DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 17 and 21-41 are pending and currently under examination.
Response to Amendment
The Amendment filed 9/3/25 has been entered. Claims 17 and 21-41 are currently pending. Applicant’s amendments to claims 17, 26, 30-31, 33, and 37-41 and the specification have overcome the 112(b) rejections and objections previously set forth in the Non-Final Office Action mailed 3/3/25.
Response to Arguments
Applicant’s arguments, see pages 9-17, filed 9/3/25, with respect to the rejections of claims 17 and 21-41 under 35 USC 101 and 103 have been fully considered and are found unpersuasive, and the 101 and 103 rejections documented in the Non-Final mailed on 3/3/25 have been revised to address claim amendments filed 9/3/25 in this Final Office Action. More detailed responses to Applicant’s arguments are provided at the end of each maintained rejection.
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 17 and 21-41 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).
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: The claims recite a judicial exception.
Claim 17 recites a law of nature and natural phenomena. Claim 17 limitation of “… prostate cancer… methylation status… expression status…” is a naturally occurring biological correlation between methylation/expression patterns and prostate cancer (see MPEP § 2106.04(b)).
Step 2A, prong two: The judicial exception is not integrated into a practical application.
Claim 17 recites extra-solution and data-gathering limitations of specific genes.
Claim 21 recites limitations unrelated to the judicial exception. Claims 22 – 23 recite extra-solution and data-gathering steps of processing the sample. Claims 24 – 25 recite limitations of the biological sample, not the judicial exception. Claim 26 recites limitations unrelated to the judicial exception. Claim 27 recites extra-solution and data-gathering steps at a high-level of generality. Claims 28 – 32 recite limitations unrelated to the judicial exception. Claim 33 recites techniques used for data-gathering.
Claims 34 – 35 and 38 – 39 recite limitations at a high-level of generality that do not apply or use the judicial exception to effect a particular treatment or prophylaxis for the disease or medical condition. Claims 36 – 37 and 40 – 41 recite particular treatments or prophylaxis, however, the limitations do not clearly specify how the judicial exception would be integrated (i.e., a specific methylation/expression profile requires a specific treatment).
Step 2B: The claims do 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.
Claim 17 recites genes that have been correlated with prostate cancer. The Cancer Genome Atlas Research Network has used the Illumina Infinium HumanMethylation450 platform to determine the methylation status of within prostate cancer samples (TCGA 2015, page 14, “Section 7: DNA Methylation Analysis”). The platform is capable of assaying “99% of RefSeq genes”, including recited genes (Illumina 2012, page 1, column 1, last sentence of paragraph 3). Furthermore, The Cancer Genome Atlas Research Network has examined gene expression status previously, using “Platforms [including] … RNA sequencing, miRNA sequencing, … DNA methylation arrays…” (TCGA 2015, page 1021, column 2, paragraph 2).
Claim 21 recites limitations unrelated to the judicial exception. Claims 22 – 23 recite extra-solution and data-gathering steps of processing the sample. Claims 24 – 25 recite limitations of the biological sample, not the judicial exception. Claim 26 recites limitations unrelated to the judicial exception. Claim 27 recites extra-solution and data-gathering steps at a high-level of generality. Claims 28 – 32 limitations are unrelated to the judicial exception. Claim 33 recites conventional techniques used for data-gathering. Claims 34 – 41 recite conventional treatments of prostate cancer that are not integrated with the judicial exception.
For the reasons set forth above, claims 17 and 21-41 are not directed to patent eligible subject matter.
Applicant’s Arguments
Applicant argues that “claim 17 relates to a combinatorial method involving both methylation of at least one of [biomarkers] and the expression status of at least one of [biomarkers]. The combination of multiple distinct criteria, which are determined through different techniques, is more than merely detecting a biomarker and correlating it with a disease. Therefore, Applicant submits that the claims are patent eligible at least at Prong Two of Step 2A because they recite, but are not wholly directed to, an alleged judicial exception” (Remarks 9/3/25, last paragraph of page 9 continued to first two paragraphs of page 10).
