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 Status
Claims 1-15 are currently pending and under exam herein.
Claims 1-15 are rejected.
Claims 1 and 5 are objected to.
Priority
This application is a U.S. national stage application of PCT International Application No. PCT/US2020/058582, filed November 2, 2020, which claims the benefit of U.S. provisional Provisional application Application No. 62/929,396, filed on November 1, 2019, and U.S. Provisional Application No. 62/946,742, filed December 11, 2019. At this point in the examination, the effective filling date of the claims is 11/01/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/12/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings filed on 07/12/2022 are accepted.
Specification
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code seen in [00146]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: there is a typographical mistake in line 5 "in the specimen, , ".
Claim 5 is objected to because of the following informalities: there is a typographical mistake in line 10 "the specimen,.".
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 5, 10-15 are 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. Appropriate correction is required.
Claims 1 and 5 recite “continuous, and an absolute amount” and “continuous, and an is absolute amount”, respectively. “Continuous” is not defined in the specification, and it can mean a value at time or over time, rendering the claims unclear.
Claim 10 recites the limitations "the stored individual cancer profiles", “the set of clinical parameters”, “the quantitative level”, “the database”, “the individual cancer profile”. Because dependent claims 11-15 incorporate the unsupported limitation of claim 10 and to not include further limitations that correct the issue, they are likewise rejected under 35 U.S.C. 112(b). The rejection might be overcome by for example, amending the claim 10 to remove “the”.
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 5, 8 and 9 are rejected under 35 U.S.C. 101 because the claimed invention does not not fall within at least one of the four categories of patent eligible subject matter (In re Nuijten, Federal Circuit, 2007) because the claims as instantly recited read on products that do not have a physical or tangible form, such as information (often referred to as "data per se") or a computer program per se (often referred to as "software per se"), as they are claimed as a product without any structural recitations (such as a "means plus function" limitation).
Claims 1-4, 6-7 and 10-15 are rejected under 35 U.S.C. 101 because the invention is directed to an abstract idea without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); and (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgment, opinion).
Subject matter eligibility evaluation in accordance with MPEP 2106:
Eligibility Step 1:
Claims 1-4 and 6-7 are directed to a method (process) of generating a database
Claims 10-15 are directed to a method (process) of providing diagnosis, prediction, or prognosis of cancer in a patient
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 1 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
A method of generating a database to provide diagnosis, prediction, or prognosis of cancer (i.e., mental processes – can done with pen and paper);
generating an individual cancer profile (ICP) from each of the plurality of subjects, the individual cancer profile comprising i) a plurality of clinical parameters that each represents a quantitative measurement of a biomarker, wherein the quantitative measurement is from an archived FFPE specimen, continuous, and an absolute amount of the biomarker in the specimen, and ii) a known clinical outcome of a cancer (i.e., mental processes – “a profile” can be a list done by pen and paper)
Dependent claims 2-4 and 6-7 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 2 further recites:
The method according to claim 1, wherein the biomarker is a protein marker (i.e., mathematical concepts – measurement of a particular type of biomarker)
Dependent claim 3 further recites:
The method according to claim 1, wherein the quantitative measurement is conducted by a quantitative dot blot (QDB) (i.e., mathematical concepts - measurement)
Dependent claim 4 further recites:
The method according to claim 1, wherein the cancer is breast cancer and the biomarker is Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDi, or Her2 (i.e., mental processes – “a cancer profile” can be a list done by pen and paper)
Dependent claim 6 further recites:
The method according to claim 1, wherein the quantitative measurement is conducted by a quantitative dot blot (QDB) (i.e., mathematical concepts - measurement)
Dependent claim 7 further recites:
The method according to claim 1, the cancer is breast cancer and the biomarker is Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDi, or Her2 (i.e., mathematical concepts – measurement of a particular type of biomarker)
Independent claim 10 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
A method of providing diagnosis, prediction, or prognosis of cancer in a patient, comprising 1) collecting a FFPE specimen of the patient (i.e., mental processes – can done with pen and paper)
comparing the quantitative level of the set of clinical parameters in the database with those measured from the FFPE specimen of the patient (i.e., mathematical concepts – determining whether one value is greater than the other and mental process – comparison);
identifying an individual cancer profile from the database that best matches the patient based on the comparison (i.e., mental processes – judgement);
Dependent claims 11-15 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claim 11 further recites:
The method according to claim 10, wherein the comparison is to determine maximum similarity between the set of clinical parameters of an individual cancer profile and those of the same set measured from the FFPE specimen of the patient (i.e., mathematical concepts – maximum similarity and measurements and mental process – comparison);
Dependent claim 12 further recites:
The method according to claim 11, wherein, when the similarity is measured, the absolute level of each biomarker is within a pre-set range of that of the same biomarker from the same set measured from the FFPE specimen of the patient (i.e., mathematical concepts –measurements)
Dependent claim 13 further recites:
the similarity is calculated based on the Euclidean distance between the two sets of quantitative clinical parameters (i.e., mathematical concepts – calculation)
Dependent claim 14 further recites:
the quantitative level of the set of clinical parameters from the FFPE specimen is conducted by a quantitative dot blot (QDB) (i.e., mathematical concepts).
