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 .
Status of Claims
Claims 1-10 are pending.
Claims 1-10 are rejected.
Claims 1-2 and 10 are objected to.
Priority
Acknowledgment is made of applicant’s claim for foreign priority to CN202210559294.6 filed 20 May 2022, under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Accordingly, the effective filing date of claims 20 May 2022.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 08 May 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner.
Drawings
The drawings filed 08 May 2023 are objected to because:
FIG. 3-4 fail to comply with 37 CFR 1.84(u)(1), which states partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. Each partial view in FIG. 3 and FIG. 4 should be relabeled as FIG. 3A, FIG. 3B, FIG. 3C, FIG. 3D, FIG. 4A, and FIG. 4B.
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.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because:
the abstract includes language which be implied, including “The present disclosure specifically provides…”; and
the abstract is longer than 150 words in length.
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 Objections
Claims 1-2 and 10 are objected to because of the following informalities:
Claims 1-2 are objected to because they include reference characters S1-S5 which are not enclosed within parentheses. Reference characters corresponding to elements recited in the detailed description of the drawings and used in conjunction with the recitation of the same element or group of elements in the claims should be enclosed within parentheses so as to avoid confusion with other numbers or characters which may appear in the claims. See MPEP § 608.01(m).
Claim 1 recites “related to three novel programmed cell death including…”, which is a grammatical error and should recite “…three novel programmed cell deaths including…”;
Claim 1 recites “S4…and training to obtain a final survival risk score prediction model…”, which is missing on object after the verb “training”. The claim 1 should be amended to recite “training the preliminary survival risk score prediction model to obtain…”.
Claim 10 recites “in an ICGC queues” which is grammatically incorrect and should recite “in ICGC queues”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “a public database TCGA”. First, the phrase “public database” is indefinite because it is not clear what databases are considered “public”. For example, it is not clear if a database public to people at a university, but not outside of the university, would be considered a “public” database. Furthermore, while the claim then specifies the public database is “TCGA”, the acronym is not defined or set forth in Applicant’s specification. Assuming TCGA is intended to refer to the cancer genome atlas, TCGA is project, whose name is subject to change and furthermore, TCGA may be an acronym not necessarily referring to the cancer genome atlas. Therefore, the metes and bounds of the claim are not clear. For purpose of examination, the limitation is interpreted to mean a first database of gene expressions is used as a training set.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “using a public database TCGA as training set, and expressing genes on the basis of differential expression…”. It is not clear if the claim intends to require a physical assay step of expression genes, or if the claim is intended to require that “expressing genes” (expressing used as an adjective for genes) is used as part of the training set. If Applicant intends for the former, it is further unclear in what way physical expression of genes is “on the basis of differential expression”, given the claims presumably have not been expressed yet. It is noted Applicant’s specification at para. [0027], with respect to S2, states an analysis of differential expression on genes from the TCGA database is performed to obtain expressing genes on the basis of differential expression, which suggests the limitation is intended to mean differentially expressed genes related to three programmed cell deaths are obtained from the training set. Therefore, or purpose of examination, S2 is interpreted to mean differentially expressed genes related to three programmed cell death from the database used as a training set are obtained. Clarification is requested via claim amendment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “differential expression related to three novel programmed cell death including cell autophagy, cell ferroptosis and cell pyroptosis…”. The term “novel” in claim 1 is a relative term which renders the claim indefinite. The term “novel” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, it is not clear what programmed cell death including cell autophagy, for example, is intended to be considered “novel” versus not. For purpose of examination, the limitation is interpreted to mean “differential expression related to three programmed cell death including cell autophagy…”.
