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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on February 11, 2026 has been entered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Status of Claims
Claims 6-18, 20-32 and 36-40 are currently pending. Claims 6 and 36-40 have been amended by Applicants’ amendment filed 02-11-2026. Claim 35 has been canceled by Applicants’ amendment filed 02-11-2026. No claims have been added by Applicants’ amendment filed 02-11-2026.
Applicant elected Group II, claims 6-33 drawn to a method for preparing a population functionalized solid support; and the election of Species with traverse as follows:
Species (A): Applicant did not elect a species of method of claim 1 further comprising an additional step (claims 2 and 4);
Species (B): wherein reacting comprises reacting the nucleic acid molecule with a dinucleotide or a trinucleotide (claim 7);
Species (C): surface reactive nucleic acid molecules in sequences of a universal sequence, barcode, a UMI and a capture sequence (claim 9);
Species (D): wherein the nucleic acid molecules comprise one or more of oligonucleotides, nucleotides…surface reactive nucleic acid molecules (claim 25);
Species (E): wherein the solid support comprises a spacer, the spacer having a functional group exposed for reaction (claim 19);
Species (F): wherein the solid support comprises a bead that is a silica bead, a hydrogel bead or a magnetic bead (clam 14);
Species (G): wherein the spacer optionally comprises: (i) a polyethylene glycol polymer (PEG) (claim 21);
Species (H): wherein PEG has a molecular weight range of about 2,0000 to 10,000 Daltons (claim 23);
Species (I): wherein the spacer comprises a photolabile linker, a fluoride ion labile linker, or a cleavable linker (claim 26), in the reply filed on May 3, 2023 was previously acknowledged.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention has been treated as an election without traverse (MPEP
§ 818.03(a)).
Claims 1-5 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 8-18, 20-24 and 26-30 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01-26-2023.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 6, 7, 25 and 36-40 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed July 20, 2022 claims the benefit of multiple US Provisional Patent Applications including 62/876,909, filed July 22, 2019.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications including US Provisional Patent Application 62/876,909, filed July 22, 2019 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 6 does not have support for: “a second functional group of the heterobifunctional spacer is exposed distally from the activated surface” and “a nucleic acid capture sequence that is exposed distally from the activated surface” in lines 5-6 and 10-11.
Therefore, the priority date for the presently claimed invention is July 22, 2020, the filing date of US16/936,197.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed February 11, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
Claim Objection
The objection of claim 36 is withdrawn due to Applicant’s amendment of the claim to spell out the abbreviation in the first encounter of the claims, in the reply filed 02-11-2026.
Double Patenting
The provisional rejection of claims 6, 7, 25 and 36-40 is withdrawn on the ground of nonstatutory double patenting as being unpatentable over: Claims 1-3, 5-20, 22-28, 30, 32, 33, 35-38, 40-42 and 44-46 of copending Application No. 16/758,485, due to a typographical error in the Application number.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Claim Rejections - 35 USC § 103
The rejection of claims 6, 7, 25 and 36-40 is withdrawn under 35 U.S.C. 103 as being unpatentable over Nicol et al. (hereinafter “Nicol”) (US Patent Application Publication No. 20180112212, published April 26, 2018; effective filing date March 11, 2015; of record) in view of Regev et al. (hereinafter “Regev”) (International Application WO2016040476, published March 17, 2016; of record); as evidenced by Gehring et al. (hereinafter “Gehring”) (US Patent No. 11492610, issued November 8, 2022; filed March 7, 2019; effective filing date March 8, 2018; of record); and Greg T. Hermanson (hereinafter “Hermanson”) (Bioconjugate Techniques, 2nd Edition, Elsevier, 2008, 1-1233); and Steelman et al. (hereinafter “Steelman”) (International Application WO2014047561, published March 27, 2014); and Biopharma PEG (Biopharma PEG Catalog, 2013, 1-12); and Kim et al. (hereinafter “Kim”) (Tissue Engineering: Part A, 2009, 15(8), 2300-2307).
The combined references of Nicol and Regev are not the best combination of references for the amended claims.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
The rejection of claims 6, 7, 25 and 35-40 is withdrawn under 35 U.S.C. 103 as being unpatentable over Chee et al. (hereinafter “Chee”) (US Patent Application Publication No. 20190145982, published May 16, 2019; effective filing date May 2, 2016) in view of Diebold et al. (hereinafter “Diebold”) (US patent Application Publication 20170268981, published September 21, 2017).
