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. Applicant previously cancels claims 1-48. Claims 49-71 are currently pending and under examination. Priority Applicant's claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of 35 U.S.C. 112 (pre-AIA). See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application s , Application Numbers PCT/US13/54797; 61/683,192 ; 61/844,804; 61/840,403; 61/800,223; 61/762,435; 61/737,374; 14/104,650; 14/175,973; 14 / 250,701 ; 61/937,344; 61/909,974; 61/896,060; and 13/966,150; all fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112 (pre-AIA), first paragraph for one or more claims of this application. The applications fail to provide support for the claims under examination, since there is no disclosure therein of a method of obtaining a nucleic acid analyte comprising epigenetic modifications, using the sequencing data to identify the epigenetic modification, the epigenetic modification comprising methylation of a nucleotide of the nucleic acid analyte and converting an unmethylated cytosine of the nucleic acid analyte to uracil . Although the applications show in a plurality of partition s , generating a barcoded product from the barcode oligonucleotide and the nucleic acid analyte, wherein the barcoded nucleic acid molecule comprises a first sequence corresponding to the nucleic acid analyte and a second sequence corresponding to the barcode sequence of the barcode oligonucleotide as well as obtaining sequence data from the barcoded product or derivative thereof , the applications do not disclose a method of obtaining a nucleic acid analyte comprising epigenetic modifications, using the sequencing data to identify the epigenetic modification, the epigenetic modification comprising methylation of a nucleotide of the nucleic acid analyte and converting an unmethylated cytosine of the nucleic acid analyte to uracil . Therefore, effective filing date of the instant application is February 14, 2014 . Information Disclosure Statement The Information Disclosure Statements filed January 05, 2022; January 06, 2023; July 09 2024; and March 03, 2025 have been considered. Specification The use of the term s Triton ® X-100, Tween ® 20 and Sarcosyl ® , ( see Page 20, [0070], Page 64, [00180]) which are trade name s or mark s used in commerce, has been noted in this application. The term s 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 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 49-71 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 49 reci tes the limitation "the barcoded nucleic acid molecule" in line 11. There is insufficient antecedent basis for this limitation in the claim. Claims 50-71 depend from claim 49 and are therefore included in this 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claims 49-55 and 57-71 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Saxonov et al. (U.S. Patent Application Publication US 2012/0316074 A1, published December 13, 2012, effectively filed April 25, 2012), cited on the IDS filed January 05, 2022. Regarding claim 49 , Saxonov teaches a method, comprising obtaining nucleic acid analytes comprising epigenetic modifications (Page 16, [0152] and Page 19, [0179]-[0181]). Saxonov teaches a barcode oligonucleotides comprising barcode sequences, the nucleic acid analytes and barcode oligonucleotides disposed amongst a plurality of partitions (Abstract, Page 1, [0004], Pages 1-2, [0016]-[0017] and Page 2, [0022]). Saxonov teaches a partition of the plurality of partitions comprises a barcode oligonucleotide of the barcode oligonucleotides, the barcode oligonucleotide of the barcode oligonucleotides comprising a barcode sequence of the barcode sequences and a nucleic acid analyte of the nucleic acid analytes (Abstract, Page 1, [0004], Pages 1-2, [0016]-[0017] and Page 2, [0022]). Saxonov teaches the nucleic acid analyte comprises an epigenetic modification of the epigenetic modifications (Page 16, [0152] and Page 19, [0179]-[0181]). Saxonov teaches in the partition, generating a barcoded product from the barcode oligonucleotide and the nucleic acid analyte, wherein the barcoded nucleic acid molecule comprises a first sequence corresponding to the nucleic acid analyte and a second sequence corresponding to the barcode sequence of the barcode oligonucleotide (Abstract, Page 1, [0004], Pages 1-2, [0016]-[0017] and Page 2, [0022]). Saxonov teaches obtaining sequence data from the barcoded product or derivative thereof and using the sequencing data to identify the epigenetic modification (Page 2, [0022] , Page 16, [0152] and Page 19, [0179]-[0181]). Regarding claim 50, Saxonov teaches the plurality of partitions is a plurality of wells (Page 7, [0076], Page 10, [0114], Page 14, [0147] and Pages 15-16, [0151]). Regarding claim 51, Saxonov teaches the plurality of partitions is a plurality of droplets (Abstract and Page 1, [0006]) . Regarding claim 52, Saxonov teaches hybridizing the barcode oligonucleotide to the nucleic acid analyte and extending the barcode oligonucleotide with aid of a polymerase, using the nucleic acid analyte as a template (Page 5, [0055]-[0057], Pages 14-15, [0146]-[0149] and Page 17, [0161]-[0162]) . Regarding claim 53, Saxonov teaches the partition comprises a bead that comprises the barcode oligonucleotide comprising the barcode sequence (Page 8, [0087], Page 12, [0134], Pages 14-15, [0146]-[0149] and Page 17, [0161]-[0162]). Regarding claim 54, Saxonov teaches the barcode oligonucleotide is releasably coupled to the bead via a labile moiety (Pages 1-2, [0016] and Pages 6-7, [0067]-[0068] . Regarding claim 55, Saxonov teaches the labile moiety is chemically labile (Page 22, [0217]) . Regarding claim 57, Saxonov teaches releasing the barcode oligonucleotide from the bead (Pages 1-2, [0016], Page 2, [0026], Page 3, [0034] and Page 18 , [0171]) . Regarding claim 58, Saxonov teaches releasing the barcode oligonucleotide from the bead via a stimulus (Pages 1-2, [0016], Page 2, [0026], Page 3, [0034] and Page 18, [0171]) . Regarding claim 59, Saxonov teaches the stimulus is a reducing agent (Pages 8-9, [0095]) . Regarding claim 60, Saxonov teaches the stimulus is in the partition (Pages 1-2, [0016], Page 2, [0026], Page 3, [0034] and Page 18, [0171]) . Regarding claim 61, Saxonov teaches sequencing the barcoded product or derivative thereof to provide the sequencing data (Abstract, Page 1, [0004], Pages 1-2, [0016]-[0017] and Page 2, [0024]) . Regarding claim 62, Saxonov teaches the epigenetic modification comprises methylation of a nucleotide of the nucleic acid analyte (Page 16, [0152] and Page 19, [0179]-[0181]) . Regarding claim 63, Saxonov teaches converting an unmethylated cytosine of the nucleic acid analyte to uracil (Page 19, [0181]) . Regarding claim 64, Saxonov teaches dividing a sample comprising the nucleic acid analytes into a plurality of aliquots (Page 7, [0080]). Saxonov teaches contacting a first aliquot of the plurality of aliquots comprising the nucleic acid analyte with a deamination agent, wherein a second aliquot of the plurality of aliquots is not contacted with the deamination agent (Page 19, [0181]) . Regarding claim 65, Saxonov teaches generating an additional barcoded product from an additional nucleic acid analyte of the second aliquot and sequencing the additional barcoded product or derivative thereof to provide additional sequencing data (Page 14, [0146]) . Regarding claim 66, Saxonov teaches comparing the sequencing data with the additional sequencing data (Page 22, [0220]-[0221]). Regarding claim 67, Saxonov teaches treating the nucleic acid analytes with a methylation specific restriction enzyme (MSRE) (Page 6, [0060]-[0061] and Page 11, [0118]-[0119]). Saxonov teaches the treating cleaves the nucleic acid analytes at one or more methylation sites (Page 6, [0060]-[0061] and Page 11, [0118]-[0119]). Regarding claim 68, Saxonov teaches dividing a biological sample comprising the nucleic acid analytes into a plurality of aliquots (Page , 7, [0080]). Saxonov teaches contacting a first aliquot of the plurality of aliquots comprising the nucleic acid analyte with a methylation specific restriction enzyme (MSRE) and a second aliquot of the plurality of aliquots is not contacted with the MSRE (Page 22, [0213] and [0221]) . Regarding claim 69, Saxonov teaches the partition comprises a cell comprising the nucleic acid analyte (Page 18, [0171]) . Regarding claim 70, Saxonov teaches lysing the cell to release the nucleic acid analyte from the cell into the partition (Page 18, [0171]) . Regarding claim 71, Saxonov teaches subsequent to the lysing, treating the nucleic acid analyte with one or more proteases (Page 14 , [0144]. Saxonov teaches each and every limitation of claims 49-55 and 57-71 therefore Saxonov anticipates claims 49-55 and 57-71. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . 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 49 is rejected under 35 U.S.C. 103 as being unpatentable over Saxonov et al. (U.S. Patent Application Publication US 2012/0316074 A1, published December 13, 2012, effectively filed April 25, 2012), cited on the IDS filed January 05, 2022, as applied to claims 49-55 and 57-71 above, in view of Uhlmann et. al (U . S . Patent No. US 9 , 580 , 708, issued February 28, 2017 , effective ly fil ed September 14, 201 2 ) . Uhlmann teaches multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker, particularly, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes’ expression levels, while exhib i ting favorable pharmacokinetic and pharmacodynamic properties (Abstract). Uhlmann teaches that relatively high levels of a monomeric oligonucleotides can be achieved in a target tissue or cell when monomeric units are connected