CTFR 17/393,994 CTFR 97752 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 canceled claims 4-5, 7-9, 11, 13-21, 25-26, 28-30, 32, 35-39, 41, 43, 45, 47, 49, 52-60, 63-73, 76-79 and 83-84. Claims 1-3, 6, 10, 12, 22-24, 27, 31, 33-34, 40, 42, 44, 46, 48, 50-51, 61-62, 74-75, 80-82 and 85-88 are currently pending and under examination. Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is Final . Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claims 31, 33 and 62 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. 07-34-05 AIA Claim 31 recites the limitation " the first detectable probe " in line 1 . There is insufficient antecedent basis for this limitation in the claim. 07-34-05 AIA Claim 31 recites the limitation " the second detectable probe " in line 2 . There is insufficient antecedent basis for this limitation in the claim. 07-34-05 AIA Claim 33 recites the limitation " the first detectable probe " in lines 2-3 . There is insufficient antecedent basis for this limitation in the claim. 07-34-05 AIA Claim 33 recites the limitation " the second detectable probe " in line 3 . There is insufficient antecedent basis for this limitation in the claim. Claim 62 depends from claim 33 and is therefore included in this rejection. 07-34-05 AIA Claim 62 recites the limitation “ the labeled capture molecule ” in line 2 . There is insufficient antecedent basis for this limitation in the claim. 07-36 AIA The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claims 6 - 7 and 62 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 6 recites the limitation “capturing an image of the sample on the fixed addressable array”, Claim 7 recites the limitation “detecting comprises imaging the copied capture molecule” and Claim 66 recites the limitation “detecting the labeled capture molecule”. Independent claim 1 requires the sample to be imaged while remaining immobilized at their respective x, y positions on the fixed addressable array, detecting the capture molecules that are labeled dNTPs as well as the detecting comprises said imaging while remaining immobilized at their respective x, y positions on the fixed addressable array, therefore dependent claims 6 and 7 do not further limit the scope of claim 1. Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (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. 07-15 AIA Claim s 1, 3, 6, 10, 12, 22-24, 27, 31, 33-34, 40, 44, 46, 48, 50-51, 61-62, 74-75, 80-82 and 85-88 are rejected under 35 U.S.C. 102 ( a)(1) and (a)(2 ) as being anticipated by So et al. (WIPO International Application Publication WO 2017/019456 A2, published February 02, 2017). This is a new rejection as necessitated by amendments . Regarding claim 1, So teaches a method of spatial and/or temporal transcriptomic and proteomic processing of a sample comprising a plurality of cells (Abstract, Page 1, [0002], Page 10, [0088], Page 20, [00120] and Page 80, [00381]). So teaches contacting the sample with one or more barcoded recognition molecules, wherein each of the one or more barcoded recognition molecules comprises an antibody specific for an epitope in a cell of the sample, and the antibody is coupled to an antibody-specific barcode (Page 9, [0085]-[0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So teaches depositing the sample on a fixed addressable array, wherein the fixed addressable array comprises a plurality of array probes (Pages 21-22, [00124]-[00125], Pages 31-32, [00159], Page 40, [00191] and Page 63, [00292]). So teaches each array probe comprising a capture molecule and a spatial barcode and each spatial barcode defines a unique x, y position of each array probe in the fixed addressable array (Page 9, [0085]-[0086], Page 12, [0098] and Page 23-24, [00131]-[00133]). So teaches operatively coupling material from the sample to the plurality of array probes of the fixed addressable array, thereby capturing the material from the sample with the capture molecule and linking the operatively coupled material from the sample with an x, y position in the fixed addressable array (Page 9, [0085]-[0086], Page 12, [0098] and Page 23-24, [00131]-[00133]). So teaches the material from the sample comprises one or more sample polynucleotides and one or more barcoded recognition molecules (Page 9, [0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So teaches copying the operatively coupled material on the fixed addressable array, thereby forming copied captured