Chee does not specifically exemplify a nucleic acid capture sequence.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Interpretation: the term “exposed distally” as recited in claim 6 is interpreted to refer to a second, unprotected, functional group and/or capture sequence that are located at any distance from the activated surface.
The term “further comprises a dinucleotide or a trinucleotide” as recited in claim 7 to refer to a solid support comprising one or more oligonucleotides (individually/separately or in series); to refer to an additional sequence comprising dinucleotides and/or trinucleotides; and/or to refer to a reaction involving dinucleotides or trinucleotides (e.g., dNTPs in PCR, sequencing, etc.).
Double Patenting
The provisional rejection of claims 6, 7, 25 and 36-40 is maintained on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-10, 12, 14-16, 19-23, 26, 28, 29, 32, 34-37, 39, 41-46, 48, 49, 51-53 and 57-59 of copending US Patent Application No. 16/758,504, for the reasons of record.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments filed February 11, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) regarding US16/758,504, Applicant requests that the provisional double patenting rejections be held in abeyance (Applicant Remarks, pg. 8, last full paragraph) through pg. 9, first partial paragraph).
Regarding (a), Applicant did not specifically indicate how the claims of the copending applications recited supra are patentably distinct from the instant claims as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 6, 7, 25 and 36-40 is maintained under 35 U.S.C. 112(b) paragraph as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 6 is indefinite for the recitation of the term “the activated surface” such as recited in claim 6, lines 3, 5, 6 and 11. There is insufficient antecedent basis for the term “the activated surface” in the claim.
Claim 6 is indefinite for the recitation of the term “exposed distally from the activated surface” such as recited in claim 6, lines 6 and 10-11 because the term is not taught in the as-filed Specification, such that it is unclear what it means for the heterobifunctional spacer and/or the nucleic acid capture sequence to be “exposed distally from the activated surface” and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “synthesizing or attaching one or more oligonucleotides to the second functional group” such as recited in claim 6, lines 7-8 because it is unclear how the solid supports are functionalized; and whether each second functional group comprises one or more oligonucleotides such as: surface—spacer—oligo 1—oligo 2—oligo 3 (e.g., where each oligonucleotide comprises a barcode, UMI and capture sequence); whether each second functional group of each heterobifunctional spacer comprises a single oligonucleotide such as: surface—spacer—oligo (e.g.,
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); and/or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claim 6 is indefinite for the recitation of the term “each activated solid support” such as recited in claim 6, line 12. There is insufficient antecedent basis for the term “each activated solid support” in the claim.
Claim 6 is indefinite for the recitation of the term “cell-specific barcode or well-specific barcode” such as recited in claim 6, lines 14-15 because claim 6 does not recite the presence of cells or wells, such that it is completely unclear how a barcode can be specific for a component that is not present in the method and, thus, the metes and bounds of the claim cannot be determined.
Claim 25 is indefinite for the recitation of the term “a T-cell receptor (TCR) or B-cell receptor (BCR) specific sequence” such as recited in claim 25, line 3 because it is unclear whether the term refers to “a T-cell receptor (TCR)-specific sequence” or “a B-cell receptor (BCR)-specific sequence;” or whether the term refers to “a T-cell receptor (TCR)” or “a B-cell receptor (BCR)-specific sequence” and, thus, the metes and bounds of the claim cannot be determined.
Claim 36 is indefinite for the recitation of the term “the surface of the solid support” such as recited in claim 36, lines 1-2. There is insufficient antecedent basis for the term “the surface of the solid support” in the claim because claim 6, lines 2 and 13 recites “activating a surface of solid supports.”
Claims 37 and 38 are indefinite for the recitation of the terms “the solid support” and “solid support” such as recited in claim 37, line 1. There is insufficient antecedent basis for the terms “the solid support” and “solid support” in the claim because claim 6, lines 2 and 8 recites the terms “solid supports” and “a population of functionalized solid supports.”
Claim 38 is indefinite for the recitation of the term “incorporating a photolabile linkage between the heterobifunctional spacer and the solid support” such as recited in claim 38, lines 2-3 because claim 38 depends from instant claim 6, wherein claim 6, lines 4-5 recite that the heterobifunctional spacer covalently couples directly to the reactive groups of the activated surface, such that no linkage can be incorporated between the heterobifunctional spacer and the solid support and, thus, the metes and bounds of the claim cannot be determined.
