DETAILED ACTION
In application filed on 03/03/2023, Claims 1-4, 9, 15-16, 31-41 and 45-47 are pending. The claim set submitted on 06/02/2023 is considered because this is the most recent claim set with some preliminary amendments. Claims 1-4, 9, 15-16, 31-41 and 45-47 are considered in the current office 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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/26/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because certain reference characters in figures, not limited to Figures 1B-1I; Fig. 2A-E and Fig. 3A-G are not legible.
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 Objections
Claims 1-2, 15, 31 and 38 are objected to because of the following informalities:
Claim 1 recites “(A) obtaining a sample collected from a subject;”.
It appears that the limitation is awkwardly recited due to a typographical error and the “;” that is the semicolon after “subject” is not required.
For the purpose of expedited examination, Examiner interprets the limitation as (A) obtaining a sample collected from a subject[[;]]”.
Appropriate correction is required.
Claim 2 recites the limitation “the level” in line 1, but earlier recited “a polypeptide level” in claim 1.
Consistent language should be used and for the purpose of expedited prosecution, Examiner interprets “the level” as “the polypeptide level”.
Appropriate correction is required.
Claim 15 recites “SRD5A and NCDN” in line 5 of the Claim.
It appears that the limitation has a typographical error and should be recited as ““SRD5A and NCDN” is awkwardly recited due to a typographical error in light of the “SRD5A2 and NCDN” recitation in Specification [Para 0084])
For the purpose of expedited examination, Examiner interprets the limitation “SRD5A and NCDN” as “SRD5A2 and NCDN”.
Appropriate correction is required.
Claim 31 recites the limitation “the level” in line 1, but earlier recited “a polypeptide level” in claim 1
Consistent language should be used and for the purpose of expedited prosecution, Examiner interprets “the level” as “the polypeptide level”.
Appropriate correction is required.
Further, Claim 31 recites the limitation “the biomarker” in line 2, but earlier recited “one or more mpMRI visibility biomarkers” in claim 1.
Consistent language should be used and for the purpose of expedited prosecution, Examiner interprets “the biomarker” as “the one or more mpMRI visibility biomarkers”.
Appropriate correction is required.
Claim 31 recites the limitation "the log2 transformed abundance".
It appears that the limitation “log2 transformed abundance” is a property of the biomarker wherein the biomarker has antecedent basis.
For the purpose of expedited examination, the limitation ““the log2 transformed abundance” is interpreted as “a log2 transformed abundance”
Applicant should provide clarification.
Claim 38 recites the limitation “the level” in line 1, but earlier recited “a polypeptide level” in claim 1.
Consistent language should be used and for the purpose of expedited prosecution, Examiner interprets “the level” as “the polypeptide level”.
Appropriate correction is required.
Further, Claim 38 recites the limitation “the one or more biomarker” in line 2, but earlier recited “one or more mpMRI visibility biomarkers” in claim 1
Consistent language should be used and for the purpose of expedited prosecution, Examiner interprets “the one or more biomarker” as “the one or more mpMRI visibility biomarkers”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claim 33 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 33 recites the limitation "the cutoff". There is insufficient antecedent basis for this limitation in the claim.
Is “the cuff-off” same as the “predetermined threshold level” in Claim 2?
This is not clear.
Applicant should provide clarification.
Further, Claim 33, which recites “the cutoff” with no units.
Is cutoff a dimensionless quantity?
Applicant should provide clarification.
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, 9, 15-16, 31-41 and 45-47 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. All claims are directed to statutory categories, i.e., a method (Claims 1-4, 9, 15-16, 31-41 and 45-47) (Step 1: YES).
Analysis:
Claim 1: Ineligible.
Claim 1 recites a method. Thus, the claim is directed to a method, which is one of the statutory categories of invention (Step 1: YES).
Claim 1 recites “selecting the subject for mpMRI if the level of the one or more mpMRI visibility biomarkers is indicative that the tumor is visible”.
Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math or mental process since claim 1 relates to using a math or mental process to “select the subject for mpMRI if the level of the one or more mpMRI visibility biomarkers is indicative that the tumor is visible”. This selection appears to be an evaluation and therefore a mental step and an abstract idea. (Step 2A, Prong 1: YES).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the using of the comparison to identify the amino acid sequence of the digested peptide of the said protein of interest is made, then no further action is taken, so no particular practical application.
In addition, it appears that the limitations “obtaining a sample collected from a subject; and measuring a polypeptide level of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS 1, NCDN, WDR5 and/or LDHB, in the sample collected from the subject; or (B) obtaining expression data and determining a polypeptide level of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS1, NCDN, WDR5 and/or LDHB, in a sample collected from a subject; and wherein the subject has or is suspected of having prostate cancer” is data gathering and therefore an insignificant extra solution activity. See MPEP 2106.05(g). (Step 2A, Prong 2: NO).
Step 2B:
Furthermore, the courts have found that limitations adding insignificant extrasolution activity to the judicial exception, such as mere data gathering in conjunction with a law of nature or abstract idea, are limitations found not to be enough to qualify as ‘significantly more’ when recited in a claim with a judicial exception (see the 2014 Interim Guidance on Patent Subject Matter Eligibility of the Federal Register dated December 16, 2014; and MPEP 2106.05(I)(A)). Note that mere data gathering is not significantly more than the abstract idea. See MPEP 2106.05(g).
Here, the steps of ““obtaining a sample collected from a subject; and measuring a polypeptide level of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS 1, NCDN, WDR5 and/or LDHB, in the sample collected from the subject; or (B) obtaining expression data and determining a polypeptide level of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS1, NCDN, WDR5 and/or LDHB, in a sample collected from a subject; and wherein the subject has or is suspected of having prostate cancer”” appears to be well-understood, routine, and conventional (WURC) in the field of clinical diagnostics, as evidenced by Salami et al. (US20210324476A1). (Step 2B: NO).
Therefore, Claim 1 is ineligible.
Moreover, Claims 2-4, 9, 15-16, 31-41 and 45-47 are rejected by virtue of dependency on Claim 1.
Claim 2: Ineligible.
Claim 2 recites “…comparing the level of the one of more mpMRI visibility biomarkers to a predetermined threshold level or statistical model”. Therefore, the claim is directed towards an abstract idea, and more specifically to the abstract idea group of a math or mental process since claim 2 relates to using a math or mental process to “…compare the level of the one of more mpMRI visibility biomarkers to a predetermined threshold level or statistical model”. (Step 2A, Prong 1: YES).
Step 2A, Prong 2:
This judicial exception is not integrated into a practical application.
Once the evaluation is made then no action is taken, so no particular practical application.(Step 2A, Prong 2: NO).
Step 2B: The claims do not recite any elements which are significantly more than the abstract idea. The steps of the method of Claim 1 appears to be well-understood, routine, and conventional (WURC) in the field of Clinical diagnostics, as evidenced by Salami et al. (US20210324476A1).
Therefore, Claim 2 is ineligible.
Moreover, Claims 3 and 32 are rejected by virtue of dependency on Claim 2.
Claim 3-4, 9, 15-16, 31-41 and 46-47: Ineligible.
Step 2A, Prong One and Prong Two: Claims 3-4, 9, 15-16, 31-41 and 46-47 further define the data gathering steps which appear to be generic and WURC.
Step 2B: The claims do not recite any elements which are significantly more.
Therefore, Claims 3-4, 9, 15-16, 31-41 and 46-47 are ineligible.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4, 9, 15, 31-32, 34-36, 40 and 45-46 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Salami et al. (US20210324476A1).