molecules, and the copied captured molecules comprise one or more copied sample polynucleotide and one or more copied barcoded recognition molecule barcode (Page 12, [0098], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches wherein the copied captured molecules are synthesized oligonucleotides complementary to the one or more captured sample polynucleotide and the one or more captured barcoded recognition molecule barcode (Page 12, [0098], Page 16, [00109], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules (Pages 125-127, [00600]-[00603]). So teaches each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode (Page 15, [00106], Pages 16-17, [00109]-[00110], Page 57, [00257] and [00263], Page 76, [00359], Page 130, [00609], Page 9, [0085]-[0086], Page 12, [0098] and Page 23-24, [00131]-[00133]). So teaches detecting the copied captured molecules, detecting the copied captured molecules comprises specifically binding a detectable probe to a copied barcoded recognition molecule barcode (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array (Page 123, [00594] and Pages 124-127, [00598]-[00601]). Regarding claim 3 , So teaches the sample polynucleotide is DNA or RNA or comprises DNA, RNA, or both (Page 9, [0086] and Pages 18-19, [00114]). Regarding claim 6, So teaches capturing an image of the sample on the fixed addressable array (Page 123, [00594] and Pages 124-127, [00598]-[00601]). Regarding claim 7, So teaches detecting comprises imaging the copied capture molecule (Page 123, [00594] and Pages 124-129, [00597]-[00606]). Regarding claim 10, So teaches annotating regions of the image of the sample (Pages 15-16, [00107]-[00108], Page 123, [00594] and Pages 124-129, [00597]-[00606]). Regarding claim 12 , So teaches assigning a cell type, cell state, or both to cells in the sample, staining the sample, recording the morphology of the stained sample, permeabilizing the sample, or any combination thereof (Pages 21-22, [00125]). Regarding claim 22 , So teaches specifically binding a concatemer to a copied barcode recognition molecule, copied sample polynucleotide, or both (Pages 20-21, [00121] and [00124], and Pages 38-39, [00187]-[00190]). Regarding claim 23 , Shah teaches the capture molecule is removed prior to detecting the copied captured molecule (Page 78, [00372] and Page 82, [00388]). Regarding claim 24 , So teaches copying the captured molecule comprises synthesizing a complementary strand from the array probe using the captured molecule (Page 6, [0052], Page 12, [0098], Page 16, [00109], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). Regarding claim 27 , So teaches preparing a cDNA library from the captured molecule and preparing the cDNA library comprises preparing a cDNA library PCR product, or both from the copied captured molecule (Page 22, [00127]-[00128], Pages 25-26, [00141]-[00142], Pages 42-43, [00202]-[00203] and Figs. 22-28). Regarding claim 31 , So teaches the first detectable probe comprises a first label and the second detectable probe comprises a second label and wherein the first label and the second label are different (Page 1, [0003]-[0004], Page 12, [0098], Page 88, [00425], Pages 123, [00594], Page 124, [00597] and Pages 125-126, [00600]). Regarding claim 33 , So teaches the detectable label on the capture molecule is different than the first label or the second label present on the first detectable probe or second detectable probes (Page 1, [0003]-[0004], Page 12, [0098], Page 88, [00425], Pages 123, [00594], Page 124, [00597] and Pages 125-126, [00600]). Regarding claim 34 , So teaches releasing the copied captured molecule from the fixed addressable array prior to generating a cDNA library, PCR product, or both (Figs. 28-30). Shah teaches sequencing the cDNA library, PCR product, or both (Figs. 22-28). Regarding claim 40 , So teaches correlating each of the cDNA molecules in the cDNA library, each PCR product, or both to a position in the sample on the fixed addressable array (Page 9, [0085], Pages 18-19, [00114], Page 21, [00124] Pages 22-23, [00127]-[0128] and Page 30, [00154]). Regarding claim 44 , So teaches sequencing the operatively coupled material (Page 10, [0089]). Regarding claim 46 , So teaches the fixed addressable array further comprises a substrate (Page 9, [0085]). So teaches the plurality of array probes of the fixed addressable array are coupled to the substrate (Page 9, [0085]). So teaches the substrate comprises a