated by claim amendment.
Claim 1 recites "a method for characterizing a functional impact of a plurality of variants identified from a genomic sample, using a variant analysis system, comprising"; claim 10 recites "a system for characterizing a functional impact of a plurality of variants identified from a genomic sample"; and claim 19 recites "a method for generating a report characterizing, within a patient context, a functional impact of a plurality of variants identified from a genomic sample, comprising."
The prior art to Kagohara discloses methods and systems as the functional impact of methylation alterations (i.e. variants) being assessed bioinformatically (i.e. variants analysis system) in targeted experiments on model organisms and across sample population (pg. 58 col. 2 para. 2); wherein high-throughput measurement technologies enable unprecedented, quantitative measurements of the epigenetic state in cancers (i.e. from genomic samples) (pg. 58 col. 2 para. 2).
The steps performed by the methods of claims 1 and 19, and by the system in claim 10 comprise:
[obtaining; claims 1 and 19 only] genomic sample information for a plurality of genes, the genomic sample information comprising at least a plurality of variants identified in a genomic sample, gene expression information obtained from the genomic sample, copy number variation for one or more of the plurality of genes in the genomic sample, and epigenetic effects on one or more of the plurality of genes in the genomic sample
• Kagohara teaches as DNA methylation of 1001 cancers being measured along with therapeutic sensitivity, copy number, somatic mutations and gene expression (pg. 55 col. 1 para. 3); wherein bioinformatics methods can aggregate over epigenetic modifications with similar effects on gene expression (i.e. epigenetic effects on one or more genes in the genomic sample) (pg. 57 col. 2 para. 3).
determining a splice status for the one or more of the plurality of variant, the splice status comprising an indication of whether a variant has an effect on splicing of a gene
• Kagohara does not teach the recitation above. However, Li teaches as a detailed accounting of the effects of genetic variants on gene regulation (pg. 600 col. 2 para. 2); teaching a new method to detect splicing variation (pg. 603 col. 2 para. 2); wherein splicing was most strongly affected by variants near splice sites (i.e. determination of whether a variant has an effect on splicing of a gene) (pg. 603 col. 3 para. 2).
determining a variant-based expression regulation status, the variant- based expression regulation status comprising an indication of whether the variant has an effect on expression of a gene
• Kagohara does not teach the recitation above. However, Li teaches as genetic variants located in active promoters, strong enhancers, and weak promoters were most likely to affect gene expression (i.e. determination of whether the variant has an effect on expression of a gene) (pg. 603 col. 3 para. 2).
determining a gene-based expression regulation status, the gene- based expression regulation status comprising an indication of whether the variant has a functional impact on a target gene in a pathway
• Kagohara does not teach the recitation above. However, Li teaches as the identification of three main pathways that mediate the impact of genetic variation on gene regulation with phenotypic and pathogenic consequences (i.e. variant having a functional impact on a target gene in a pathway) (pg. 604 col. 1 para. 5 and Fig. 4D in pg. 603).
determining a gene-based copy number variant (CNV) and epigenetic impact status, the gene-based CNV and epigenetic impact status comprising an indication of whether the CNV and/or epigenetic impact has an impact on expression of one or more of the plurality of genes in the genomic sample
• Kagohara does not teach the recitation above. However, Geistlinger teaches as an integrative study on copy number variation (CNV) and genome wide gene expression where CNV is frequently observed deviation from the diploid state due to duplication or deletion of genomic regions and where expression changes coincided with CNVs in the respective genes (pg. 1 para. 1).
adjusting, based on the gene-based CNV and epigenetic impact status, the variant-based expression regulation status and/or the gene-based expression regulation status
• Kagohara does not teach the recitation above. However, Geistlinger teaches as a variety of long-range CNV effects that modulated gene expression in an orchestrated and intertwined fashion; with CNVs being able to fine-tune core regulators (i.e. CNV based adjustment of gene expression) located in their vicinity, propagating these effects to genome-wide gene expression (i.e. epigenetic impact) (pg. 8 para. 6).
Claim 1 only further recites:
reporting at least the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status for each of the plurality of variants and/or the plurality of genes in the genomic sample
• Kagohara does not teach the recitation above. However, Geistlinger teaches as samples carrying either 0n for R727 gene or 3n for R2440 gene individually displayed increased expression of associated genes (adjusted expression based on CNV), showing a strong synergistic effect for samples carrying both expression-increasing alleles (pg. 5 para. 4); which was reported as boxplots (pg. 7 Fig. 5a/b).