Applicant also argues that “None of the cited prior art documents discloses a method of diagnosing or testing for prostate cancer comprising assessing one or more biomarkers from the first list in the claim specifically by measuring methylation status in combination with assessing the expression status of one or more of the biomarkers from the second list in the claim” (Remarks 9/3/25, page 10, paragraph 5).
Response to Applicant’s Arguments
The rejection of claims 17 and 21-41 under 35 USC 101 has been revised as stated above in this Final Office Action that specifically addresses the Amendments filed 9/3/25.
The claims are directed towards a law of nature and natural phenomena: the naturally occurring relationship between the methylation and expression levels of genes and prostate cancer. This correlation exists in nature, as the genotype (such as a gene’s methylation and expression statuses) necessarily informs and forms the phenotype (such as prostate cancer).
The Examiner respectfully disagrees with the assertion that the claims are eligible at Prong Two of Step 2A. The claim, as a whole, does not integrate the judicial exception into a practical application. The extra-solution and data-gathering techniques of determining both gene expression and gene methylation status do not integrate the judicial exception into a practical application. See MPEP 2106.04(d).
Per MPEP 2106.05(g), the gene expression and methylation determinations are considered insignificant extra-solution activity, as they are considered steps of gathering data for use in a claimed process. The claims do not recite any additional element that applies, refines, or modifies the naturally occurring relationship between genotype and phenotype in a meaningful way, nor do they effect an improvement in any technology or technical field.
The Examiner respectfully disagrees with the assertion that none of the cited prior art documents discloses a method of diagnosing or testing for prostate cancer comprising assessing one or more biomarkers’ methylation and expression. As cited above and within the 103 rejections, The Cancer Genome Atlas Research Network has performed extensive genetic analyses of prostate cancer (Title: The Molecular Taxonomy of Primary Prostate Cancer), as they teach “We characterized isolated biomolecules from these 333 tumor samples using four platforms: whole-exome sequencing for somatic mutations, array-based methods for profiling both somatic copy-number changes and DNA methylation, and mRNA sequencing. We also performed microRNA (miRNA) sequencing on 330 of these samples, reverse-phase protein array (RPPA) on 152 samples, and low-pass and high-pass whole-genome sequencing (WGS) on 100 and 19 tumor/normal pairs, respectively (Supplemental Experimental Procedures). For 19 samples, non-malignant adjacent prostate samples were also examined for DNA methylation and RNA/miRNA expression analyses” (TCGA; 2015; NPL citation W in page 1 of PTO-892 filed 3/3/25; page 1012, column 2, paragraph 2). This teaching demonstrates that the cited prior art performs large-scale methylation and expression analyses to test for prostate cancer.
The Examiner maintains the 35 USC 101 rejection of claims 17 and 21-41 as the claims are not directed to patent eligible subject matter.
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 17, 21-27, and 33 remain/are rejected under 35 U.S.C. 103 as being unpatentable over The Cancer Genome Atlas Research Network (TCGA; 2015; NPL citation W in page 1 of PTO-892 filed 3/3/25; “The Molecular Taxonomy of Primary Prostate Cancer”; Cell 163, 1011–1025; http://dx.doi.org/10.1016/j.cell.2015.10.025) in view of Illumina (2012; NPL citation U in page 1 of PTO-892 filed 3/3/25; Infinium HumanMethylation450 BeadChip Datasheet) and Rigau et al. (2013; NPL citation V in page 1 of PTO-892 filed 3/3/25; “The Present and Future of Prostate Cancer Urine Biomarkers”; Int. J. Mol. Sci. 2013, 14, 12620-12649; doi:10.3390/ijms140612620).
This rejection is necessitated by claim amendments filed 9/3/25.