Claim 38 is indefinite for the recitation of the term “the functionalized supports” such as recited in claim 38, lines 3-4. There is insufficient antecedent basis for the term “the functionalized solid supports” in the claim because claim 6, lin 8 recites the term “a population of functionalized solid supports.”
Claim 39 is indefinite for the recitation of the term “the solid supports” such as recited in claim 39, line 2. There is insufficient antecedent basis for the term “the solid supports” in the claim because claim 6, lin 8 recites the term “a population of functionalized solid supports.”
Claim 40 is indefinite for the recitation of the term “a uniform density of oligonucleotides” such as recited in claim 40, lines 2-3 because it is unclear how beads having a uniform density of oligonucleotides are selected if each bead comprises a single oligonucleotide as provided for in claim 6, lines 7 and 9 and, thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite insofar as it ultimately depends from instant claim 6.
New Objections/Rejections
Claim Rejections - 35 USC § 112(d)
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 38 and 40 are rejected under 35 U.S.C. 112(d) 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 38 recites (in part): “monitoring synthesis quality by incorporating a photolabile linkage between the heterobifunctional spacer and solid support” in lines 1-3 because claim 38 depends from instant claim 6, wherein claim 6, lines 3-5 recites that the first functional group of the heterobifunctional spacer covalently couples directly to the reactive groups of the activated surface, such that no photolabile linkage can be incorporated into the directly bound spacer. Thus, claim 38 is an improper dependent claim 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 40 recites (in part): “based on size gates to select beads having a uniform density of oligonucleotides” in lines 2-3 because claim 40 depends from instant claims 6 and 38, wherein claims 6 and 38 clearly recite that each solid support can comprise one or more oligonucleotides, such that no bead can be selected as having a uniform density of oligonucleotides if each bead comprises a single oligonucleotide. Thus, claim 40 is an improper dependent claim 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.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 6, 7, 25 and 37-40 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Bent et al. (hereinafter “Bent”) (US Patent No. 10745742, issued August 18, 2020; filed December 21, 2018; effective filing date November 15, 2017).
Regarding claim 6, Bent teaches methods of generating supports (e.g., beads) comprising barcode molecules coupled thereto, wherein the barcode can comprise a barcode sequence and a functional sequence, such that the barcode molecule can be generated using two or more ligation reactions in a combinatorial fashion; as well as, a support comprising two or more different barcode molecules can be useful for analyzing or processing one or more analytes such as nucleic acid molecules, proteins, and/or perturbation agents (interpreted as beads comprising barcodes bound to a bead, claim 6) (Abstract). Bent teaches that in cases where the polymer precursor material comprises a linear polymer material, such as a linear polyacrylamide, PEG, or other linear polymeric material, the activation agent can comprise a cross-linking agent, or a chemical that activates a cross-linking agent within the formed droplets, such that for polymer precursors that comprise polymerizable monomers, the activation agent can comprise a polymerization initiator (interpreted as activating a surface of solid supports with a reactive group; and reacting the surface with a heterobifunctional spacer, where the second functional group is exposed distally from the activated surface, claim 6) (col 49, lines 14-25). Bent teaches that the polymer or gel can include one or more of disulfide cross-linked polyacrylamide, agarose, alginate, polyvinyl alcohol, polyethylene glycol (PEG)-diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-alkyne, other acrylates, chitosan, hyaluronic acid, collagen, fibrin, gelatin, or elastin, where the polymer or gel can comprise any other polymer or gel (interpreted as activating the surface with reactive groups, and reacting the activated surface with heterobifunctional spacers, claim 6) (col 50, lines 9-16). Bent teaches that the bead can comprise covalent or ionic bonds between polymeric precursors (e.g., monomers, oligomers, linear polymers), nucleic acid molecules (e.g., oligonucleotides), primers, and other entities (interpreted as covalent coupling to reactive groups, claim 6) (col 54, lines 25-29). Bent teaches that a