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. Claims 1-9,11-19 and 21-22 are pending and currently under examination. Priority This application 18/265,571 filed on 12/21/2023 is a 371 national phase of PCT/ US2021/062436 filed on 12/08/2021 , and claims the benefit of provisional U.S. Patent Application No. 63/122,606 , filed on 12/08/2020 . The priority date of claim s 1 and 7 and their dependent claims is determined to be 12/08/2020 , the filing date of provisional U.S. Patent Application No. 63/122,606 . No support can be found in provisional application 63/122,606 for independent claim 15 and its dependents, regarding the limitations “ determining a benefit score based on the normalized expression information; comparing the benefit score to a pre-determined benefit threshold; and determining, a level of chemotherapy responsiveness for human subject based on the comparing the benefit score to the pre-determined benefit threshold ”. The priority date of independent claim 15 and its dependents is determined to be 12/08/2021 , the filing date of PCT/ US2021/062436 . Specification The use of terms which are trade names or marks used in commerce (including Nanostring ® ), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Claim Objections Claim 1 is objected to because of the following informalities: The claim recites “A method – comprising ; obtaining—from a subject : ” . Please correct to add a colon (:) following comprising and a semicolon (;) following subject, i.e. at the end of the step. Appropriate correction is required. Claim 1 recites “a method of predicting disease prognosis in of a human subject diagnosed with lung cancer –" . Standard grammar would recite either “prognosis in ” or “prognosis of ”. Please choose one and correct. Claim 15 is objected to because of the following informalities: The claim recites “A method – comprising ; obtaining—from a subject : ”. Please correct to add a colon (:) following comprising and a semicolon (;) following subject, i.e. at the end of the step. Appropriate correction is required. Claim 15 further recites “ determining, a level of chemotherapy responsiveness ”. The comma following determining is unnecessary. 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. 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. Claim s 1-9, 11-19, 21 and 22 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. Claim 1 recites the limitation “ a lung cancer sample from a subject ”. It is unclear what criteria define a lung cancer sample . It is unclear if the sample is intended to be a cell type, tissue, blood, or other source from the subject . Claim 1 recites “a method of predicting disease prognosis in of a human subject diagnosed with lung cancer comprising; obtaining expression information for a seven gene signature in a lung cancer sample obtained from a subject” . “A subject” lacks antecedent basis and does not make clear if the lung cancer sample is obtained from the human subject diagnose with lung cancer. Claim 1 recites the limitation “ high risk”. The term “ high ” is a relative term which renders the claim indefinite. The term “ high ” 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. The limitation "risk of tumor progression" is rendered indefinite by use of the term "high". Claims 2-6, 21, and 22 are similarly indefinite because they directly or indirectly depend from claim 1. Claim 1 recites the limitation “a plurality of fresh frozen lung cancer samples”. It is unclear what criteria define fresh frozen lung cancer sample s . It is unclear if the sample is intended to be a cell type, tissue, blood, or other source from the subject . It is also unclear what source the samples are required to come from, e.g. a human subject with or without lung cancer. Claim 6 recites the limitation “ generating a validation dataset comprising expression information --- comparing a high-risk group of patients predicted to benefit from a chemotherapy treatment based on the one-dimensional risk scores t o a group of patients having a beneficial chemotherapy treatment outcome included in the validation dataset. ” It is unclear what elements the limitation intends to compare. The claim recites “ combining the three principal component scores for each gene to generate a one- dimensional risk score ” for the validation dataset, but does not provide steps for generating a one- dimensional risk score for a high-risk group of patients. If the limitation is intended to compare one- dimensional risk score s between a high-risk group of patients and patients having a beneficial chemotherapy treatment outcome , the claim appears to be missing steps necessary for performing the claimed method. Claim 6 appears to be incomplete for omitting essential steps , such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 6 recites “ generating a validation dataset comprising expression information obtained from a plurality of fresh frozen lung cancer samples ”. Claim 6 further recites the limitation “ a group of patients having a beneficial chemotherapy treatment outcome included in the validation dataset ”. No active steps are provided for identifying or separately classifying patients having a beneficial chemotherapy treatment outcome included in the validation dataset . Claim 7 recites the limitation “ a