Relevant to claim 17, The Cancer Genome Atlas Research Network has used the Illumina Infinium HumanMethylation450 platform to determine the methylation status of within prostate cancer biological samples (TCGA 2015, page 14, “Section 7: DNA Methylation Analysis”). The platform is capable of assaying “99% of RefSeq genes”, including recited genes (Illumina 2012, page 1, column 1, last sentence of paragraph 3). This methylation assay performed on the Illumina array reads on determining a methylation status of one or more genes selected from the group consisting of GSTP1, APC, SFRP2, IGFBP3, IGFBP7, PTGS2. The Cancer Genome Atlas Research Network teaches that GSTP1 was “epigenetically silenced in almost all tumors” (page 1016, column 1, paragraph 1), reading on determining a methylation status of one…gene[s]. Further relevant to claim 17, determining… an expression status of one or more genes selected from the group consisting of… has also been previously performed by The Cancer Genome Atlas Research Network within the same 2015 publication, using “Platforms [including] … RNA sequencing, miRNA sequencing…” (TCGA 2015, page 1021, column 2, paragraph 2).
Relevant to claim 22, the biological sample[s] [are] processed prior to determining the expression status within TCGA Supplemental Experimental Procedures Section 1: Biospecimens and Analysis Centers on pages 2-3. Relevant to claim 25, TCGA Supplemental Experimental Procedures Section 8: MicroRNA Analysis on page 18 teaches that they “aligned reads to the GRCh37/hg19 reference human genome,” reading on claim 25 the sample is from a human.
Relevant to claims 27 and 33, The Cancer Genome Atlas Research Network page 1021, column 2, paragraph 2 teaches that “DNA, RNA, and protein were purified and distributed throughout the TCGA network”, and that their “Platforms included exome and whole genome DNA sequencing, RNA sequencing, miRNA sequencing, SNP arrays, DNA methylation arrays, and reverse phase protein arrays”, reading on claim 27 expression status… determined by one or more methods including protein quantification, methylation status, RNA extraction… or RNA sequencing. This teaching also reads on claim 33 determining the expression status… quantifying the expression status of an RNA transcript… quantified using… RNA sequencing.
The Cancer Genome Atlas Research Network does not explicitly report the expression statuses of the claimed genes (claim 17), biopsy determinations (claim 21), RNA extractions from extracellular vesicles (claim 23), urine samples (claim 24), or serum PSA levels (claim 26).
However, relevant to claims 17, 21, and 24, Rigau et al. Table 1 teaches a “summary of PCa [prostate cancer] biomarkers in the literature” and includes the claim 17 genes within the excerpt included below:
Gene
Expression
Type of biomarker
Sample
APC
APC methylation higher in PCa than in BPH [benign prostatic hyperplasia]. Methylation level correlates positively with Gleason score
Diagnostic and prognostic
Tissue and Urine
DNA
GSTP1
Loss of GSTP1 expression due to
the promoter hypermethylation (>90% of PCa).
Correlates with the number of cores
found to contain PCa
Diagnostic (indicator for repeat biopsy)
Tissue and urine
DNA
HPN
Over-expressed in 90% PCa tumors
(highly produced in HGPIN
and PCa compared with BPH)
Diagnostic
Tissue
PCA3
Prostate specific and highly up-regulated in PCa
Diagnostic (indicator for repeat biopsy)
Tissue and urine
TIMP4
Highest expression in HGPIN
and decline in cancer, possible
involvement in formation of early cancer.
Progression
Tissue RNA
TMPRSS2:ERG
The most common gene fusion
in PCa. Over-expressed PCa
and related to PCa aggressiveness
Prognostic for aggressive PCa and
detection of PCa
Tissue and urine
Relevant to claim 21, Rigau et al. Table 1 teaches that the GSTP1 and PCA3 genes’ methylation and expression statuses are indicators for repeat biopsies, reading on the method can be used to determine whether a patient should be biopsied.
Relevant to claim 24, Rigau et al. Table 1 teaches that the biological samples for APC, GSTP1, PCA3, and TMPRSS2:ERG gene statuses were determined from urine sample[s].
