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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/02/2025 was filed before the mailing date of the final. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 8, 10, 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Sogard (US20080009071A1 published 01/10/2008) in view of Peter et al (US20150148239A1 published 05/28/2015; hereinafter Peter).
Regarding claim 1, Sogard teaches an apparatus comprising:
(a) a flow cell comprising (suitable container, for example, a dish or a flow cell – paragraph 37) (i) a top solid support (a top of the container with an inlet and outlet – Fig. 1) and (ii) a bottom solid support (a bottom of the container housing a microarray – Fig. 1), wherein the flow cell is configured to be opened and taken apart (the container is capable of being disassembled – paragraphs 49-50); and
(b) the bottom solid support is configured to accommodate a tissue section (the bottom of the container is capable of accommodating a tissue section – Fig. 1), wherein the top solid support or the bottom solid support comprises a pattern of discrete features (an oligonucleotide array – paragraph 15), wherein a feature (a left side of the oligonucleotide array – paragraph 15) in the pattern of discrete features comprises a plurality of nucleic acid capture probes (the left side of the oligonucleotide array comprising probes for performing hybridization assay between a target nucleic acid molecule – paragraph 16 and Fig. 1),
wherein a nucleic acid capture probe of the plurality comprises i) a spatial tag sequence (a portion of the attached oligonucleotide probe with different, known sequences, at discrete, known locations – paragraph 15), and ii) a target capture sequence (the portion of the oligonucleotide probe that binds with the singular target molecule – paragraph 16), the same spatial tag sequence corresponding to a unique location on the top solid support or the bottom solid support (the bottom of the container comprising the array of oligonucleotide probes with different, known sequences, at discrete, known locations – paragraph 15).
However, Sogard does not teach wherein the spatial tag sequence is distinct from the target capture sequence, and the target capture sequence is common to all the nucleic acid capture probes on the top solid support or the bottom solid support.
Peter teaches a method for analyzing a sample comprising an array of spatially addressed features wherein the spatial tag sequence (a unique barcode sequence associating it with that feature on the array – paragraph 6 and 44 and Fig. 2) is distinct from the target capture sequence (an oligonucleotide may act as a primer for reverse transcription of target RNA in the sample – Fig. 2 and paragraphs 43 and 73),
wherein the plurality of nucleic acid capture probes at the feature comprise the same spatial tag sequence corresponding to a unique location (a feature – Fig. 2) on the top solid support (the same barcode sequence located at a feature – paragraph 6 and Fig. 2) or the bottom solid support and the target capture sequence is common to all the nucleic acid capture probes on the top solid support or the bottom solid support (the same reverse primer for the entire array – Fig. 2 and paragraph 73). Peter teaches to use the molecular barcode to identify the location of the oligonucleotide on the array, i.e., in which "feature" the oligonucleotide is present (paragraph 59).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the device, as taught by Sogard, with the molecular barcode and array, taught by Peter, to gain the ability to identify the location of the oligonucleotide on the array, i.e., in which "feature" the oligonucleotide is present (paragraph 59).
Regarding claim 8, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the bottom solid support comprises the plurality of nucleic acid capture probes (the bottom of the container with a microarray of covalently attached oligonucleotide probes – Sogard paragraphs 15-16 and Fig. 1).
Regarding claim 10, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the feature in the pattern of discrete features is selected from the group consisting of: beads, wells (the bottom of the container is a well with a microarray of covalently attached oligonucleotide probes – Sogard paragraphs 15-16 and Fig. 1), channels, raised regions , and posts, and wherein the features in the pattern of discrete features have an average pitch of less than 1 micron (Oligonucleotide arrays preferably have a density of at least one million or at least 10 million features per square cm – paragraph 30) (a density of at least one million features per square cm has a spacing less than 1 micron)(a density of at least 10 million features per square cm has a spacing less than 0.31 micron).
Regarding claim 14, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the nucleic acid capture probe further comprises a primer binding site ("Target" refers to a nucleic acid molecule or protein that has an affinity for a given probe – Sogard paragraph 34).
Regarding claim 15, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the bottom solid support comprises fiducial markers (These tags can be radioactive, fluorescent, or luminescent, for example – Sogard paragraph 3) (a fluorescent or luminescent of the microarray is interpreted under BRI as a fiducial marker).
Regarding claim 16, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the bottom solid support comprises a gel coating (the container holds samples such as whole blood, peripheral blood lymphocytes or PBMC, skin, hair or semen – Sogard paragraph 52) (the samples are interpreted under BRI to read on the limitation gel coating).
Regarding claim 17, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the flow cell is a sequencing flow cell (the suitable container or flow cell is capable of being used for sequencing – Sogard paragraph 37).
Regarding claim 18, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the tissue section is a fresh-frozen tissue section (Per MPEP 2115 inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims) (the suitable container or flow cell is capable of holding a fresh-frozen tissue section – Sogard paragraph 37).
Regarding claim 19, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the tissue section is a fixed tissue section (Per MPEP 2115 inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims) (the suitable container or flow cell is capable of holding a fixed tissue section – Sogard paragraph 37).
