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 .
Claims 1-4 and 6-15 are currently pending and under examination. Claims 1, 6, 9-10, and 13-14 are amended. Claims 5 and 16 are cancelled.
Response to Amendment
The Amendment filed 12/8/25 has been entered. Claims 1-4 and 6-15 are pending. Applicant’s amendments to the specification and claims 1, 9-10, and 13-14 have overcome the objections, 112(b), and 102 rejections previously set forth in the Non-Final Office Action mailed 9/22/25.
Response to Arguments
Applicant’s arguments, see pages 9-10, filed 12/8/25, with respect to the rejections of claims 1-4 and 6-15 under 35 USC 101 have been fully considered and are found unpersuasive, and the 101 rejections documented in the Non-Final mailed 9/22/25 have been revised to address claim amendments filed 12/8/25 in this Final Office Action. More detailed responses to Applicant’s arguments are provided at the end of each maintained rejection.
Applicant’s arguments, see page 11, filed 12/8/25, with respect to the rejections of claims 1-4 and 6-15 under 35 USC 103 have been fully considered and are found persuasive. Therefore, the rejections documented in the Non-Final mailed 9/22/25 have been withdrawn. However, upon further consideration, new grounds of rejections necessitated by claim amendments are made in this Final Office Action.
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 1-4 and 6-15 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4 Monday, January 7, 2019).
This rejection is revised/updated in response to claim amendments filed 12/8/25.
Step 1: The claim is directed to the statutory category of a process.
Step 2A, prong one: The claim recites a judicial exception.
Claim 1 recites “identifying one or more genomic regions associated with kidney disease and/or its treatment” with an active step of using amplified cDNA alignments to “identify”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)).
Step 2A, prong two: The judicial exception is not integrated into a practical application.
Claims 1-4 and 6-15 recite extra-solution, data-gathering limitations at high levels of generality. Additionally, although the claims include administration of drug classes, the claims are not directed to a particular treatment or prophylaxis (see MPEP 2106.04(d)(2)). Amended claim 1 limitation of RNA isolation, sequencing, and alignment are considered extra-solution and data-gathering activities as well, since the steps are associated with generating the data needed for the mental process of “identifying”.
Step 2B: The claim does not provide an inventive concept.
MPEP 2106.05(d)):
The courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity:
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs. Ltd., 818 F.3d at 1377, 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
The claims are directed to well-understood, routine, and conventional activities in the life science arts recited at a high-level of generality. Identifying one or more genomic regions associated with kidney disease and/or its treatment is not inventive (see Agrawal et al. (2016; NPL citation U in PTO-892 filed 9/22/25; “Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome”; Sci Rep 6:24392; DOI: 10.1038/srep24392); and Jiang et al. (2016; NPL citation V in PTO-892 filed 9/22/25; “RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways”; Sci Rep 6:35671; DOI: 10.1038/srep35671)). Additionally, amended claim 1 limitation of RNA isolation, sequencing, and alignment is not inventive (Jiang et al. (2016; NPL citation V in PTO-892 filed 9/22/25; “RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways”; Sci Rep 6:35671; DOI: 10.1038/srep35671) and Illumina TruSeq RNA Sample Preparation v2 Guide (2014; https://support.illumina.com/downloads/truseq_rna_sample_preparation_v2_guide_15026495.html).
For the reasons set forth above, claims 1-4 and 6-15 are not directed to patent eligible subject matter.
Applicant’s Arguments
Applicant argues that “Because the claimed invention is not directed to an abstract idea, involves transformation, does not pre-empt the natural principle, provides an innovative benefit, and includes an inventive concept, Applicants respectfully request that the rejection of claim 1 for being directed to non-patentable subject matter be withdrawn” (Remarks 12/8/25, page 10, paragraph 4).