solid substrate, a semi- solid substrate, a liquid substrate, or a hydrogel (Page 13, [00100]-[00101] and Page 16, [00110]). Regarding claim 48 , So teaches the substrate comprises a polymer, wherein the polymer forms a layer on a surface of the substrate, and wherein the plurality of array probes are coupled to the polymer (Page 13, [00100]-[00101] and Page 72, [00338]). Regarding claim 50, So teaches the substrate comprises an optically transparent material (Page 13, [00100]-[00101]). Regarding claim 51 , So teaches releasing the plurality of array probes from the substrate and the releasing comprises cleaving a cleavable linker on each array probe of the plurality of array probes (Page 32, [00160]). Regarding claim 61 , So teaches detecting the copied sample polynucleotides, labeled dNTPs, the copied captured molecule, or any combination thereof comprises in-situ sequencing, laser scanning, fluorescent microscopy, DNA microscopy, FISH, smFISH, in situ PCR, or any combination thereof (Page 9, [0086]). Regarding claim 62 , So teaches detecting the labeled capture molecule (Page 1, [0003]-[0004], Page 123, [00594] and Pages 124-127, [00598]-[00601]). Regarding claim 74, So teaches one or more array probes comprises an oligonucleotide sequence (Pages 19-20, [00118]). Regarding claim 75, So teaches the capture molecule(s), the target molecule(s), or both comprises a Tn5 sequence, a 16S sequence, a poly(d)T sequence, a poly(d)A, sequence a random hexamer sequence, a trypsin molecule, an antibody, an aptamer, a Protein Epitope Signature Tag (PrEST) sequence, a DNA sequence or structural variation, or any combination thereof (Page 122, [00585]-[00587]). Regarding claim 80, So teaches operatively coupling material from the sample comprises directly capturing material from the sample by the capture molecule of the array probe that is in spatial proximity to the captured material (Page 50, [00228]). Shah teaches capturing a sample polynucleotide by hybridizing the sample polynucleotide to the capture molecule of the array probe that is in spatial proximity to the sample polynucleotide or binding a labeled recognition molecule to a target present in the sample (Page 61, [00283]). Regarding claim 81 , So teaches operatively coupling material from the sample comprises indirectly capturing material from the sample by a capture molecule of an array probe that is in spatial proximity to the captured material (Pages 46-47, [00218]). So teaches specifically binding a barcoded recognition molecule to a target present in the sample, wherein the barcoded recognition molecule comprises a recognition molecule barcode (Page 12, [0098]). So teaches capturing the barcoded recognition molecule barcode by the capture molecule of the array probe that is in spatial proximity to the target (Page 12, [0098] and Pages 21-22, [00124]). Regarding claim 82 , So teaches a method of spatial and/or temporal transcriptomic and proteomic processing of a sample comprising a plurality of cells (Abstract, Page 1, [0002], Page 10, [0088], Page 20, [00120] and Page 80, [00381]). So teaches contacting the sample with one or more barcoded recognition molecules, wherein each of the one or more barcoded recognition molecules comprises an antibody specific for an epitope in a cell of the sample, and the antibody is coupled to an antibody-specific barcode (Page 9, [0085]-[0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So teaches depositing the sample on a fixed addressable array or a decoded bead array (Pages 21-22, [00124]-[00125], Page 22-23, [0128], Pages 28-29, [00146]-[00147], Pages 31-32, [00159], Page 40, [00191] and Page 63, [00292]). So teaches operatively coupling material from the sample to a plurality of array probes of the fixed addressable array or to a plurality of bead probes of the decoded bead array, thereby capturing the material from the sample with a capture molecule and linking the operatively coupled material from the sample with an x, y position in the fixed addressable array or the decoded bead array (Page 9, [0085]-[0086], Page 12, [0098], Page 22-23, [0128], Pages 28-29, [00146]-[00147], and Page 23-24, [00131]-[00133]).). So teaches the material from the sample comprises one or more sample polynucleotides and one or more barcoded recognition molecules (Page 9, [0085]-[0086], Page 12, [0098] and Page 23-24, [00131]-[00133]). So teaches copying the operatively coupled material on the fixed addressable