Relevant to claim 23, Rigau et al. teaches that “exosomes are small, secreted membranous vesicles formed in multivesicular bodies through an inward budding mechanism that encapsulates cytoplasmic components” and have “nucleic acid contents, such as mRNA, small ncRNA, miRNA and mitochondrial DNA (mtDNA), which can be transported to other cells” (page 12634, Section 2.7 Exosomes as a Source of Urine Biomarkers, paragraph 1). The exosomes of Rigau et al. read on the extracellular vesicles of claim 23. Additionally, Rigau et al. teaches that “known RNA markers for PCa, such as TMPRSS2-ERG fusion transcripts and PCA3, could be detected in urine-derived and PCa cell line-derived exosomes” (page 12634, Section 2.7 Exosomes as a Source of Urine Biomarkers, paragraph 2). Collectively, these teachings read on claim 23 determining the expression status of the one or more genes comprises extracting RNA from the biological sample, optionally wherein the RNA is extracted from extracellular vesicles.
Relevant to claim 26, Rigau et al. Figure 2 proposes that urine-based diagnostic tests, such as those summarized within Rigau et al. Table 1, should be included with serum PSA screening as a “future improvement in the PCa diagnostic scheme”, reading on serum PSA level of the subject is also used in the method of diagnosing or testing for prostate cancer.
Collectively, The Cancer Genome Atlas Research Network and Illumina method and Rigau et al. reported genes read on a method of diagnosing or testing for prostate cancer in a subject comprising determining the methylation status… and the expression status of one or more genes… in a biological sample from the subject.
The skilled artisan would be motivated to combine the method of The Cancer Genome Atlas Research Network and Illumina to specifically examine the genes of Rigau et al. because Rigau et al. teaches that the genes are “promising DNA, RNA, miRNA, protein and metabolite based urine biomarkers” (page 12623, last sentence). The skilled artisan would recognize that the large datasets generated by The Cancer Genome Atlas Research Network and Illumina benefit from focusing on the biomarker genes that Rigau et al. summarizes from the literature, as the biomarkers have been validated for diagnostic and prognostic applications within the field.
Additionally, the skilled artisan would be motivated to incorporate The Cancer Genome Atlas Research Network method with urine samples, PSA serum levels, and guidance regarding biopsy determinations because Rigau et al. teaches that “A future goal is therefore the development of a low cost, point of care, multiplexed, urine-based detection test for PCa which could be incorporated seamlessly into routine clinical practice to better determine which patients should undergo biopsy, and to highlight those patients that have a high risk of PCa metastasis/CRPC [castration-resistant prostate cancer], and which therefor require treatment, at the earliest possible point in time” (page 12635, paragraph 3). As taught by Rigau et al. Figure 2 for further motivation, the combinations of urine-based diagnostics, serum PSA level evaluations, and digital rectal examinations during screening can lead to “less FALSE POSITIVES, save approximately unnecessary Biopsies, [and] differentiate indolent from non-indolent diseases.” Furthermore, the skilled artisan would be motivated to include the exosome (or extracellular vesicle) RNA extractions of Rigau et al. because Rigau et al. page 12634, last two sentences of paragraph 2 teach that biomarker detection within exosomes “demonstrated a potential for diagnosis, as well as a strategy for the successful monitoring of the status of cancer patients. miRNAs have also been detected in extracellular fractions, stabilized by their encapsulation in microvesicles such as exosomes. Exosomes are thus a prime non-invasive source of biomarkers for cancer and other diseases.” The skilled artisan would have a reasonable expectation of success based on the disclosures of TCGA in view of Illumina and Rigau et al.
Applicant’s Arguments
Applicant argues that “there is nothing in any of the cited references that would motivate one of ordinary skill in the art to combine the teachings of these references to produce the presently claimed invention. Moreover, there is nothing in any of the cited references that would provide one of ordinary skill in the art with a reasonable expectation of success in making the combination in the presently claimed invention” (Remarks 9/3/25, page 13, paragraph 1).
