DETAILED ACTION Status of the Application Claims 24-46 are pending. Claims 24-46 are under examination. The following Office Action is in response to Applicant's communication dated 0 7/26/2023 . The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Interpretation For purposes of examination, the claims are interpreted according to their plain language as would be understood by one of ordinary skill in the art. Where the claim language is internally inconsistent or unclear, the Office does not infer unstated limitations or supply missing relationships. The interpretations set forth below are adopted solely to permit examination and do not resolve ambiguities in the claim language. Claim 32 recites that “ the tag sequence comprises a second tag sequence ” , however, the term “ the tag sequence ” is not defined in claim 24 , upon which claim 32 depends . Because the claim introduced new element without prior reference or explanation, the scope of this limitation is unclear as written. For purposes of examination only, and to facilitate a complete analysis of the claim, the Examiner interprets “ the tag sequence ” as referring to the previous introduced “label sequence” associated with adaptor- or bead-derived labeling oligonucleotides incorporated into nucleic acid fragments, since these are the only sequence elements described in the base claim as performing a tagging or indexing function. This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language. Claim 4 2 recites that “ one strand of the nucleic acid molecules ”, however, the claim does not specify whether “one strand” refers to a genomic DNA strand, a cDNA strand, or an adaptor-derived strand appended during library construction. The scope of this limitation is unclear as written. For purposes of examination only, and to facilitate a complete analysis of the claim, the Examiner interprets the “one strand” as a labeled library strand containing adaptor- or primer-derived sequence components . This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language. Claim 43 further recites a kit comprising transposase adaptor having “ different first label sequence ” , but the claim does not specify whether the differences arise between adaptor molecules within the kit, between separate reaction partitions, or through combinatorial indexing steps performed during use. F or purposes of examination only, and to facilitate a complete analysis of the claim, because the claim is directed to a kit rather than a method of use, and does not recite partitioning or sequential indexing steps, the phrase “ different first label sequence ” is interpreted as requiring only that the kit includes a plurality of adaptor complexes carrying distinguishable labels, regardless of how those sequences are deployed during downstream reactions. This interpretation is adopted solely for examination and does not resolve the lack of clarity in the claim language. 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 appl icant regards as his invention. Claim 32 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 32 recites the limitation “ the tag sequence ” . T here is insufficient antecedent basis for this limitation in the claim. The phrase " the tag sequence " is not defined in claim 24 , upon which claim 32 depends. Because the claim introduced new element without prior reference or explanation, a one of ordinary skill in the art cannot determine with reasonable certainty the scope of protection. Hence, the metes and bounds of the claim are unascertainable. 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) 24-27, 29-30, 32-36, 38-39, 41, and 43-44 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Song et al. ( US11939622B2 , EFD: 07/22/2019 ) Regarding claim 24 , Song discloses a method for generating labeled nucleic acid molecules, comprising the following steps: (a) providing multiple bead particles comprising coupled oligonucleotide molecules, wherein said oligonucleotide molecules contains a labeling sequence comprising a second label sequence, wherein each bead particle has multiple oligonucleotide molecules, and the multiple oligonucleotide molecules on the same bead particle have the same second label sequence, while oligonucleotide molecules on different bead particles have different second label sequences; (e.g. the bead is conjugated to a UMI [Fig 12 ] and plurality of oligonucleotide can be immobilized on the synthetic particle (e.g. beads) [column 83, lines 19-20] . And “ the cell label is identical for all barcodes attached to a given solid support (e.g., a bead), but different for different solid supports (e.g., beads). ” [ column 31, lines 28-30 ] ) (b) providing multiple cells or cell nuclei comprising RNA; (e.g. Fig. 12 shows the beginning sample comprising cells) (c) performing processing on the RNA including a reverse transcription step to form double-stranded nucleic acids containing cDNA chains; (e.g. Fig. 12 shows reverse transcription as part of RNA processing step) (d) incubating the double-stranded nucleic acids with a transposase complex comprising a transposase and a transposon sequence that the transposase is used to recognize and bind, and is capable of cleaving or breaking the double-stranded nucleic acids, wherein the transposon sequence contains a transfer chain and a non-transfer chain, the transfer chain comprising a transposase recognition sequence, a first label sequence, and a first common sequence, wherein the first label sequence is located upstream of the transposase recognition sequence, and the first common sequence is located upstream of the first label sequence, and wherein the incubation is performed under conditions that allow the double-stranded nucleic acids to be fragmented by the transposase complex into nucleic acid fragments and for the transposon sequence to be connected to the end of the nucleic acid fragments, thereby forming a group of nucleic acid fragments within the cells or cell nuclei, the nucleic acid fragments comprising cDNA fragments wherein the sequences of the transfer chains are connected to the 5' end of the cDNA fragments and, the nucleic acid fragments contain the