Regarding Claim 1, Salami teaches a method comprising:
(A) obtaining a sample collected from a subject (See Para 0009… receiving a sample from a subject); and
measuring a polypeptide level (See Para 0008, 0013…level of expression) of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS 1, NCDN, WDR5 and/or LDHB, in the sample collected from the subject (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject),
wherein the subject has or is suspected of having prostate cancer” (See Para 0008… a method of performing an MRI imaging on a subject suspected of having prostate).
Based on how the Claim is currently recited, Examiner submits that the limitation “(B) obtaining expression data and determining a polypeptide level of one or more mpMRI visibility biomarkers selected from SRD5A2, GNA11, CAPNS1, NCDN, WDR5 and/or LDHB, in a sample collected from a subject, and selecting the subject for mpMRI if the level of the one or more mpMRI visibility biomarkers is indicative that the tumor is visible”, is interpreted as optional (or an alternative limitation) due to the recited “or” proceeding the limitation and thus not explicitly required by the Claim.
Regarding Claim 2, Salami teaches a method of claim 1, further comprising comparing (See Para 0011… the altered expression is over or under expression relative to a control level, thereby teaching “comparing” ) the level (See Para 0008, 0013…level of expression) of the one of more mpMRI visibility biomarkers (See Para 0010… presence or absence of altered expression of one or more genes selected from, for example, …SRD5A2…) to a predetermined threshold level (see Para 0011… a control level (e.g., the level in a sample of a subject not suspected of having prostate cancer, thereby teaching “predetermined threshold level”; Also See Claim 4) or statistical model (the claimed “or statistical model” in interpreted as optional). (See Para 0011… In some embodiments, the altered expression is over or under expression relative to a control level (e.g., the level in a sample of a subject not suspected of having prostate cancer)).
Regarding Claim 4, Salami teaches a method of claim 1, wherein the one or more mpMRI visibility biomarkers (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject) are all of the mpMRI visibility biomarkers (See Para 0011……SRD5A2…are underexpressed in MRI visible tumors; See Para 0011… MRI is multi-parametric MRI (mpMRI).).
Examiner submits that the claimed “wherein the one or more mpMRI visibility biomarkers are at least 2, 3, 4, or 5 of the mpMRI visibility biomarkers or” is optional (or an alternative limitation) in light of the recited “or” and thus not required by the Claim.
Regarding Claim 9, Salami teaches a method of claim 1,wherein the one or more mpMRI visibility biomarkers (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject) is or comprises SRD5A2, GNA11, CAPNS1, NCND, WDR5, or LDHB (See Para 0011……SRD5A2…are underexpressed in MRI visible tumors; See Para 0011… MRI is multi-parametric MRI (mpMRI).).
Regarding Claim 15, Salami teaches a method of claim 1, wherein the one or more mpMRI visibility biomarkers (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject) is or comprises SRD5A2, GNA11, and LDHB (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject).
Regarding Claim 31, Salami teaches a method of claim 1, wherein the level (See Para 0008, 0013…level of expression) is the log2 transformed abundance (‘change’) of the biomarker (See Claim 9, Para 0011….said genes are over or underexpressed by a log2-fold change of 1 to 2.5. thereby teaching “the log2 transformed abundance”).
Regarding Claim 32, Salami teaches a method of claim 2, wherein the statistical model (See Para 0073… the gene expression signature using 2000 stratified bootstrapped sets of performance statistics to determine an optimal cut-off point for the gene expression signature; See Para 0075… 27 Statistical analyses were performed in R version 3.3.3, and all statistical tests were two-sided using a 0.05 significance level) comprises one or more of logistic regression, linear discriminant analysis, multivariate adaptive regression splines, naive Bayes, neural network, support vector machine, functional tree, LAD tree, Bayesian network, elastic net regression, and random forest (See Para 0078… Using DE analysis and RF classifier to identify candidate differentially expressed genes, four separate logistic regression models for predicting mpMRT tumor visibility status; Also see Para 0083…signature was developed with multivariable ridge logistic-regression model using cross validation for 2 hyperparameter selection, thereby teaching “logistic regression”.