Response to Applicant’s Arguments
The rejection of claims 17, 21-27, and 33 under 35 USC 103 has been revised as stated above in this Final Office Action that specifically addresses the amended limitations recited in the Amendments filed 9/3/25.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In this case, the skilled artisan would recognize that the TCGA disclosure presents a comprehensive molecular taxonomy of primary prostate cancer, wherein they successfully tested prostate cancers for biomarkers within multiple molecular analyses (including DNA methylation and RNA expressions), as seen in the TCGA Graphical Abstract. The skilled artisan would recognize that this comprehensive disclosure provides a successfully executed resource for other skilled artisans. This is established through the TCGA teaching that “In summary, our integrative assessment of 333 primary prostate cancers has confirmed previously defined molecular subtypes across multiple genomic platforms and identified novel alterations and subtype diversity. It provides a resource for continued investigation into the molecular and biological heterogeneity of the most common cancer in American men” (page 1021, last paragraph of “DISCUSSION” section).
The skilled artisan would recognize that statement as motivation for “continued investigation into the molecular and biological heterogeneity” of prostate cancer. This motivation is present within Rigau et al. as well, since Rigau et al. provides a literature review of previously successful continued investigations. The Rigau et al. Table 1 teaches that several of the claimed biomarkers have notable methylation and expression patterns present within prostate cancer, indicating that skilled artisans recognize that both methylation and expression of prostate cancer biomarkers has been successfully assayed before.
Thus, the Examiner respectfully disagrees with the assertions that there is no motivation to combine the teachings and that there is no reasonable expectation of success. The teachings of TCGA in view of Illumina and Rigau et al. obviate the instant invention. The skilled artisan would have a reasonable expectation of success because the claimed process has been successfully performed within TCGA and Rigau et al. using commercially- and widely-available Illumina technology which has previously analyzed the claimed biomarkers within the claimed prostate cancer.
Claims 28-29 remain/are rejected under 35 U.S.C. 103 as being unpatentable over The Cancer Genome Atlas Research Network (TCGA; 2015; NPL citation W in page 1 of PTO-892 filed 3/3/25; “The Molecular Taxonomy of Primary Prostate Cancer”; Cell 163, 1011–1025; http://dx.doi.org/10.1016/j.cell.2015.10.025) in view of Illumina (2012; NPL citation U in page 1 of PTO-892 filed 3/3/25; Infinium HumanMethylation450 BeadChip Datasheet) and Rigau et al. (2013; NPL citation V in page 1 of PTO-892 filed 3/3/25; “The Present and Future of Prostate Cancer Urine Biomarkers”; Int. J. Mol. Sci. 2013, 14, 12620-12649; doi:10.3390/ijms140612620), as applied to claims 17, 21-27, and 33 above, and further in view of Hendriks et al. (2017; NPL citation X in page 1 of PTO-892 filed 3/3/25; “A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection”; The Prostate. 2017;77:1401–1407; DOI: 10.1002/pros.23401).
The teachings of the TCGA in view of Illumina and Rigau et al. are applied to instantly rejected claims 28-29 as they were previously applied to claims 17, 21-27, and 33. TCGA in view of Illumina and Rigau et al. renders obvious a method of diagnosing or testing for prostate cancer via determination of biomarker expression and methylation guiding biopsy determination. These teachings are silent to combinations with MRI or multiparametric-MRI (MP-MRI) imaging.
