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. 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. Election/Restrictions Applicant’s election without traverse of Invention Group I and Species Group A2 in the reply filed on 03/02/2026 to the office action dated 12/02/2025 is acknowledged. Election was made without traverse in the reply filed on 03/02/2026. Status of claims Canceled: 3-4, 6, 14-29, 32-33, 37-43, 45-75, 77-179 Amended: 1-2, 7, 12, 76 Pending: 1-2, 5, 7-13, 30-31, 34-36, 44, 76, 180 New: 180 Withdrawn: none Examined: 1-2, 5, 7-13, 30-31, 34-36, 44, 76, 180 Independent: 1, 76 Allowable: none Priority As detailed on the 12/14/2022 filing receipt, this application claims priority to as early as 04/19/2019. Drawings The drawings filed 10/18/2021 are accepted. Information Disclosure Statement The Information Disclosure Statements filed on 05/04/2022, 08/18/2023, 10/17/2024, 05/02/2025, 08/25/2025 and 03/02/2026 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action. 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. Claims 1-2, 5, 7-13, 30-31, 34-36, 44, 76 and 180 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. Independent claim 1 recites “(d) determining…”; “(d) colocalizing…” and “(e) repeating (c), (d) and (e) a plurality of times…” It is unclear which step (d) is step (e) referring to since there are 2 step (d)s. Claim 1 (step f) recites “…wherein the colocalization improves decoding accuracy for the creating...” The term “improves” is a relative term which render the claim indefinite. The term “improves” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claim 76 (last step) recites “…wherein the colocalization improves decoding accuracy for the creating...” The term “improves” is a relative term which render the claim indefinite. The term “improves” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims are rejected for depending on rejected claims. 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. Claims 1-2, 5, 7-13, 30-31, 34-36, 44, 76 and 180 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. 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: Mental processes recited include: Claim 1 recites: " (b) determining the phenotype, following expression of the guide RNA sequence, of the population of cells; (c) determining positions of RNA molecules expressed from the reporter portion of the introduced DNA within the plurality of cells by determining the reporter portions wherein labeled oligonucleotides are hybridized to the expressed RNA and imaged; (d) determining a read sequence on the RNA molecules expressed from the introduced DNA comprising the reporter portion and the identification portion within the plurality of cells by exposing the cells to a readout probe able to bind to the read sequence; and (f) creating codewords corresponding to the binding of the colocalized readout probes, wherein the values of the digits of the codewords are based on the binding of the readout probes to the read sequences. Determining and creating codewords are acts of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper (See MPEP 2106.04(a)(2) subsection III). Claim 2 recites: “identifying the guide portion for individual cells based on the created codewords.” Identifying is an act of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper. Claim 10 recites: “wherein the read sequences are determined sequentially.” Determining is an act of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper. Claim 13 recites: “wherein the reporter portion encodes a protein detectable by fluorescence.” Detection is involved with the act of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper. Claim 36 recites: “…at least 50% of the cells contains no more than one type of introduced DNA.” This limitation is involved with the act of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper. Claim 44 recites: “wherein for at least some of the created codewords, matching the codeword to valid codewords wherein, if no match is found, either discarding the codeword or applying error correction to the codeword to form a valid codeword.” This limitation is involved with the act of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper. Claim 76 recites: " determining positions of RNA molecules expressed from the reporter portion of the introduced DNA within the plurality of mammalian cells by determining the reporter portions wherein labeled oligonucleotides are hybridized to the expressed RNA and imaged; determining the read sequences within the plurality of cells by exposing the cells to a plurality of readout probes each able to bind to a read sequence, colocalizing the binding of the readout probes with the positions of the RNA molecules expressed from the reporter portion of the introduced DNA; and creating codewords corresponding to the binding of the colocalized readout probes, wherein the values of the digits of the codewords are based on the binding of the readout probes to the read sequences ." Determining and creating codewords are acts of evaluating, analyzing, observing and judging data that could be practically performed in the human mind and/or with pen and paper (See MPEP 2106.04(a)(2) subsection III). Mathematical