Claim 1, and claims dependent therefrom is indefinite for recitation of “S3, determining genes related to the lifetime…”. There is insufficient antecedent basis for this limitation in the claim because the claim previously does not recite any lifetime. Therefore, it is not clear what genes are intended to be determined. Furthermore, even if the claim recited “related to a lifetime”, given all genes are inherently related to a person’s lifetime, it is unclear what would be meant by “genes related to a lifetime”. For purpose of examination, the limitation is interpreted to mean “genes related to survival…”, in light of Applicant’s specification which pertains to survival prediction based on genes.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “S5…the gene-related expression quantity…”. There is insufficient antecedent basis for this limitation in the claim because the claim does not previously recite “a gene-related expression quantity”. Instead, claim 1 recites “expressing genes”, “determining genes…”, and “screened genes”. Therefore, it is further not clear what gene, “the gene” is referring to, and it is not clear what value “the gene-related expression quantity” is referring to. For purpose of examination, the limitation is interpreted to mean a risk index is calculated according to a gene expression quantity.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “S5…the survival prediction of the database TCGA”. There is insufficient antecedent basis for this limitation because the claim did not previously recite a survival prediction of the database TCGA. It is unclear what survival prediction is being referenced.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “another public database, ICGC”. The limitation “public database, ICGC” is indefinite for the same reasons discussed above regarding the “public database TCGA”. Furthermore, the acronym “ICGC” is used across various industries and may represent different meanings. As a result it is further unclear which database is being referred to. For purpose of examination, the limitation is interpreted to refer to a second database of gene expressions.
Claim 7, and claims dependent therefrom, are indefinite for recitation of “wherein patients in a TCGA queues are divided into a high-risk group and a low-risk group…, and a Kaplan-Meier survival curve is drawn…”.Examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: (B) "wherein" clauses. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). See MPEP 2111.04 I. In the instant case, it is not clear if the wherein clause of claim 7 is merely expressing an intended result or use of the method of claim 1, given claim 1 does not recite any patients in “TCGA queues”, or if claim 7 intends to require the method of claim 1 to further comprise dividing patients in TCGA queues and drawing a Kaplan-Meir survival curve. Claim 7 also recites “TCGA queues” which is indefinite for the same reasons discussed above for claim 1. For purpose of examination, claim 7 is interpreted to mean the method of claim 1 further comprises dividing patients into a high-risk group and low-risk group and drawing a Kaplan-Meier survival curve.
Claim 7, and claims dependent therefrom, are indefinite for recitation of “the Cox regression analysis”. Claim 1, from which claim 7 depends, recites a “single-factor Cox regression analysis” and a “multi-factor Cox regression analysis”. As a result, it is not clear which cox regression analysis is being referenced in claim 7.
Claim 7, and claims dependent therefrom, are indefinite for recitation of “the risk score prediction model”. Claim 1, from which claim 7 depends, recites “a preliminary survival risk score prediction model” and “a final survival risk score prediction model”, and therefore it is not clear which risk score prediction model “the risk score prediction model” in claim 7 is referring to. For purpose of examination, claim 7 is interpreted to mean independent clinical factors obtained from a Cox regression analysis combined with the final survival risk score prediction model.
Claim 8 is indefinite for recitation of “…wherein the prediction performance of the risk index on a total survival time is evaluated through…”. First, there is insufficient antecedent basis for “the prediction performance of the risk index”, and claims 1 and 7 do not previously recite a prediction performance of the risk index. As a result, it is not clear what metric of prediction performance, “the prediction performance” is referring to (e.g. accuracy, sensitivity?). Furthermore, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: (B) "wherein" clauses. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). See MPEP 2111.04 I. In the instant case, neither claims 1 or 7 recite a step of evaluating the prediction performance of the risk index, and as a result, it is not clear if the wherein clause is merely reciting an intended use or result of the calculated risk index of claim 1, if claim 8 intends to further limit S5 of claim 1 in some way, or if claim 8 intends to require an additional step of evaluating prediction performance of the risk index. For purpose of examination, claim 8 is interpreted to mean claim 7 further requires a step of evaluating a prediction performance…”.