Dependent claim 15 further recites:
the cancer is breast cancer and the set of clinical parameters comprise Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDl, Her2, or a combination thereof (i.e., mental processes – breast cancer in “a cancer profile” can be a list done by pen and paper)
Therefore, claims 1, 2-4, 6-7 and 10-15 recite an abstract idea.
[Step 2A Prong One: YES]
Eligibility 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); MPEP 2106.05(a-h)). 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 judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Dependent claims 2-4, 6-7, 11-15 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional element in independent claim 1 include:
providing a plurality of subjects each having a known clinical outcome of a cancer)
and storing the generated individual cancer profiles of the plurality of subjects in the database
The additional element in independent claim 10 include:
i) the stored individual cancer profiles and ii) the set of clinical parameters used in the database
outputting a clinical outcome of the identified individual cancer profile from the database
The additional elements of providing a plurality of subjects each having a known clinical outcome of a cancer and storing the generated individual cancer profiles of the plurality of subjects in the database (claim 1); the stored individual cancer profiles and outputting a clinical outcome of the identified individual cancer profile from the database (claim 10) are insignificant extra-solution activities that are part of the data gathering process used in the recited judicial exceptions (see MPEP 2106.05(g)).
When all limitations in Claims 1-4, 6-7 and 10-15 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore Claims 1-4, 6-7 and 10-15 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because the reasons noted below.
Dependent claims 2-4, 6-7, 11-15 do not recite any elements in addition to the judicial exception(s). The additional elements recited in independent claim 1, and independent claim 10 are identified above, and carried over from Step 2A: Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at step Step 2A: Prong Two was re-evaluated at step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of providing a plurality of subjects each having a known clinical outcome of a cancer (claim 1) is identified above as non-abstract elements (EIA) related to data gathering do not rise to the level of significantly more than the judicial exception. Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).
The additional elements of storing the generated individual cancer profiles of the plurality of subjects in the database (claim 1) and the stored individual cancer profiles (claim 10) equate to well-understood, routine and conventional generic computer functions because the courts have identified limitations for storing and retrieving information in memory as well-understood, routine and conventional activities in Versata, 793 F.3d at 1312-13, 115 USPQ2d at 1685.
The additional element of outputting a clinical outcome of the identified individual cancer profile from the database (claim 10) merely invokes a computer tool and does not improve the technology of a generic computer (see MPEP 2106.05(a)).
Therefore, when taken alone, all additional elements in independent claim 1 and independent claim 10 do not amount to significantly more than the above-identified judicial exceptions(s). Even when evaluated as combination, the additional elements fail to transform the exceptions (s) into patent-eligible application of that exception. Thus, claims 1-4, 6-7 and 10-15 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
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 1-2, 4-5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Güler (European Journal of Breast Health, vol. 13, no. 4, 27 Sept. 2017, pp. 168–174) in view of Chao et al. (Journal of Proteomics, vol. 73, no. 8, Winter 2010, pp. 1641–6).
Claim 1 and claim 5 are drawn to a method of creating a collection of data to provide diagnosis, prediction, or prognosis of cancer that contain data on more than one subjects having a known clinical outcome of a cancer, creating an having a known clinical outcome of a cancer from the subjects which contain clinical parameters that each represents a quantitative measurement of a biomarker coming from an archived FFPE specimen, continuous, and an absolute amount of the biomarker in the specimen and known clinical outcome of a cancer and storing the generated individual cancer profiles of the subjects in the database. In some embodiments: the biomarker is a protein marker (claim 2); the cancer is breast cancer and the biomarker is Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDi, or Her2 (claim 4 and claim 7).
