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 .
Priority
The present application filed on 02/26/2024, is a 371 of PCT/US 2020/075655, filed on 08/30/2022, and claims benefit of U.S. Provisional Application No. 63/239,379, filed on 08/31/2021.
The limitations recited in instant claims 1-4, 11-12, 26-28, 31, 35, 38-40, 43, 50, 52, and 61 are supported in the original disclosure provided in U.S. Provisional Application No. 63/239,379, filed on 08/31/2021, thus instant claims 1-4, 11-12, 26-28, 31, 35, 38-40, 43, 50, 52 have an effective filing date of 08/31/2021.
The limitation(s) recited in instant claim 5, “detectable moieties comprise an optical moiety, a luminescent moiety, an electrochemically active moiety, a nanoparticle, or a combination thereof, and wherein: the luminescent moiety comprises a chemiluminescent moiety, an electroluminescent moiety, a photoluminescent moiety, or a combination thereof; the photoluminescent moiety comprises a fluorescent moiety, a phosphorescent moiety, or a combination thereof; the fluorescent moiety comprises a fluorescent dye; and/or the nanoparticle comprises a quantum dot” is not supported in the original disclosure provided in U.S. Provisional Application No. 63/239,379, filed on 08/31/2021, thus instant claim 5 has an effective filing date of 02/26/2024.
The limitation(s) recited in instant claim 14, “partitioning the plurality of samples to a plurality of partitions, wherein a partition of the plurality of partitions comprises a single sample of the plurality of samples; and contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents; or (b) contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents; and partitioning the plurality of samples to a plurality of partitions, wherein a partition of the plurality of partitions comprises a single sample of the plurality of samples” is not supported in the original disclosure provided in U.S. Provisional Application No. 63/239,379, filed on 08/31/2021, thus instant claim 14 has an effective filing date of 02/26/2024.
Information Disclosure Statement
Two Information Disclosure Statement(s) (IDS), filed on 06/12/2024 and 10/22/2025, are acknowledged and considered.
Claim Status
Claims 1-5, 11-12, 14, 26-28, 31, 35, 49-40, 43, 50, 52, 61 are pending. Claims 6-10, 13, 15-25, 29-30, 32-34, 36-37, 41-42, 44-49, 51, and 53-60 are cancelled. Claims 1-5, 11-12, 14, 26-28, 31, 35, 39-40, 43, 50, 52, 61 are examined herein below.
Claim Rejections - 35 USC § 112
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.
Claim 50 is 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. For instance, instant claim 50 recites “The method of claim 1, wherein at least two solid support oligonucleotides of a solid support of the plurality of solid comprises an identical capture sequence for binding to one of the reagent-specific sequences, and wherein a solid support oligonucleotide of a first solid support and a solid support oligonucleotide of a second solid support of the plurality of solid supports comprise different capture sequences for binding to two different reagent-specific sequences of the reagent-specific sequences,” which is/are limitation(s) fully recited in independent claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1-5, 11-12, 14, 26-28, 31, 35, 39-40, 43, 50, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamoto et al., (WO 2020159757A1, Pub Date 08/06/2020), as evidenced by see Glezer et al., (Glezer et al., WO2013070990, Date: 05/16/2013, provided in IDS filed on 06/12/2024, FOR Cite No. 711).
Throughout the disclosure, Nakamoto teaches systems, methods, compositions, and kits for quantitative analysis of cellular component targets of cells of interest. Nakamoto teaches embodiments comprising an oligonucleotide associated with a cellular component-binding reagent, which may comprise a protein, an antibody, a tetramer, among others. Nakamoto teaches embodiments where the oligonucleotide associated with a binding reagent is also associated with one or more detectable moieties, which may comprise luminescent moieties, fluorescent moieties, or a phosphorescent moieties, among other. In some embodiments, the presence of the detectable moiety in the binding reagent oligonucleotide enables the cellular component-binding reagent to be employed for both fluorescence analysis and sequence analysis. Nakamoto teaches embodiments comprising one or more solid supports associated with a plurality of oligonucleotide (probes) and which may also be associated with a detectable moiety. Nakamoto teaches reagent oligonucleotides and support oligonucleotides may include sequences, or barcodes, for binding specific target samples and/or associating reagent oligonucleotides with support oligonucleotides (probes).
