DETAILED ACTION Comments The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. 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. Claims 1-20 are pending and examined in the instant application. Information Disclosure Statement The IDSs filed have been considered. Claim Interpretation The following is a quotation of 35 U.S.C. 112(f): (f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof. The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph: An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof. This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “importance module,” “prioritization module,” “interpretation module,” “endotype identification module,” and “batch correction module” in claims 19-20. Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof. If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. 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 appl icant regards as his invention. Claims 19-20 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 limitations “importance module,” “prioritization module,” “interpretation module,” “endotype identification module,” and “batch correction module” have been evaluated under the three-prong test set forth in MPEP § 2181, subsection I, but the result is inconclusive. Thus, it is unclear whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the specification only recites the functions of these modules without indicating their structures. For the purpose of examination, these modules are interpreted to comprise either hardware or software. The boundaries of this claim limitation are ambiguous; therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. In response to this rejection, applicant must clarify whether this limitation should be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. Mere assertion regarding applicant’s intent to invoke or not invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph is insufficient. Applicant may: (a) Amend the claim to clearly invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by reciting “means” or a generic placeholder for means, or by reciting “step.” The “means,” generic placeholder, or “step” must be modified by functional language, and must not be modified by sufficient structure, material, or acts for performing the claimed function; (b) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, should apply because the claim limitation recites a function to be performed and does not recite sufficient structure, material, or acts to perform that function; (c) Amend the claim to clearly avoid invoking 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, by deleting the function or by reciting sufficient structure, material or acts to perform the recited function; or (d) Present a sufficient showing that 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, does not apply because the limitation does not recite a function or does recite a function along with sufficient structure, material or acts to perform that function. 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. 35 U.S.C. 101 Rejection #1 : Claim 18 -20 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matte r. While claim 18 is drawn to computer-readable media, there is no limiting description in the specification constraining the computer-readable media to be non- transitory. Consequently, computer-readable media is broadly construed to encompass transitory media, such as carrier waves, which are not subject matter eligible. Claims 19-20 are drawn to systems comprising encoders and modules. Since encoders and modules comprise software, the systems are interpreted to be software. Software, per se, is not subject matter eligible. 35 U.S.C. 101 Rejection #2 : Claim(s) 1-20 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. Claims 1-17 are drawn to methods . In accordance with MPEP § 2106, claims found to recite statutory subject matter ( Step 1 : YES ) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon ( Step 2A, Prong 1 ). In the instant application, the claims recite the following limitations that equate to an abstract idea: Claim s 1 and 18-19 recite the mental step of encoding data related to the patients with latent variables. Claims 1 and 18-19 recite the mental step of determining one or more importance measures of the latent variables. Claims 1 and 18-19 recite the mental step of prioritizing the latent variables using importance measures. Claims 1 and 18-19 recite the mental step of identifying a disease endotype that is represented by one or more of the interpreted latent variables. Claim 2 recites the mental step of constraining the type of data. Claims 3 and 20 recite the mental step of performing batch correction on the data. Claims 4-5 recite the mental step and mathematical limitation of using linear factor model. Claim 6 recites the mental step of applying sparsity constraints to the latent variables. Claim 7 recites the mental steps of extracting data and using latent variables to predict clinical attributes. Claim 8 recites the mental steps of encoding the data multiple times and determining importance measures of a latent variable comprising determining an extent of recurrence of the latent variable. Claim 9 recites the mental step of determining the contribution of the latent variable to a proportion of