Claim 9 is indefinite for recitation of “…wherein the area under the Kaplan-Meier survival curve in 1 year, 2 years, and 3 years is calculated”. Examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: (B) "wherein" clauses. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). See MPEP 2111.04 I. It is unclear if the wherein clause is merely reciting an intended use of the Kaplan-Meier curve of claim 7, or if the claim intends to require a step of calculating the area under the Kaplan-Meier survival curve. For purpose of examination, claim 9 is interpreted to require calculating the area under the KM-curve in 1 year, 2 years, and 3 years.
Claim 10 is indefinite for recitation of “wherein…analysis results on survival prognosis of TCGA are verified by results of the ICGC queues”. Examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are: (B) "wherein" clauses. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). See MPEP 2111.04 I. It is unclear if the wherein clause of claim 10 is expressing an intended use of the method of claim 9, given claim 9 does not involve any steps of analyzing results on survival prognosis, if claim 10 intends to require a step of verifying analysis results on survival prognosis of TCGA, or if claim 10 is intended to require the external validation of claim 1 comprises verifying analysis results on survival prognosis of TCGA by results of the ICGC queues. Claim 10 also recites “prognosis of TCGA” and “ICGC queues” which is indefinite for the same reasons discussed above for claim 1 regarding TCGA and ICGC.
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 1-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim 1 being representative) is directed to a method for predicting survival. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 1 recites the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
S1, constructing a preliminary survival risk score prediction model for hepatocellular carcinoma patients (mental process and mathematical concept);
S2, using a public database TCGA as a training set, and expressing genes on the basis of differential expression related to three novel programmed cell death including cell autophagy, cell ferroptosis and cell pyroptosis (mental process);
S3, determining genes related to the lifetime through single-factor Cox regression analysis and clinical data of patients with hepatocellular carcinoma obtained from the database TCGA (mental process);
S4, screening the genes related to the lifetime through multi-factor Cox regression analysis to determine genes for constructing a risk score model, and inputting the screened genes into the preliminary survival risk score prediction model for hepatocellular carcinoma patients and training to obtain a final survival risk score prediction model for hepatocellular carcinoma patients (mental process and mathematical concept); and
S5, calculating a risk index according to the gene-related expression quantity and a risk-related coefficient, analyzing the survival prediction of the database TCGA by using the risk index and performing external verification through another public database, ICGC as a verification set (mental process and mathematical concept).
The identified claim limitations falls into one of the groups of abstract ideas of mathematical concepts and/or mental processes, for the following reasons. In this case, constructing a preliminary survival risk score prediction model encompass constructing a linear regression model that represents a mathematical relationship between expression levels and a risk, as in claim 6. Furthermore, constructing such a linear regression model can be practically performed in the human mind aided by pen and paper by fitting expression data to known risk values. Furthermore, obtaining differentially expressed genes related to programmed cell death from a database of gene expression values can be practically performed in the mind by comparing expression levels of genes from subjects or cells with and without programmed cell death to identify differences in expression levels. Screening genes using multi-factor cox regression analysis recites a mathematical calculation (i.e. performing regression). Inputting screened genes into a preliminary risk score prediction model and training the model encompasses iteratively inputting expression values into a linear regression model to calculate a risk, calculating a loss from a loss function, and adjusting model coefficients to minimize the loss, which is a textual equivalent to performing mathematical calculations. Calculating a risk index according to gene expression and a risk-related coefficient recites a mathematical calculation, and also can be practically performed in the mind by performing weighted addition (see claim 6). Last, performing external validation through another database can be practically performed in the mind by performing data comparisons between results of the model on a first database and a second external database.
Dependent claims 2-10 further recite an abstract idea and/or are part of the abstract idea of claim 1. Dependent claims 3-5 further limit the mathematical concept of performing a multi-factor cox regression analysis, and therefore are part of the abstract idea of claim 1. Dependent claim 6 further limits the mathematical concept of calculating the risk index to be according to the recited equation, therefore further reciting a mathematical formula. Dependent claim 7 further recites the mental process and mathematical concept of dividing patients into high or low risk groups using a median and creating a Kaplan-Meier survival curve, which represents a mathematical relationship between survival probability and time. Dependent claim 8 further recites the mathematical concept of evaluating a prediction performance by a time-dependent ROC curve. Dependent claim 9 further recites the mathematical concept of calculating an area under the Kaplan Meier survival curve in 1 year, 2 years, and 3 years. Dependent claim 10 further recites the mental process and mathematical concept of dividing patients into low and high-risk groups based on a median, and the mental process of verifying results of analysis results (i.e. data comparisons.