Regarding claim 20, Sogard, modified by Peter, teaches the apparatus of claim 1, wherein the tissue section is from a plant, a nematode, a fish, or a mammal (Per MPEP 2115 inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims) (the suitable container or flow cell is capable of holding a tissue section from a plant, a nematode, a fish, or a mammal – Sogard paragraph 37).
Claims 2-4, 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Sogard, modified by Peter, in view of Silva et al (US20030134410A1 published 07/17/2003; hereinafter Silva).
Regarding claim 2, Sogard, modified by Peter, teaches the apparatus of claim 1.
However, Sogard, modified by Peter, does not further comprising a spacer disposed between the top solid support and the bottom solid support.
Silva teaches a hybridization chamber with arrays of oligonucleotide probes further comprising a spacer (a first adhesive layer 15 such as double-sided adhesive tape – paragraph 102) disposed between the top solid support and the bottom solid support (the first adhesive layer 15 is between and attaches a substrate 11 to a flexible layer 16 – Figs. 1A-B and paragraph 99). Silva teaches to use double-sided adhesive tape so that it can be die cut from a sheet of adhesive material (paragraph 102) with a geometries that eliminate corners to prevent bubble formation in the device (paragraph 100).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the construction of the container, as taught by Sogard as modified by Peter, with the double-sided adhesive tape between two substrates, to gain a geometries that eliminate corners to prevent bubble formation in the device.
Regarding claim 3, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 2, wherein the spacer comprises one or more openings (one or more first notches 70 are cut into first adhesive layer 15 – Silva paragraph 99).
Regarding claim 4, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 3, wherein the one or more openings comprise one or more fluidic channels (one or more first notches 70 are connected to area 14 bounded by the adhesive layer 15 – Silva Figs. 1A-B and paragraph 99).
Regarding claim 21, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 2, comprising one or more adhesives that connect the top solid support and the bottom solid support of the flow cell (the first adhesive layer 15 is a double sided tape that contains an adhesive connecting the substrate 11 to the flexible layer 16 – Silva Figs. 1A-B and paragraph 99).
Regarding claim 22, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 21, wherein an adhesive of the one or more adhesives is disposed between the spacer and the top solid support (the first adhesive layer 15 is a double sided tape that contains an adhesive between the first adhesive layer 15 and the substrate 11– Silva Figs. 1A-B and paragraph 99).
Regarding claim 23, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 21, wherein an adhesive of the one or more adhesives is disposed between the spacer and the bottom solid support (the first adhesive layer 15 is a double sided tape that contains an adhesive between the first adhesive layer 15 and the flexible layer 16 – Silva Figs. 1A-B and paragraph 99).
Regarding claim 24, Sogard, as modified by Peter modified by Silva, teaches the apparatus of claim 21, wherein a first adhesive of the one or more adhesives is disposed between the spacer and the top solid support (the first adhesive layer 15 is a double sided tape that contains an adhesive on a first side between the first adhesive layer 15 and the substrate 11– Silva Figs. 1A-B and paragraph 99) and a second adhesive of the one or more adhesives is disposed between the spacer and the bottom solid support (the first adhesive layer 15 is a double sided tape that contains an adhesive on a second side between the first adhesive layer 15 and the flexible layer 16 – Silva Figs. 1A-B and paragraph 99).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Sogard, modified by Peter, in view of Cao et al (US Pat No. 6,794,138 B1 published 09/21/2004; hereinafter Cao)
Regarding claim 12, Sogard, modified by Peter, teaches the apparatus of claim 1.
However, Sogard, modified by Peter, does not teach wherein the target capture sequence comprises a poly(T) sequence.
Cao teaches methods for the amplification of nucleic acids wherein the target capture sequence comprises a poly(T) sequence (a second oligonucleotide sequence with the poly d(T) – column 6 lines 5-7 and Fig. 1). Cao teaches to use the second oligonucleotide sequence with the poly d(T) so that a functional promoter operably linked to the target sequence (Fig. 1 and column 6 lines 10-11).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the oligonucleotide sequences, as taught by Sogard as modified by Peter, with the oligonucleotide sequence with the poly d(T), taught by Cao, to gain the ability to link a functional promoter to the target sequence. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Sogard, Peter, Cao teaches amplification reactions for sample analysis.
Response to Arguments
Applicant's arguments filed 12/02/2025 have been fully considered but they are not persuasive.
Point 1: The applicant’s argument that “there is no teaching or suggestion in Sogard that a portion of the oligonucleotide probe includes "different, known sequences, at discrete, known locations" while another, distinct portion of the same oligonucleotide binds with the singular target molecule”” is not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., “distinct spatial tag and capture sequences in the same oligonucleotide”) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant’s addition arguments with respect to the 103 rejections of the claims have been considered, and the prior art rejection has been modified in order to address the amended claim language.
Conclusion
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.
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/T.C.S./Examiner, Art Unit 1796
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798