concepts recited include : Claim 36 recite: “…at least 50% of the cells contains no more than one type of introduced DNA.” Determining the percentage of cells is a mathematical concept and/or formula. Claims 1-2, 10, 13, 44 and 76 , as indicated above, recite mental processes, such as determining, identifying, matching and creating codewords. The claim elements as indicated above are involved with acts of evaluating, analyzing, observing and judging data as discussed above. Acts of evaluating and analyzing data could be practically performed in the human mind and/or with pen and paper because they merely require making observations, evaluations, judgments, and opinions (See MPEP 2106.04(a)(2) subsection III). Overall, under the broadest reasonable interpretation, the indicated claims above can be practically carried out in the human mind or with pen and paper as claimed, which falls under the "Mental processes" grouping of abstract ideas. Claim 36, as indicated above, is involved with determining the percentage of cells, which is a mathematical concept that requires performing a series of calculations. Therefore, under the broadest reasonable interpretation, the indicated claims above falls under the “mathematical concepts” grouping of abstract ideas. As such, claims 1-2, 5, 7-13, 30-31, 34-36, 44, 76 and 180 recite an abstract idea (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 ). The above indicated judicial exceptions are not integrated into a practical application because the claims do not recite an additional elements that apply, rely on or use the judicial exception in such a manner to amount to integration into a practical application. For example, there are no limitations that reflect an improvement to technology or applies or uses the recited judicial exception in some other meaningful way. Rather, the instant claims recite additional elements that equate to mere instructions to implement an abstract idea or insignificant extra solution activity. Specifically, the instant claims recite the following additional elements: Claim 1 recites "(a) introducing, into the plurality of mammalian cells, DNA comprising a guide RNA recognition sequence, a reporter portion, and an identification portion comprising read sequences" Claim 5 recites “wherein the introduced DNA arises from a library of nucleic acids generated by pooled cloning.” Claim 30 recites : "introducing the DNA into the plurality of cells using a virus. " Claim 34 recites : "introducing the DNA into the plurality of cells comprises electroporating the DNA into the plurality of cells." Claim 76 recites "introducing, into the plurality of mammalian cells, DNA comprising a guide RNA recognition sequence, a reporter portion, and an identification portion comprising read sequences…" The elements of claims 1, 5, 30, 34 and 76 as indicated above equate to insignificant extra solutional activities. Extra-solution activity includes both pre-solution and post-solution activity. An example of pre-solution activity is a step of gathering data for use in a claimed process, e.g., a step of obtaining information about credit card transactions, which is recited as part of a claimed process of analyzing and manipulating the gathered information by a series of steps in order to detect whether the transactions were fraudulent. An example of post-solution activity is an element that is not integrated into the claim as a whole, e.g., a printer that is used to output a report of fraudulent transactions, which is recited in a claim to a computer programmed to analyze and manipulate information about credit card transactions in order to detect whether the transactions were fraudulent (See MPEP 2106.05(g)). Additionally, the listed additional elements are mere instructions to apply an exception because they recite no more than an idea of a solution or outcome and does not recite a technological solution to a technological problem. (See MPEP 2106.05(f)(1)). As such, as currently recited, the claims do not appear to recite an improvement to technology or apply or use the recited judicial exception in some other meaningful way. Therefore, claims 1-2, 5, 7-13, 30-31, 34-36, 44, 76 and 180 are directed to an abstract idea (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 well-understood, routine and conventional activities, insignificant extra-solution activity or mere instructions to implement the abstract idea on a generic computer. The instant claims recite the following additional elements: Claim 1 recites "(a) introducing, into the plurality of mammalian cells, DNA comprising a guide RNA recognition sequence, a reporter portion, and an identification portion comprising read sequences." Luo (Luo, Dan, and W. Mark Saltzman. "Synthetic DNA delivery systems." Nature biotechnology 18.1 (2000): 33-37.; as cited on the attached 892 form) discloses that the introduction of DNA into mammalian cells are known methods. Church ( US 2018 / 0320226 A1, published Nov. 8, 2018; cited on the 05/04/2022 IDS Document) discloses that DNA comprising a guide RNA recognition sequence is known with “Such DNA binding proteins include RNA-guided DNA binding proteins readily known to those of skill in the art to bind