array or decoded bead array, thereby forming copied captured molecules, wherein the copied captured molecules comprise one or more copied sample polynucleotide and one or more copied barcoded recognition molecule barcode (Page 12, [0098], Pages 20-21, [00121]-[00122], Page 22-23, [0128], Pages 28-29, [00146]-[00147], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches the copied captured molecules are synthesized oligonucleotides complementary to the one or more captured sample polynucleotide and the one or more captured barcoded recognition molecule barcode (Page 12, [0098], Page 16, [00109], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules and each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode (Page 15, [00106], Pages 16-17, [00109]-[00110], Page 57, [00257] and [00263], Page 76, [00359], Page 130, [00609], Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133] and Pages 125-127, [00600]-[00603]). So teaches detecting the copied captured molecules (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches detecting comprises specifically binding a detectable probe to a copied barcode recognition molecule barcode and imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280], Page 130, [00609], Page 123, [00594] and Pages 124-127, [00598]-[00601]). Regarding claim 85, So teaches a method of spatial and/or temporal transcriptomic and proteomic processing of a sample comprising a plurality of cells (Abstract, Page 1, [0002], Page 10, [0088], Page 20, [00120] and Page 80, [00381]). So contacting the sample with one or more barcoded recognition molecules, and each of the one or more barcoded recognition molecules comprises an antibody specific for an epitope in a cell of the sample and the antibody is coupled to an antibody-specific barcode (Page 9, [0085]-[0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So teaches depositing the sample on a decoded bead array (Page 31, [0159], Page 22-23, [0128] and Pages 28-29, [00146]-[00147]). So teaches the decoded bead array comprises a plurality of conductive beads comprising a plurality of bead probes, each comprising a target molecule and a spatial barcode (Page 11, [0093], Page 13, [00100], Page 25, [0138], Pages 25-29, [0140]-[0149], Page 40, [0191], Pages 44-46, [00213]-[00214], Page 47, [00220], Pages 50-51, [00228]-[00229], Page 12, [0098], and Pages 80-81, [00381]-[00383]). So teaches the plurality of conductive beads are transiently fixed in spatial position to a first side of the decoded bead array by an electromagnetic field applied to a second side of the decoded bead array and wherein the first side and the second side are opposite sides of the decoded bead array (Page 49, [00464] and Page 11, [0093]). So teaches operatively coupling material from the sample to a plurality of bead probes of the decoded bead array and capturing the material from the sample with a capture molecule and linking the operatively coupled material from the sample with an x, y position in the decoded bead array (Pages 22-25, [00128]-[00138]). So teaches the material from the sample comprises one or more sample polynucleotides and one or more barcoded recognition molecules (Page 9, [0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So teaches copying the operatively coupled material on the decoded bead array, thereby forming a copied captured molecules, wherein the copied captured molecules comprise one or more copied sample polynucleotide and one or more copied barcoded recognition molecule (Page 12, [0098], Page 16, [00108],Page 17, [00112], Pages 20-21, [00121]-[00122], Page 22-23, [0128], Pages 28-29, [00146]-[00147]Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches the copied captured molecules are synthesized oligonucleotides complementary to the one or more captured sample polynucleotide and the one or more captured barcoded recognition molecule barcode (Page 12, [0098], Page 16, [00109], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules and each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode (Page 15, [00106], Pages 16-17, [00109]-[00110], Page 57, [00257] and [00263], Page 76, [00359], Page 130, [00609], Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133] and Pages 125-127, [00600]-[00603]). So teaches detecting the copied captured molecules (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280] and Page 130, [00609]). So teaches detecting comprises specifically binding a detectable probe