The claims further recite the law of nature of a natural correlation between gene expression of programmed cell death related genes and a hepatocellular carcinoma cancer survival, analogous to the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of a medication called iloperidone, Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018). See MPEP 2106.04(b). Therefore, claims 1-10 recite an abstract idea and law of nature. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception.
This judicial exception is not integrated into a practical application because claims 1-10 do not recite any elements in addition to the judicial exception. As such, the claims as a whole do not integrate the abstract idea into practical application. Thus, claims 1-10 are directed to an abstract idea and law of nature. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any additional elements.
Thus, the claims as a whole do not amount to significantly more than the judicial exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
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 (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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (2022).
Cited reference: Zhang, Fan, Wang et al., Non-Apoptotic Programmed Cell Death-Related Gene Signature Correlates With Stemness and Immune Status and Predicts the Responsiveness of Transarterial Chemoembolization in Hepatocellular Carcinoma, 29 April 2022, Frontiers in cell and Developmental Biology, 10, pg. 1-17 and supplemental).
Regarding claim 1, Zhang discloses a method for predicting response to treatment in hepatocellular carcinoma (HCC) patients based on a programmed cell death-related gene signature (Abstract), which comprises the following steps:
Zhang discloses (S1) constructing a prognostic model for predicting risk in HCC patients (Abstract; pg. 5, col. 1, para. 3 to col. 2, para. 1; Figure 1; Table S3)
Zhang discloses (S2) obtaining transcriptome data of hepatocellular carcinoma patients from TCGA, and identifying expression differences in autophagy, ferroptosis, and pyroptosis related genes (pg. 2, col. 2, para. 3 to pg. 3, col. 1, para. 2).
Zhang discloses (S3) determining 13 Autophagy, 9 Ferroptosis, and 7 Pyroptosis prognostic related differentially expressed genes (DEGs) by performing a univariate (i.e. single-factor) Cox regression analysis to evaluate the association between the differentially expressed genes and patient survival (i.e. the determined genes are related to lifetime) and based on clinical data of HCC patients from TCGA (pg. 3, col. 1, para. 2; Figure 1, e.g. univariate cox regression analysis and clinical data used to identify related DEGs; pg. 5, col. 1, para. 2).
Zhang discloses (S4) performing a multi-variate Cox regression analysis on the 13 Autophagy, 9 Ferroptosis, and 7 Pyroptosis prognostic related differentially expressed genes (DEGs) related to survival to identify a 10-gene signature of 5 Autophagy, 3 Ferroptosis, and 2 Pyroptosis related DEGs with independent prognostic values for patient survival (pg. 3, col. 2, para. 3; Figure 1, e.g. multivariate cox regression analysis to filter genes), and training the predictive model using the screened 10 genes to obtain a final predictive model for HCC patients (pg. 5, col. 1, para. 3, e.g. multivariate cox regression performed among genes; Figure 1; Table S2-S3, e.g. training model training creates final model from preliminary model).
Zhang discloses (S5) calculating a risk index using gene expressions of the 10-gene signature (pg. 3, col. 1, para. 2-3; pg. 5, col. 1, para. 3 to col. 2, para. 1, e.g. the risk score was calculated as follows:..). Zhang further discloses dividing patients in the TCGA into high- and low-risk based on a median risk index, and then analyzing survival of patients in each risk group (i.e. analyzing the survival prediction of the database TCGA by using the risk index) (pg. 5, col. 2, para. 1-2; Figure 2). Zhang further discloses performing external validation using another database ICGC as a verification set (Figure 2; pg. 15, col. 1, para. 2; Table S3, e.g. model was validated using ICGC data).