Response to Applicant’s Arguments
The Examiner respectfully disagrees with the assertion that the claimed is not directed to an abstract idea. The claim 1 recitation of “identifying one or more genomic regions associated with kidney disease and/or its treatment” with an active step of using amplified cDNA alignments to “identify” is an abstract mental process (see MPEP 2106.04(a)(2)(III)). The act of “identifying” is performed within one’s mind following the non-inventive, extra-solution, and data-gathering steps of claims 1-4 and 6-15. See the below 103 rejection for further expansion on how these limitations do not provide “an innovative benefit” or include “an inventive concept”.
Claim Rejections - 35 USC § 103
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.
Claims 1-4 and 6-15 are rejected under 35 U.S.C. 103 as being unpatentable over Agrawal et al. (2016; NPL citation U in PTO-892 filed 9/22/25; “Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome”; Sci Rep 6:24392; DOI: 10.1038/srep24392) in view of Jiang et al. (2016; NPL citation V in PTO-892 filed 9/22/25; “RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways”; Sci Rep 6:35671; DOI: 10.1038/srep35671) and Illumina TruSeq RNA Sample Preparation v2 Guide (2014; https://support.illumina.com/downloads/truseq_rna_sample_preparation_v2_guide_15026495.html).
This new 103 rejection is necessitated by claim amendments filed 12/8/25.
(i) Agrawal et al. teaches limitations relevant to claims 1-4 and 7-8.
Relevant to claims 1-2, and 4, Agrawal et al. teaches "We recently reported direct protective effects of GCs [glucocorticoids] and TZDs [thiazolidinediones] on podocytes, potentially due to crosstalk between the GC and TZD nuclear receptor-mediated signaling pathways, as demonstrated by the ability of TZDs to modulate the GC signaling pathway [citation]. We thus hypothesized that nuclear receptor crosstalk between podocyte TZD and GC pathways could be exploited to enhance the proteinuria-reducing effects of GCs during NS [nephrotic syndrome] treatment. To test this hypothesis we: 1) Determined the ability of pioglitazone to protect and enhance the efficacy of GCs in reducing proteinuria in puromycin aminonucleoside (PAN)-induced NS, and 2) Analyzed the potential mechanistic pathways for protection in the glomeruli of rats with PAN-induced NS treated with combinations of GC and/or the TZD pioglitazone. and 3) Analyzed the potential of pioglitazone to enhance GC efficacy in reducing proteinuria in a child with refractory NS" (last paragraph of page 1 continued to first paragraph of page 3).
Relevant to claim 3, Agrawal et al. teaches "A group of PAN injected rats (n = 13) were left untreated and received sham oral gavage vehicle solution…, while the treatment groups (n = 13/group) also received: (i) Low-dose GC (Methylprednisolone…) by intraperitoneal (IP) injection daily, (ii) High-dose GC (15 mg/kg; n = 13), (iii) Pioglitazone… by oral gavage daily, (iv) Combined low-dose GC + pioglitazone [(Pio + low-dose GC; n = 13), and (v) Combined high-dose GC + pioglitazone (Pio + high-dose GC; n = 4)] starting at Day 0" (page 7, "Animal Study Design").
Relevant to claims 7-8, Agrawal et al. Figure 3 and associated caption teach "Pioglitazone and Glucocorticoids Enhance the Glomerular Expression of Podocyte Markers and Reduce COX-2 Expression. Total RNA was extracted from glomeruli isolated from control, PAN-injected, and PAN-injected rats treated with high-dose GC, Pio, and Pio + low-dose GC (n = 3 per group). Relative mRNA levels of (A) Synpo, (B) Nphs1 and (C) Ptgs2 were measured by quantitative reverse transcription–polymerase chain reaction and normalized to Gapdh. Data are presented as Mean ± SEM (*P < 0.05 vs. control; #P < 0.05 vs. PAN; determined by t-test)."
As seen in Agrawal et al. Figure 3, there are genomic regions that are upregulated or downregulated in disease, first, and second groups.
(ii) Agrawal et al. is silent to specifics regarding RNA sequencing, target-drug interaction networks, genes of interest, and cell-specific characterizations (relevant to claims 1, 6 and 9-15). However, these limitations were known in the prior art and taught by Jiang et al. and Illumina.