variation. Claim 10 recites the mental step of determining the ability of the latent variable to separate patients from a control group. Claim 11 recites the mental step of determining an extent to which the latent variable is predictive of a patient attribute. Claim 12 recites the mental step of rewarding a latent variable that is predictive of a patient attribute that is relevant to the disease. Claim 13 recites the mental step of constraining the types of disease attributes. Claim 14 recites the mental step of penalizing the latent variable that is predictive of a patient attribute that is not relevant to the disease. Claim 15 recites the mental step of describing attributes not relevant to the disease. Claim 16 recites the mental step of applying gene enrichment analysis to the latent variables Claim 17 recites the mental step of identifying a biological process underlying the disease using a gene expression pattern encoded in the latent variables. These recitations are similar to the concepts of collecting information, analyzing it and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claim(s) 1-20 recite(s) an abstract idea/law of nature/natural phenomenon ( Step 2A, Prong 1 : YES ). Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not ( Step 2A, Prong 2 ). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to a ffect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. As such, claims 1-20 is/are directed to an abstract idea/law of nature/natural phenomenon ( Step 2A, Prong 2 : NO ). Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself ( Step 2B ). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exc e ption in a generic way or in a generic computing environment. As discussed above, there are no additional limitations to indicate that the claimed analysis engine requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. MPEP 2106.05(f) discloses that mere instructions to apply the judicial exception cannot provide an inventive concept to the claims. The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself ( Step 2B : No ). As such, claims 1-20 is/are not patent eligibl e . Claim Rejections - 35 USC § 102 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. Claim(s) 1- 2 , 7, 1 1 -13 , and 17 -19 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wong et al. [US PGPUB 2019/0065666 A1; on IDS] . Claim 1 is drawn to a method of stratifying a population of patients into disease endotypes. The method comprises encoding data relating to the patients as latent variables. The method comprises determining one or more importance measures of the latent variables. The method comprises prioritizing the latent variables using the importance measures. The method comprises interpreting one or more of the latent variables. The method comprises identifying a disease endotype that is represented by one or more of the interpreted latent variables. Claim 18 is drawn to similar subject matter as claim 1, except claim 18 is drawn to a computer readable medium. Claim 19 is drawn to similar subject matter as claim 1, except claim 19 is drawn to a system. Paragraphs 7-8, 73, and 76 of Wong et al. teaches stratification into disease endotypes for septic shock. Paragraphs 74 and 77 of Wong et al. teach computer implementation. Paragraphs 175-182 of Wong et al. teach the classification and regression tree methodology involving encoding gene expression data (i.e. data relating to the patients as latent variables) which determine whether the patient data matches the criteria of terminal tree nodes. . Paragraphs 175-182 of Wong et al. teach variable reduction involving determining the important measure of how many subjects in the root node are in each terminal node. Paragraphs 175-182 of Wong et al. teach that the associated latent variables are prioritized using this importance measure since the terminal nodes with <5% of the subjects in the root node are pruned. Paragraphs 175-182 of Wong et al. teach that the only purpose of the classification and regression tree methodology is to apply the decision tree for deriving decisions, which in this case is the identification of the disease (i.e. septic shock) endotype and which necessarily involves interpreting the latent variables associated with the terminal tree nodes. With regard to claim 2, paragraph 9 of W o ng et al. teaches genomic data. With regard to claim 7, the figures of Wong et al. teach extracted and labelled data using latent variables to predict clinical attributes. With regard to claim 11, paragraph 182 and Table 15 of Wong et al. teach the accuracy of prediction of latent variables in patient survival. With regard to claim 12, the prioritization of latent variables in paragraphs 175-182 of Wong et al. teaches rewarding latent variables (i.e. latent variables prioritized higher) that a predictive of a patient attribute that is relevant for the disease. With regard to claim 13, paragraph 60 of Wong et al. teaches patient survival time. With regard to claim 17, paragraph 100 of Wong et al. teach identifying a biological process underlying the disease using a gene expression pattern encoded for by latent variables. Claim Rejections - 35 USC § 103 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. 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. 