Regarding claim 1, Nakamoto teaches a method of cellular component quantification comprising: contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents each associated with a reagent oligonucleotide, wherein two of the plurality of cellular component binding reagents are capable of binding to two different cellular components, or two different regions of a cellular component (pg. 5, lines 4-33- pg. 6, lines 1-6), and wherein each reagent oligonucleotide comprises (i) a reagent-specific sequence specific to the cellular component binding reagent associated thereto (pg. 5, lines 4-33- pg. 6, lines 1-6) and (ii) a detection sequence, to obtain cells comprising cellular components bound to cellular component binding reagents of the plurality of cellular component binding reagents (pg.5, lines 4-33- pg. 6, lines 1-6; pg. 8, lines 23-29; and pg. 68, lines 26-33; Fig. 12, component 1224, and Fig. 11 [poly-A tail= detection region); removing cellular component binding reagents of the plurality of cellular component binding reagents not bound to the cells (pg. 106, lines 15-22); contacting reagent oligonucleotides associated with cellular component binding reagents of the plurality of cellular component binding reagents, not removed, with a plurality of solid supports, wherein each of the plurality of solid supports is associated with one or more first detectable moieties, or precursors thereof, and comprises a plurality of solid support oligonucleotides (pg. 106, lines 26-33; pg. 42, lines 14-16; pg. 40, lines 11-33- pg. 41, lines 1-12; pg. 57, lines 9-12; pg. 76, lines 19-33; pg. 8, lines 23-29 and Fig. 11 [poly-A tail = detection sequence] and Fig. 12 [component 1224]), wherein at least two solid support oligonucleotides of a solid support of the plurality of solid supports comprises an identical capture sequence for binding to one of the reagent-specific sequences (pg. 40, lines 11-33), and wherein a solid support oligonucleotide of a first solid support and a solid support oligonucleotide of a second solid support of the plurality of solid supports comprise different capture sequences for binding to two different reagent-specific sequences of the reagent-specific sequences, to obtain reagent oligonucleotides bound to the plurality of solid supports (pg. 38, lines 28-33; pg. 39, lines 1-16; pg. 40, lines 11-33; pg. 41, lines 11-12); contacting the reagent oligonucleotides bound to the plurality of solid supports (1)with a detection oligonucleotide associated with one or more second detectable moieties, or (2) precursors thereof and comprising a binding sequence capable of binding to the detection sequences of the reagent oligonucleotides to obtain reagent oligonucleotides bound to the plurality of solid supports and the detection oligonucleotide (pg.5 lines 4-33- pg. 6, lines 1-6; pg. 8, lines 23-29; pg. 26, lines 24-33- pg. 27, lines 1-6; pg. 42, lines 14-16; pg. 68, lines 26-33; Fig. 1; Fig. 11 [poly-A tail = detection sequence]; Fig. 12, component 1224); and detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports to determine the identity and the quantity, respectively, of each of the cellular components for each of the plurality of samples (pg. 76, lines 19-33; pg. 92, lines 4-20; pg. 94, lines 1-3; pg. 9, lines 30-33 - pg. 10, lines 1-15; pg. 75, lines 11-33; Fig. 1).
