DETAILED ACTION
Applicant's response, filed 3/18/2026, 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 .
Claims status
Claims 1, 4, 7-9, 27-33, and 36-37are pending.
Claims 10, 24-26, and 34-35 are cancelled.
Claims 1, 4, 7-9, 27-33, and 36-37are rejected.
Drawings
Response to Amendment
In view of applicant’s amendments to the drawings, previous objections to the drawings have been withdrawn.
The drawings are objected to because the second page is named “Fig. 2 continued”, which is an improper way to name partial views in accordance with 37 CFR 1.84(u). It must be updated to be Fig. 2A and 2B. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
Response to Amendment
In view of applicant’s amendments to the claims, specifically the cancellation of claims 10, and 34-35, the rejections of said claims under 35 U.S.C. 112 have been withdrawn.
Claim Rejections - 35 USC § 101
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections sunder 35 U.S.C. 101 have been updated and provided for review below.
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, 4, 7-9, 27-33, and 36-37 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method of determining pathogenicity of a genetic variant via the use of multiple training datasets on a model
Framework with which to Analyze Subject Matter Eligibility:
Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? [see MPEP § 2106.03]
Claims are directed to statutory subject matter, specifically a method (claims 1, 4, 7-9, and 27-28), and a system (claims 29-33, and 36-37).
Step 2A Prong One: Do the claims recite a judicially recognized exception, i.e., an abstract idea, law of nature, or natural phenomenon? [see MPEP § 2106.04(a)]
The claims herein recite abstract ideas.
With respect to the step 2A Prong One evaluation, the instant claims are found herein to recite abstract ideas that fall into the groupings of mental processes and mathematical concepts.
Claims 1 and 29: Predicting expression data, determining whether a variant has a statistically significant effect, and assessing a risk of the subject having a genetic condition or disease, are processes of comparing/contrasting, calculating, and selecting that can be done via pen and paper or within the human mind are therefore abstract ideas, specifically mental processes. Determining whether a variant has a statistically significant effect is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claims 4 and 30: Normalizing and standardizing expression levels, and resampling data are verbal articulations of mathematical processes and are therefore abstract ideas, specifically mathematical concepts.
Claims 7 and 31: The first and second datasets including data from the specified tissues is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claims 8 and 32: The gene of interest being associated with those conditions specified is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claims 9 and 33: The expression data comprising those data specified is directed to the definition of the information itself, and information is an abstract idea itself, therefore the definition is an abstract idea, specifically a mental process.
Claims 27 and 36: Determining whether the gene of interest has a statistically significant effect on regulation of downstream genes is a process of comparing/contrasting, and calculating that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Claims 28 and 37: Determining whether the variant of the genes of interest is associated with the phenotype of interest is a process of comparing/contrasting, and calculating that can be done via pen and paper or within the human mind and is therefore an abstract idea, specifically a mental process.
Step 2A Prong Two: If the claims recite a judicial exception under prong one, then is the judicial exception integrated into a practical application? [see MPEP § 2106.04(d)]
Because the claims do recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract elements:
Claims 1 and 29: Obtaining a first dataset, training a model to predict expression levels, and obtaining a second dataset are insignificant extra solution activities, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839 40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. A system, processors, a computer-readable storage medium, and instructions are all generic and nonspecific elements of a computer that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claims 28 and 37: Obtaining a third and fourth dataset is an insignificant extra solution activity, specifically mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839 40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
The claims appear to require nothing more than generic computer parts to perform the functions that constitute the judicial exception, and additional steps that are either insignificant extra solution activity or are well understood, routine and conventional within the art [see MPEP § 2106.05(d), (f), (g)]. Therefore, these are mere instructions to apply the judicial exceptions using computer systems. The additional elements of a system and processor do not integrate the abstract idea or law of nature into a practical application. [see MPEP § 2106.04(d)(I) and MPEP § 2106.05(f)]
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? [see MPEP § 2106.05]
Because the additional claim elements do not integrate the abstract idea into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept.
The claims do not recite additional elements that are sufficient to amount to significantly more than the judicial exceptions because the claims recite additional elements that are generic, conventional, nonspecific, or mere data gathering. These additional elements include:
The additional elements of a system, processors, a computer-readable storage medium, and instructions are all generic and nonspecific elements of a computer that are well-understood, routine and conventional within the art and therefore do not improve the functioning of any computer or technology described therein (Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(d)(II)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of obtaining a first dataset (Conventional: Specification Paragraph [0041]-[0043] – specifically the use of databases and prior methods known within the art (i.e. KEGG, Expression Atlas, HGMD, ClinGen, etc.)), training a model to predict expression levels (Conventional: Crisci et al. 2012 – page 117, column 2, Section 3.4 Describes current well understood methods in supervised learning (trained models) specifically looking at SVMs, which in view of Specification Paragraph [0047]-[0048] listing SVM as the model used render training as well-understood, routine and conventional within the art), obtaining a second dataset (Conventional: Specification Paragraph [0041]-[0043] – specifically the use of databases and prior methods known within the art (i.e. KEGG, Expression Atlas, HGMD, ClinGen, etc.)), and obtaining a third and fourth dataset (Conventional: Specification Paragraph [0041]-[0043] – specifically the use of databases and prior methods known within the art (i.e. KEGG, Expression Atlas, HGMD, ClinGen, etc.)), are all insignificant extra solution activities, specifically mere data gathering and necessary data outputting (See Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), TLI Communications LLC v. AV Auto. LLC, 823 F.3d 607, 610, 118 USPQ2d 1744, 1745 (Fed. Cir. 2016) (using a telephone for image transmission), OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015) (sending messages over a network), 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), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(g)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
Therefore, claims 1, 4, 7-9, 27-33, and 36-37, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant's arguments filed 3/18/2026 have been fully considered but they are not persuasive.