35 U.S.C. 103 Rejection #1 : Claim (s) 1- 3 , 6 -7 , 11-13, and 1 5 - 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. [US PGPUB 2019/0065666 A1; on IDS] in view of Tsalik et al. [WO 2018/140256 A1; on IDS]. Paragraphs 7-8, 73, and 76 of Wong et al. teaches stratification into disease endotypes for septic shock. Paragraphs 74 and 77 of Wong et al. teach computer implementation. Paragraphs 175-182 of Wong et al. teach the classification and regression tree methodology involving encoding gene expression data (i.e. data relating to the patients as latent variables) which determine whether the patient data matches the criteria of terminal tree nodes.. Paragraphs 175-182 of Wong et al. teach variable reduction involving determining the important measure of how many subjects in the root node are in each terminal node. Paragraphs 175-182 of Wong et al. teach that the associated latent variables are prioritized using this importance measure since the terminal nodes with <5% of the subjects in the root node are pruned. Paragraphs 175-182 of Wong et al. teach that the only purpose of the classification and regression tree methodology is to apply the decision tree for deriving decisions, which in this case is the identification of the disease (i.e. septic shock) endotype and which necessarily involves interpreting the latent variables associated with the terminal tree nodes. Tsalik et al. studies gene expression signatures useful to predict or diagnose sepsis [title]. With regard to claims 3 and 20, the last paragraph on page 24 of Tsalik et al. teaches performing batch correction on data. With regard to claim 6, the first paragraph on page 15 of Tsalik et al. teaches applying sparsity constraints to the latent variables. It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant invention to modify the disease stratification algorithm of Wong et al. by use of the gene expression algorithms of Tsalik et al. wherein the motivation would have been that the gene expression algorithms of Tsalik et al. add additional mathematical algorithms to facilitate the disease stratification algorithm [ line 1 of page 15 to line 25 of page 16 of Tsalik et al.]. There would have been a reasonable expectation of success in combining Wong et al. and Tsalik et al. because both studies are analogously applicable to analysis of sepsis. 35 U.S.C. 103 Rejection # 2 : Claim (s) 1-2, 4-5, 7 -1 4 , and 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. [US PGPUB 2019/0065666 A1; on IDS] in view of Metzger et al. [WO 2020/072977 A1; on attached 892 form]. Paragraphs 7-8, 73, and 76 of Wong et al. teaches stratification into disease endotypes for septic shock. Paragraphs 74 and 77 of Wong et al. teach computer implementation. Paragraphs 175-182 of Wong et al. teach the classification and regression tree methodology involving encoding gene expression data (i.e. data relating to the patients as latent variables) which determine whether the patient data matches the criteria of terminal tree nodes.. Paragraphs 175-182 of Wong et al. teach variable reduction involving determining the important measure of how many subjects in the root node are in each terminal node. Paragraphs 175-182 of Wong et al. teach that the associated latent variables are prioritized using this importance measure since the terminal nodes with <5% of the subjects in the root node are pruned. Paragraphs 175-182 of Wong et al. teach that the only purpose of the classification and regression tree methodology is to apply the decision tree for deriving decisions, which in this case is the identification of the disease (i.e. septic shock) endotype and which necessarily involves interpreting the latent variables associated with the terminal tree nodes. Metzger et al. teaches systems and methods for identifying bioactive agents utilizing unbiased machine learning [title]. Paragraph 82 of Metzger et al. teaches an unsupervised machine learning method comprising an autoencoder that processes data multiple times to predict . Paragraph 82 of Metzger et al. teaches a standard deviation which is indicative of proportion of variation and extent of recurrence of the variable. Paragraph 82 of Metzger et al. teaches a disease phenotype from a wild type phenotype. Paragraph 82 of Metzger et al. teaches removing the distance between wild type and disease phenotypes as the distance is not relevant to predicting disease and toxicity. It would have been obvious to someone of ordinary skill in the art at the time of the effective filing date of the instant invention to modify the disease stratification algorithm of Wong et al. by use of the autoencoder to predict disease and toxicity of Metzger et al. wherein the motivation would have been that the machine learning of Metzger et al. is an additional mathematical technique that facilitates the disease stratification algorithm of Wong et al. [paragraph 82 of Metzger et al.]. Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Russell Negin, whose telephone number is (571) 272-1083. This Examiner can normally be reached from Monday through Thursday from 8 am to 3 pm and variable hours on Fridays. If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Larry Riggs, Supervisory Patent Examiner, can be reached at (571) 270-3062. /RUSSELL S NEGIN/ Primary Examiner, Art Unit 1686 23 March 2026