With respect to the limitation of a method of generating a database to provide diagnosis, prediction, or prognosis of cancer, Güler teaches identifying “70 genes which differentiate between patients diagnosed with breast cancer as good profile and poor profile depending on the risk of developing metastasis within 5 years as of diagnosis” (Table 3; col.1, para. 2, lns.3-5, pg. 169), and that “MammaPrint is an independent prognostic factor in patients with ALN-negative breast cancer (Table 3; col.1, para. 2, lns11-13, pg. 169), demonstrating organized collection of patient gene information in a “database” such as table 3, to connect gene patterns with risk of cancer categories.
With respect to the limitation of providing a plurality of subjects each having a known clinical outcome of a cancer, Güler teaches that a “gene profile was developed based on a gene study conducted with 78 ALN-negative patients below the age of 55 and diagnosed with invasive breast cancer a tumor size <5 cm” (Table 3; col.1, para. 2, lns.5-8, pg. 169).
With respect to the limitation of generating an individual cancer profile (ICP) from each of the plurality of subjects, the individual cancer profile comprising i) a plurality of clinical parameters that each represents a quantitative measurement of a biomarker, wherein the quantitative measurement is from an archived FFPE specimen, continuous, and an absolute amount of the biomarker in the specimen, Güler teaches individual cancer profile per patient (Table 3; col.1, para. 2, lns. 4-5, pg.170), and that cancer profiles contain parameters representing measurements of a biomarker (Tables 1-3; introduction, para.2, lns.3-7, pg.169), these measurements coming from FFPE specimen (Table 3; col.1, para. 2, lns.9-11, pg. 169), which are continuous (Table 3; col.1, para.2, lns.4-5, pg.170).
With respect to the limitation of a known clinical outcome of a cancer, Güler teaches “This gene profile was developed based on a gene study conducted with 78 ALN-negative patients below the age of 55 and diagnosed with invasive breast cancer a tumor size <5 cm” (Table 3; col.1, para. 2, lns.5-8, pg. 169).
With respect of the limitation of storing the generated individual cancer profiles of the plurality of subjects in the database, Güler teaches “They identified 70 genes which differentiate between patients diagnosed with breast cancer as good profile and poor profile depending on the risk of developing metastasis within 5 years as of diagnosis” (Table 3; col.1, para. 2, lns.3-5, pg. 169), the profiles are individual, and stored as either good or bad.
With respect to claim 2, Güler teaches protein biomarkers “Ki67”, hormone receptors “ER/PR” and “HER2” (table 1, pg. 169).
With respect to claim 4 and claim 7, Güler teaches the cancer is breast cancer and the biomarker is Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDi, or Her2 (table 1, pg. 169).
Güler is silent to absolute quantification of biomarkers in specimen.
Chao et al. teach the use of absolute quantification of biomarkers in specimen “This tissue-specific absolute quantitation method (TEAM) would employ matrix specific TEAM standards (e.g., blood serum, blood plasma, amniotic fluid, urine, etc.), since the protein composition and abundance varies widely among the different biological materials” (col.2, para.2, lns.18-22, pg.1644).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the biomarker quantitative measurement of Güler to add the absolute quantification of biomarkers of Chao et al. because Chao et al. show that their method improves sensitivity and specificity “For instance, for each identified protein the specificity and sensitivity for the detection of a case sample for a range of concentrations can be determined” (col.2, para.2, lns. 38-40, pg.1644). A person of ordinary skill in the art would therefore have been motivated to utilize this method to avoid low sensitivity and specificity issues leading to “potential false diagnosis and unnecessary treatment” (col.2, para.1, lns.10-11, pg.1644). One would have had a reasonable expectation of success for making the combination because using absolute quantitation of biomarkers lead to improved specificity and sensitivity, which are critical for clinical diagnostic performance.
Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Güler (European Journal of Breast Health, vol. 13, no. 4, 27 Sept. 2017, pp. 168–174) in view of Chao et al. (Journal of Proteomics, vol. 73, no. 8, Winter 2010, pp. 1641–6) as applied to claims 1-2, 4-5 and 7 above, and further in view of Ayako et al. (JP 2015006164 A).
Claim 8 is drawn to an apparatus for diagnosing cancer in a patient, the apparatus comprising the collection of data; Claim 9 is drawn to a kit for diagnosing cancer in a patient, comprising the collection of data.
The limitations of claims 1-2, 4-5 and 7 have been taught by Güler and Chao et al. above.
Güler and Chao et al. are silent to an apparatus for diagnosing cancer (claim 8) and a kit for diagnosing cancer (claim 9). However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Ayako et al.