to a copied barcode recognition molecule barcode and imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280], Page 130, [00609], Page 123, [00594] and Pages 124-127, [00598]-[00601]). Regarding claim 86 , So teaches operatively coupling material from the sample comprises directly capturing material, indirectly capturing material, or both from the sample by a capture molecule of an array probe that is in spatial proximity to the captured material, thereby linking the captured material from the sample with an x, y position in the decoded bead array (Pages 22-25, [00128]-[00138] and Page 12, [0098]). So teaches directly capturing material from the sample comprises capturing a sample polynucleotide by hybridizing the sample polynucleotide to the capture molecule of the array probe that is in spatial proximity to the sample polynucleotide or binding a labeled recognition molecule to a target present in the sample (Page 12, [0098], Page 16, [00109], Page 22, [00127] and Pages 82-83, [00392]). So teaches indirectly capturing material from the sample comprises specifically binding a barcoded recognition molecule to a target present in the sample, wherein the barcoded recognition molecule comprises a recognition molecule barcode (Pages 9-10, [0085]-[0091], Page 16, [00109], Pages 46-47, [00218] and Page 12, [0098]). So teaches capturing the barcoded recognition molecule barcode by the capture molecule of the array probe that is in spatial proximity to the target (Pages 9-10, [0085]-[0091] and Page 12, [0098]). Regarding claim 87, So teaches operatively coupling the material from the sample to the bead array comprises depositing the sample comprising a plurality of cells on the decoded array and allowing at least some of the plurality of conductive beads to each couple to one or more of the plurality of cells (Page 20, [00120], Pages 22-23, [00128] and Pages 28-29, [00146]-[00147]). Regarding claim 88, So teaches contacting the sample with one or more barcoded recognition molecules and operatively coupling material from the sample to the plurality of array probes of the fixed addressable array are performed under identical reaction conditions (Page 10, [0089] and Page 54 [00244]). So teaches each and every limitation of claims 1, 3, 6, 10, 12, 22-24, 27, 31, 33-34, 40, 44, 46, 48, 50-51, 61-62, 74-75, 80-82 and 85-88 and therefore So anticipates claims 1, 3, 6, 10, 12, 22-24, 27, 31, 33-34, 40, 44, 46, 48, 50-51, 61-62, 74-75, 80-82 and 85-88 . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claims 2 and 42 are r ejected under 35 U.S.C. 103 as being unpatentable over S o et al. (WIPO International Application Publication WO 2017/019456 A2, published February 02, 2017) as applied to claims 1, 3, 6, 10, 12, 22-24, 27, 31, 33-34, 40, 44, 46, 48, 50-51, 61-62, 74-75, 80-82 and 85-88 above, in view of Shah et al. (WIPO International Publication 2020/123319 A2, published June 6, 2020, previously cited in Office Action January 24, 2025). This is a new rejection as necessitated by amendments. R egarding claim 2, Shah teaches correlating the operatively coupled material to a position in the sample on the fixed addressable array (Page 9, [0085], Pages 18-19, [00114], Page 21, [00124] Pages 22-23, [00127]-[0128] and Page 30, [00154]). Regarding claim 42 , So teaches the capture molecule comprises a polynucleotide guided nucleic acid targeting system or molecule thereof, an antibody or fragment thereof, an aptamer, or a combination thereof (Page 17, [00111] and Page 9, [0086]). So does not teach or suggest correlating comprises assigning pixel coordinates to an image of the sample, an image of the copied captured molecule and coordinating the assigned pixel coordinates to the x,y position in the fixed addressable array. So does not teach or suggest the polynucleotide guided nucleic acid targeting system or molecule thereof is a CRISPR-Cas system. Shah teaches a method of spatial and/or temporal transcriptomic and proteomic processing of a sample comprising a plurality of cells comprising depositing the sample comprising a plurality of cells on a fixed addressable array (Page 60, Lines 11-13 and Page 97, Line 30—Page 97, Line 3, Page 4, Lines 5-11, Page 96, Line 34, Page 115, Lines 26-27, Page 212, Lines 29-32, Page 257, Line 21, Page 258, Line 21 and Page 340, Lines 11-34). Shah teaches an analyte binding moiety of the analyte capture agent that can include an antibody or an epitope binding fragment