Relevant to claim 1, Jiang et al. section “RNA extraction, cDNA library construction and sequencing.” The section includes isolating RNA from the kidneys of the subjects; determining the expression of genomic regions using RNA sequencing of the RNA isolated from the kidney. Within this section, Jiang et al. teaches usage of the Illumina TruSeq RNA Sample Preparation v2 kit, which teaches reverse transcription of the RNA into cDNA, amplifying the cDNA using PCR (Illumina Introduction, page 2).
Further relevant to claim 1, Jiang et al. teaches alignment to a representative genomic sequence in section “RNA-seq data mining.”
Relevant to claim 6, although Jiang et al. performs RNA sequencing on RNA isolated from podocyte cell lines – and not kidney glomeruli – the skilled artisan would find this limitation obvious because Agrawal et al. teaches that "Total RNA was extracted from glomeruli isolated from" their rat models for qRT-PCR (Agrawal et al. Figure 3 caption). RNA sequencing and qRT-PCR are common methods for analyzing expression of input isolated RNA, and Agrawal et al. has successfully examined gene expression from “Total RNA… extracted from glomeruli”, indicating that the kidney glomeruli would be an obvious sample for RNA isolation and sequencing.
Relevant to claims 9 and 11, Jiang et al. teaches "A total of 2,276 genes were identified as differentially expressed genes between the dexamethasone group and the control group taking into account the paired design across the 3 cell lines, and used for further analysis. For gene clustering and visualization, the gene expression matrix was analyzed by the supraHex package [citation]. Genes with similar expression changes were self-organised onto nearby regions of a supra-hexagonal map. The resulting map was visualized to display sample-specific expression changes, and was also further partitioned to obtain 7 gene meta-clusters. For each meta-cluster, enrichment analysis was conducted using the function dEnricher in the dnet package [citation] to identify enriched functions (represented as Gene Ontology terms), enriched pathways (from BioCarta, KEGG and Reactome), and enriched transcription factor binding sites (TFBS)" (page 9, paragraph 1).
Relevant to claims 10 and 12, Jiang et al. Figure 2 includes "Enrichment analysis of the clustered genes", which include functions such as extracellular matrix disassembly/organization, cell cycle, growth factor activity, cytokine activity, cell proliferation.
Relevant to claim 13, Jiang et al. Table 1 includes cluster 6, which has 31 genomic regions of interest identified as part of the "Actin/microtubule-related genes upregulated by dexamethasone" (Table 1 caption).
Relevant to claim 14, Jiang et al. Supplementary Table 1 teaches the “List of differentially expressed genes identified from RNA-seq in dexamethasone-treated human podocytes” that contains all but 14 of the recited genes, reading on claim 14.
Relevant to claims 15, Jiang et al. teaches "Dexamethasone-upregulated genes are linked to cytoskeleton-related process. Genes in cluster 5–7 are related to the structure of the podocyte" (page 3, paragraph 2).
(iii) Although Agrawal et al. does not explicitly teach the Jiang et al. and Illumina RNA sequencing, target-drug interaction networks, genes of interest, and cell-specific characterizations, it would have been prima facie obvious to the skilled artisan. It is noted that Agrawal et al., Jiang et al., and Illumina are analogous disclosures to the instant biomarker identification field.
The skilled artisan would have been motivated to combine the analogous art. Jiang et al. Abstract teaches that “To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes.”
Thus, the skilled artisan would have been motivated to include the Illumina-generated Jiang et al. target-drug interaction networks, genes of interest, and cell-specific characterizations within the methodology obviated by Agrawal et al. The skilled artisan would have been motivated to perform RNA sequencing and characterize interaction networks, genes of interest, and cell-specific genomic regions because Jiang et al. establishes that gene regulatory networks for critical signaling pathways are impacted upon treatment with the glucocorticoid dexamethasone. The skilled artisan would have a reasonable expectation of success based on the disclosures of Agrawal et al. view of Jiang et al. and Illumina, as discussed in the preceding paragraphs.
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.
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/SARAH JANE KENNEDY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682