DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Claim 1 is pending and under consideration in this action.
Priority
The instant application is a CON of 15/952,022, filed 04/12/2018, now U.S. Patent No. 11441189, which is a DIV of 14/115,327, filed 11/01/2013, now U.S. Patent No. 9951388, which is a 371 of PCT/EP2012/058356, filed 05/07/2012, which claims benefit to U.S. Provisional Application No. 61/483,928, filed 05/09/2011, as reflected in the filing receipt mailed 08/24/2022. The claim for domestic benefit for claim 1 is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/05/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
It is further noted that certain references lack appropriate volume numbers (NPL #15). The Examiner has annotated those references herein. Applicant is kindly reminded to provide proper citations in compliance with 37 CFR 1.97 in all future submissions to the office.
Specification
The abstract of the disclosure is objected to because it appears there is a spurious “b” before “cancer” in line 4 of the abstract. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Framework with which to evaluate Subject Matter Eligibility as outlined in MPEP § 2106:
Step 1: Are the claims directed to a process, machine, manufacture or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework as it pertains to the instant claims:
Step 1:
In the instant application, claim 1 is directed towards a method, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claim 1 recites a mathematical concept (i.e., a multivariate analysis, e.g., a regression analysis, see at least Specification Pg. 4, Lines 29-32 and Pg. 18, Lines 1-7) in “performing a multivariable analysis of said single sample to generate a multivariable data set comprising both quantitative cell morphology data from step (b) and molecular marker data from step (a)”; a mental process (i.e., an evaluation/comparison of datasets) in “comparing the multivariable analysis data set obtained in step (b) with a reference multivariable analysis data set created by obtaining both molecular marker data and quantitative cell morphology data from cancer and non-cancer cell samples taken from individuals with known clinical outcome”; and a mental process (i.e., an evaluation of combinations of markers for statistical associations) and law of nature (i.e., correlating marker data to a clinical outcome) in “predicting a clinical outcome defined by specific combinations of cell morphologic markers and molecular markers statistically associated with cancer progression, metastases or other determinant of clinical outcome seen in the reference multivariable analysis dataset”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), and organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Specifically, claim 1 involves nothing more than performing multivariable analysis, comparing the multivariable data with reference multivariable data, and predicting a clinical outcome defined by combinations of markers. The step reciting performing multivariable analysis is, under the BRI, performed using mathematical operations. The instant Specification (see Pg. 4, Lines 29-32) recites that statistical relevance of measurable phenotypic features and molecular markers derived through regression analysis of multiple morphological and molecular marker variables from a single sample belonging to a population of cancer cells. Additionally, since there are no specifics in the methodology, the steps reciting comparing the multivariable data with reference multivariable data, and predicting a clinical outcome defined by combinations of markers, are something that under the BRI, one could perform mentally. Therefore, the claimed steps are not further defined beyond something that reads on performing a calculation, and merely looking at data and making a determination. As such, said steps are directed to judicial exceptions. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following independent claims recite limitations that equate to additional elements:
Claim 1 recites “obtaining molecular marker data from a single sample from a subject comprising a single cell or population of cells from a tissue”; and “obtaining quantitative cell morphology data from the same single cell or population of cells used in step (a)”.
Regarding the above cited limitations in claim 1 of (i) obtaining molecular marker data from a single sample from a subject comprising a single cell or population of cells from a tissue; and (ii) obtaining quantitative cell morphology data from the same single cell or population of cells used in step (a). These limitations equate to insignificant, extra-solution activity of mere data gathering because these limitations gather data before or after the recited judicial exceptions of performing multivariable analysis, comparing the multivariable data with reference multivariable data, and predicting a clinical outcome defined by combinations of markers (see MPEP § 2106.04(d)). As such, claim 1 is directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant independent claims recite the same additional elements described in Step 2A, Prong Two above.
Regarding the above cited limitations in claim 1 of (i) obtaining molecular marker data from a single sample from a subject comprising a single cell or population of cells from a tissue; and (ii) obtaining quantitative cell morphology data from the same single cell or population of cells used in step (a). These limitations are considered to be insignificant extra-solution activity of mere data gathering. These steps are incidental to the primary process of performing multivariable analysis, comparing the multivariable data with reference multivariable data, and predicting a clinical outcome defined by combinations of markers, wherein the obtained molecular markers and quantitative cell morphology data are merely inputs for the subsequent multivariable analysis and clinical outcome prediction. These steps are analogous the following examples of mere data gathering activity that the courts have found to be insignificant extra-solution activity: (i) Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989); and (ii) Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis) (see MPEP § 2106.05(g)).
These additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claim 1 is not patent eligible.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 1 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Han et al. (ETS Gene Aberrations in Atypical Cribriform Lesions of the Prostate: Implications for the Distinction Between Intraductal Carcinoma of the Prostate and Cribriform High-grade Prostatic Intraepithelial Neoplasia. Am J Surg Pathol. 34(4): 478-485 (2010); published 04/2010; cited in the IDS dated 08/05/2022).