Regarding Claim 34, Salami teaches a method of claim 1, wherein the subject is a subject (See Para 0009… receiving a sample from a subject) with grade 1 or grade 2 prostate cancer as defined by ISUP (See Table 3, Page 9…ISUP Grade Group , GG1, GG2 , where GG is Grade group [ Para 0018, Page 10]; or Para 0074…pathologic grade group (GG)).
Regarding Claim 35, Salami teaches a method of claim 1, wherein the sample (See Para 0009… receiving a sample from a subject) is a prostate cancer biopsy (See Claim 2… A method of performing a prostate cancer detection assay on a subject suspected of having prostate cancer…performing nom-MRI imaging or prostate biopsy on said subject when the absence of said altered expression is detected.)
Regarding Claim 36, Salami teaches a method of claim 35, wherein the sample is a treatment- naive sample (See Para 0052…a sample of a subject not suspected of having prostate cancer, thereby teaching “treatment- naive sample”).
Regarding Claim 40, Salami teaches a method of claim 1, wherein the method further comprises performing mpMRI (See Para 0051… the present disclosure is not limited to particular MRI methods. In some exemplary methods, the MRI is multi-parametric MRI (mpMRI); See Para 0069…patients with clinically localized disease who underwent preoperative mpMRI…).
Regarding Claim 45, Salami teaches a method of claim 1, further comprising providing a prognosis or an assessment of aggressiveness of the tumour to the subject (See Table 3 for the ISUP Grade Groups; Gleason Scores: GG1-GG5, where it is known GG1 is the least aggressive tumor and GG5 the most aggressive tumor, thereby teaching “providing a prognosis or an assessment of aggressiveness of the tumour to the subject”.)
As evidenced by Srigley at al. Srigley et al. ("One is the new six: The International Society of Urological Pathology (ISUP) patient-focused approach to Gleason grading." Canadian Urological Association Journal 10.9-10 (2016): 339), it is known, according to the Gleason scores/grade groupings that GG1 is the least aggressive tumor while GG5 is the most aggressive tumor. Srigley et al. further teaches that Grade 5 is the highest ISUP grade…; ISUP grade 4 tumours consisting of Gleason patterns 5 + 3 have been shown to have the worst prognosis compared to those with only pattern 4 or 3 + 5 and may be more appropriately included in ISUP grade 5. (See Table 2; See Page 340, Right column).
Regarding Claim 46, Salami teaches a method of claim 45, further comprising selecting a suitable treatment plan and/or risk stratification (See Para 0062…the prepared format may represent a diagnosis or risk assessment for the subject, along with recommendations for particular treatment options; Also See Para 0064…For example, the data may be used to further optimize the inclusion or elimination of markers as useful indicators of a particular condition or stage of disease or as a companion diagnostic to determine a treatment course of action. In some embodiments, the results are used to select candidate therapies for drug screening or clinical trials).
Examiner submits that the claimed “and/or risk stratification” is interpreted as optional (or an alternative limitation) due to the recited “and/or” preceeding the limitation and thus not explicitly required by the Claim.
Claim 47 is rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Golz et al. (WO2008104293A1).
Regarding Claim 47, Golz teaches a kit (See Page 50…lines 14-30…Page 51, lines 1-4…a kit for identifying a disease, wherein the disease is associated with an altered LDHB level) comprising at least two detection agents (See Page 35, lines 6-8…Diagnostic assays for LDHB include methods which utilize the antibody and a label to detect LDHB in body fluids…, thereby teaching two detection agents), each specific for a polypeptide selected from SRD5A2, GNA11, CAPNS1, NCDN, WDR5 and/or LDHB (See Page 35, line 7…the antibody and a label to detect LDHB).
Also, on the Examiner applying an alternative prior art towards Claim 47:
Claim 47 is rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Huang et al. (CN106319061A).