to DNA for various purposes.” ([0048]). Claim 5 recites “wherein the introduced DNA arises from a library of nucleic acids generated by pooled cloning.” Pooled cloning strategies are known as disclosed by Peters (page 123, col. 2, para. 2). (Peters, Jason M., et al. "Bacterial CRISPR: accomplishments and prospects." Current opinion in microbiology 27 (2015): 121-126.; as cited on the attached 892 form) Claim 30 recites : "introducing the DNA into the plurality of cells using a virus. " Luo (Luo, Dan, and W. Mark Saltzman. "Synthetic DNA delivery systems." Nature biotechnology 18.1 (2000): 33-37.; as cited on the attached 892 form) discloses that the use of viral system for DNA delivery is a known method (page 33, col. 1, para. 4). Claim 34 recites : "introducing the DNA into the plurality of cells comprises electroporating the DNA into the plurality of cells." Luo (Luo, Dan, and W. Mark Saltzman. "Synthetic DNA delivery systems." Nature biotechnology 18.1 (2000): 33-37.; as cited on the attached 892 form) discloses that electroporation is a known method (page 34, Table 1) and (page 34, col. 1, para. 5). Claim 76 recites "introducing, into the plurality of mammalian cells, DNA comprising a guide RNA recognition sequence, a reporter portion, and an identification portion comprising read sequences…" Luo (Luo, Dan, and W. Mark Saltzman. "Synthetic DNA delivery systems." Nature biotechnology 18.1 (2000): 33-37.; as cited on the attached 892 form) discloses that the introduction of DNA into mammalian cells are known methods. Church ( US 2018 / 0320226 A1, published Nov. 8, 2018; cited on the 05/04/2022 IDS Document) discloses that DNA comprising a guide RNA recognition sequence is known with “Such DNA binding proteins include RNA-guided DNA binding proteins readily known to those of skill in the art to bind to DNA for various purposes.” ([0048]). The additional elements indicated above 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. The limitations equate to insignificant extra solutional activities. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional. (see MPEP 2106.05(g)). As indicated above, the additional elements are known methods. Luo discloses that the introduction of DNA via electroporation or viral methods are well-known in the art; Peters discloses that pool cloning is also a known method and Church discloses that DNA comprising a guide RNA recognition sequence is known. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No ). As such, claims 1-2, 5, 7-13, 30-31, 34-36, 44, 76 and 180 are not patent eligible. 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 . Claims 1-2, 7-13, 30-31, 34-36, 44 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (Spatially resolved, highly multiplexed RNA profiling in single cells. Science348, aaa6090(2015). DOI:10.1126/science.aaa6090; cited on the 05/04/2022 IDS Document ), in view of Zhang (US 2016/0153005, published Jun. 2, 2016; cited on the 05 / 04 /202 2 IDS Document ). Regarding independent claim 1, Chen teaches the claim limitation of (a) introducing, into the plurality of mammalian cells, DNA comprising a reporter portion, and an identification portion comprising read sequences with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “ We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale) ; Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of (c) determining positions of RNA molecules expressed from the reporter portion of the introduced DNA within the plurality of cells by determining the reporter portions wherein labeled oligonucleotides are hybridized to the expressed RNA and imaged with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of (d) determining a read sequence on the RNA molecules expressed from the introduced DNA comprising the reporter portion and the identification portion within the plurality of cells by exposing the cells to a readout probe able to bind to the read sequence with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of (d) colocalizing the binding of the readout probe with the positions of the RNA molecules expressed from the reporter portion of the introduced DNA with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of (e) repeating (c), (d) and (e) a plurality of times using different read sequences with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of (f) creating codewords corresponding to the binding of the colocalized readout probes, wherein the values of the digits of the codewords are based on the binding of the readout probes to the read sequences and wherein the colocalization improves decoding accuracy for the creating codewords with “We then constructed binary words from the observed fluorescent spots based on their on-off patterns across the 16 hybridization rounds (Fig.2, B to D). If the word exactly matched one of the140 MHD4 code words (exact matches) or differed by only one bit (error-correctable matches), we assigned it to the corresponding RNA species (Fig. 2D). Within the single cell depicted in Fig. 2,A and B, more than 1500 RNA molecules corresponding to 87% of the 130 encoded RNA species were detected after error correction (Fig. 2E).” (page aaa6090-2, col. 2, para. 3) Chen does not teach claim 1 (a) DNA