Regarding claim 2, Nakamoto teaches a method of cellular component quantification comprising:(a) providing one or more cells from each of a plurality of samples and with cellular components bound to cellular component binding reagents of a plurality of cellular component binding reagents (1) capable of binding to different cellular components, or regions thereof (Abstract, pg. 1, lines 24-33- pg. 2, lines 1-17; pg. 5, lines 5-33- pg. 6, lines 1-6 and lines 25-33; pg. 76, lines 1-31;), and (2) each associated with a reagent oligonucleotide comprising (i) a reagent-specific sequence specific to the cellular component binding reagent associated thereto, and (ii) a detection sequence (Abstract; pg. 1, lines 24-33; pg. 5, lines 5-33- pg. 6, lines 1-6 and lines 25-33; pg. 8, lines 23-29; Fig. 12, component 1224); and for each of the plurality of samples:(b) contacting reagent oligonucleotides, associated with or previously associated with the cellular component binding reagents bound to the cellular components of or from the cells of the sample, with a plurality of solid supports (pg. 106, lines 26-33; pg. 42, lines 14-16; pg. 40, lines 11-33- pg. 41, lines 1-12; Figs. 11-12 (component 1224); pg. 57, lines 9-12), wherein each of the plurality of solid supports is associated with one or more first detectable moieties, or precursors thereof, and comprises a plurality of solid support oligonucleotides, and wherein different solid supports of the plurality of solid supports comprise different capture sequences for binding to different reagent-specific sequences of the reagent oligonucleotides, thereby obtaining reagent oligonucleotides bound to the plurality of solid supports thereof (pg. 40, lines 11-33- pg. 41, lines 1-12); (c) contacting the reagent oligonucleotides bound to the plurality of solid supports with a detection oligonucleotide associated with one or more second detectable moieties, or precursors, and comprising a binding sequence capable of binding to the detection sequences of the reagent oligonucleotides, thereby obtaining reagent oligonucleotides bound to both the plurality of solid supports and the detection oligonucleotide (pg.5 lines 4-33- pg. 6, lines 1-6 and lines 25-33; pg. 8, lines 23-29; pg. 26, lines 24-33- pg. 27, lines 1-6; pg. 42, lines 14-16 ; pg. 68, lines 26-33; pg. 76, lines 1-31, pg. 82, lines 11-16; Fig. 1; and Fig. 12, component 1224); and(d) detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports to determine the identity and the quantity, respectively, of each of the cellular components for each of the plurality of samples (pg. 9, lines 30-33 - pg. 10, lines 1-15; pg. 42, lines 14-16; pg. 92, lines 4-20; pg. 94, lines 1-3; Fig. 1).
Regarding claim 3, Nakamoto further teaches the method of claim 1 wherein determining the identity and the quantity of each of the cellular components for each of the plurality of samples comprises: detecting the presence and/or amount of the one or more first detectable moieties and/or amount of the one or more first detectable moieties (pg. 92, lines 4-20; pg. 94, lines 1-3 - pg. 9, lines 30-33- pg. 10, lines 1-15) and the one or more second detectable moieties for each of the plurality of solid supports, wherein the presence and/or amount of the one or more first detectable moieties and the presence and/or amount of the one or more second detectable moieties determined for a solid support indicate the identity and the quantity, respectively, of each of the cellular components for each of the plurality of samples (pg. 75, lines 11-33; pg. 42, lines 14-16; Fig. 1).
Regarding claim 4, Nakamoto teaches the method of claim 3 wherein detecting the presence and/or amount of the one or more first detectable moieties and the one or more second detectable moieties comprises: measuring emissions of the one or more first detectable moieties and the one or more second detectable moieties with an instrument (pg. 92, lines 4-33).
Regarding claim 5, Nakamoto teaches the method of claim 1 herein one or more of the first detectable moieties and/or the second detectable moieties comprise an optical moiety, a luminescent moiety, an electrochemically active moiety, a nanoparticle, or a combination thereof, and wherein: the luminescent moiety comprises a chemiluminescent moiety, an electroluminescent moiety, a photoluminescent moiety, or a combination thereof; the photoluminescent moiety comprises a fluorescent moiety, a phosphorescent moiety, or a combination thereof; the fluorescent moiety comprises a fluorescent dye; and/or the nanoparticle comprises a quantum dot (pg. 94, lines 16-33; pg. 97, lines 9-23; pg. 157, line 33- pg. 158, lines1-7).