lung cancer sample obtained from the subject ”. It is unclear what criteria define a lung cancer sample from a subject . It is unclear if the sample is intended to be a cell type, tissue, blood, or other source from the subject . Claim 7 recites “a method of predicting a response to an adjuvant chemotherapy (ACT) in a human subject diagnosed with lung cancer comprising; determining expression levels--- in a lung cancer sample obtained from a subject” . “A subject” lacks antecedent basis and does not make clear if the lung cancer sample is obtained from the human subject diagnose with lung cancer. Claim 7 recites the limitation “wherein an alteration in the expression of the genes, as compared to an average expression in lung cancer” . The phrase “alteration in expression” is indefinite . As written, the limitation includes changes in gene expression that are both increased and decreased compared to an average expression. Claim 7 recites the limitation “compared to an average expression in lung cancer”. It is unclear what specifically is being compared. It is unclear what samples the average expression is determined in, whether a specific cell type or tissue or global expression level. Claims 8-9 and 11-14 are similarly indefinite because they directly or indirectly depend from claim 7. Claim 15 recites the limitation “ a lung cancer sample obtained from said subject ”. It is unclear what criteria define a lung cancer sample from a subject . It is unclear if the sample is intended to be a cell type, tissue, blood, or other source from the subject . Claim 15 recites the limitation “ a lung cancer sample obtained from said subject ”. “Said subject” lacks antecedent basis and should be corrected to “the human subject” as in the preamble. Claim 15 recites the limitation “ a level of chemotherapy responsiveness ”. It is not clear what criteria would define a level of chemotherapy responsiveness . It is unclear if the “level” is intended to be a number, a probability, a likelihood, or something else. The specification does not provide guidance as to what a “ level of chemotherapy responsiveness ” consists of. Claims 16-19 are similarly indefinite because they directly or indirectly depend from claim 7. Claim 18 recites “ a second lung cancer sampl e”. It is unclear what criteria define a second lung cancer sample . It is unclear if the sample is intended to be a cell type, tissue, blood, or other source. Claim 18 recites “performing an observational follow up on the patient , ---in a second lung cancer sample obtained from the patient . “ There is insufficient antecedent basis for “the patient”. Claim 15, which claim 18 depends from does not include a limitation of a patient. Claim Rejections - 35 USC § 112(d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.— Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4 recites the limitations “ identifying a set of 12 genes that predicts a likelihood -- ; calculating -- f or each gene included in the set of 12 genes ; --- identifying the seven gene signature from the set of 12 genes ---” . Independent c laim 1, which claim 4 depends from includes the limitation “ obtaining expression information for a seven gene signature ”. Claim 4 fails to further limit the recited limitations of claim 1 in term of the relationship between “ obtaining expression information for a seven gene signature in a lung cancer sample ” recited in claim 1 and “ identifying a set of 12 genes that predicts a likelihood that the human subject will benefit for a chemotherapy treatment ” recited in claim 4 . Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. 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. Clai FILLIN "Pluralize the word 'Claim' if necessary and then identify the claim(s) being rejected." ms 1-9, 11-19, 21, and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. 35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p] henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II. Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility. Step 1 The claimed invention is directed to the statutory category of a process. Step 2A, Prong One The claims are taken to be directed to abstract idea s , judicial exception s . Claim 1 is directed to a method comprising “ obtaining expression information for a seven gene signature in a lung cancer sample obtained from a subject: normalizing the expression information to generate normalized expression information; determining a risk score based on the normalized expression information; comparing the risk score to a pre-determined risk threshold; and determining whether the human subject has a high risk of tumor progression based on the comparison of the risk score to the pre-determined risk threshold ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)) and mathematical concepts (see MPEP 2106.04(a)(2)(I) ) . As written, the obtaining, comparing and determining (whether a human subject has a high risk) steps encompasses the mental step s of looking up gene expression information, reading a score, looking at two sets of data and making mental judg e ments. In addition, the normalizing and determining a risk score steps are mathematical concept s (i.e. calculating, etc ). As written, the step s encompass mathematical concepts such as performing mathematical