With respect to claim 8, Ayako et al. teach a method directed to cancer diagnosis and the apparatus to diagnose cancer “ Then, information such as the presence or absence of a cancer cell is obtained based on the analysis result of the methylation state of the marker, and a cancer diagnosis is performed using this as an index” (pg.1,para.4, lns.4-6) and “one form of apparatus suitable for carrying out the method of the present invention will be described with reference to the drawings” (Figure 9).
With respect to claim 9, Ayako et al. teach a kit of cancer in a patient, comprising the database “Another object of the present invention is to provide a kit suitably used for the method” (pg.7, para.3, lns.1-2).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Güler’s database where the quantitative measurement of biomarkers is continuous with the absolute quantification of biomarkers of Chao et al., with the apparatus and kit of Ayako et al. because the authors teach the apparatus and kit for cancer diagnosis, and not prognosis only. A person of ordinary skill in the art would therefore have been motivated to utilize the apparatus and kit for cancer diagnosis because an apparatus and kit makes diagnosis faster, and combining diagnosis and prognosis provides comprehensive medical decision making providing a patient with earlier treatment decisions. One would have had a reasonable expectation of success for making the combination because using an apparatus and kit for cancer would be faster and more effective.
Claims 3, 6 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Güler (European Journal of Breast Health, vol. 13, no. 4, 27 Sept. 2017, pp. 168–174) in view of Chao et al. (Journal of Proteomics, vol. 73, no. 8, Winter 2010, pp. 1641–6) as applied to claims 1-2, 4-5 and 7 above, and further in view of Tian et al. (Oncotarget, vol. 8, no. 35, 19Apr2017).
Claim 3 and claim 6 are drawn to the biomarker quantitative measurement being conducted by a quantitative dot blot (QDB). Claim 14 is drawn to the quantitative level of the set of clinical parameters from the FFPE specimen is conducted by a quantitative dot blot (QDB);
The limitations of claims 1-2, 4-5 and 7 have been taught by Güler and Chao et al. above.
Güler and Chao et al. are silent to the biomarker quantitative measurement being conducted by a quantitative dot blot (QDB). However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Tian et al.
With respect to claim 3 and claim 6, Tian et al. teach quantitative dot blot analysis (QDB) to measure biomarkers “Using QDB technique, we were able to observed an age-dependent significant alteration of CAPG protein expression level in TRAMP mice” (Fig.4; abstract), meaning CAPG protein is being studied in a “prostate cancer” (col.1, para.1, lns.2-4, pg.58557) context, so it functions as a candidate protein biomarker
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Güler.’s database where the quantitative measurement of biomarkers is continuous with the absolute quantification of biomarkers of Chao et al., with the quantitative measurement being conducted by a of Tian et al. because Tian et al. show that “the QDB analysis is a convenient, affordable, versatile, quantitative, reliable and robust method” (col.2, para.3, lns.1-3, pg. 58559). A person of ordinary skill in the art would therefore have been motivated to utilize the quantitative dot blot (QDB) method because of “its reliability and accuracy and its significant saving in research resources” (col.2, para.3, lns.3-4, pg. 58559). One would have had a reasonable expectation of success for making the combination because it is a reliable method for quantifying biomarkers and “this technique will find its application in many areas of biological and biomedical research including association studies at protein level” (col.2, para.3, lns.5-7, pg. 58559).
Claims 10-13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Güler (European Journal of Breast Health, vol. 13, no. 4, 27 Sept. 2017, pp. 168–174) in view of Chao et al. (Journal of Proteomics, vol. 73, no. 8, Winter 2010, pp. 1641–6) as applied to claims 1-2, 4-5 and 7 above, and further in view of Pai et al. (Molecular Systems Biology, vol. 15, no. 3, Mar. 2019).
Claim 10 is drawn to a method of providing diagnosis, prediction, or prognosis of cancer in a patient, comprising collecting a FFPE specimen of the patient, obtaining from a collection of data, the stored individual cancer profiles and the set of clinical parameters used in the collection of data, comparing the quantitative level of the set of clinical parameters in the collection of data with those measured from the FFPE specimen of the patient, identifying an individual cancer profile from the collection of data that best matches the patient based on the comparison and outputting a clinical outcome of the identified individual cancer profile from the collection of data. In some embodiments: the comparison is to determine maximum similarity between the set of clinical parameters of an individual cancer profile and those of the same set measured from the FFPE specimen of the patient (claim 11); the absolute level of each biomarker is within a pre-set range of that of the same biomarker from the same set measured from the FFPE specimen of the patient (claim 12); the similarity is calculated based on the Euclidean distance between the two sets of quantitative clinical parameters (claim 13); the cancer is breast cancer and the set of clinical parameters comprise Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDl, Her2, or a combination thereof (claim 15).