It would have been prima facie obvious, at the time of filing, to combine different embodiments taught by Nakamoto, in the same reference, to arrive at the claimed invention comprising oligonucleotide-conjugated antibodies bound to solid supports associated with first and second detectable moieties and detecting and quantifying the different cellular components in one and/or more samples by detecting the first and second detectable moieties. A skilled artisan would have been further motivated to combine these embodiments and immobilize the oligonucleotide-conjugated antibodies, which may have specific target sequences for the same or different target/component, because it would enable performing multiplexed assays (see Glezer et al., WO2013070990, Date: 05/16/2013, pg. 14). At the time of filing, in some embodiments, Nakamoto taught solid supports with a plurality of support oligonucleotides (probes) that can have binding sequences that may be identical or may be different for binding different reagent-specific sequences. At the time of filing, in separate embodiments, Nakamoto taught that support oligonucleotides bind reagent oligonucleotides by binding to reagent oligonucleotide detection sequences, which in some embodiments comprises a poly-A sequence, to form an oligonucleotide-conjugated antibody (Fig. 11 and pg. 106, lines 23-33). At the time of filing, Nakamoto taught separate embodiments where the reagent oligonucleotide is associated with one or more detectable moieties that may be the same or different and taught a solid support may also be associated with a detectable moiety. At the time of filing, in different embodiments, Nakamoto taught detecting a first and second detectable moiety for identifying and quantifying one or more target cellular components present in one or more samples and performing experiments, including measuring, identifying, quantifying and sequencing. Thus, a skilled artisan would have recognized that the plurality of solid supports bound to the reagent oligonucleotides should be associated with a plurality of first and second detectable moieties in order to detect and quantify each of the cellular components present in each of the samples. At the time of filing, the single reference taught by Nakamoto explicitly taught all components and elements recited in the instant claim and explicitly suggested combining elements/components. Thus, at the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining the different embodiments taught by Nakamoto amounts to combining known elements/components according to known methods, where known elements/components are known to have the same function separately as they do when combined, to yield expected and predictable results.
Regarding claim 11, Nakamoto teaches the method of claim 1 further comprising: contacting two or more solid supports with two or more predetermined concentrations of a cellular component binding reagent, wherein each of the two or more solid supports is contacted with a different predetermined concentration of the cellular component binding reagent; contacting the two or more solid supports with the reagent oligonucleotides; and measuring emissions of the one or more second detectable moieties of each of the two or more first solid supports with an instrument to generate a calibration curve relating the quantity of at least one cellular component to emissions of the one or more second detectable moieties (pg. 92, lines 16-33; pg.137, lines 29-33, pg. 138, lines 1-33,pg. 139, lines 1-7 and lines 29-33, and pg. 140, lines 1-4).
Regarding claim 12, Nakamoto teaches the method of claim 4 wherein the instrument comprises a flow cytometer, and wherein the flow cytometer comprises a conventional flow cytometer, a spectral flow cytometer, a hyperspectral flow cytometer, an imaging flow cytometer, or any combination thereof (pg. 94, lines 21-25).
Regarding claim 14, Nakamoto teaches the method of claim 1 wherein contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents comprises:(a) partitioning the plurality of samples to a plurality of partitions, wherein a partition of the plurality of partitions comprises a single sample of the plurality of samples; and contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents; or (b) contacting one or more cells of each of a plurality of samples with a plurality of cellular component binding reagents; and partitioning the plurality of samples to a plurality of partitions, wherein a partition of the plurality of partitions comprises a single sample of the plurality of samples (pg. 7, lines 2-13; pg. 9, lines 30-33 - pg. 10, lines 1-15; pg. 43, lines 4-12; pg. 89, lines 4-21).
Regarding claim 26, Nakamoto teaches the method of claim 14, wherein detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports comprises: detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports of each sample of the plurality of samples separately, thereby determining the identity and the quantity, respectively, of each of the cellular components for each sample of the plurality of samples, wherein detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports of each sample of the plurality of samples separately comprises detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports of each partition separately (pg. 92, lines 4-20; pg. 94, lines 1-3; pg. 9, lines 30-33 - pg. 10, lines 1-15; pg. 75, lines 11-33; pg. 42, lines 14-16; pg. 43, lines 4-12; pg. 89, lines 4-21; pg. 76, lines 19-33; Fig. 1, support oligonucleotide having barcode/label for identifying and quantifying).
