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 1-10,12,14-18,20,22-26,28-29,31-35 are pending. Claims 11,13,19,21,27,30,36-70 have been cancelled. An action on the merits is set forth below. 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 1-10,12,14-18,20,22-26,28-29,31-35 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 1-10,12,14-18,20,22-26,28-29,31-35 are indefinite over the steps of claim 1. In particular the claims are unclear as the second polynucleotide comprises “a modified base oppo si te to the me thl ycytosine ”, however “the first polynucleotide ” in the hybridizing step does not require a methylcytosine. Furthermore, with regard to the wherein clause the limitation of the modified base is unclear. The phrase recites “the modified base comprise a solvatochromatic nucleotide or a modified based comprise a target”. Therefor it is not clear if “a modified base” in the wherein clause is the same as the modified base in a second polynucleotide or if the claim is intending another modified base. Claim 2 is indefinite over “ include a fluorophore ”. It is not clear if the claim is intended to limit claim 1 to “ target capable of coupling to a fluorophore ” as recited in claim 1 or if the claim inte nd s a further modified base including a fluorophore . Claim 20 is indefinite over “SNAP” and “CLIP”. The terms are abbreviations which should be spelled out with the terms in parentheses for clarity. Further claim contains the trademark/trade name SNAP and CLIP. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe protein/label and, accordingly, the identification/description is indefinite. Claim 22 contains the trademark/trade name SpyTag and SpyCatcher . Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe protein/label and, accordingly, the identification/description is indefinite. Claim 2 4 is indefinite over NTA . The terms are abbreviations which should be spelled out with the terms in parentheses for clarity. Further claim contains the trademark/trade name His-Tag and NTA . Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe protein/label and, accordingly, the identification/description is indefinite. 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) 1,2, 12 is/are rejected under 35 U.S.C. 102 (a) as being anticipated by Kat et al. (US Patent Application 2003/0017465 January 23, 2003). With regard to claim 1, Kay et al. teaches a method for detect ion a first polynucleotides to a second (para 32-34). Kay et al. teaches that the second polynucleotide that comprises a methlycytosine coupled to a fluorophore for detection (para 3 and 55-62). With regard to claim 2, Kay et al. teaches using a fluorophore (para 59). With regard to claim 12, Kay et al. teaches a modified guanine (3, 55-60). C laims 1-10,12 is/are rejected under 35 U.S.C. 102(a) as being anticipated by Balmforth et al. (WO2015/121675 August 20, 2015 cited on IDS). With regard to claim 1, Balmforth et al. . teaches a method for detecting a first polynucleotides to a second ( example 1-2, para 102-106, 141-143, 186-188, 203, 225-227 ). Balmforth et al. teaches that the second polynucleotide that comprises a me thl ycytosine coupled to a fluorophore for detection ( example 1-2, para 102-106, 141-143, 186-188, 203, 225-227 ). With regard to claim 2, Balmforth et al.. teaches using a fluorophore ( p 12 ). With regard to claim 3, Balmforth et al.. teaches a method of detecting fluorescence that is responsive to excitation ligh t ( p 12 ). With regard to claims 4-5, Balmforth et al.. teaches method wherein in the fluorescence is a protein coupled to methlycytosine (p. 7-8). With regard to claims 6-9, Balmforth et al.. teaches methods of dissociation of the fluorophore at a first and second intensity that can be different from the first (p 6-7). With regard to claim 12, Balmforth et al.. teaches a modified guanine or adenosine (p 10 ). 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) 14-18,20,23,25,28-29,31-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Balmforth et al. (WO2015/121675 August 20, 2015 cited on IDS) in view of Schildkraut et al. (US Application Publication 2018/0195061 July 12, 2018). Balmforth et al.. teaches a method for detecti on a first polynucleotides to a second (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al. teaches that the second polynucleotide that comprises a me thl ycytosine coupled to a fluorophore for detection (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al.. teaches using a fluorophore (p 12). Balmforth et al.. teaches a method of detecting fluorescence that is responsive to excitation ligh t (p 12). Balmforth et al.. teaches method wherein in the fluorescence is a protein coupled to me thl ycytosine (p. 7-8). However, Balmforth et al.. teaches that the targets can be proteins, however, does not teach that the targets comprise epitope and antibody. With regard to claim s 14 and 20, Schildkraut et al. teaches a method of labeling an oligonucleotide with a SNAP or Clip tag (para 6). Schildkraut et al. teaches that the SNAP or Clip with benzylcytosine (para 199). Schildkraut et al. suggests methods of detecting changes including methylcytosine (para 193). With regard to claim 15, Schildkraut et al. teaches that the fluorophore is attached to a second protein (para 211). With regard to claim 16-17, Schildkraut et al. teach multiple proteins that bind to the fluorophore (para 199-204). Schildkraut et al. teaches an epitope finding to an antibody (para 211). With regard to claim 18, Schildkraut et al. teaches that the first protein can be coupled tot eh second with a linker (para 122). With regard to claim 23, Schildkraut et al. teaches a method of using biotin and streptavidin (para 10). With regard to claim 25, Schildkraut et al. teaches FRET labeling (para 211) so that the fluorophore is split between a quencher on one protein and a reporter on another protein. With regard to claims 28-29, Schildkraut et al. teaches that the p olynucleotides can be hybridized prior to coupling and coupling to a substrate (para 101-128 and 146). With regard to claims 31-32, Schildkraut et al. teaches a substrate (microbead) coupled to a multiple oligonucleotides that are coupled to a code (affinity tag) (para 28-29). With regard to claim 33, Schildkraut et al. teaches that the oligonucleotide of interest can be attached to a bead by an oligonucleotide (para 105-120). With regard to claim 34, Schildkraut et al. teaches a microbead (para 109). With regard to claim 35, Schildkraut et al. suggests using suggests methods of detecting changes including methylcytosine (para 193). Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Balmforth et al. to include the affinity tag and microbead of Schildkraut et al. in order to detect methylcytosine in a sample of interest. The ordinary artisan would have a reasonable expectation of success as Schildkraut et al. suggests methods of methylcytosine detection using these tag constraints. It would be obvious to one of ordinary skill in the art to modify Balmforth et al. to use on of the finite methods of label detection including the one taught by Schildkraut et al. in order to detect changes in a target. Claim(s) 14 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Balmforth et al. (WO2015/121675 August 20, 2015 cited on IDS) in view of Merriman et al. (US Patent Application Publication 2017/0044605 Feb 16, 2017) Balmforth et al.. teaches a method for det ection a first polynucleotides to a second (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al. teaches that the second polynucleotide that comprises a me thl ycytosine coupled to a fluorophore for detection (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al.. teaches using a fluorophore (p 12). Balmforth et al.. teaches a method of detecting fluorescence that is responsive to excitation ligh t (p 12). Balmforth et al.. teaches method wherein in the fluorescence is a protein coupled to methlycytosine (p. 7-8). However, Balmforth et al.. teaches that the targets can be proteins, however, does not teach that the targets are labeled with a Spycat ch er or Spytag . With regard to claim 14 and 22, Merriman et al. teaches detection of methylcytosine targets with SpyCatcher and SpyTag peptide linkers (para 66). Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Balmforth et al. to include the affinity tag with Spycatcher or SpyTag as taught by Merriman et al. in order to detect methylcytosine in a sample of interest. The ordinary artisan would have a reasonable expectation of success as Merriman et al. suggests methods of methylcytosine detection using these tag constraints. It would be obvious to one of ordinary skill in the art to modify Balmforth et al. to use on of the finite methods of label detection including the one taught by Merriman et al. in order to detect changes in a target. Claim(s) 14 and 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Balmforth et al. (WO2015/121675 August 20, 2015 cited on IDS) in view of Spiegelman et al (US Patent Application 20210063414 effective filing data 2/12/2018) . Balmforth et al.. teaches a method for detect ion a first polynucleotides to a second (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al. teaches that the second polynucleotide that comprises a me thl ycytosine coupled to a fluorophore for detection (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al.. teaches using a fluorophore (p 12). Balmforth et al.. teaches a method of detecting fluorescence that is responsive to excitation light (p 12). Balmforth et al.. teaches method wherein in the fluorescence is a protein coupled to me thl ycytosine (p. 7-8). However, Balmforth et al.. teaches that the targets can be proteins, however, does not teach that the targets comprise His-Tag and NTA. . With regard to claims 14 and 2 4 , Spiegelman et al teaches me thl ycytosine detection by using his-tag and NTA detection combinations (para 28-32). Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Balmforth et al. to include the tag of his-tag and NTA of Spiegelman et al in order to detect methylcytosine in a sample of interest. The ordinary artisan would have a reasonable expectation of success as Spiegelman et al suggests methods of methylcytosine detection using these tag constraints. It would be obvious to one of ordinary skill in the art to modify Balmforth et al. to use on of the finite methods of label detection including the one taught by Spiegelman et al in order to detect changes in a target. Claim(s) 14 and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Balmforth et al. (WO2015/121675 August 20, 2015 cited on IDS) in view of He et al. (US Patent Application Publication 2020/0032330 Jan 30, 2020). Balmforth et al.. teaches a method for detecti on a first polynucleotides to a second (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al. teaches that the second polynucleotide that comprises a me th ylcytosine coupled to a fluorophore for detection (example 1-2, para 102-106, 141-143, 186-188, 203, 225-227). Balmforth et al.. teaches using a fluorophore (p 12). Balmforth et al.. teaches a method of detecting fluorescence that is responsive to excitation ligh t (p 12). Balmforth et al.. teaches method wherein in the fluorescence is a protein coupled to meth l ycytosine (p. 7-8). However, Balmforth et al.. teaches that the targets can be proteins, however, does not teach that the targets comprise Methyl binding protein . With regard to claims 14 and 2 6 , He et al teaches methylcytosi n e detection by using Meth l y binding proteins (para 10, 44). Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Balmforth et al. to include the methyl binding proteins of He et al. in order to detect methylcytosine in a sample of interest. The ordinary artisan would have a reasonable expectation of success as He et al. suggests methods of methylcytosine detection using these tag constraints. It would be obvious to one of ordinary skill in the art to modify Balmforth et al. to use on of the finite methods of label detection including the one taught by He et al. in order to detect changes in a target. 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