comprising a guide RNA recognition sequence and claim 1 (b) determining the phenotype, following expression of the guide RNA sequence, of the population of cells. However, these limitations are taught by Zhang. Zhang teaches the claim limitation of (a) DNA comprising a guide RNA recognition sequence with “Aspects of the invention relate to Cas9 enzymes having improved liver-targeting specificity in a CRISPR-Cas9 system having guide RNAs having optimal activity, smaller in length than wild-type Cas9 enzymes and nucleic acid molecules coding therefor, and chimeric Cas9 enzymes, as well as methods of improving the targeting specificity of a Cas9 enzyme or of designing a CRISPR-Cas9 system comprising designing or preparing guide RNAs having optimal activity and/or selecting or preparing a Cas9 enzyme having a smaller size or length than wild-type Cas9 whereby packaging a nucleic acid coding therefor into a delivery vector is more advanced as there is less coding therefor in the delivery vector than for wild-type Cas9, and/or generating chimeric Cas9 enzymes.” ([0010]). Zhang teaches the claim limitation of (b) determining the phenotype, following expression of the guide RNA sequence, of the population of cells with “As discussed elsewhere, we have been able to show, in vivo, that phenotypic change can be detected. This is a significant step forward as a deficiency often leveled at RNAi is that no lasting effect is seen. With the present invention, phenotypic change can be seen in the liver for the first time.” ([0010]) and “What was particularly encouraging was that not only was a genotypic change seen in a “gold-standard” gene for liver such as ApoB, but phenotypic changes were also recorded. Previous work with PCSK9 had shown genotypic, but not phenotypic changes, so the phenotypic changes seen with ApoB validate the plausibility of CRISPR delivery to, and its ability to effect phenotypic change in, the Liver. This is in combination with the more therapeutically acceptable means of delivery ( i.v. compared to hydrodynamic delivery). As such, viral delivery of CRISPR-Cas9 system (guide and Cas9) is preferred, especially intravenously).” ([0247]). It would have been prima facia obvious to combine the teachings of Chen and Zhang to arrive at the claimed invention. A person of ordinary skill in the art would have been motivated to modify the method of Chen to include a guide RNA as taught by Zhang for the purpose of directing sequence-specific binding to the target sequence . Furthermore, there would have been a reasonable expectation of success, since both Chen and Zhang teach methods that pertain to the analysis and detection of nucleic acid sequences. Regarding claim 2, Chen teaches the claim limitation of identifying the guide portion for individual cells based on the created codewords with “We then constructed binary words from the observed fluorescent spots based on their on-off patterns across the 16 hybridization rounds (Fig.2, B to D). If the word exactly matched one of the140 MHD4 code words (exact matches) or differed by only one bit (error-correctable matches), we assigned it to the corresponding RNA species (Fig. 2D). Within the single cell depicted in Fig. 2, A and B, more than 1500 RNA molecules corresponding to 87% of the 130 encoded RNA species were detected after error correction (Fig. 2E).” (page aaa6090-2, col. 2, para. 3). Regarding claim 9, Chen teaches wherein each read sequence represents a value of a position within a codeword with “We then constructed binary words from the observed fluorescent spots based on their on-off patterns across the 16 hybridization rounds (Fig.2, B to D). If the word exactly matched one of the140 MHD4 code words (exact matches) or differed by only one bit (error-correctable matches), we assigned it to the corresponding RNA species (Fig. 2D). Within the single cell depicted in Fig. 2,A and B, more than 1500 RNA molecules corresponding to 87% of the 130 encoded RNA species were detected after error correction (Fig. 2E).” (page aaa6090-2, col. 2, para. 3); Figure 2 and Figure 2 legend. Regarding claim 10, Chen teaches the claim limitation of wherein the read sequences are determined sequentially with “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Regarding claim 13, Chen teaches the claim limitation of wherein the reporter portion encodes a protein detectable by fluorescence with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Regarding claim 35, Chen teaches the claim limitation of wherein the cells comprise cells in tissue with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Regarding claim 36, Zhang teaches introducing the DNA into the plurality of cells such that at least 50% of the cells contains no more than one type of introduced DNA with “FIG. 62 shows Liver Tissue Slice Immunohistochemistry Staining Image from AAV-CMV-EGFP and AAV-CMV-SaCas9-U6-sgRNA ( Pcsk9 ) injected animal (Verification of SaCas9 protein expression, 2 weeks post injection).” (para. [0179]). Regarding claim 44, Chen teaches wherein for at least some of the created codewords, matching the codeword to valid codewords wherein, if no match is found, either discarding the codeword or applying error correction to the