first common sequence, the first label sequence, the transposase recognition sequence, and the cDNA fragment from the 5' end to the 3' end; (e.g. Song discloses contacting double-stranded nuclear target-associated DNA with a conjugate comprising a transposome including a transposase and adaptor sequences to generate fragmented dsDNA having adaptor-derived 5’ overhangs. The transposome includes a first adaptor and a second adaptor, each comprising barcode sequences . The adaptor sequence further includes sequencing adaptor and universal primer handle regions, corresponding to common sequences. Because adaptor-loaded Tn5 transposase inserts these adaptor transfer strands into fragment termini during tagmentation, Song discloses a transfer chain comprising a transposase recognition sequence, a label sequence, and a common sequence inserted at 5’ ends of ds nucleic acid fragments [co lumn 74, lines 33-67][column 90 , lines 45-column 92, line 32 ] ) (e) contacting the processed cells or cell nuclei of step (d) with the bead particles, wherein the nucleic acid fragments and the oligonucleotide molecules generate labeled nucleic acid molecules comprising the sequence of the nucleic acid fragments and the complementary sequence of the labeling sequence from the 5' end to the 3' end, or comprise the labeling sequence and the complementary sequence of the nucleic acid fragments. (e.g. Song discloses contacting nucleic acid templates with a bead substrate comprising an oligonucleotide probe having a hybridization domain that hybridizes to a complementary sequence on the template strand, follow by ligation of the template strand to the probe to generate label nucleic acid molecules. The resulting molecules comprise a nucleic acid fragment sequence and the complementary of the labeling probe. [column70, line 65-column 71, line 29][Figs. 7A-7C] ) Regarding claim s 2 5 and 26 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses the sample comprise plurality of cells from animals, plants, or microorganisms, or any combination thereof. [column 25, lines 22-47] Regarding claim 27 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses the RNA is reverse- transcribed using a reverse transcriptase to form hybrid double-stranded nucleic acid comprising RNA and cDNA chains. [column 33, lines 34-46] Regarding claim s 29 and 45 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses the nucleic acid fragment pool is used for constructing a transcriptome library or for transcriptome sequencing. [column 67, lines 12-17] Regarding claim 30 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses step (a), at least 2 of the processed cells or cell nuclei are provided, and/or, at least 2 beads are provided. [column 30, lines 31-33] [column 83, lines 19-20 ] Regarding claim 32 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses the tag sequence comprises a second tag sequence and is selected from the following elements: a first amplification primer sequence, a second common sequence, a unique molecular tag sequence, a template switching sequence, or any combination thereof. (e.g. bead’s second tag sequence [Fig 6], tag mented dsDNA’s second tag sequence [column 90, lines 45-column 92, line 32]) Regarding claim 33 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses contacting nucleic acid fragment s to bead-immobilized oligonucleotide s by (e1) lysing cells or cell nuclei [column 7, lines 33-34]. Regarding claim 34 , Song discloses a method for constructing a library of nucleic acid molecules comprising: (i) generating multiple labeled nucleic acid molecules according to claim 24 , and (ii) recovering and/or combining multiple labeled nucleic acid molecules to obtain a library of nucleic acid molecules. [column 42, li n e s 8-10 ] Regarding claim s 35 and 39 , Song discloses a method for constructing a library of nucleic acid molecules of claim 34 as discussed fully above and incorporated here. Song further discloses enriching the labeled nucleic acid molecules. [column 25, line 31] Regarding claim 36 , Song discloses a method for constructing a library of nucleic acid molecules of claim 35 as discussed fully above and incorporated here. Song further discloses primer carrying a tag that can bind a partner molecule for enrichment [e.g. Biotin label in Fig 7B] Regarding claim 38 , Song discloses a method for constructing a library of nucleic acid molecules of claim 35 as discussed fully above and incorporated here. Song further discloses (iv) recovering and purifying the enriched products [column 51, line s 47-50] Regarding claim 41 , Song discloses a method fo r sequencing nucleic acids from cells or cell nuclei, comprising: constructing a nucleic acid library according to claim 34 ; and sequencing the nucleic acid library. [column 63, lines 17-28] Regarding claim s 43 and 44 , Song discloses a kit comprising: reverse transcriptase, transposase, at least 2 labeled transposome adaptors, where the transfer strand comprises common sequence, label sequence, and transposase recognition sequence barcoded beads[column 71, lines 30-54], where same barcode per bead and different barcode between beads (e.g. the bead is conjugated to a UMI [Fig 12] and “ the cell label is identical for all barcodes attached to a given solid support (e.g., a bead), but different for different solid supports (e.g., beads). ” [column 31, lines 28-30]). 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. Song et al. and Di et al. Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Song et al. ( US11939622B2 , EFD: 07/22/2019) in view of Di et al. ( Proc Natl Acad Sci U S A . 