It would have been prima facie obvious, at the time of filing, to combine the different embodiments of Nakamoto to arrive at the recited method in the claimed invention comprising oligonucleotide-conjugated antibodies bound to solid supports associated with first and second detectable moieties and detecting and quantifying the different cellular components in one and/or more samples by detecting the first and second detectable moieties within each single sample partition. A skilled artisan would have been motivated to combine these embodiments to arrive at the claimed invention because partitioning samples and identifying and quantifying cellular components in each partition would enable absolute quantification of each cellular component detected including using Poisson distribution/statistics (see Nakamoto pg. 106, lines 6-12). A person having ordinary skill in the art would have a reasonable expectation of success because, at the time of filing, Nakamoto taught each recited limitation is separate embodiments, thus combining these embodiments amounts to combining known elements/components, known to have the same function separately as they do when combined and combining according to known methods, to yield expected and predictable results.
Regarding claim 27, Nakamoto teaches the method of claim 14, wherein the one or more first detectable moieties of the plurality of solid supports situated in each partition are predetermined, wherein said predetermined one or more first detectable moieties are distinct to each partition, and wherein detecting the one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports comprises: detecting the predetermined one or more first detectable moieties and the one or more second detectable moieties for each of the plurality of solid supports of each sample of the plurality of samples concurrently; and associating the detected predetermined one or more first detectable moieties of each of the solid supports with the partition from which said solid support derived, thereby determining the identity and the quantity, respectively, of each of the cellular components for each sample of the plurality of samples (pg. 92, lines 4-33; pg. 94, lines 1-3; pg. 9, lines 30-33 - pg. 10, lines 1-15; pg. 75, lines 11-33; pg. 42, lines 14-16; pg. 40, lines 11-33- pg. 41, lines 1-12; pg. 43, lines 4-12; pg. 89, lines 4-21; pg.137, lines 29-33; pg. 138, lines 1-33; pg. 139, lines 1-7 and lines 29-33 -pg. 140, lines 1-4; and Fig. 1, oligo barcode/label used for identifying and quantifying).
Regarding claim 28, in separate embodiments, Nakamoto teaches the method of claim 14, further comprising pooling the solid supports from each partition of the plurality of partitions (pg. 109, lines 28-30; pg. 26 lines 1-3; pg. 46, lines 23-29; pg. 81, lines 9-20).
It would have been prima facie obvious, at the time of filing, to combine the different embodiments of Nakamoto to arrive at the claimed invention comprising oligonucleotide-conjugated antibodies bound to solid supports associated with first and second detectable moieties and detecting and quantifying the different cellular components in one and/or more samples by detecting the first and second detectable moieties and wherein samples are partitioned and then solid supports are pooled from each partition. A skilled artisan would have been motivated to combine these embodiments to arrive at the claimed invention because it would enable identification and absolute quantification of more than one target of interest (see Nakamoto, pg. 81, lines 9-20; and pg. 106, lines 6-12). A person having ordinary skill in the art would have a reasonable expectation of success because, at the time of filing, Nakamoto taught each recited limitation is separate embodiments, thus combining these embodiments amounts to combining known elements/components according to known methods, where the known elements/components are known to have the same function separately as they do when combined, to yield expected and predictable results.
Regarding claim 31, Nakamoto teaches the method of claim 1, comprising isolating one or more populations of interest from a starting population to obtain the plurality of samples, wherein each of the samples is a population of interest, wherein two or more of the samples of the plurality of samples comprise phenotypically different populations of interest, interest, and wherein isolating one or more populations of interest from a starting population comprises flow cytometry (pg. 2, lines 18-26; pg. 84, lines 22-33; pg. 104, lines 13-17; pg. 105, lines 1-5; pg. 141, lines 19-23; pg. 135, lines 30-32- pg. 136, lines 1-11).