Regarding Claim 47, Huang teaches a kit (See Abstract… kits that colorectal cancer auxiliary diagnosis is used for based on WDR5 gene) comprising at least two detection agents (See Abstract… reagent A and reagent B, thereby teaching “at least two detection agents”), each specific for a polypeptide selected from SRD5A2, GNA11, CAPNS1, NCDN, WDR5 and/or LDHB (See Abstract… Reagent A is the primer pair for detecting WDR5 gene expression doseReagent B is the reagent for detecting WDR5 protein content).
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 3 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Salami et al. (US20210324476A1) as applied to claim 2 above, and further in view of Shak et al. (US20120028264A1).
Regarding Claim 3, Salami does not teach that the predetermined threshold level is determined from a plurality of normal tissue adjacent to tumour (NAT) samples.
In the analogous art of a method for using gene expression to determine prognosis of prostate cancer, Shak teaches that the predetermined threshold level (See Para 0007…measurement of expression level(s) of one or more genes…from a biological sample; See Para 0065… expression level(s) of one or more genes and/or microRNAs may be measured in tumor tissue) is determined from a plurality of normal tissue adjacent to tumour (NAT) samples (See Para 0008… The biological sample may be obtained from standard methods, including surgery, biopsy, or bodily fluids. It may comprise tumor tissue or cancer cells, and, in some cases, histologically normal tissue, e.g., histologically normal tissue adjacent the tumor tissue; See Para 0065…The tumor tissue may be or include histologically “normal” tissue, for example histologically “normal” tissue adjacent to a tumor.)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate that the predetermined threshold level is determined from a plurality of normal tissue adjacent to tumour (NAT) samples, as taught by Salami for the benefit of determining the likelihood of cancer recurrence which could be described in terms of a score based on clinical or biochemical recurrence-free interval (Shak, Para 0006), allowing for the provision of pathologic staging methods having reproducibility and therefore may provide precise estimates of individual patient risk of prostate cancer (Shak, Para 0005).
Regarding Claim 38, Salami teaches a method of claim 1, wherein the level (See Para 0008, 0013…level of expression) of the one or more biomarkers (See Para 0010… presence or absence of altered expression of one or more genes selected from, for example, …SRD5A2…) is measured (See Para 0010… performing a prostate cancer detection assay).
Salami does not teach that the level of the one or more biomarkers is measured by IHC or ELISA.
In the analogous art of a method for using gene expression to determine prognosis of prostate cancer, Shak teaches that the level of the one or more biomarkers (See Para 0065… The expression level(s) of one or more genes and/or microRNAs may be measured in tumor tissue; See Para 0066…The expression product that is assayed can be, for example, RNA or a polypeptide) is measured by IHC or ELISA (See Para 0067…Polypeptide expression product may be assayed using immunohistochemistry (IHC)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate that that the level of the one or more biomarkers is measured by IHC or ELISA, as taught by Salami for the benefit of measuring the expression level(s) of one or more genes and/or microRNAs in tumor tissue (Shak, Para 0065), allowing for the provision of pathologic staging methods having reproducibility and therefore may provide precise estimates of individual patient risk of prostate cancer (Shak, Para 0005).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Salami et al. (US20210324476A1) as applied to claim 1 above, and further in view of Luca et al. (US20200263255A1).
Regarding Claim 16, Salami teaches a method of claim 1, wherein the one or more mpMRI visibility biomarkers (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject) is or comprises SRD5A2 and GNA1; SRD5A2 and LDHB; GNA11 and LDHB; CAPNS1 and GNA1; CAPNS1 and SRD5A2; CAPNS1 and LDHB; CAPNS1 and WDR5; CAPNS1 and NCDN; GNA11 and WDR5; GNA11 and NCDN;SRD5A2 and WDR5; SRD5A and NCDN; LDHB and WDR5; LDHB and NCDN; or WDR5 and NCDN. (See Para 0009…detecting the presence of altered expression of one or more genes selected from, for example, …SRD5A2… in a sample from said subject).