thereof (Page 90, Lines 5 and Lines 14-20). Shah teaches a capture agent barcode domain that includes an analyte binding moiety barcode and an analyte capture sequence, where the term "analyte binding moiety barcode" refers to a barcode that is associated with or otherwise identifies the analyte binding moiety and that binding moiety may be an antibody ( i.e., different than a spatial barcode, Page 93, Lines 3-20). Shah teaches by identifying an analyte binding moiety and its associated analyte binding moiety barcode, the analyte to which the analyte binding moiety binds can also be identified (Page 93, Lines 6-8). Shah teaches the fixed addressable array comprising a plurality of array probes, each array probe comprising a capture molecule and a spatial barcode, wherein each spatial barcode defines a unique x,y position of each array probe in the fixed addressable array (Page 4, Lines 5-11). Shah teaches the operatively coupling material from the sample to the plurality of array probes of the fixed addressable array, thereby capturing the material from the sample with the capture molecule and linking the operatively coupled material from the sample with an x,y position in the fixed addressable array (Fig. 26 and Example 2). Shah teaches material from the sample comprises one or more sample polynucleotides and one or more barcoded recognition molecule (Page 315, Lines 3-8, Page 311, Lines 22-32, Page 67, Lines 21-26, Page 83 Lines 1-4 and Page 85, Lines 5-8). Shah teaches copying operatively coupled material thereby forming a copied captured molecule, wherein the copied captured molecule is a copied sample polynucleotide and a copied barcoded recognition molecule barcode (Page 97, Lines 9-17, Page 250, Lines 10-19 and Page 255, Lines 13-23). Shah teaches the copied capture molecule are synthesized oligonucleotide complementary to the captured sample polynucleotide and the captured barcoded recognition molecule barcode (Page 97, Lines 9-17, Page 54, Lines 14-27 and Page 122, Lines 18-25). Shah teaches detecting the copied capture molecule wherein detecting the copied capture molecule comprises specifically binding a first detectable probe to a first copied capture molecule corresponding to a first target material and specifically binding at least a second detectable probe to a second copied capture molecule corresponding to a second target material, wherein the second target material is separate and different from the first target material (Page 242, Lines 1-34 and Page 56, Lines 11-12). Shah teaches using polynucleotide guided nucleic acid targeting system or molecule thereof is a CRISPR-Cas system (Page 314, Lines 1-15). Shah teaches correlating the operatively coupled material to a position in the sample on the fixed addressable array (Page 270, Lines 1-34). Shah teaches a resolution of 1 to 10 μm (Page 160, Lines 16-25). Shah teaches correlating comprises assigning pixel coordinates to an image of the sample, an image of the copied captured molecule and coordinating the assigned pixel coordinates to the x,y position in the fixed addressable array (Page 270, Lines 1-34). Shah teaches imaging fluorescence using pixel positions (Page 270, Lines 19-33). Shah teaches assigning pixel coordinates to an image of the sample allows for visualization of probe location as well as excluding errors from alignment analysis (Page 270, Lines 31-33). Shah teaches using a CRISPR-Cas system with capture probes the level of multiplexing capabilities for analyte detection can be improved (Page 136, Lines 21-29). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of So with the teachings of Shah to assign pixel coordinates to an image of the sample, an image of the copied captured molecule and coordinating the assigned pixel coordinates to the x,y position in the fixed addressable array as well as a polynucleotide guided nucleic acid targeting system or molecule thereof is a CRISPR-Cas system. Assigning pixel coordinates to an image of the sample allows for visualization of probe location as well as excluding errors from alignment analysis and using a CRISPR-Cas system with capture probes the level of multiplexing capabilities for analyte detection can be improved as taught by Shah (Page 270, Lines 31-33 and Page 136, Lines 21-29). Double Patenting 08-33 AIA 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 1, 3, 10, 12, 34, 44, 46, 48, 51, 62, and 74-75 are rejected on the grounds of nonstatutory