codeword to form a valid codeword with “Fluorescence spots in different hybridization rounds were connected into a single string, corresponding to a potential RNA molecule, if the distance between spots was smaller than 1 pixel(167 nm). For each string of spots, the on-off sequence of fluorescent signals in all hybridization rounds were used to assign a binary word to the potential RNA molecule, in which 1 was as-signed to the hybridization rounds that contained a fluorescent signal above threshold and 0was assigned to the other hybridization rounds. Measured words were then decoded into RNA species by using the 16-bit MHD4 code or the 14-bit MHD2 code discussed in the main text. In the case of the 16-bit MHD4 code, if the measured binary word matched the code word of a specific RNA perfectly or differed from the code word by one single bit, it was assigned to that RNA. In the case of the 14-bit MHD2 code, only if the measured binary word matched the code word of a specific RNA perfectly was it assigned to that RNA. To determine the copy number per cell, the number of each RNA species was counted in in-dividual cells within each 40- by 40-mm imaging area. This number accounts for the majority but not all RNA molecules within a cell because a fraction of the cell could be outside the imaging area or focal depth. Tiling images of adjacent areas and adjacent focal planes could be used to improve the counting accuracy.” (Page aaa6090-11, col. 2, para. 2); “The first sum corresponds to all of the ways in which exactly four mistakes can be made. Similarly, the second and third sums correspond to all of the ways in which exactly three or five mistakes can be made. Equation 5 provides an upper bound for the misidentification rate be-cause not all 3-, 4-, or 5-bit errors produce a word that matches or would be corrected to another legitimate word. Again because the number of1 bits can differ between words, the average mis-identification rate reported in Fig. 1D is calculated as a weighted average of Eq. 5 over the number of words that have m 1 bits.” (Page aaa6090-12, col. 2, para. 2) and “…where the first term represents the probability of observing an exact match of the code word and the second term represents the probability of observing an error-corrected match (with 1-bit error). The values of the per-bit error rate pi foreach RNA species are determined by the specific code word for that RNA and the measured 1→0or 0→1 error rates for each round of hybridization. If the code word of the RNA contains a 1 in the ith bit, then pi is determined from the 1→0 error rate for the ith hybridization round; if the word contains a 0 in the ith bit, pi is determined from the0→1 error rate for the ith hybridization round.” (Page aaa6090-12, col. 3, para. 2). Chen does not teach wherein identities of associated pairs of guide portion and identification portion on the DNA are determined by sequencing ermining based on the measures of difference, individual weightings for individual models of the plurality of models and second individual weightings for individual components of the plurality of components of claim 7; wherein the introduced DNA allows association of the guide portion and identification portion to occur of claim 8; wherein the guide portion further comprises a Cas protein binding sequence of claim 11; wherein the guide portion further comprises a Cas protein binding sequence of claim 12; introducing the DNA into the plurality of cells using a virus of claim 30; wherein the virus is a lentivirus of claim 31; and wherein the virus is a lentivirus of claim 34 . However, these limitations are taught by Zhang . Regarding claim 7, Zhang teaches wherein identities of associated pairs of guide portion and identification portion on the DNA are determined by sequencing with “The CRISPR-Cas system does not require the generation of customized proteins to target specific sequences but rather a single Cas enzyme can be programmed by a short RNA molecule to recognize a specific DNA target. Adding the CRISPR-Cas system to the repertoire of genome sequencing techniques and analysis methods may significantly simplify the methodology and accelerate the ability to catalog and map genetic factors associated with a diverse range of biological functions and diseases. To utilize the CRISPR-Cas system effectively for genome editing without deleterious effects, it is critical to understand aspects of engineering, optimization and cell-type/tissue/organ specific delivery of these genome engineering tools, which are aspects of the claimed invention.” (paragraph [0007]). Regarding claim 8, Zhang teaches wherein the introduced DNA allows association of the guide portion and identification portion to occur with “There exists a pressing need for alternative and robust systems and techniques for nucleic acid sequence targeting with a wide array of applications. Aspects of this invention address this need and provide related advantages. An exemplary CRISPR complex comprises a CRISPR enzyme complexed with a guide sequence hybridized or hybridizable to a target sequence within the target polynucleotide. The guide sequence is linked to a tracr mate sequence, which in turn hybridizes to a tracr