calculations. Claims 2- 6 , 21, and 22 depend from claim 1 , and require the same step s of obtaining, normalizing, determining, and comparing. Claim 4 i s directed to a method comprising “ identifying a set of 12 genes that predicts a likelihood that the human subject will benefit for a chemotherapy treatment; calculating a regression coefficient for each gene included in the set of 12 genes; determining a regression value threshold using a cross validation process; and identifying the seven gene signature from the set of 12 genes based on a comparison of the regression coefficient for each gene to the regression value threshold ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)) and mathematical concepts (see MPEP 2106.04(a)(2)(I ) ) . As written, the identifying step s encompass the mental step s of looking at gene expression results and making mental judgements. In addition the c alculating and determining ( a regression value ) steps . are mathematical co ncept s (i.e. calculating, etc ). As written, the step s encompass mathematical concepts such as performing mathematical calculations. Claim 5 is directed to a method comprising “ wherein the normalized expression information adjusts the expression information for technical assay variation, background noise and RNA content ”. This limitation is a mathematical concept (i.e. calculating, etc ) (see MPEP 2106.04(a)(2)(I) ) . As written, the step encompasses mathematical concepts such as performing mathematical calculations. Claim 6 is directed to a method comprising “ generating a validation dataset comprising expression information obtained from a plurality of fresh frozen lung cancer samples; determining three principal component scores for each gene included in the seven gene signature based on the expression information; combining the three principal component scores for each gene to generate a one- dimensional risk score for each principal component; and comparing a high-risk group of patients predicted to benefit from a chemotherapy treatment based on the one-dimensional risk scores to a group of patients having a beneficial chemotherapy treatment outcome included in the validation dataset ”. Th ese limitation s are abstract mental process e s (see MPEP 2106.04(a)(2)(III)) and mathematical concepts (see MPEP 2106.04(a)(2)(I ) ) . As written, the generating and comparing step s encompass the mental step s of producing a report of selected gene expression data and looking at gene expression of two groups and making mental judgements. In addition, the determining (three principal component scores) and combining steps are mathematical concept s (i.e. calculating, etc ). As written, the step s encompas s mathematical concepts such as performing mathematical calculations. Claim 7 is directed to a method comprising “ determining expression levels of a gene set comprising RRM2, AURKA, NKX2-1, COL4A3, ATP8A1, C 1 orf 1 16, and HSD17B6, in a lung cancer sample obtained from the subject, wherein an alteration in the expression of the genes, as compared to an average expression in lung cancer, indicates that the subject will respond favorably to adjuvant chemotherapy ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the determining step e ncompasses the mental step of looking at sequencing reads . Claims 8, 9 and 11-14 depend from claim 7 , and require the same step s of determining. Claim 14 is directed to a method comprising “ determining a risk score of the subject by combining expression information of the genes, and predicting a risk group of the subject by comparing the risk score of the subject to a one-dimensional risk score ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the determining , predicting and comparing step s encompass the mental step of compiling gene expression information and making a mental judgment . Claim 15 is directed to a method comprising “ obtaining expression information for a seven gene signature in a lung cancer sample obtained from said subject: normalizing the expression information to generate normalized expression information; determining a benefit score based on the normalized expression information; comparing the benefit score to a pre-determined benefit threshold; and determining, a level of chemotherapy responsiveness for human subject based on the comparing the benefit score to the pre-determined benefit threshold ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the obtaining, comparing and determining (a level of chemotherapy responsiveness) encompasses the mental step s of looking up gene expression information, reading a score, looking at two sets of data and making mental judgements. In addition, the normalizing and determining a benefit score steps are mathematical concepts (i.e. calculating, etc ). As written, the steps encompass mathematical concepts such as performing mathematical calculations. Claims 16-19 depend from claim 15 , and require the same step s of obtaining, normalizing, determining, and comparing. Claim 16 is directed to a method comprising “ determining whether the human subject will benefit from chemotherapy treatment based on the level of chemotherapy responsivenes s” . Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the determining step encompasses the mental step of looking at data and making a mental judg e ment. Claim 17 is directed to a method comprising “ determining whether the human subject will not benefit from chemotherapy treatment based on the level of chemotherapy responsiveness ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the determining step encompasses the mental step of looking at data and making a mental judg e ment. Claim 18 is directed to a method comprising “ performing an observational follow up on the patient ”. Th ese limitation s are abstract mental process es (see MPEP 2106.04(a)(2)(III)). As written, the performing step encompasses the mental step of looking at data. Step 2A, Prong Two The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. C laim 2, which depends from claim 1 , further recites “ treating the human subject with a chemotherapy treatment in response to determining the human subject has a high risk for tumor progressio n” . Claim 8, which depends from claim 7 , further recites “ treating the subject with one or more adjuvant chemotherapies ”. Claim 16, which depends from claim 15, additionally recites the step of “ administering to the human subject a chemotherapy treatment ”. Claim 17, which depends from claim 15, additionally recites the step of “ administering to the human subject at least one of an immunotherapy or targeted therapy ”. Claims 2, 8, 16, and 17 include steps of treating or administering a treatment. These claims do not include a step of administering a particular agent to the human subject to treat a disease after determining that the subject will be responsive to that particular agent. See MPEP 2106.04(d)(2). Furthermore claim 2 direct s that the treating occurs “ in response to ” a determination . Such limitation amounts to no more than a mere instruction to apply the treatment (See MPEP 2106.05(f)). Claim 18 further recites “ the observational follow up comprises an analysis of expression information for the seven gene signature set in a second lung cancer sample obtained from the patient ”. T his is not an integration of the exception into a practical application. Instead, this element is data gathering required to perform the method. Furthermore, analysis of expression information and collection of additional samples are considered routine and conventional in the art. Step 2B The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to “ administering or treating ” are presented a ahigh level of generality and do not include steps of administering a particular agent that a subject is predicted to response specifically to. Additional techniques that are routine, conventional, and well-known in the art are demonstrated in the 102 and 103 rejection s documented below. 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. Claim(s) FILLIN "Insert the claim numbers which are under rejection." \d "[ 1 ]" 1, 3, 5, 21, and 22 is/are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and (a)(2) as being FILLIN "Insert either—clearly anticipated—or—anticipated—with an explanation at the end of the paragraph." \d "[ 3 ]" anticipated by Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018 , referred to here as Xie2019 ) . Regarding claim 1 , Xie2019 teaches a gene signature for predicting patient prognosis in patients with NSCLC (lung cancer) (p. 2, col. 1). Xie teaches measuring gene expression information for 12 genes (p. 2, col. 1), normalizing the expression data (p. 3, col. 2 ), and determining a risk score (p. 4, col. 1). Xie teaches separating patients into high risk and low risk groups based on the patients risk score and using a predefined cutoff (i.e., pre-determined risk threshold) (p. 4, col. 1). Xie further teaches that high risk group patients had worse prognosis (i.e. a high risk of tumor progression) (p. 4, col. 2 and Fig. 2C) . Regarding claim 3 , Xie2019 teaches a gene signature including RRM2, AURKA, NKX2-1, COL4A3, ATP8A1, Clorf116 and HSD17B6 (p. 2, col. 1). Regarding claim 5 , Xie2019 teaches normalization of gene expression data for input variation, background signals , and internal-positive controls (p. 3, col. 2). Regarding claim 21 , Xie2019 teaches samples include FFPE and fresh frozen tissue samples (p. 2, col. 1). Regarding claim 22 , Xie2019 teaches the lung cancer is NSCLC (p. 2, col. 1). Claim(s) 7-9 and 11-14 is/are rejected under 35 U.S.C. 102 FILLIN "Insert either \“(a)(1)\” or \“(a)(2)\” or both. If paragraph (a)(2) of 35 U.S.C. 102 is applicable, use form paragraph 7.15.01.aia, 7.15.02.aia or 7.15.03.aia where applicable." \d "[ 2 ]" (a)(1) and (a)(2) as being FILLIN "Insert either—clearly anticipated—or—anticipated—with an explanation at the end of the paragraph." \d "[ 3 ]" anticipated by Xie et al. ( US 20150017210 , referred to here as Xie2015 ) . Regarding claim 7 , Xie2015 teaches predicting the chemotherapeutic response of a human subject diagnosed with a non-small cell lung cancer tumor comprising obtaining expression information of ARUKA (i.e. AURKA) , NKX2-1 , COL4A3 , ATP8A1, Clorf116 , and HSD17B6 in a non-small cell lung cancer sample obtained from said subject ; wherein an alteration in the expression 6 or more of said genes, as compared to the average expression in non-small cell lung cancer, indicates that said subject will respond favorably to adjuvant chemotherapy (paras 11-12). Xie2015 additionally teaches determining