While Salami teaches only SRD5A2,
Salami does not teach that the one or more mpMRI visibility biomarkers is or comprises SRD5A2 and GNA1; SRD5A2 and LDHB; GNA11 and LDHB; CAPNS1 and GNA1; CAPNS1 and SRD5A2; CAPNS1 and LDHB; CAPNS1 and WDR5; CAPNS1 and NCDN; GNA11 and WDR5; GNA11 and NCDN;SRD5A2 and WDR5; SRD5A and NCDN; LDHB and WDR5; LDHB and NCDN; or WDR5 and NCDN.
In the analogous art of a method relating to the classification of cancers, in particular prostate cancers, using samples from patients, Luca teaches that teaches that the one or more mpMRI visibility biomarkers is or comprises SRD5A2 and GNA11; SRD5A2 and LDHB; GNA11 and LDHB; CAPNS1 and GNA1; CAPNS1 and SRD5A2; CAPNS1 and LDHB; CAPNS1 and WDR5; CAPNS1 and NCDN; GNA11 and WDR5; GNA11 and NCDN;SRD5A2 and WDR5; SRD5A and NCDN; LDHB and WDR5; LDHB and NCDN; or WDR5 and NCDN ( See Table 4, Para 0075…Genes that exhibit significant different expression between DESNT and NON-DESNT cancers includes… CAPNS1 and SRD5A2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate that the one or more mpMRI visibility biomarkers is or comprises SRD5A2 and GNA1; SRD5A2 and LDHB; GNA11 and LDHB; CAPNS1 and GNA1; CAPNS1 and SRD5A2; CAPNS1 and LDHB; CAPNS1 and WDR5; CAPNS1 and NCDN; GNA11 and WDR5; GNA11 and NCDN;SRD5A2 and WDR5; SRD5A and NCDN; LDHB and WDR5; LDHB and NCDN; or WDR5 and NCDN, as taught by Luca for the benefit of showing that the genes including CAPNS1 and SRD5A2 can be classified as genes with significantly altered expression between DESNT and non-DESNT cancers (Luca, Para 0409, Para 0075, Table 4), allowing for the provision of a more reliable diagnostic test for prostate cancer and to better assist in distinguishing between aggressive cancer, which may require treatment, and non-aggressive cancer, which perhaps can be left untreated and spare the patient any side effects from unnecessary interventions (Luca, Para 0004).
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Salami et al. (US20210324476A1) as applied to claim 32 above.
Regarding Claim 33, Salami teaches a method of claim 32, wherein the cutoff value is 0.5. (See Para 0078…The optimal probability cutoff for predicting mpMRI-visible tumor was greater than 0.46).
While Salami does not explicitly teach that the cutoff value is 0.5, Salami teaches that the cutoff value which is 0.5 by using an overlapping range disclosure where the cutoff wavelength is 0.5 (See Para 0078…The optimal probability cutoff for predicting mpMRI-visible tumor was greater than 0.46).
As a result, since the claimed limitation overlap the range disclosed by the prior art, a prima facie case of obviousness exists. Please see MPEP 2144.05 (I) and In re Wertheim, 541 F.2d 257, 191USPQ 90 (CCPA 1976) for further details.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate a cutoff value of 0.5, for the benefit of predicting mpMRI visibility status (mpMRI-visible tumor) (Salami, Para 0078), allowing for the provision of techniques for determining the MRI visibility of prostate lesions. (Salami, Para 0005).
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Salami et al. (US20210324476A1) as applied to claim 35 above, and further in view of Semmes et al. (US20080248500A1).
Regarding Claim 37, Salami does not teach that the sample is taken from a treatment-naive subject
While Salami teaches sample at control level (e.g., the level in a sample of a subject not suspected of having prostate cancer) (See Para 0052),
Salami does not explicitly teach that the sample is taken from a treatment-naive subject.