The limitations of claims 1-2, 4-5 and 7 have been taught by Güler and Chao et al. above.
With respect to claim 15, Güler teach the cancer is breast cancer and the set of clinical parameters comprise Estrogen receptor (ER), Progesterone Receptor (PR), Ki67, p53, cyclinDl, Her2, or a combination thereof (table 1, pg. 169).
With respect to claim 12, Chao et al. teach absolute concentration of protein biomarkers from biological specimens and evaluating their diagnostic performance across a range of concentrations “For instance, for each identified protein the specificity and sensitivity for the detection of a case sample for a range of concentrations can be determined” (col.2, para.2, lns-53-55, pg.1644).
Güler and Chao et al. is silent to comparing FFPE-derived quantitative parameters to stored profiles, identifying a matching ICP and outputting the clinical outcome of that matched ICP. However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Pai et al.
With respect to comparing the quantitative level of the set of clinical parameters in the collection of data with those measured from the FFPE specimen of the patient, Pai et al. teach “Each PSN node is an individual patient, and an edge between two patients corresponds to pairwise similarity for a given feature” (col1., para.2, lns.4-6, pg.2) and “patients of unknown status can be classified based on their similarity to patients with known status” (col.1, para.2, lns.2-3, pg.2), meaning patient profiles are stored, comparison of quantitative molecular parameters “mRNA, miRNA, and protein expression; DNA methylation; and somatic copy number aberrations” (col.2, para.1, lns. 14-15, pg.3) is performed.
With respect to the limitation of identifying an individual cancer profile from the collection of data that best matches the patient based on the comparison, Pai et al. teach “This is equivalent to the query, “given predictive networks for patient class L, rank all patients by similarity to known examples of L”. netDx then assigns test patients to the class for which it has the highest similarity” (col.2, para.1, lns.10-13, pg.2), meaning patient similarity matching.
With respect to the limitation of outputting a clinical outcome of the identified individual cancer profile from the database, Pai et al. teach “survival curves were constructed based on netDx-predicted classes of test samples” (Fig.2; col.2, para.4, lns.1-2, pg.8), meaning the classifier matches patients to a high risk or low risk group, then outputs the probability of survival (outcome).
With respect to claim 11, Pai et al. teach “netDx then assigns test patients to the class for which it has the highest similarity” (col.1, para.3, lns.12-13, pg.2).
With respect to claim 13, Pai et al. teach “For similarity metrics, we tested normalized similarity, Pearson correlation with and without exponential scaling, radial basis function, and Euclidean-distance-based similarity with exponential scaling” (col.1, para.1, lns.6-9, pg.5).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Güler’s database where the quantitative measurement of biomarkers is continuous with the absolute quantification of biomarkers of Chao et al., with the similarity based patient classification and outcome outputting of Pai et al., Furthermore, Pai et al. show that their method “is clinically intuitive because it is analogous to clinical diagnosis, which often involves a physician relating a patient to a mental database of similar patients they have seen. As demonstrated below, netDx has strengths in classification performance, heterogeneous data integration, and interpretability” (col.1, para.2, lns.6-11, pg.2). A person of ordinary skill in the art would therefore have been motivated to utilize such method because it “identifies biological pathways important for outcome prediction, as demonstrated in breast cancer and asthma. netDx can serve as a patient classifier and as a tool for discovery of biological features characteristic of disease” (abstract, lns.16-19, pg.1). One would have had a reasonable expectation of success for making the combination because both references relate to predicting cancer outcomes using quantitative data and patients with known clinical results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims [1-3 and 5], 9, 10 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over Claim 14, 19, 17 respectively of Application No. 16/022,259 in view of Güler (European Journal of Breast Health, vol. 13, no. 4, 27 Sept. 2017, pp. 168–174).