Regarding claim 2, Zhang discloses the differentially expressed genes related to survival comprise 5 Autophagy, 3 Ferroptosis, and 2 Pyroptosis related DEGs (pg. 3, col. 2, para. 3; Figure 1, e.g. multivariate cox regression analysis to filter genes).
Regarding claim 3, Zhang discloses the five cell autophagy genes are BIRC5, SQSTM1, HDAC1, RHEB, and ATIC (pg. 5, col. 1, para. 3 to col. 2, para. 1; pg. 13, col. 1, para. 1).
Regarding claim 4, Zhang discloses the three cell ferroptosis genes are G6PD, ACACA, and SLC1A5 (pg. 5, col. 1, para. 3 to col. 2, para. 1; pg. 13, col. 1, para. 1).
Regarding claim 5, Zhang discloses the two cell pyroptosis genes are BAK1 and GSDME ((pg. 5, col. 1, para. 3 to col. 2, para. 1; pg. 13, col. 1, para. 1).
Regarding claim 6, Zhang discloses the risk score was calculated as follows: (0.1450955×expression level of BIRC5 + 0.19642991 × expression level of SQSTM1 + 0.37106235 × expression level of HDAC1 + 0.3770679 × expression level of RHEB+0.34668129 × expression level of ATIC + 0.16196511 × expression level of G6PD + 0.4035343 × expression level of ACACA + 0.20555184 × expression level of SLC1A5 +0.28470975 × expression level of BAK1 + 0.44820065 ×expression level of GSDME) (pg. 5, col. 1, para. 3 to col. 2, para. 1).
Regarding claim 7, Zhang discloses dividing TCGA patients into a high-risk group and low-risk group based on a median risk index (pg. 5, col. 2, para. 1) and drawing a Kaplan-Meier survival curve using clinical factors including age, gender, race, and grade determined through univariate Cox analysis in addition to risk scores from the final prediction model (pg. 5, col. 2, para. 1-2, Figure 3A-C, e.g. A shows clinical factors obtained by Cox analysis, and C shows KM-curves drawn for risk score and clinical factors).
Regarding claim 8, Zhang discloses evaluating prediction performance of the risk index on overall survival using an ROC-curve over time (FIG. 3C; pg. 8, col. 1, para. 1, e.g. ROC curve analysis showed risk score had better predictive accuracy of prognosis).
Regarding claim 9, Zhang discloses calculating an AUC for the Kaplan-Meier curve for each of 1-year, 2-year, and 3-year (Figure 3C).
Regarding claim 10, Zhang discloses dividing patients from a ICGC cohort into a high-risk group and a low-risk group based on the median risk index value and determining results of survival on TCGA were similar to survival results of the ICGC cohort (i.e. verifying results of TCGA using results of ICGC) (pg. 3, col. 1, para. 3, e.g. ICGC cohort used to verify results; pg. 7, col. 1, para. 1 to col. 2, para. 2; Figure 2F).
Therefore, Zhang anticipates the claimed invention.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Huo et al., A Ferroptosis and Pyroptosis Molecular Subtype-Related Signature Applicable for Prognosis and Immune Microenvironment Estimation in Hepatocellular Carcinoma, 2021, Sec. Molecular and Cellular Oncology, pg. 1-19.
Huo discloses a method for determining prognosis in hepatocellular carcinoma (HCC) using programmed cell death, including ferroptosis and pyroptosis, related genes (Abstract), and identifies a 12-gene risk score with high accuracy in predicting overall survival in HCC patients (Abstract; Figure 1). Huo similarly uses a median risk score to divide patients into low and high risk groups for survival analysis (pg. 11, col. 2, para. 1 to pg. 12, col. 1, para. 2; Figure 8).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAITLYN L MINCHELLA whose telephone number is (571)272-6485. The examiner can normally be reached 7:00 - 4:00 M-Th.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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