2020;117(6):2886-2893. ) Regarding claim 28 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song teaches transpose mediated fragmentation of nucleic acid during library preparation workflow that include reverse transcription of RNA to generate RNA-cDNA hybrid intermediates. However, Song does not explicitly disclose the transposase complex fragments RNA-cDNA duplexes. Di teaches that Tn5 transposase directly fragments RNA-DNA hybrid duplexes generated during reverse transcription. It would have been obvious to one of ordinary skill in the art to apply the known capability of Tn5 to fragment RNA-DNA hybrid duplexes in the Song workflow because both references concern transpose-based transcriptome library preparation. This reasoning is consistent with KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, A) Song et al. Claim(s) 31, 37, 40, and 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Song et al. ( US11939622B2 , EFD: 07/22/2019) Regarding claim 31 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song further discloses plurality of oligonucleotide can be immobilized on the synthetic particle (e.g. beads). One of ordinary skill would have understood that optimizing the number of oligonucleotide per bead (e.g. at least 10) is the matter of routine optimization base on desired capture efficiency, bead size, and reaction sensitivity. Accordingly, at least 10 oligonucleotide molecules on the bead is deemed prima facie obvious to a person of ordinary skill in the art . Regarding claim 3 7 , Song discloses a method for constructing a library of nucleic acid molecules of claim 35 as discussed fully above and incorporated here. Song discloses amplification of labeled nucleic acid molecules using adaptor-associated primer during library preparation [Fig. 13]. Song further teaches oligonucleotides comprising labeling molecules such as biotin that interact with binding partner such as streptavidin to enable capture and enrichment of nucleic acid products [Figs 7B and 7C]. Because affinity-labeled PCR primers routinely used to generate enrich amplification products via binding interactions, Song teaches or renders obvious performing amplification using first primer and/or the second labeled primer s as recited in claim 38 . Regarding claim 40 , Song discloses a method for constructing a library of nucleic acid molecules of claim 39 as discussed fully above and incorporated here. Song teaches sequencing workflow for profiling nucleic acid targets from cells and nuclei using adaptor-based labeling and library construction methods applicable to transcriptomic and genomic targets. It would have been obvious to one of ordinary skill in the art to apply the method to immune receptor sequences such as TCR and/or BCR sequences, because these targets were well known and routinely analyzed using nucleic acid sequencing workflows at the time of the invention. Accordingly, the additional limitation in claim 40 is deemed prima facie obvious to a person of ordinary skill in the art. This reasoning is consistent with KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, E) Regarding claim 42 , Song discloses a n ucleic acid library comprising multiple nucleic acid molecules, wherein one strand of the nucleic acid molecules comprises a first common sequence, a first label sequence, a cDNA fragment sequence, a unique molecular tag sequence [Fig 12], a transposase recognition sequence (because Song uses adaptor-loaded Tn5 transposomes, the adaptor sequences necessarily include the claimed transposase recognition sequence ), template switching sequence [column 14, line 47] , a second label sequence, and a complementary sequence of a second common sequence [Fig 6] , wherein the cDNA fragment comprises a sequence complementary to the 5' end sequence of RNA [column 43, lines 54-62] . The complementary sequences recite in claim 42 correspond to obvious complementary strands of adaptor elements disclosed by Song, and providing labels at both fragment ends or rearranging adaptor element order represent routine optimization design choice because such sequences are modular and interchangeable in sequencing library construct. Accordingly, the additional limitation in claim 4 2 is deemed prima facie obvious to a person of ordinary skill in the art. This reasoning is consistent with KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, E) Song et al. and Zhu et al. Claim(s) 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Song et al. ( US11939622B2 , EFD: 07/22/2019) in view of Zhu et al. ( Nat Struct Mol Biol 26, 1063–1070 (2019). ) Regarding claim 46 , Song discloses a method for generating labeled nucleic acid molecules of claim 24 as discussed fully above and incorporated here. Song discloses contacting nucleic acid with transposase complexes comprising labeling sequences to generate labeled nucleic acid fragments but does not teach dividing cells or nuclei into subsets and incubating each subset separately with transposase complexes having different first label sequences prior t combining subsets. Zhu (Paired-Seq) discloses split-pool combinatory indexing in which cells or nuclei are partitioned into subsets, treated with indexed transposase adaptor complexes containing different barcode sequences, and subsequently pooled such that fragments from each subset contain distinct label sequences identifying their subset origin. [abstract ] As of the application’ s effective filing date, one of ordinary skill in the art would have had a reasonable expectation of success and motivated to combine these teachings to modify Song’s method to incorporate Zhu’s subset-specific indexed transposase labeling prior to pooling because s pilt-pool indexing with different adaptor barcodes was a known strategy for increasing multiplex capacity and enabling identification of nucleic acid fragments from different cell populations in high-throughput single-cell sequencing workflow [Zhu’s abstract] . Accordingly, the additional limitation in claim 4 6 is deemed prima facie obvious to a person of ordinary skill in the art. See KSR International Co. v. Teleflex Inc. , 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 214 3, D ) . Conclusion No claims are allowed Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Khai Quynh Tien Pham whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-6998 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-T, 9-4 ET . 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 Heather Calamita can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (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. /KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684 /JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684