In the analogous art of polypeptide-based biomarkers that are differentially present in subjects having prostate cancer, Semmes teaches that the sample (See Para 0074… biological samples taken from normal or healthy subjects) is taken from a treatment-naive subject (See Para 0074…’biological samples taken from normal or healthy subjects”, thereby teaching “treatment-naïve subject’). Further See Para 0074…a biomarker can be a polypeptide which is present at an elevated level or at a decreased level in biological samples from subjects having prostate cancer or BPH as compared to comparable biological samples taken from normal or healthy subjects).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate that the sample is taken from a treatment-naive subject, as taught by Semmes for the benefit of differentially determining the presence of polypeptide-based biomarkers in the biological samples of subjects having prostate cancer, in particular, prostate cancer versus the biological samples of taken from normal (non-prostate cancer) subjects (Semmes, Para 0074), allowing for the provision of new methods towards the fight against prostate cancer and providing specific methods and reagents for the diagnosis, staging, prognosis, and monitoring of prostate cancer (Semmes, Para 0013).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Salami et al. (US20210324476A1) as applied to claim 1 above, and further in view of Brugarolas et al. (US20210085634A1).
Regarding Claim 41, Salami does not teach that the method further comprises repeating the method after an interval.
In the analogous art of a method of treatment that is provided comprising determining if cancerous cells (including prostate cancer cells) of a patient have a HIF2A, HIF1B, or TP53 resistance mutation, Brugarolas teaches that the method (See Para 0060… Multiparametric MRI (mpMRI) was performed…) further comprises repeating the method after an interval (See Para 0060…. blood samples were collected during screening, on treatment (at 2 weeks, 6-7 weeks, and 16 weeks), and at progression. Optional core tumor biopsies were performed during screening, on treatment (at weeks 6-7), and at progression. Additional core biopsies could be obtained from a responding or progressing lesion at one additional time point while the patient was on treatment., whereby mpMRI was performed on the tumor samples [Para 0017]).
Examiner submits that the duration (…(at 2 weeks, 6-7 weeks, and 16 weeks),…) at which the blood samples are collected hereby teaches “ repeating the method after an interval”.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Salami to incorporate that the method further comprises repeating the method after an interval, as taught by Brugarolas for the benefit of collecting data towards a companion study involving a subset of patients in the phase I clinical trial “Phase I, Multiple-Dose, Dose-Escalation Trial of PT2385 Tablets, a HIF-2α Inhibitor, in Patients with Advanced Clear Cell Renal Cell Carcinoma (NCT02293980)” (Brugarolas, Para 0058), allowing for the provision of methods to identify patients who have resistance to HIF-2 inhibitors or who develop resistance to HIF-2 inhibitors after treatment for cancer including prostate cancer (Brugarolas, Para 0005).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Srigley et al. ("One is the new six: The International Society of Urological Pathology (ISUP) patient-focused approach to Gleason grading." Canadian Urological Association Journal 10.9-10 (2016): 339) teaches that the ISUP grades, which are based on the grouping of Gleason scores and patterns, are shown in Table 2,where it is disclosed that that Grade 5 is the highest ISUP grade and consists of Gleason scores 9 and 10. These latter tumours are associated with poor prognosis.32-34 From a practical perspective, it is recommended that the ISUP grade be reported in all needle biopsies, along with the corresponding Gleason patterns and scores. While ISUP grading represents a significant advance in prostate pathology, future modifications will likely be required. In particular, ISUP grade 4 tumours consisting of Gleason patterns 5 + 3 have been shown to have the worst prognosis compared to those with only pattern 4 or 3 + 5 and may be more appropriately included in ISUP grade 5.35 Other problem areas include the level (individual core, specimen, case) at which ISUP grading should apply, the handling of grade diversity across specimens, and whether ISUP grade should be based on the worst or composite Gleason score. A further major unresolved issue is the lack of consensus as to how tertiary patterns should be handled in radical prostatectomy specimens.(See Page 340, Right column).
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/OYELEYE ALEXANDER ALABI/ Examiner, Art Unit 1797