However, relevant to claims 28-29, Hendriks et al. teaches in page 1402, column 1, paragraph 3 that “Recently various biomarkers have been studied to improve detection of PCa, especially to identify patients with clinically significant disease. These new biomarkers include the urinary prostate cancer gene 3 (PCA3) and the prostate health index (PHI). To improve early detection of clinically significant PCa and to reduce additional expenses, novel biomarkers could be used to select patients for mpMRI or these biomarkers could be combined with mpMRI to select for prostate biopsy indication.” This teaching provides for the combination of biomarker detection and MRI – specifically MP-MRI – imaging to better guide biopsy determinations, reading on claim 28 method is used in combination with MRI imaging data to determine whether a patient should be biopsied and claim 29 MRI imaging data is generated using multiparametric-MRI (MP-MRI). Additionally, this teaching provides the skilled artisan with the motivation to combine the method of TCGA in view of Illumina and Rigau et al. with the imaging of Hendriks et al. in order to “improve early detection of clinically significant PCa and to reduce additional expenses.” The skilled artisan would have a reasonable expectation of success based on the disclosures of TCGA in view of Illumina and Rigau et al., and further in view of Hendriks et al.
Applicant’s Arguments
Applicant argues that “The law regarding obviousness under 35 U.S.C. §103, and the deficiencies of TCGA, Illumina, and Rigau are discussed elsewhere herein and, although not repeated here for the sake of brevity, are equally applicable to the instant rejection of claims 28-29 under 35 U.S.C. §103. Hendriks fails to remedy the deficiencies of TCGA, Illumina, and Rigau” (Remarks 9/3/25, page 15, paragraph 2).
Response to Applicant’s Arguments
The rejection of claims 28-29 under 35 USC 103 has been revised as stated above in this Final Office Action that specifically addresses the amended limitations recited in the Amendments filed 9/3/25.
The response to the “deficiencies of TCGA, Illumina, and Rigau” are presented in the above rejection of claims 17, 21-27, and 33. Hendriks et al. is not relied upon to remedy the deficiencies of claims 17, 21-27, and 33. Thus, the only independent claim is obvious, and as such, all of the claims are obvious.
Claims 30-32 remain/are rejected under 35 U.S.C. 103 as being unpatentable over The Cancer Genome Atlas Research Network (TCGA; 2015; NPL citation W in page 1 of PTO-892 filed 3/3/25; “The Molecular Taxonomy of Primary Prostate Cancer”; Cell 163, 1011–1025; http://dx.doi.org/10.1016/j.cell.2015.10.025) in view of Illumina (2012; NPL citation U in page 1 of PTO-892 filed 3/3/25; Infinium HumanMethylation450 BeadChip Datasheet) and Rigau et al. (2013; NPL citation V in page 1 of PTO-892 filed 3/3/25; “The Present and Future of Prostate Cancer Urine Biomarkers”; Int. J. Mol. Sci. 2013, 14, 12620-12649; doi:10.3390/ijms140612620), as applied to claims 17, 21-27, and 33 above, and further in view of Fujita et al. (2018; NPL citation U in page 2 of PTO-892 filed 3/3/25; “Urinary biomarkers of prostate cancer”; International Journal of Urology (2018) 25, 770-779; doi: 10.1111/iju.13734) and Stern et al. (2015; WO 2015/109234 A1; FOR citation N in page 1 of PTO-892 filed 3/3/25).
The teachings of the TCGA in view of Illumina and Rigau et al. are applied to instantly rejected claims 30-32 as they were previously applied to claims 17, 21-27, and 33. TCGA in view of Illumina and Rigau et al. renders obvious a method of diagnosing or testing for prostate cancer via determination of biomarker expression and methylation guiding biopsy determination. These teachings are silent to performing the method on patients under active surveillance or performing the method to predict disease progression, volume of prostate cancer, and/or low risk disease in patients.
However, relevant to claim 30, Fujita et al. teaches in page 774, column 1, last sentence of paragraph 1 that the PCA3 biomarker was obtained “during active surveillance,” indicating the success of determining expression of biomarkers wherein a patient is currently undergoing or has been recommended for active surveillance.