first molecule (e.g., a first nucleic acid molecule) can be provided that is capable of attaching to a starter sequence attached to a bead, wherein the first molecule can be a nucleic acid molecule and/or can comprise an amino acid, peptide, polyethylene glycol (PEG) moiety, hydrocarbon chain, or another moiety (interpreted as a PEG linker; and comprising amine, hydroxyl, thiol, and methoxy groups, claims 6 and 37) (col 18, lines 15-20). Bent teaches that functionalization of beads for attachment of nucleic acid molecules (e.g., oligonucleotides) can be achieved through a wide range of different approaches, including activation of chemical groups within a polymer, incorporation of active or activatable functional groups in the polymer structure, or attachment at the pre-polymer or monomer stage in bead production (interpreted as activating the surface with reactive groups, and reacting the activated surface with heterobifunctional spacers; and attaching one or more oligonucleotides to a second functional group, claim 6) (col 55, lines 18-24). Bent teaches that precursors (e.g., monomers, cross-linkers) that are polymerized to form a bead can comprise acrydite moieties, such that when a bead is generated, the bead also comprises acrydite moieties, which can be attached to a nucleic acid molecule (e.g., oligonucleotide), which can include a priming sequence (e.g., a primer for amplifying target nucleic acids, random primer, primer sequence for messenger RNA) and/or one or more barcode sequences (interpreting acrydite moieties as a heterobifunctional spacer; interpreting the method as attaching one or more oligonucleotides to a second functional group; interpreted as comprising a barcode and a capture sequence; and exposed distally from the surface, claim 6) (col 55, lines 25-34). Bent teaches that Figure 8 illustrates an example of a barcode carrying bead, where nucleic acid molecule 802, such as an oligonucleotide, can be coupled to a bead 804 by a releasable linkage 806, such as a disulfide linker; and the same bead 804 can be coupled (e.g., via releasable linkage) to one or more other nucleic acid molecules 818, 820, such that the nucleic acid molecule 802 can be or comprise a barcode including a number of sequence elements described herein; as well as, a functional sequence 808, which can be used in subsequent processing (col 55, lines 59-67; and Figure 8). Figure 8 is shown below:
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Figure 8
Bent teaches that the barcode sequence 810 can be bead-specific such that the barcode sequence 810 is common to all nucleic acid molecules (e.g., including nucleic acid molecule 802) coupled to the same bead 804; and/or alternatively or in addition, the barcode sequence 810 can be partition-specific (interpreted as attaching barcoded nucleic acids to a bead; and comprising well-specific barcodes, claim 6) (col 56, lines 9-14). Bent teaches that nucleic acid molecule 802 can comprise a specific priming sequence 812, such as an mRNA specific priming sequence (e.g., poly-T sequence), a targeted priming sequence, and/or a random priming sequence, wherein the nucleic acid molecule 802 can comprise an anchoring sequence 814 to ensure that the specific priming sequence 812 hybridizes at the sequence end (e.g., of the mRNA), such that the anchoring sequence 814 can include a random short sequence of nucleotides, such as a 1-mer, 2-mer, 3-mer or longer sequence, which can ensure that a poly-T segment is more likely to hybridize at the sequence end of the poly-A tail of the mRNA (interpreting the polyT sequence as a capture sequence; oligonucleotides further comprise dinucleotides or trinucleotides; and including an amplification primer, claims 6, 7 and 25) (col 56, lines 17-28). Bent teaches that the nucleic acid molecule 802 can comprise a unique molecular identifying sequence 816 (UMI), where the UMI can provide a unique identifier of the starting mRNA molecule that was captured in order to allow quantitation of the number of original expressed RNA (interpreted as comprising a UMI; and UMIs as origin-specific barcodes, claim 6) (col 56, lines 29-31 and 41-44). Bent teaches that the number of different UMIs can be indicative of the quantity of mRNA originating from a given partition, and thus from the biological particle (e.g., the cell) (interpreting UMIs as origin-specific barcodes, claim 6) (col 57, lines 9-12). Bent teaches that the addition of moieties to a gel bead after gel bead formation can be advantageous, where the addition of an oligonucleotide (e.g., barcoded oligonucleotide) after gel bead formation can avoid loss of the species during chain transfer termination that can occur during polymerization (col 58, lines 25-30).