sequence.” (Para. [0008]). Regarding claim 11, Zhang teaches wherein the guide portion further comprises a Cas protein binding sequence with “Aspects of the invention relate to Cas9 enzymes having improved liver-targeting specificity in a CRISPR-Cas9 system having guide RNAs having optimal activity, smaller in length than wild-type Cas9 enzymes and nucleic acid molecules coding therefor, and chimeric Cas9 enzymes, as well as methods of improving the targeting specificity of a Cas9 enzyme or of designing a CRISPR-Cas9 system comprising designing or preparing guide RNAs having optimal activity and/or selecting or preparing a Cas9 enzyme having a smaller size or length than wild-type Cas9 whereby packaging a nucleic acid coding therefor into a delivery vector is more advanced as there is less coding therefor in the delivery vector than for wild-type Cas9, and/or generating chimeric Cas9 enzymes.” (Para. [0010]). Regarding claim 12, Zhang teaches wherein the guide portion allows the targeting of the Cas protein to DNA or RNA to perturb the sequence or expression of a gene with “The invention in some embodiments comprehends a method of modifying a genomic locus of interest by minimizing off-target modifications by introducing into a cell containing and expressing a double stranded DNA molecule encoding a gene product of interest an engineered, non-naturally occurring CRISPR-Cas system comprising a Cas protein having one or more mutations and two guide RNAs that target a first strand and a second strand of the DNA molecule respectively, whereby the guide RNAs target the DNA molecule encoding the gene product and the Cas protein nicks each of the first strand and the second strand of the DNA molecule encoding the gene product, whereby expression of the gene product is altered; and, wherein the Cas protein and the two guide RNAs do not naturally occur together.” (para. [0069]). Regarding claim 30, Zhang teaches introducing the DNA into the plurality of cells using a virus with “The invention also provides methods of preparing the vector systems of the invention, in particular the viral vector systems as described herein. The invention in some embodiments comprehends a method of preparing the AAV of the invention comprising transfecting plasmid(s) containing or consisting essentially of nucleic acid molecule(s) coding for the AAV into AAV-infected cells, and supplying AAV rep and/or cap obligatory for replication and packaging of the AAV. In some embodiments the AAV rep and/or cap obligatory for replication and packaging of the AAV are supplied by transfecting the cells with helper plasmid(s) or helper virus(es). In some embodiments the helper virus is a poxvirus, adenovirus, herpesvirus or baculovirus. In some embodiments the poxvirus is a vaccinia virus. In some embodiments the cells are mammalian cells. And in some embodiments the cells are insect cells and the helper virus is baculovirus. In other embodiments, the virus is a lentivirus.” ([0051]) and “Examples include electrical transfection methods (such as electroporation, nucleofection, and single-cell electroporation); chemical transfection methods (such as Ca2+ phosphate co/precipitation and lipofection); viral delivery (such as Adenoviral, Adeno-Associated Virus (AAV), Lentiviral and Herpes Simplex Virus); and physical transfection methods (such as microinjection and biolistics (DNA-coated gold particles). All of these can be used for delivery of the CRISPR-Cas9 system, but lipofection or viral methods are preferred, especially AAV or Lentiviral.” (Para. [0306]). Regarding claim 31, Zhang teaches wherein the virus is a lentivirus with “The invention also provides methods of preparing the vector systems of the invention, in particular the viral vector systems as described herein. The invention in some embodiments comprehends a method of preparing the AAV of the invention comprising transfecting plasmid(s) containing or consisting essentially of nucleic acid molecule(s) coding for the AAV into AAV-infected cells, and supplying AAV rep and/or cap obligatory for replication and packaging of the AAV. In some embodiments the AAV rep and/or cap obligatory for replication and packaging of the AAV are supplied by transfecting the cells with helper plasmid(s) or helper virus(es). In some embodiments the helper virus is a poxvirus, adenovirus, herpesvirus or baculovirus. In some embodiments the poxvirus is a vaccinia virus. In some embodiments the cells are mammalian cells. And in some embodiments the cells are insect cells and the helper virus is baculovirus. In other embodiments, the virus is a lentivirus.” ([0051]) and “Examples include electrical transfection methods (such as electroporation, nucleofection, and single-cell electroporation); chemical transfection methods (such as Ca2+ phosphate co/precipitation and lipofection); viral delivery (such as Adenoviral, Adeno-Associated Virus (AAV), Lentiviral and Herpes Simplex Virus); and physical transfection methods (such as microinjection and biolistics (DNA-coated gold particles). All of these can be used for delivery of the CRISPR-Cas9 system, but lipofection or viral methods are preferred, especially AAV or Lentiviral.” (Para. [0306]). Regarding claim 