Claim 10 only further recites:
a user interface configured to report at least the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status for each of the plurality of variants and/or the plurality of genes in the genomic sample
• Kagohara teaches as genome browsers used as tools to visualize and integrate epigenetics data from publicly available repositories; with an unique interface, set of features and capacity for data integration from external data sources (pg. 55 col. 2 para. 4).
Claim 19 only further recites:
associating, in a database, the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status with one or more of a response to therapy, a diagnosis, or a prognosis of a patient to generate one or more associations;
executing a matching algorithm that identifies one or more matches between a patient genomic profile of a patient and the stored one or more associations, wherein identifying the one or more match comprises generating a response of the patient to therapy, a diagnosis, or a prognosis; and
reporting, via a clinical report generated relevant to the patient, the identified one or more identified matches, including the generated response of the patient to therapy, a diagnosis, or a prognosis
• Kagohara teaches current resources to discover reversible epigenetic events in cancer (i.e. adjusting variant-based expression regulation status) that may be targeted therapeutically in cancer (pg. 50 col. 2 para. 2) and techniques to determine the functional impacts of chromatin regulation (i.e. adjusting gene-based expression regulation status) from time course data of cancer development, metastasis and therapeutic resistance (i.e. response to therapy, a diagnosis, or a prognosis of a patient to generate one or more associations) (pg. 57 col. 2 para. 3); wherein complete data integration to determine epigenetic regulation of gene expression can be performed for data sets containing both gene expression data and
epigenetic data to determine their functional impact in cancer (i.e. associating in a database and executing a matching algorithm that identifies one or more matches between a patient genomic profile of a patient and the stored one or more associations, wherein identifying the one or more match comprises generating a response of the patient to therapy, a diagnosis, or a prognosis) (pg. 58 Fig. 4).
• Furthermore, Kagohara teaches a Web-based tool that stores all DNA methylation data from The Cancer Genome Atlas for gene-level analysis using a database to query by gene and tumor type (i.e. report relevant to the matches) and then correlates clinical covariates and expression with measurements of DNA methylation for that gene from The Cancer Genome Atlas, which involves an analysis across all probes in the array for the query gene to distinguish the impact of epigenetic alterations (i.e. reporting, via a clinical report generated relevant to the patient, the identified one or more identified matches, including the generated response of the patient to therapy, a diagnosis, or a prognosis) (pg. 56 col.1 para. 3).
Claims 2 and 11 recite:
filtering at least some of the plurality of variants or genes based at least on the adjusted variant-based expression regulation status and/or the adjusted gene-based expression regulation status associated with each respective variant and/or gene
• Kagohara does not teach the recitation above. However, Geistlinger teaches as the analysis of expression effects including filtering genes for sufficient expression and samples with overlapping CNV calls (pg. 2 para. 4).
Claims 3 and 16 recite:
ranking at least some of the plurality of variants or genes
• Kagohara teaches as the frequency of mutations in histone modifying genes varying by tumor type, occurring with highest frequency in brain tumors and leukemias (30% of the cases (pg. 51 col. 2 para. 2).
Claims 4 and 17 recites:
wherein the splice status further comprises an indication of a strength of splicing evidence for the effect on splicing of the gene
• Kagohara does not teach the recitation above. However, Li teaches as splicing being most strongly affected by variants near splice sites and by synonymous and missense variants (i.e. indication of a strength of splicing evidence for the effect on splicing of the gene) (pg. 603 col. 3 para. 2).
Claims 5 and 14 recite:
wherein the variant-based expression regulation status further comprises an indication of whether an affected gene is local or remote
• Kagohara does not teach the recitation above. However, Geistlinger teaches as CNV-expression analysis showing local effects, where expression changes coincide with CNVs in the respective genes and distal effects, where CNVs supposedly affect trans-acting regulators (pg. 3 para. 4).
Claims 6 and 15 recite:
wherein the gene-based expression regulation status further comprises an indication of whether the target gene is upregulated or downregulated
• Kagohara does not teach the recitation above. However, Geistlinger teaches as the distal expression effects of copy number variation with indication of how many genes showed either an increase (orange) or decrease (green) in expression with gain in copy number in the corresponding region (pg. 4 Fig. 3).
Claims 7 and 18 recite:
wherein the gene-based copy number variant (CNV) and epigenetic impact status further comprises an indication of whether the copy number variant (CNV) and/or the epigenetic factor results in upregulation or downregulation of the one or more of the plurality of genes in the genomic sample
• Kagohara does not teach the recitation above. However, Geistlinger teaches as the distal expression effects of copy number variation with indication of genes showing a high degree of variation in copy number for substantial subsets of the population with a significant decrease in expression upon loss of copies (pg. 2 para. 6).