The instant claims Claim 1 and Claim 5 are drawn to a method of generating a database to provide diagnosis, prediction, or prognosis of cancer that contain data on more than one subjects having a known clinical outcome of a cancer, creating an having a known clinical outcome of a cancer from the subjects which contain clinical parameters that each represents a quantitative measurement of a biomarker coming from an archived FFPE specimen, continuous, and an absolute amount of the biomarker in the specimen and known clinical outcome of a cancer and storing the generated individual cancer profiles of the subjects in the database. In some embodiments: the biomarker is a protein marker (Claim 2); the quantitative measurement is conducted by a quantitative dot blot (QDB) (Claim 3). Instant Claim 10 is drawn to a method of providing diagnosis, prediction, or prognosis of cancer in a patient, comprising collecting a FFPE specimen of the patient, obtaining from a collection of data, the stored individual cancer profiles and the set of clinical parameters used in the collection of data, comparing the quantitative level of the set of clinical parameters in the collection of data with those measured from the FFPE specimen of the patient, identifying an individual cancer profile from the collection of data that best matches the patient based on the comparison and outputting a clinical outcome of the identified individual cancer profile from the collection of data. Instant Claim 9 is drawn to a kit for diagnosing cancer in a patient.
Claim 14 of co-pending Application No. 16/022,259 is drawn to a reference database for diagnosing cancer in a patient based on antibody-based quantitative analysis of a marker in a formalin-fixed paraffin-embedded (FFPE) biopsy sample from the patient, comprising a plurality of reference profiles, each of the plurality of the reference profile prepared by:(a) providing a formalin-fixed paraffin-embedded (FFPE) biopsy sample from a cancer patient with a known diagnosis; (b) measuring said marker with quantitative dot blot (QDB) analysis for the biopsy sample, wherein the quantitation result is an absolute amount of said marker in the biopsy sample, normalized by the protein weight thereof; and (c) associating the quantitation result with the known diagnosis of the cancer patient thereby obtaining a reference profile. Claim 17 of co-pending Application No. 16/022,259 is drawn to a method for diagnosing cancer in a patient, comprising: providing a reference database of claim 14; obtaining a biopsy sample from the patient; measuring the marker used in the reference database in the biopsy sample with QDB analysis, wherein the measured result is an absolute amount of the marker in the biopsy sample; comparing the quantitation result of the marker with that of each reference profile stored in the reference database; and identifying a reference profile in the reference database that has the best match and outputting the known diagnosis associated with the identified reference profile. Claim 19 of co-pending Application No. 16/022,259 is drawn to a kit for diagnosing cancer in a patient.
In view of the combined teachings of claim 14, claim 17 and claim 19 of co-pending Application No. 16/022,259, it would have been obvious to one of ordinary skilled in the art to create individual cancer profile (ICP), add a continuous amount of the biomarker to store the generated individual cancer profiles of the plurality of subjects in the database.
The difference between the reference database for diagnosing cancer in a patient from claim 14, claim 17 and claim 19 of co-pending Application No. 16/022,259 above and the method of generating a database to provide diagnosis, prediction, or prognosis of cancer recited in instant claims [1-3 and 5], 9, 10 is that it does not teach individual cancer profile (ICP), a continuous amount of the biomarker, and storing the generated individual cancer profiles of the plurality of subjects in the database.
With respect to the limitations of creating individual cancer profiles (ICO), and a continuous amount of the biomarker, Güler teaches individual cancer profile per patient (Table 3; col.1, para. 2, lns. 4-5, pg.170), and that cancer profiles contain parameters representing measurements of a biomarker (Tables 1-3; introduction, para.2, lns.3-7, pg.169), these measurements coming from FFPE specimen (Table 3; col.1, para. 2, lns.9-11, pg. 169), which are continuous (Table 3; col.1, para.2, lns.4-5, pg.170).
With respect of the limitation of storing the generated individual cancer profiles of the plurality of subjects in the database, Güler teaches “They identified 70 genes which differentiate between patients diagnosed with breast cancer as good profile and poor profile depending on the risk of developing metastasis within 5 years as of diagnosis” (Table 3; col.1, para. 2, lns.3-5, pg. 169), the profiles are individual, and stored as either good or bad.
It would have been obvious to one of ordinary skilled in the art to modify the reference database for diagnosing cancer in a patient of claim 14 of co-pending Application No. 16/022,259, and to implement the continuous quantification, individual cancer profiles and storing the profile in the database as in instant claims [1-3 and 5], 9, 10, because Güler shows that such databases help cancer prognosis and are “cost-efficient” and “enable us to provide individualized therapies for patients” (col.1, para.1-3, pg. 172). A person of ordinary skill in the art would therefore have been motivated to utilize such method because individualized treatment can lead to more personalized treatment that often improve survival rates and reduce side effects. One would have had a reasonable expectation of success for making the combination because the database method would be more cost efficient and provide personalized cancer prognosis to patients.
Conclusion
No claims are allowed.
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/A.S.E./
Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687