The skilled artisan would be motivated to perform the modified TCGA methodology on the Fujita et al. patients undergoing active surveillance because Stern et al. teaches that “’Active surveillance’ or ‘watchful waiting’ are options that are least favored by most patients” (page 1, paragraph 0003, lines 23-24). This teaching indicates that patients would prefer clinical interventions, such as those rendered obvious by TCGA in view of Illumina and Rigau et al., and further in view of Fujita et al. and Stern et al., than to continue under delayed treatment.
Relevant to claim 31, Stern et al. teaches systems “for predicting progression and/or recurrence of PCa” (Abstract) based on gene expression profiles of patients with Gleason scores of 8-10, 7 ((4+3) or (2+5); (4+3) or (5+2)), and ≤6 (Table 1). These teachings read on claim 31 predict disease progression in patients with a Gleason score of <10, <9, <8, <7, or <6. Stern et al. teaches that the Gleason Score is a predictor for patient prognosis, wherein different patient disease specific survivals are observed for different levels of Gleason Score (page 10, paragraph 0036, lines 2-17). Therefore, the skilled artisan would be motivated to include the predictive techniques of Stern et al. within the diagnostic techniques of TCGA in view of Illumina, Rigau et al. to better identify, treat, and improve the prognoses of more aggressive cancers.
Relevant to claim 32, Fujita et al. Table 3 teaches that the detection of PCA3 is associated with the prognoses of prediction of “upgrading to Gleason score ≥ 7” and prediction of “tumor volume,” reading on the method can be used to predict: (i) the volume of… Gleason >4 prostate cancer. Further relevant to claim 32, Stern et al. page 20, paragraph 0071 teaches that the predictive methodology can be used to “report the risk status of each patient,” including those that may be considered low-risk and view “active surveillance and delayed treatment” as desirable (page 15, paragraph 0055, line 12), reading on the method can be used to predict… (ii) low risk disease that will not require treatment… The skilled artisan would be motivated to include the prognosis predictions because Stern et al. teaches that “Having improved risk prediction models would offer stronger re-assurance to low-risk patients, which will reduce over-treatment of indolent disease, lower the financial burden on patients, and improve the quality of life among these PCa cancer survivors” (page 14, paragraph 0055, lines 15-18).
The skilled artisan would have a reasonable expectation of success based on the disclosures of TCGA in view of Illumina and Rigau et al., and further in view of Fujita et al. and Stern et al.
Applicant’s Arguments
Applicant argues that “The law regarding obviousness under 35 U.S.C. §103, and the deficiencies of TCGA, Illumina, and Rigau are discussed elsewhere herein and, although not repeated here for the sake of brevity, are equally applicable to the instant rejection of claims 28-29 [potential typo: perhaps intended claims 30-32?] under 35 U.S.C. §103” (Remarks 9/3/25, page 16, paragraph 2).
Response to Applicant’s Arguments
The rejection of claims 30-32 under 35 USC 103 has been revised as stated above in this Final Office Action that specifically addresses the amended limitations recited in the Amendments filed 9/3/25.
The response to the “deficiencies of TCGA, Illumina, and Rigau” are presented in the above rejection of claims 17, 21-27, and 33. Fujita et al. and Stern et al. are not relied upon to remedy the deficiencies of claims 17, 21-27, and 33. Thus, the only independent claim is obvious, and as such, all of the claims are obvious.
Claims 34-41 remain/are rejected under 35 U.S.C. 103 as being unpatentable over The Cancer Genome Atlas Research Network (TCGA; 2015; NPL citation W in page 1 of PTO-892 filed 3/3/25; “The Molecular Taxonomy of Primary Prostate Cancer”; Cell 163, 1011–1025; http://dx.doi.org/10.1016/j.cell.2015.10.025) in view of Illumina (2012; NPL citation U in page 1 of PTO-892 filed 3/3/25; Infinium HumanMethylation450 BeadChip Datasheet) and Rigau et al. (2013; NPL citation V in page 1 of PTO-892 filed 3/3/25; “The Present and Future of Prostate Cancer Urine Biomarkers”; Int. J. Mol. Sci. 2013, 14, 12620-12649; doi:10.3390/ijms140612620), as applied to claims 17, 21-27, and 33 above, and further in view of Schettini et al. (2015; US 2015/0301058 A1; USPat citation A in page 1 of PTO-892 filed 3/3/25).
