DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claim 6 is objected to because of the following informalities:
The claim recites (in part (iv) of the claim) “use of a m microarray” where the phrase “use of an [[m]] microarray” is likely intended.
The claims recites (in part (ii) of the claim “a PCR based method, which method comprises a polymerase chain reaction (PCR)”, where the second portion of the phrase is redundant because “a PCR based method” is any method that “comprises a polymerase chain reaction (PCR)”.
Appropriate correction is required.
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, 6, 7, 11 and 12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea which is a judicial exception to patentability without significantly more.
The claim(s) recite(s) classifying based on expression levels, and the normalization of expression levels. These aspects of the claims are abstract ideas; they are a mental process (e.g.: MPEP 2106.04(a)(2)(III) ) that is the evaluation of data and information to reach a conclusion (i.e.: classification). Normalizing gene expression levels with a housekeeping gene is a mathematical concept (e.g.: MPEP 2106.04(a)(2)(I) ) where one value is adjusted or modified based on a second value.
Additionally, where the claims are directed to classifications (including the presence or risk of cancer) based on gene expression levels, the claims are directed to a natural phenomenon (e.g.: MPEP 2106.04(b)(I) ) which is the relationship between the transcriptome of a cell and its phenotype.
This judicial exception is not integrated into a practical application because there are no practical steps that are performed in response to any particular classification (e.g.: MPEP 2106.04(d) ). The claims end with classifying a urine sample, which is an abstract idea as detailed above.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of the claim are typical steps of data collection that are well understood, routine and conventional in the related art (e.g.: MPEP 2106.05). For example, Tamura et al (2021) is a prior art review of the analysis of biomarkers in extracellular vesicles for the detection of cancer, including the analysis of RNA in urinary extracellular vesicles (Table 2) and the use of digital PCR for nucleic acid analysis (e.g.: p.158 - EV-ASSOCIATED NUCLEIC ACID; p.162 - EV RNAs to monitor cancer progression and drug resistance); and Wang et al (2021) (cited on the IDS of 09/24/2024) provides an exemplification of the analysis of free mRNA in urine using PCR. The additional elements, which are the steps related to taking a urine sample, extracting RNA, and determining expression levels are thus not sufficient to create a method that is significantly more than the judicial exceptions to which the claims are directed.
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.
Claim(s) 1-4, 6, 7, and 11 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Rinaldetti et al (2018) in view of Kohaar et al (2021).
Relevant to the method of claim 1, Rinadletti et al teaches gene expression associated with bladder cancer classification, including obtaining a sample and extracting RNA from the sample, and determining the expression level of biomarkers in the RNA including ERBB2, FGFR2 and FGFR3 (relevant to claims 3 and 4) using the nCounter assay, and normalization using CALM2 expression levels (e.g.: p.25943 -Gene expression profiling). Rinaldetti et al teaches that overexpression of ERBB2, FGFR2 and FGFR3 is indicative of the luminal phenotype (e.g.: p.25941 – right col; Fig 4A).
Relevant to claims 6 and 7, Rinaldetti et al teaches that RNA was analyzed by the nCounter standard chemistry, which is a hybridization methods in which labeled single stranded probes are used (relevant to (i) of claim 6).
Relevant to claim 11, Rinaldetti et al teaches that ERBB2, FGFR2 and FGFR3 is indicative of the luminal phenotype and that the luminal subtype showed worst 8-year
disease specific survival (DSS) in patients treated by radical cystectomy (RC) only (e.g.: abstract) and that risk stratification based on luminal versus not-luminal MIBC proved to be an independent predictor for DSS.
Rinaldetti et al does not teach the analysis of biomarker in a urine sample (relevant to claim 1), or exosomes in a urine sample (claim 2), but detection of RNA biomarkers in urinary exosomes was known in the prior art and is taught by Kohaar et al.
Kohaar et al teaches the collection of urine samples and the extraction of RNA from isolated urinary exosomes, followed by the detection of RNA biomarkers using droplet digital PCR (e.g.: p.421 - Urine Collection and Exosome Preparation; Urine Assay), relevant to the limitations of claims 1, 2, 6 and 7.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have performed the detection of the RNA biomarker ERBB2, FGFR2 and FGFR3 as indicators of the luminal type of bladder cancer associated with high risk of poor DSS for risk stratification, as taught by Rinaldetti et al, using urinary exosome samples as taught by Kohaar et al. The skilled artisan would have been motivated to use urinary exosomes based on the expressed teachings of Kohaar et al that such samples are suitable for the noninvasive detection of tumor related RNA biomarkers. The skilled artisan would have a resonalbe expectation of success based on the teaching of Rinaldetti et al that ERBB2, FGFR2 and FGFR3 are biomarkers in bladder tumor tissue, and the teachings of Kohaar et al that RNA biomarkers validated in tumor tissue are detectable in urinary exosomes.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rinaldetti et al (2018) in view of Kohaar et al (2021) as applied to claims 1-4, 6, 7, and 11 above, and further in view of Pos et al (2020).
Rinaldetti et al in view of Kohaar et al renders obvious the methods of claim 1 including classification of bladder cancer using determined expression of RNA biomarkers ERBB2, FGFR2 and FGFR3 obtained from urine samples.
Rinaldetti et al in view of Kohaar et al does not teach isolation of biomarker nucleic acids from urine using silica-coated magnetic particles and a chaotropic salts. But such methods were known in the prior art and are taught by Pos et al.
Pos et al teaches that (e.g.: p.17 - Approaches for the Extraction of cfNAs from Various Body Fluids) nucleic acids are isolated from bodily fluids using silica-based magnetic beads and teaches that nucleic acids bind to a silica surface under high chaotropic salt conditions and are detached at low salt concentration.
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to used the known methods of nucleic acid isolation, as taught by Pos et al, to obtain RNA biomarkers form urine for the analysis rendered obvious by Rinaldetti et al in view of Kohaar et al. The use of any known particular methodology would have been the simple substitution of one known element for another with predictable results.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kulkarni (2011) teaches details of the nCounter assay used by Rinaldetti et al, including that the assay utilizes a labeled single-stranded probe (e.g.: Figure 25B.10.1).
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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