Regarding claim 1, Han et al. teaches a method to understand the biological and molecular basis of distinction between high-grade prostatic intraepithelial neoplasia (HGPIN) and intraductal carcinoma of the prostate (IDC-P) using break-apart fluorescence in-situ hybridization assay to assess ETS gene aberrations and morphological criteria. ERG break-apart fluorescence in-situ hybridization assay provides insight into understanding the molecular basis of cribriform HGPIN and IDC-P and has potential clinical implications in their distinction on needle biopsies (i.e., a multivariate cancer diagnostic method wherein said method determines the presence of both molecular markers and phenotypic morphological markers at the cellular level in a single cell or single sample containing a population of cells from a tissue) (Abstract). Han et al. further teaches that to study the molecular basis of cribriform HGPIN and IDC-P, a total of 81 aggressive prostate carcinoma (PCa) cases with atypical cribriform lesions (ACLs) on radical prostatectomy specimens were selected from pathologic archives of University of Michigan Health System and Cleveland Clinic between 1995 to 1996 and 2005 to 2009 (Pg. 479, Col. 2, Para. 3-4). Han et al. further teaches that a previously validated break-apart probe FISH approach was used to investigate gene rearrangement involving ETS transcription factors (ERG, ETV1, ETV4, and ETV5). Briefly, normal signal patterns for ETS family genes were indicated by 2 pairs of colocalized green and red signals, insertion was indicated by break apart of 1 of the 2 colocalized signals, and deletion was indicated by the loss of either one 50 or 30 signal. A duplication pattern of rearrangement was indicated as the presence of 2 or more 50 or 30 signals. ERG break-apart probes design and its interpretation is illustrated in Figure 1 (i.e., obtaining molecular marker data from a single sample from a subject comprising a single cell or population of cells from a tissue) (Pg. 480, Col. 1, Para. 3; and Pg. 480, Fig. 1). Han et al. further teaches that a total of 64 cases with ACLs were divided into two categories similar to their previous study which focused on understanding the morphologic differences between IDC-P and cribriform HGPIN: ACL associated with PCa was admixed with or within 3mm of the border of PCa (ACL-PCa), presumed to be spectrum of IDC-P and ACL not associated with PCa, or isolated ACL was more than 3mm distant from the closest carcinoma in any single section and 4mm from the closest carcinoma on the adjacent section above or below (isolated ACL), presumed to be isolated cribriform HGPIN based on findings from their previous study. All IDC-P cases were further divided into 2 categories: group A with marked nuclear atypia (nuclear size 6x normal or larger) and/or comedonecrosis as suggested by Guo and Epstein and group B lesions which did not fulfill these morphologic criteria (i.e., obtaining quantitative cell morphology data) (Pg. 480, Col. 1, Para. 1). Han et al. further teaches that for each case total seven 5 mm serial sections were cut from paraffin block for analysis: the first and the seventh sections were used for hematoxylin and eosin staining to verify the presence of ACL under study and sections 2 to 6 were used for FISH screen (i.e., from the same single cell or population of cells as used in step (a)) (Pg. 479, Col. 2, Para. 4). Han et al. further teaches that a dual-color break-apart FISH assay was used to validate 16 isolated cribriform HGPIN and 48 IDC-P cases for ETS gene aberrations on radical prostatectomy specimens. Of IDC-P cases, 19 (40%) fulfilled the classic criteria of IDC-P [marked nuclear atypia (nuclear 6x normal or larger] and/or comedonecrosis] as suggested by Guo and Epstein, and were designated as group A. Remaining 29 (60%) did not fulfill these criteria of IDC-P, designated as group B. Of note, the presence of minor component with histologically low-grade ACL was also noted in some cases of group A (i.e., performing a multivariable analysis of said single sample to generate a multi variable data set comprising both quantitative cell morphology data from step (b) and molecular marker data from step (a)) (Pg. 480, Col. 2, Para. 2 – Pg. 481, Col. 1, Para. 1; and Pg. 480, Fig. 2). Han et al. further teaches the comparison of normal and cancer cells in the ERG break-apart probes (Pg. 480, Fig. 1). Han et al. further teaches the comparison of the size of nuclear atypia (i.e., quantitative cell morphology data) in both normal and cancer cells (i.e., comparing the multivariable analysis data obtained in step (b) with a reference analysis data set created by obtaining both molecular marker data and quantitative cell morphology data from cancer and non-cancer cell samples taken from individuals with known clinical outcome) (Pg. 480, Col. 2, Para. 2). Han et al. further teaches that there was no significant difference of ERG gene aberrations between 2 different histological groups of IDC-P. Group A in this cohort characterized by marked nuclear atypia (nuclear size 6x normal or larger) and/or comedonecrosis represents classic morphologic pattern of IDC-P, which can be recognized on needle biopsy with sufficient reliability. By contrast, group B IDC-P represents low-grade morphology with significant overlap between cribriform HGPIN and IDC-P. Their data, for the first time, suggests that the majority of ACL-PCa with low-grade histologic features in fact represent IDC-P with low-grade histologic spectrum, rather than cribriform HGPIN. This is further supported by two other observations. First, the prevalence of Edel2+ was not significantly different between high and low-histologic grade IDC-P (20% vs. 14%). Second, a comparison of clinicopathologic features between these two groups showed no significant difference in GS, tumor size, tumor grade, or PSA recurrence, suggesting that IDC-P with low-grade histology is similar to high-histologic grade IDC-P in its biologic characteristics (i.e., predicting a clinical outcome defined by specific combinations of cell morphological markers and molecular markers statistically associated with cancer progression, occurrence, metastases or other determinant of clinical outcome seen in the reference multivariable analysis data set) (Pg. 483, Col. 2, Para. 1 – Pg. 484, Col. 1, Para. 1).
Therefore, regarding claim 1, it would have been obvious to one of ordinary skill in the art to modify the order of teachings of Han et al. In the absence of a secondary consideration to the contrary, combining such teachings would have been prima facie obvious as an example of combining prior art elements according to known methods to yield predictable results. Combining such teachings would have also been prima facie obvious as an example of choosing from a finite number of identified (i.e., taught within the same reference) predictable solutions, with a reasonable expectation of success. Therefore, regarding claim 1, the instant invention is prima facie obvious (MPEP § 2142 and § 2143).
Conclusion
No claims allowed.
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/D.P.S./Examiner, Art Unit 1687
/Lori A. Clow/Primary Examiner, Art Unit 1687
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