by a cleavable linker ( e.g ., an endonuclease-sensitive l inker) and administered as a multimer, such that linker properties can be tuned to control the extent to which monomeric units are released in a particular tissue-type or cell-type to be targeted ( C ol umn 1, L ines 51-55 and 59-61). Uhlmann teaches that the product of the gene mediates gene expression through an epigenetic mechanism ( C ol umn 5, L ines 59-60). Uhlmann teaches that rapidly degradable linkers are referred as "cleavable" such as a nuclease-sensitive, phosphodiester, linkage or a linker comprising a disulfide bond, while more stable linkages, such as, e.g ., nuc l ease-resistant phosphorothioates, as referred to as "non-cleavable" ( C ol umn 7, L ines 21-26). Uhlmann teaches the term "cleavage" refers to the breaking of one or more chemical bonds in a relatively large molecule in a manner that produces two or more relatively small molecules, such that cleavage in the mammalian extract can be mediated by a nuclease, peptidase, protease, phosphatase, oxidase, or reductase, for example; and the term "cleavable," as used herein, refers to rapidly degradable linkers, such as, e.g., phosphod i ester and disulfides ( Column 10, L ines 35-43). Uhlmann teaches that the linker is a non-nucleotide linker, for example, a single phosphodiester bridge, wherein cleavable linkers are a chemical group comprising a disulfide bond, for example, -~(CH 2 ) n S -~S(CH 2 ) m --, wherein n and mare integers from 0 to 10 (disulfide bonds to be cleavable l inker, Column 26, L ines 63-67). Uhlmann teaches that the linker is pH sensitive including a low pH-labile bond that is selectively broken under acidic conditions (pH<7), such that the linker can comprises an amine, an imine, an ester, a benzoic imine, an amino ester, a diorthoester , a polyphosphoester, a polyphosphazene , an acetal, a vinyl ether, a hydrazone, an azidomethylmethylmaleic anhydride , a thiopropionate , a masked end osomolytic agent or a citraconyl group (chemically labile bonds , Column 28, L ines 4-15). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention to have modified the teachings of Saxonov to incorporate the teachings of Uhlman n, to use a chemically liable disulfide bond, because in accordance with MPEP 2141 section Ill (A) citing KSR International Co. v. Teleflex Inc . (KSR), 550 U.S. 398, 82 USPQ2d 1385, 1395 (2007) “ ... a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. Therefore, in view of the benefits of tuning linker properties as exemplified by Uhlmann, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the methods of single cell analysis, single cell transcriptome sequencing, and/or genomic methylation analysis including the steps of separating cells or barcoded adaptors into unique partitions, subdividing a sample comprising multiple polynucleotides into partitions, and merging partitions to form one or more tagged polynucleotides as disclosed by Saxonov to include the methods of cleaving labile linkers such as disulfide linkers as taught by Uhlmann with a reasonable expectation of success in designing linkers and/or partitions to be sensitive to cleavage or disruption within different organs, tissues, cells, and/or sub cellular compartments; in selectively tuning linker elements and/or droplets to release, merge, and/or distribute barcoded polynucleotide fragments, small molecules, monomers, and/or therapeutic compounds at selected in vitro or in vivo locations; and/or in chemically linking a target polynucleotides to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the target polynucleotide. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto- processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claims 49 - 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 21-22 and 41, of U.S. Patent No. 11,932,899. Although the claims at issue are not identical, they are not patentably distinct from each other because while the preambles are slightly different, it appears that the steps of the claims are identical, so it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a method of obtaining nucleic acid analytes comprising epigenetic modifications and /or preforming a method for determining an epigenetic characteristic of a nucleic acid molecule from a cell , using those same steps. Therefore, the claims are not deemed to be patentably distinct. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JESSICA DANIELLE PARISI whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8025 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon - Friday 7:30-5:00 Eastern with alternate Fridays off . 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, Heather Calamita can be reached at 571-272-2876 . 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. /JESSICA D PARISI/ Examiner, Art Unit 1684 /HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684