It would have been prima facie obvious, at the time of filing, to combine the different embodiments of Nakamoto to arrive at the recited method and isolate one or more populations of interest. A skilled artisan would have been motivated to combine these embodiments and include isolating one or more populations of interest because it would enable removing (background) noise (see Nakamoto, pg. 125, lines 15-21). A person having ordinary skill in the art would have a reasonable expectation of success because, at the time of filing, Nakamoto taught each recited limitation is separate embodiments, thus combining these embodiments amounts to combining known elements/components according to known methods, where the known elements/components are known to have the same function separately as they do when combined, to yield expected and predictable results.
Regarding claim 35, Nakamoto teaches the method of claim 1, comprising permeabilizing and/or fixating the cells prior to contacting the cells of each of the plurality of samples with the plurality of cellular component binding reagents (pg. 9, lines 12-17).
Regarding claim 38, Nakamoto teaches the method of claim 1, comprising: lysing the cells, prior to contacting the reagent oligonucleotides with the plurality of solid supports (pg. 44, lines 18-26; pg. 109, lines 12-19; pg. 111, lines 9-13).
It would have been prima facie obvious, at the time of filing, to combine the different embodiments of Nakamoto to arrive at the claimed invention and lyse cells prior to contacting reagent nucleotides with solid supports. A skilled artisan would have been motivated to combine these embodiments to comprise this lysing step because it would enable target cellular components contained inside the cells to be captured. A person having ordinary skill in the art would have a reasonable expectation of success because, at the time of filing, Nakamoto taught each recited limitation is separate embodiments, thus combining these embodiments amounts to combining known elements/components according to known methods, where the known elements/components are known to have the same function separately as they do when combined, to yield expected and predictable results.
Regarding claim 39, Nakamoto teaches the method of claim 1, comprising: dissociating the reagent oligonucleotides from the cellular component binding reagents bound to or previously bound to the cellular components of or from the cells of the sample, prior to contacting the reagent oligonucleotides with the plurality of solid supports, wherein dissociating the reagent oligonucleotides comprises: detaching the reagent oligonucleotides from the cellular component binding reagents bound to or previously bound to the cellular components of or from the cells of the sample by UV photocleaving, chemical treatment, heat treatment, enzyme treatment, or a combination thereof (pg. 8, lines 14-22 and pg. 107, lines 4-11).
Regarding claim 40, Nakamoto teaches the method of claim 1, wherein: the cellular components comprise a protein, a lipid, a carbohydrate, or a combination thereof, and/or wherein the cellular components comprise an extracellular cellular component, a cell surface cellular component, an intracellular cellular component, or a combination thereof (pg. 8, lines 1-4; pg. 57, lines 1-3; pg. 105, lines 6-15); the plurality of cellular component binding reagents comprises a protein, an antibody, an aptamer, a tetramer, a protein scaffold, or a combination thereof; and/or the plurality of cellular component binding reagents comprises at least 10 cellular component binding reagents (pg. 56, lines 25-27; pg. 58, lines 11-13; pg. 62, lines 2-3).
Regarding claim 43, Nakamoto teaches the method of claim 1, wherein the reagent oligonucleotide: is attached, releasably attached, covalently attached, non-covalently attached, and/or conjugated to the cellular component binding reagent; is associated with the cellular component through a UV photocleavable group and/or a chemical labile group: is associated with the cellular component through a linker, wherein the linker comprises a carbon chain; and/or is 10 to 500 nucleotides in length, wherein the reagent-specific sequence is 5 to 495 nucleotides (pg. 7, lines 32-33- pg. 8, lines 1-13; pg. 58, lines 21-33; pg. 77, lines 1-33; pg. 146, lines 25-33- pg. 147, line 1-13).
Regarding claim 50, Nakamoto teaches the method of claim 1, wherein at least two solid support oligonucleotides of a solid support of the plurality of solid comprises an identical capture sequence for binding to one of the reagent-specific sequences, and wherein a solid support oligonucleotide of a first solid support and a solid support oligonucleotide of a second solid support of the plurality of solid supports comprise different capture sequences for binding to two different reagent-specific sequences of the reagent-specific sequences (Fig. 1, target-binding sequence; pg. 38, lines 28-33; pg. 39, lines 1-16; Figs. 11-12, component 1224; pg. 40, lines 11-33- pg. 41, lines 1-12).
