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. Election/Restrictions Applicant's election with traverse of KCNA3 in the reply filed on 7/08/2025 is acknowledged. The traversal is on the ground(s) that there is no under search burden (p. 1) . This is not found persuasive because the requirement for species is under the national stage application requirements which do not require a search burden. The requirement is still deemed proper and is therefore made FINAL. Claim 15-21 are pending. Claims 1-14 have been cancelled. An action on the merits is provided below. Claim Objections Claim 15-21 are objected to because of the following informalities: The gene names should be spelled out for clarity in claim 1. Furhtermore, the term “TET enzyme” should be spelled out for clarity so that it is clear that “TET” is ten eleven translocation . Appropriate correction is required. Improper Markush Claims 15-21 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y). The Markush groupings of the combinations of at least of the genes in claim 1 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: It is first noted that MPEP 706.03(y) states that “A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an “improper Markush grouping” if either: (1) the members of the Markush group do not share a “single structural similarity” or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). “ Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2). The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved” (see MPEP 706.03(y)IIA). Herein, the recited alternative species do not share a single structural similarity, as each gene has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the comprise the generic structure of nucleotides. The fact that the genes have a generic structure per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of the being correlated to breast cancer and they do not share a substantial structural similarity essential to this activity. Further, the recited genes do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that genes behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited sequences possess the common property of being associated with urine cancer treatment . There is no evidence of record to establish that it is clear from their very nature that the recited markers possess the common property of being having a relationship of urine cancer treatment. Claim Rejections - 35 USC § 112 The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 15-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The claims are drawn to a method of treating bladder cancer comprising obtaining a sample from a subject, measuring the level of methylation at a CpG site in KCNA3, identifying the subject having an increased level of methylation and administering a treatment for bladder cancer. The claims are drawn to a very large genus of examining and comparing any CpG site increased methylation levels in any sample from any subject. The specif ication states that when unmethylation or hypermethylation occurs the expression of the gene is increased (p 7). The specifi cation teaches that KCNA3 is unmethylated (p. 10) and as such based upon the definition of page 7 the expression of the gene is increased. The specific ation has not provided that methylation levels of KCNA3 is identified in any sample or any subject and admi nistration of treatment for bladder cancer. Based upon the description in the specification although the skilled artisan could readily use a methylation analysis for comparison, the artisan would first need to determine if it functionally detectable of origin or tissue type based upon the compassion of any number of CpG sites in KCNA3 and any number of methylation/unmethylation sites in a vast array of potential cells or tissue samples. The specification has not provided written support for the structures with the recited functionality. Further, the art does not provide guidance to sufficiently describe relevant identifying characteristics or functional attributes that would distinguish different members of the claimed genus. In the instant case it is not clear that the functionality can be extrapolated to non-human individuals or in any sample based upon any methylome atlas. This finding is supported by Feng (PNAS 2010 Vol 107 No 19 pages 8689-8694). Specifically, Feng teaches that although DNA methylation likely has a conserved role in gene silencing, the levels and patterns of DNA methylation appear to vary drastically among different organisms (abstract). In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that "Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed." (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.) In the instant case, the specification fails to teach the necessary common attributes or features of the methylation of molecules to any methylome atlas in view of the species disclosed. As such, one of skill in the art would not recognize that applicant was in possession of the genus encompassed by the broadly claimed invention. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claim s 15-21 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. Claims 15-21 are indefinite over the steps of claim 15. In particular the claims are drawn to administering a treatment for bladder cancer, however, the claims do not make clear that the subject has bladder cancer. As such it would be unclear if the claim intends to administer treatments that would encompass “ treatment for bladder cancer” but is not treating bladder cancer. For example, chemotherapy could be encompassed by step d, however, if the subject does not have bladder cancer the preamble would not be performed. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claim s 15-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract step without significantly more. The claim(s) recite(s) the judicial exception of an abstract step of “identifying the subject” . This judicial exception is not integrated into a practical application because the claims require steps o f measuring the level of methylation it does not provide a step to integrate the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not integrate the judicial exception to steps that are not considered routine and conventional steps. These judicial exceptions are not integrated into a practical application because the claims only recite the abstract ideas and routine and convention steps, wherein the routine and convention steps does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge in the prior art as exemplified by the prior (as discussed below). According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility. Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process. Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, an abstract idea. The step of identifying is considered an abstract idea as it would encompass looking at data Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application. Step d is drawn to administering however, the step is not integrated because regardless of step c the subject is administered a treatment. Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception. The steps that are not considered judicial expectations are the steps of determining methylation and treating a subject with a bladder cancer treatment. Feber et al. (US Patent Application Publication 2018/0305765 October 25, 2018) teaches obtaining a sample from a subject (para 265). Feber et al. teaches measuring the level of methylation of a CpG sites in KCNA3 (table 1). Feber et al. teaches identifying increased level of methylation at the CpG site relative to the control (para 98-102, 148-165, and Table 1). Feber et al. teaches treating the subject with a treatment for bladder cancer (para 173-178). The dependent claims only limit the claims to well known samples and method steps to well-known methylation assays. These methods are considered generic recitations of general methods of expression determination that do not overcome the rejection. 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. Claim(s) 15-17,19-21 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Feber et al. (US Patent Application Publication 2018/0305765 October 25, 2018). With regard to claim 15, Feber et al. teaches obtaining a sample from a subject (para 265). Feber et al. teaches measuring the level of methylation of a CpG sites in KCNA3 (table 1). Feber et al. teaches identifying increased level of methylation at the CpG site relative to the control (para 98-102, 148-165, and Table 1). Feber et al. teaches treating the subject with a treatment for bladder cancer (para 173-178). With regard to Claim 16, Feber et al. teaches obtaining urine samples from patients from hematuria clinic (para 245). With regard to claim 17, Feber et al teaches methods using bisulfite conversion (para 236). With regard to claim 19, Feber et al. teaches a measuring step using methylation specific PCR (para 111-112). With regard to claim 20, Feber et al. teaches that the sample can be a bladder biopsy (para 167). With regard to claim 21, Feber et al. teaches that the sample can be peripheral blood (para 167). 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. 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. Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Feber et al. (US Patent Application Publication 2018/0305765 October 25, 2018) in view of Tao et al. (US Patent Application Publication 2019/0167708 June 6, 2019) . Feber et al. teaches obtaining a sample from a subject (para 265). Feber et al. teaches measuring the level of methylation of a CpG sites in KCNA3 (table 1). Feber et al. teaches identifying increased level of methylation at the CpG site relative to the control (para 98-102, 148-165, and Table 1). Feber et al. teaches treating the subject with a treatment for bladder cancer (para 173-178). However, Feber et al. does not teach measuring comprises a treatment with a TET enzyme. With regard to claim 18, Tao et al. teaches that TET enzymes can be used for detection of CpG methylation (para 113). Tao et al. teaches that TET enzymes provides a fundamental etiologic role of CpG methylation in human cancers (para 113). Therefore it would be prima facie obvious to one of ordinary skill at the time of the effective filing date to modify Feber et al. to further use TET enzymes in the method as taught by Tao et al. The ordinary artisan would be motivated to use TET enzymes as Tao et al. teaches that TET enzymes provides a fundamental etiologic role of CpG methylation in human cancers (para 113). Conclusion No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT KATHERINE D SALMON whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-3316 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT 9-530 . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Wu Cheng (Winston) Shen can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 5712723157 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /KATHERINE D SALMON/ Primary Examiner, Art Unit 1682