the expression of RRM2 (para 290, Table 4). Regarding claim 8 , Xie2015 teaches treating said patient with adjuvant chemotherapy (para 12). Regarding claim 9 , Xie2015 teaches use o f fresh-frozen tumor samples (para 259). Regarding claim 11 , Xie2015 teaches the lung cancer is NSCLC (p ara s 12, 259 ). Regarding claim 12 , Xie2015 teaches adjuvant chemotherapies including paclitaxel , vinorelbine and cisplatin (para 296 and para 228). Regarding claim 13 , Xie2015 teaches treating subjects with adjuvant chemotherapy improves survival (Fig. 5). Regarding claim 14 , Xie2015 teaches construct ing a prediction mode based on the linear combinations of gene expressions of a gene set ; deriv ing a risk score for each sample based on their gene expression ; and divi ding the samples into risk groups (para 273) . 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. Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018 , referred to here as Xie2019 ) in view of Xie et al. ( US 20150017210 , referred to here as Xie2015 ) . The teachings of Xie2019 as they relate to claim 1 are stated in the 102 rejection above in this office action. Regarding claim 2 , Xie2019 teaches treating subjects with predicted adjuvant chemotherapy with chemotherapy (Abstract ) but does not explicitly teach treating a subject in response to determining the human subject has a high risk for tumor progression. Xie2015 is directed to a method predicting prognosis of lung cancer, the method comprising: obtaining gene expression information in a patient with lung cancer, and predicting survival (i.e. disease prognosis) (Abstract and claim 1). Xie2015 further teaches the method comprises treating a patient with an aggressive therapy if predicted to have a worse than average prognosis for survival (claim 3), which reads on high risk of tumor progression . Xie 2015 further teaches aggressive therapy comprises chemotherapy (claim 11). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Xie2019 and Xie2015 to arrive at the instantly claimed invention. The modification would have entailed using the prediction results of Xie2019 in the method of Xie2015 to choose the appropriate treatment for a patient . It would have been obvious to one of sill in the art to use the predictive accuracy of Xie2019 to adapt treatment plans as taught by Xie2015. Indeed Xie2015 teaches using a similar predictive model to determine treatment. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018 , referred to here as Xie2019 ) in view of Tsao et al. (US 20100184063) . Regarding claim 4 , Xie2019 teaches determining a coefficient value for clinical variables (p. 3, col. 1) and for genes between measurements in different sample types (p. 4, col. 2) but does not teach calculating a regression coefficient for each gene included in the set of 12 genes; determining a regression value threshold using a cross validation process; and identifying the seven gene signature from the set of 12 genes based on a comparison of the regression coefficient for each gene to the regression value threshold. Tsao teaches a method for determining prognostic gene signatures for NSCLC (Non-Small Cell Lung Cancer) and adjuvant chemotherapy, the method comprising performing MAximizing R Square Algorithm (MARSA) , predicting regression coefficients for genes, performing cross-validation, and using a cutoff for selecting a gene signature set (para 242 and 262). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Xie2019 and Tsao to arrive at the instantly claimed invention. The modification would have entailed using the m ethod of Tsao to identify the 7 genes of Xie2019 within a larger set. One would have been motivated by the availability of a known and proven method for identifying genes signatures able to predict disease prognosis in patients with lung cancer. Further, methods of regression analysis would have been known to one in the art at the time of filing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. Claim 6 is rejected under 35 U.S.C. 10 3 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018 , referred to here as Xie2019 ) in view of Tang et al. (A 12-Gene Set Predicts Survival Benefits from Adjuvant Chemotherapy in Non–Small Cell Lung Cancer Patients. Clin Cancer Res 15 March 2013; 19 (6): 1577–1586, on IDS dated 06/06/2023) . Regarding claim 6 , Xie2019 teaches generation validation datasets (p. 2, col. 2); using prediction models generated by performing supervised principal component analysis for 12 genes and assigning a risk score (one-dimensional risk scores plotted in Supplemental Fig. S1A) (p. 4, col. 1). Xie2019 further teaches comparing high-risk (i.e., adjuvant chemotherapy benefit) or low-risk (i.e., adjuvant chemotherapy nonbenefit ) group s based on the patient's risk score ( p.4 , col. 1). Xie2019 does not specifically teach the principal component analysis was obtained by determining three principal component scores for each gene included in the seven gene signature based on the expression information . However, Tang , which Xie2019 cites as the sources of its prediction model, teaches constructing a prediction model based on the linear combinations of gene expressions of the provided gene set in the training dataset using the first 3 principal components (p. 1579, col. 2). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Xie2019 and Tang to arrive at the instantly claimed invention. The modification would have entailed r eplicating the prediction model generation of Tang. One would have been motivated by the fact that the prediction model of Tang was referenced by Xie2019 and provided a known method. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. Claim s 15 , 16, and 19 are rejected under 35 U.S.C. 10 3 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157 , published first October 4, 2018 , referred to here as Xie2019 ) . Regarding claim 15 , Xie2019 teaches a gene signature for predicting patient prognosis in patients with NSCLC (lung cancer) (p. 2, col. 1). Xie teaches measuring gene expression information for 12 genes (p. 2, col. 1), normalizing the expression data (p. 3, col. 2), and determining a risk score (p. 4, col. 1). Xie teaches separating patients into high risk and low risk groups based on the patients risk score and using a predefined cutoff (i.e., pre-determined risk threshold) (p. 4, col. 1). Xie further teaches that the high risk group is a adjuvant chemotherapy benefit group and the low risk group is a adjuvant chemotherapy nonbenefit group (p. 4, col. 1), which reads on determining, a level of chemotherapy responsiveness. Xie2019 does not explicitly teach a benefit score or benefit threshold. However Xie teaches that a high risk score is equivalent to benefit from adjuvant chemotherapy and a low risk score is equivalent to nonbenefit from adjuvant chemotherapy (p. 4, col. 1) . However, i t would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Xie2019 to arrive at the instantly claimed invention. The modification would have entailed referring to the risk score as a benefit score and the risk threshold as a benefit threshold. Xie2019 repeatedly references the benefit of chemotherapy in relation to the scores. One would have been motivated to make the change in order to emphasize the predicted benefits associated with scores in the high risk group. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. Regarding claim 16, Xie2019 teaches determining if a patient will benefit from adjuvant therapy (p. 4, col. 1) based on sorting into groups by score. Xie2019 further teaches administering adjuvant chemotherapy (ACT) (Fig. 3). Regarding claim 19 , Xie2019 teaches a gene signature including RRM2, AURKA, NKX2-1, COL4A3, ATP8A1, Clorf116 and HSD17B6 (p. 2, col. 1). Claim 1 7 is rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018, referred to here as Xie2019 ) as applied to claim s 15 , 16, and 19 above, and further in view of Xie et al. (US20150017210, referred to here as Xie2015 ). Regarding claim 17 , Xie2019 teaches patients with predicted benefit of nonbenefit from chemotherapy (Abstract) , but does not explicitly teach administering an alternative treatment to chemotherapy for patients with predicted nonbenefit . Xie2015 teaches a method of predicting the chemotherapeutic response of a human subject diagnosed with a non-small cell lung cancer tumor , the method comprising treating said subject with a non-chemotherapy cancer treatment if predicted to be a non-responder , which reads on a subject who will not benefit from chemotherapy treatment (claim 28) . Xie2015 teaches that non-chemotherapy treatments including immunotherapy (paras 237-242). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Xie2019 with Xie2015 to arrive at the instantly claimed invention. The modification would have entailed using the prediction results of Xie2019 in the method of Xie2015 to choose the appropriate treatment for a patient. It would have been obvious to one of sill in the art to use the predictive accuracy of Xie2019 to adapt treatment plans as taught by Xie2015. Indeed Xie2015 teaches using a similar predictive model to determine treatment. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. Claim 1 8 is rejected under 35 U.S.C. 103 as being unpatentable over Xie et al. (Validation of the 12-gene Predictive Signature for Adjuvant Chemotherapy Response in Lung Cancer. Clin Cancer Res 1 January 2019; 25 (1): 150–157.published first October 4, 2018, referred to here as Xie2019 ) as applied to claims 15, 16, and 19 above, and further in view of Tamayo et al. ( US20030073083A1 ) . Regarding claim 18 , Xie2019 teaches follow-up (p. 4, col. 1) but does not teach an observational follow up on the patient, wherein the observational follow up comprises an analysis of expression information for the seven gene signature set in a second lung cancer sample obtained from the patient . Tamayo teaches methods for predicting treatment sensitivity or resistance based on gene expression (Abstract). Tamayo teaches long-term clinical follow-up of patients, including measuring gene expression after treatment (para 41, Fig. 4). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Xie2019 and Tamayo to arrive at the instantly claimed invention. The modification would have entailed measuring gene expression at a later timepoint, after treatment, as taught by Tamayo. One would have been motivated to do so for the benefit of further tracking or confirming association between gene expression and response to treatment. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art. 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