34, Zhang teaches wherein introducing the DNA into the plurality of cells comprises electroporating the DNA into the plurality of cells with “Examples include electrical transfection methods (such as electroporation, nucleofection, and single-cell electroporation); chemical transfection methods (such as Ca2+ phosphate co/precipitation and lipofection); viral delivery (such as Adenoviral, Adeno-Associated Virus (AAV), Lentiviral and Herpes Simplex Virus); and physical transfection methods (such as microinjection and biolistics (DNA-coated gold particles). All of these can be used for delivery of the CRISPR-Cas9 system, but lipofection or viral methods are preferred, especially AAV or Lentiviral.” (Para. [0306]) and “Plasmids carrying guide sequences are transfected into human embryonic kidney (HEK293T) or human embryonic stem ( hES ) cells, other relevant cell types using lipid-, chemical-, or electroporation-based methods.” (Para. [0830]). It would have been prima facia obvious to combine the teachings of Chen and Zhang to arrive at the claimed invention. A person of ordinary skill in the art would have been motivated to modify the method of Chen to include the method of associating the guide portion and identification portion and a Cas protein binding sequence as taught by Zhang to allow for nucleic acid sequence targeting. A person of ordinary skill in the art would have also been motivated to modify the method of Chen to include introducing the DNA into the plurality of cells using a virus and/or electroporation as taught by Zhang for the purpose of transfecting cells with DNA or the CRISPR-Cas9 system . Furthermore, there would have been a reasonable expectation of success, since both Chen and Zhang teach methods that pertain to the analysis of nucleic acid sequences. Regarding independent claim 76, Chen teaches the claim limitation of introducing, into a plurality of mammalian cells, DNA comprising a guide portion comprising a recognition sequence, a reporter portion, and an identification portion comprising read sequences with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of determining positions of RNA molecules expressed from the reporter portion of the introduced DNA within the plurality of cells by determining the reporter portions wherein labeled oligonucleotides are hybridized to the expressed RNA and imaged with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of determining the read sequences within the plurality of cells by exposing the cells to a plurality of readout probes each able to bind to a read sequence, colocalizing the binding of the readout probes with the positions of the RNA molecules expressed from the reporter portion of the introduced DNA with “We first imaged 140 RNA species in human fibroblast cells using MERFISH with 16 rounds of hybridization and a modified Hamming code capable of both error detection and correction. We obtained ~80% detection efficiency and observed excellent correlation of RNA copy numbers determined with MERFISH with both bulk RNA sequencing data and conventional smFISH measurements of individual genes.” (page 412, col. 3, para. 2, Results); “We labeled each cellular RNA with a set of encoding probes, which contain targeting sequences that bind the RNA and readout sequences that bind fluorescently labeled readout probes. Each RNA species is encoded with a particular combination of read-out sequences. We used successive rounds of hybridization and imaging, each with a different readout probe, to identify the readout sequences bound to each RNA and to decode the RNA.” (page 412, col. 2, para. 2, Rationale); Figure 1 and with Figure 1 legend. Chen teaches the claim limitation of creating codewords corresponding to the binding of the colocalized readout probes, wherein the values of the digits of the codewords are based on the binding of the readout probes to the read sequences and wherein the colocalization improves decoding accuracy for the creating codewords with “We then constructed binary words from the observed fluorescent spots based on their on-off patterns across the 16 hybridization rounds (Fig.2, B to D). If the word exactly matched one of the140 MHD4 code words (exact matches) or differed by only one bit (error-correctable matches), we assigned it to the corresponding RNA species (Fig. 2D). Within the single cell depicted in Fig. 2,A and B, more than 1500 RNA molecules corresponding to 87% of the 130 encoded RNA species were detected after error correction (Fig. 2E).” (page aaa6090-2, col. 2, para. 3) Chen does not teach DNA comprising a guide RNA recognition sequence and wherein the guide portion is operably linked to a first promoter and the reporter portion and identification portion are operably linked to a second promoter in claim 76 . However, th ese limitation s are taught by Zhang. Zhang teaches the claim limitation of DNA comprising a guide RNA recognition sequence with “Aspects of the invention relate to Cas9 enzymes having improved liver-targeting specificity in a CRISPR-Cas9 system having guide RNAs having optimal activity, smaller in length than wild-type Cas9 enzymes and nucleic acid molecules coding therefor, and chimeric Cas9 enzymes, as well as methods of impr