Step 2A, Prong 1:
Applicant asserts on page 3 of the Remarks filed 3/18/2026 that the claims do not recite an abstract idea, specifically that "predicting ... expression data", and "determining ... whether the genetic variant of the gene of interest has a statistically significant effect on regulation of the one or more downstream genes" are not mental process but rather cannot be practically performed within the human mind as "applying the trained model to the second expression data" as recited in claim 1 cannot practically be performed in the human mind. Examiner reminds applicant that the use of computer technology does not preclude the ability of the human mind to perform said task without computer technology as outlined in MPEP 2106.04(a)(2) subsection (III) - Nor do the courts distinguish between claims that recite mental processes performed by humans and claims that recite mental processes performed on a computer. As the Federal Circuit has explained, "[c]ourts have examined claims that required the use of a computer and still found that the underlying, patent-ineligible invention could be performed via pen and paper or in a person’s mind." Versata Dev. Group v. SAP Am., Inc., 793 F.3d 1306, 1335, 115 USPQ2d 1681, 1702 (Fed. Cir. 2015), and in MPEP 2106.05(f) subsection (2) - Whether the claim invokes computers or other machinery merely as a tool to perform an existing process. 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 or 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).
Furthermore, applicant asserts on page 4 of the Remarks filed 3/18/2026 that "determining ... whether the genetic variant of the gene of interest has a statistically significant effect on regulation of the one or more downstream genes," as recited in claim 1, is not recite a mental process, because there is nothing in the record to suggest that determining whether a variant of a gene of interest has a statistically significant effect on regulation of one or more downstream genes is practically performable in the human mind. However, examiner reminds applicant that “whether the genetic variant of the gene of interest has a statistically significant effect” is merely a process of calculating information, determination of statistical effect is even outlined in paragraphs [0050] and [0052]-[0056] of the specification “Classification can be performed using a host of techniques, for instance, linear regression, linear and nonlinear SVM, logistic regression, random forest, naive bayes, adaboost and/or other methods of combining different kinds of classifiers”, and the ubiquitous mathematical equations describing associations between variant, effect size, and a phenotype, which inherently calculate p-value or significance of various effects.
Additionally, applicant asserts that “there is nothing in the record to suggest that determining whether a variant of a gene of interest has a statistically significant effect on regulation of one or more downstream genes is practically performable in the human mind” – Remarks page 4. However, the mere act of association is simply a series of simple regressions, and while time consuming, is very much performable by hand (Hayes et al. 2013 – Page 150, Equation 1).
Step 2A, Prong 2:
Applicant asserts on page 4 of the Remarks filed 3/18/2026 that the claims are directed to an improvement to the technical field of computational genetic screening, specifically that the choice of cells can be different as long as they are consistent, no further experimentation is needed to measure functional phenotype, and the method is more reliable. However, examiner reminds applicant that MPEP 2106.05(a) states It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements, i.e. the improvement cannot be directed to an abstract idea of which the power, reliability, accuracy, etc., are. Furthermore, the invention is not directed to a particular machine, but rather claims generic, routine and conventional computer components as recited above and performs mere data gathering and data analysis as described above which in MPEP 2106.05(a) subsection (II) states - Examples that the courts have indicated may not be sufficient to show an improvement to technology include:…(ii) Using well-known standard laboratory techniques to detect enzyme levels in a bodily sample such as blood or plasma, Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1355, 1362, 123 USPQ2d 1081, 1082-83, 1088 (Fed. Cir. 2017); (iii) Gathering and analyzing information using conventional techniques and displaying the result, TLI Communications, 823 F.3d at 612-13, 118 USPQ2d at 1747-48. Finally, MPEP 2106.04(d) states “A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception” and in section I “The courts have also identified limitations that did not integrate a judicial exception into a practical application: Merely reciting the words "apply it" (or an equivalent) with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, Adding insignificant extra-solution activity to the judicial exception. Therefore, applicant’s argument for improvement to technology/field, is not persuasive.
Subject Matter Potentially Free From the Prior Art
Independent claims 1 and 29 are potentially allowable over the prior art as while similar ideas and concepts exist within the space of expression analysis, such as the prediction of expression data sets, or the use of GSA (Gene Set Enrichment analysis) no prior art was found which would read on the method/system of the respective claims either individually or in combination. As a specific example Rydenfelt et al. 2020 (SPEED2: inferring upstream pathway activity from differential gene expression) infers pathway expression from downstream expression. However, said method does nothing to tie in the identification of significant genetic variants. Likewise, methods such as GSA or eQTL analysis such as those described in Lee et al. 2016 (A method to predict the impact of regulatory variants from DNA sequence) are able to predict significant variants, but only from eQTL data. Therefore, the current invention is potentially novel in terms of link between the two types of information. As such, dependent claims are necessarily potentially allowable under said analysis.
Conclusion
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 KEENAN NEIL ANDERSON-FEARS whose telephone number is (571)272-0108. The examiner can normally be reached M-Th, alternate F, 8-5.
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/K.N.A./Examiner, Art Unit 1687
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685