Regarding claim 52, Nakamoto teaches the method of claim 1, wherein all solid supports of the plurality of solid supports are distinguishable from each other by the presence and/or amount of the one or more first detectable moieties associated thereto, and wherein: two solid supports of the plurality of solid supports comprise different quantities of the one or more first detectable moieties, and wherein: two solid supports of the plurality of solid supports comprise different quantities of the one or more first detectable moieties, and/or two solid supports of the plurality of solid supports comprise different first detectable moieties (pg. 5, lines 5-33- pg. 6, lines 1-6 and 25-33; pg. 42, lines 7-16; pg. 92, lines 4-15 and pg. 76, lines 19-33).
Claim(s) 61 is rejected under 35 U.S.C. 103 as being unpatentable over Nakamoto et al., (WO 2020159757A1, Pub Date 08/06/2020), as applied to claim 1, in view of Fan et al, (US 2018/0267036 A1, Pub. Date: 09/10/2018, provided in IDS filed on 10/22/2025, US Patent Cite No. 130).
The teachings of Nakamoto are discussed herein above.
Regarding claim 61, Nakamoto teaches a kit comprising : a plurality of cellular component binding reagents (1) capable of binding to different cellular components, or regions thereof, a reagent oligonucleotide comprising (i) a reagent-specific sequence specific to a cellular component binding reagent associated with the reagent oligonucleotide and (ii) a detection sequence; and/or a detection oligonucleotide associated with one or more second detectable moieties, or precursors thereof, (pg. 166, lines 28-33- pg. 168, lines 1-5). Nakamoto does not teach a kit comprising a plurality of solid supports associated with one or more first detectable moieties and comprising different capture sequences for binding different reagent oligonucleotides; plurality of solid support oligonucleotides; and solid supports comprising a binding sequence capable of binding to the detection sequences of the reagent oligonucleotides.
Throughout the disclosure, Fan teaches compositions comprising a protein binding reagent conjugated with an oligonucleotide. Fan teaches the oligonucleotide comprises a unique identifier for the protein binding reagent, and the protein binding reagent is capable of specifically binding to a target. Fan teaches methods and kits for quantitative analysis of a plurality targets in a sample. Fan further teaches systems and methods for preparing a labeled biomolecule reagent, including a labeled biomolecule agent comprising a protein binding reagent conjugated with an oligonucleotide.
Fan, in separate embodiments, teaches a kit comprising a plurality of solid supports, wherein each of the plurality of solid supports is associated with one or more first detectable moieties, or precursors thereof, and comprises a plurality of solid support oligonucleotides, and wherein different solid supports of the plurality of solid supports comprise different capture sequences for binding to different reagent-specific sequences of reagent oligonucleotides; and/or a detection oligonucleotide associated with one or more second detectable moieties, or precursors thereof; and comprising a binding sequence capable of binding to the detection sequences of the reagent oligonucleotides (paras 0009-0010, 0045, 0057-0058, and 0513).
It would have been prima facie obvious, at the time of filing, to combine the kit comprising binding reagents associated with reagent oligonucleotides as recited in the claimed invention, and as taught by Nakamoto, with the kit comprising a plurality of solid supports each associated with a plurality of support oligonucleotides, capable of binding reagent oligonucleotides, and associated with detectable moieties, as taught by Fan. A skilled artisan would have been further motivated to combine these teaching because it would enable using immobilized oligonucleotide-conjugated antibodies for detecting one or more cellular component targets in one or more samples in a multiplexed format. A person having ordinary skill in the art would have a reasonable expectation of success because, at the time of filing, Nakamoto taught each recited limitation is separate embodiments, thus combining these embodiments amounts to combining known elements/components according to known methods, where the known elements/components are known to have the same function separately as they do when combined, to yield expected and predictable results.
Conclusion
All claims are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA L LIRIANO-NG whose telephone number is (571)272-0085. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm (EST).
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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.
/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 July 10, 2026
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