double patenting over claims 1, 2, 4, 6, 8, 11, 12, 14, 16, 17, 18, 22, 23, 25, 27-29, 33-34, 40, 43, 44, 46, 47, 48, 51 of US Patent No. 12,529,092 in view of So et al. (WIPO International Application Publication WO 2017/019456 A2, published February 02, 2017). This is a new rejection as necessitated by amendments. Although the conflicting claims are not identical, they are not patentably distinct from one another. The instant claims are drawn to a method of spatial and/or temporal processing that comprises a sample, comprising a plurality of cells on a fixed addressable array comprising array probes that comprise a capture molecule and spatial barcode that defines a unique x,y, position of the probe in the array; or a decoded bead array comprising conductive beads that are fixed into position in the array by an electromagnetic field and coupling captured sample material to the array probes of the fixed addressable array or the bead probes, thereby linking the operatively coupled material from the sample with an x,y position on either the fixed addressable array or decoded bead array. US Patent No. 12,529,092 claims are drawn to a method of spatial and/or temporal processing of a sample comprising a plurality of cells comprising: depositing a sample comprising a plurality of cells on an array, wherein the array comprises: comprising a capture molecule and a spatial barcode, wherein each spatial barcode defines a unique x,y, position in the array (Claim 1). US Patent No. 12,529,092 claims operatively coupling material from the sample thereby linking the operatively coupled material from the sample with an x,y position in the array (Claim 1). US Patent No. 12,529,092 fails to claim a plurality of array probes as the capture molecule on a fixed addressable, or decoded bead array, that comprises: a plurality of conductive beads comprising a plurality of bead probes, each comprising a target molecule and a spatial barcode, wherein the plurality of conductive beads are transiently fixed in spatial position to a first side of the fixed addressable array by an electromagnetic field applied to a second side of the fixed addressable array and wherein the first side and the second side are opposite sides of the fixed addressable array, wherein the conductive beads are optionally magnetic beads. US Patent No. 12,529,092 fails to claim each of the one or more barcoded recognition molecules comprises an antibody specific for an epitope in a cell of the sample, as well as the antibody is coupled to an antibody-specific barcode. US Patent No. 12,529,092 fails to claim copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules and each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode. US Patent No. 12,529,092 fails to claim detecting the copied captured molecules comprises specifically binding a detectable probe to a copied barcoded recognition molecule barcode and imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array. However, So discloses a plurality of array probes as the capture molecule on a fixed addressable, or decoded bead array, that comprises: a plurality of conductive beads comprising a plurality of bead probes, each comprising a target molecule and a spatial barcode, wherein the plurality of conductive beads are transiently fixed in spatial position to a first side of the fixed addressable array by an electromagnetic field applied to a second side of the fixed addressable array and wherein the first side and the second side are opposite sides of the fixed addressable array, wherein the conductive beads are optionally magnetic beads (Pages 21-22, [00124]-[00125], Page 22-23, [0128], Pages 31-32, [00159], Page 40, [00191], Page 63, [00292], Page 11, [0093], Page 13, [00100], Page 25, [0138], Pages 25-29, [0140]-[0149], Pages 44-46, [00213]-[00214], Page 47, [00220], Pages 50-51, [00228]-[00229], Page 12, [0098], Page 49, [00464], Page 11, [0093] and Pages 80-81, [00381]-[00383]). So discloses each of the one or more barcoded recognition molecules comprises an antibody specific for an epitope in a cell of the sample, as well as the antibody is coupled to an antibody-specific barcode (Page 9, [0085]- [0086], Page 12, [0098], Page 17, [00111] and Page 116, [00560]). So discloses copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules and each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode (Page 15, [00106], Pages 16-17, [00109]-[00110], Page 57, [00257] and [00263], Page 76, [00359], Page 130, [00609], Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133] and Pages 125-127, [00600]-[00603]). So discloses detecting the copied captured molecules comprises specifically binding a detectable probe to a copied barcoded recognition molecule barcode and imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array (Abstract, Page 9, [0085]-[0086], Page 12, [0098], Page 23-24, [00131]-[00133], Pages 20-21, [00121]-[00122], Page 35, [00173], Page 37, [00180], Pages 60-61, [00280], Page 130, [00609], Page 123, [00594] and Pages 124-127, [00598]-[00601]). So discloses using the method described allows for advantageously multiplexing different target nucleic acids in a spatially distinguishable manner (Page 130, [00609]). It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have combine the use of So’s capture probes and antibody-specific barcode, on a fixed addressable array (or bead array) and conductive magnetic capture beads in the method of spatiotemporal processing of a sample of a plurality of cells, as claimed by the instant application and US Patent No. 12,529,092 to allow for multiplexing different target nucleic acids in a spatially distinguishable manner as demonstrated by So. Response to Arguments Applicant’s arguments and amendments filed March 03, 2026, with respect to the rejection under 35 U.S.C. § 103 and the double patenting rejection have been fully considered and are persuasive, therefore these rejections have been withdrawn. However, upon further consideration, new rejections under 35 U.S.C. § 112(b), 112(d), 102 and 103 are made in view of Applicant’s amendments. As discussed above, newly cited So discloses copying the operatively coupled material on the fixed addressable array, thereby forming copied captured molecules and copying the capture molecules comprises incorporating fluorescently-labeled dNTPs into the copied captured molecules. So additionally discloses each copied captured molecule is covalently linked to the capture molecule of the array probe at the unique x, y position of the spatial barcode as well as detecting the copied captured molecules, wherein detecting the copied captured molecules comprises specifically binding a detectable probe to a copied barcoded recognition molecule barcode, and imaging the detectable probe and the labeled dNTPs incorporated into the copied captured molecules while the copied captured molecules remain immobilized at their respective x, y positions on the fixed addressable array. Therefore, for all these reasons, and those listed above, So, as well as So in view Shah are deemed to render the instant invention anticipated/obvious. Conclusion 07-40 AIA Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL . See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached 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 Application/Control Number: 17/393,994 Page 2 Art Unit: 1684 Application/Control Number: 17/393,994 Page 3 Art Unit: 1684 Application/Control Number: 17/393,994 Page 4 Art Unit: 1684 Application/Control Number: 17/393,994 Page 5 Art Unit: 1684 Application/Control Number: 17/393,994 Page 6 Art Unit: 1684 Application/Control Number: 17/393,994 Page 7 Art Unit: 1684 Application/Control Number: 17/393,994 Page 8 Art Unit: 1684 Application/Control Number: 17/393,994 Page 9 Art Unit: 1684 Application/Control Number: 17/393,994 Page 10 Art Unit: 1684 Application/Control Number: 17/393,994 Page 11 Art Unit: 1684 Application/Control Number: 17/393,994 Page 12 Art Unit: 1684 Application/Control Number: 17/393,994 Page 13 Art Unit: 1684 Application/Control Number: 17/393,994 Page 14 Art Unit: 1684 Application/Control Number: 17/393,994 Page 15 Art Unit: 1684 Application/Control Number: 17/393,994 Page 16 Art Unit: 1684 Application/Control Number: 17/393,994 Page 17 Art Unit: 1684 Application/Control Number: 17/393,994 Page 18 Art Unit: 1684 Application/Control Number: 17/393,994 Page 19 Art Unit: 1684 Application/Control Number: 17/393,994 Page 20 Art Unit: 1684 Application/Control Number: 17/393,994 Page 21 Art Unit: 1684 Application/Control Number: 17/393,994 Page 22 Art Unit: 1684 Application/Control Number: 17/393,994 Page 23 Art Unit: 1684 Application/Control Number: 17/393,994 Page 24 Art Unit: 1684 Application/Control Number: 17/393,994 Page 25 Art Unit: 1684 Application/Control Number: 17/393,994 Page 26 Art Unit: 1684
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