Claims 8 and 20 recite:
wherein reporting comprises a table or other data structure comprising a list of variants and/or genes and functional impact information associated with each variant and/or gene
• Kagohara does not teach the recitation above. However, Geistlinger teaches as table for the functional characterization of distal CNV regions with phenotype for significant expression changes associated with the corresponding CNV region (pg. 5 Table 1).
Claims 9 and 13 recite:
wherein the functional impact information comprises, for one or more of a plurality of remaining variants, an indication of an effect of the variant on expression of one or more of the one or more genes in the genomic sample
• Kagohara does not teach the recitation above. However, Geistlinger teaches as table for the functional characterization of distal CNV regions with phenotype for significant expression changes associated with the corresponding CNV region (pg. 5 Table 1).
Claim 12 recites:
wherein the adjusted variant-based expression regulation status and/or the gene-based expression regulation status comprises a table or other data structure comprising a list of variants and/or genes and functional impact information associated with each variant and/or gene
• Kagohara does not teach the recitation above. However, Geistlinger teaches as a variety of long-range CNV effects that modulated gene expression in an orchestrated and intertwined fashion; with CNVs being able to fine-tune core regulators (i.e. CNV based adjustment of gene expression) located in their vicinity, propagating these effects to genome-wide gene expression (i.e. epigenetic impact) (pg. 8 para. 6); where said CNV effects are listed in a table describing the functional characterization of distal CNV regions with phenotype for significant expression changes associated with the corresponding CNV region (pg. 5 Table 1).
Rationale for combining (MPEP §2142-2143)
Regarding claims 1-20, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine, in the course of routine experimentation and with a reasonable expectation of success, the methods of Kagohara in view of Li and Geistlinger because all references disclose methods for associating genetic variation to gene regulation and functional impact. The motivation would have been to:
• incorporate a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation (pg. 1 para. 1 Li) and
• incorporate the detection of multi-level associations at the interface of copy number variation, gene expression and phenotype (i.e. functional impact) (pg. 6 Fig. 4 Geistlinger).
Therefore it would have been obvious to one of ordinary skill in the art to substitute the associating genetic variation to gene regulation and functional impact method of Kagohara to the methods by Li and Geistlinger because such a substitution is no more than the simple substitution of one known element for another. One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for associating genetic variation to gene regulation and functional impact.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 103
The Remarks of 03/17/2026 have been fully considered but are not persuasive for the reasons below:
Applicant asserts starting in pg. 15 para. 2
With regard to independent claims 1 and 10, Kagohara in view of Li and Geistlinger fails to suggest or render obvious, for example … However, that CNVs are shown to be modulators of gene expression (such as "in an orchestrated and intertwined fashion"), does not disclose the adjustment of the claimed determined "variant-based expression regulation status and/or gene-based expression regulation status." Indeed, the claimed determined variant-based expression regulation status comprises "an indication of whether the variant has an effect on expression of a gene," and the claimed determined gene-based expression regulation status comprises "an indication of whether the variant has a functional impact on a target gene in a pathway." The gene-based copy number variant (CNV) and epigenetic impact status, which comprises "an indication of whether a CNV and/or an epigenetic factor has an impact on expression of one or more of the plurality of genes in the genomic sample," is utilized to adjust one or both of those regulation statuses (i.e., the variant based expression regulation status and/or the gene-based expression regulation status). At best, Geistlinger teaches that CNV s modulate gene expression. However, the claims do not recite simply "adjusting gene expression based on CNV status." Rather, the claims recite a complex, multi-step process in which a specific determined "variant-based expression regulation
Applicant affirms in pg. 15 para. 2 that prior art to Kagohara, Li and Geistlinger does not teach or suggest a list of claim elements but does not provide arguments that point to exact teachings that have been described in the previous office action. Then, in pg. 17 para. 3 Applicant argues that the "variety of long-range CNV effects that modulated gene expression in an orchestrated and intertwined fashion; with CNV s being able to fine-tune core regulators" as taught by Geistlinger does not read on the recited adjusting step "for characterizing a functional impact of a plurality of variants identified from a genomic sample." The modulation of gene expression inherently yields a functional impact adjustment because alterations in genetic expression are directly correlated to functional alterations as evidenced by Kagohara (pg. 50 col. 1 para. 3-4). Therefore a gene regulator as taught by Geistlinger would inherently cause an adjustment in functional impact.
Therefore the prima facie case of obviousness has been established. MPEP 2141.III for "RATIONALES TO SUPPORT REJECTIONS UNDER 35 U.S.C. 103"; wherein "(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention." Furthermore, in this instant application, the amendments support existing claim rejections, in which the recited limitations are all addressed, see Claim Rejections above.
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.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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