The teachings of the TCGA in view of Illumina and Rigau et al. are applied to instantly rejected claims 34-41 as they were previously applied to claims 17, 21-27, and 33. TCGA in view of Illumina and Rigau et al. renders obvious a method of diagnosing or testing for prostate cancer via determination of biomarker expression and methylation guiding biopsy determination. These teachings are silent to specific therapies.
However, relevant to claims 34 and 38, Schettini et al. teaches that biosignatures (that can “include an expression level… of one or more biomarkers”, page 51, paragraph 0356) “can be used to evaluate diagnostic criteria such as presence of disease, disease staging, disease monitoring” and can “also be used clinically in making decisions concerning treatment modalities including therapeutic intervention. A biosignature can further be used clinically to make treatment decisions, including whether to perform surgery or what treatment standards should be used along with surgery (e.g., either pre-surgery or post-surgery)” (page 52, paragraph 0362).
The prior art teaches using biosignatures to determine which treatments are suitable for treating prostate cancer, therefore, it would have been obvious to use the method of TCGA in view of Illumina and Rigau et al. to determine the biomarkers (i.e., biosignature) of a patient having prostate cancer and then administer to the patient one of the appropriate therapies, as taught by Schettini et al. These teachings read on claims 34 and 38 method of treating prostate cancer, comprising administering to a patient a therapy for treating prostate cancer after the patient has been diagnosed (claim 34) or determined (claim 38) to have prostate cancer.
Relevant to claims 35-37 and 39-41, Schettini et al. Table 8 teaches therapies for prostate cancer including surgery (including “transurethral resection of [a] prostate”), watchful waiting (active surveillance), chemotherapy (including bicalutamide, cabazitaxel, degarelix, docetaxel, mitoxantrone, nilutarnide, and sipuleucel-T), hormone therapy, biologic therapy (immunotherapy), and radiation therapy (radiotherapy).
The skilled artisan would be motivated to combine the diagnostic methods of TCGA in view of Illumina and Rigau et al. with the therapies of Schettini et al. because the TCGA teaches that “Molecular and genetic profiles are increasingly being used to subtype cancers of all types and to guide selection of more precisely targeted therapeutic interventions” (page 1011, column 2, first sentence of paragraph 2). The skilled artisan would recognize the benefits of targeting, or personalizing, the therapy to the patient-unique cancer to ensure efficient treatment regimens. The skilled artisan would have a reasonable expectation of success based on the disclosures of TCGA in view of Illumina and Rigau et al., and further in view of Schettini et al.
Applicant’s Arguments
Applicant argues that “The law regarding obviousness under 35 U.S.C. §103, and the deficiencies of TCGA, Illumina, and Rigau are discussed elsewhere herein and, although not repeated here for the sake of brevity, are equally applicable to the instant rejection of claims 28-29 [potential typo: perhaps intended claims 34-41?] under 35 U.S.C. §103” (Remarks 9/3/25, page 17, paragraph 1).
Response to Applicant’s Arguments
The rejection of claims 34-41 under 35 USC 103 has been revised as stated above in this Final Office Action that specifically addresses the amended limitations recited in the Amendments filed 9/3/25.
The response to the “deficiencies of TCGA, Illumina, and Rigau” are presented in the above rejection of claims 17, 21-27, and 33. Schettini et al. is not relied upon to remedy the deficiencies of claims 17, 21-27, and 33. Thus, the only independent claim is obvious, and as such, all of the claims are obvious.
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 Sarah J Kennedy whose telephone number is (571)272-1816. The examiner can normally be reached Monday - Friday 8a - 5p.
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, Winston Shen can be reached at 571-272-3157. 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.
/SARAH JANE KENNEDY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682