Regarding claim 7, Bent teaches that nucleic acid molecule 802 can comprise a specific priming sequence 812, such as an mRNA specific priming sequence (e.g., poly-T sequence), a targeted priming sequence, and/or a random priming sequence, wherein the nucleic acid molecule 802 can comprise an anchoring sequence 814 to ensure that the specific priming sequence 812 hybridizes at the sequence end (e.g., of the mRNA), such that the anchoring sequence 814 can include a random short sequence of nucleotides, such as a 1-mer, 2-mer, 3-mer or longer sequence, which can ensure that a poly-T segment is more likely to hybridize at the sequence end of the poly-A tail of the mRNA (interpreted as further comprising an amplification primer; and where the polyT sequence is a capture sequence; and oligonucleotides further comprise dinucleotides or trinucleotides, claims 6 and 7) (col 56, lines 17-28).
Regarding claim 25, Bent teaches that nucleic acid molecule 802 can comprise a specific priming sequence 812, such as an mRNA specific priming sequence (e.g., poly-T sequence), a targeted priming sequence, and/or a random priming sequence, wherein the nucleic acid molecule 802 can comprise an anchoring sequence 814 to ensure that the specific priming sequence 812 hybridizes at the sequence end (e.g., of the mRNA), such that the anchoring sequence 814 can include a random short sequence of nucleotides, such as a 1-mer, 2-mer, 3-mer or longer sequence, which can ensure that a poly-T segment is more likely to hybridize at the sequence end of the poly-A tail of the mRNA (interpreted as further comprising an amplification primer; and where the capture sequence is an oligo-dT, claim 25) (col 56, lines 17-28).
Regarding claim 36 (in part), Bent teaches that the attachment can be reversible, such that when the disulfide bond is broken (e.g., in the presence of a reducing agent), the attached species is released from the bead; and in other cases, an acrydite moiety can comprise a reactive hydroxyl group that can be used for attachment (interpreted as a hydroxyl group, claim 36) (col 55, lines 12-17).
Bent teaches that precursors comprising a functional group that is reactive or capable of being activated such that it becomes reactive can be polymerized with other precursors to generate gel beads comprising the activated or activatable functional group, wherein the functional group can then be used to attach additional species (e.g., disulfide linkers, primers, other oligonucleotides, etc.) to the gel beads, where some precursors comprising a carboxylic acid (COOH) group can co-polymerize with other precursors to form a gel bead that also comprises a COOH functional group; an acrylic acid (a species comprising free COOH groups), acrylamide, and bis(acryloyl)cystamine can be copolymerized together to generate a gel bead comprising free COOH groups, such that the COOH groups of the gel bead can be activated (e.g., via 1-Ethy 1-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) or 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM)) such that they are reactive (e.g., reactive to amine functional groups where EDC/NHS or DMTMM are used for activation), wherein the activated COOH groups can then react with an appropriate species (e.g., a species comprising an amine functional group where the carboxylic acid groups are activated to be reactive with an amine functional group) comprising a moiety to be linked to the bead (interpreted as activating the surface using an agent including carbodiimide, claim 36) (col 57, lines 26-51).
Regarding claim 37, Bent teaches that the methods of the present disclosure can be used to generate barcode molecules comprising one or more amino acids, peptides, proteins, PEG moieties, hydrocarbon chains, and/or other moieties (interpreted as a PEG linker; and comprising amine, hydroxyl, thiol, and methoxy groups, claim 37) (col 16, lines 56-59). Bent teaches that a first molecule (e.g., a first nucleic acid molecule) can be provided that is capable of attaching to a starter sequence attached to a bead, wherein the first molecule can be a nucleic acid molecule and/or can comprise an amino acid, peptide, polyethylene glycol (PEG) moiety, hydrocarbon chain, or another moiety (interpreted as a PEG linker; and comprising amine, hydroxyl, thiol, and methoxy groups, claim 37) (col 18, lines 15-20). Bent teaches that the polymer or gel can include one or more of disulfide cross-linked poly-acrylamide, agarose, alginate, polyvinyl alcohol, polyethylene glycol (PEG)-diacrylate, PEG-acrylate, PEG-thiol, PEG-azide, PEG-alkyne, other acrylates, chitosan, hyaluronic acid, collagen, fibrin, gelatin, or elastin, where the polymer or gel can comprise any other polymer or gel (interpreted as different functional groups including amine, hydroxyl, thiol and methoxy, claim 37) (col 50, lines 9-16).
Regarding claim 38, Bent teaches that biological samples in partitions can be subjected to various processes, such as chemical processes or physical processes, wherein samples in partitions can be subjected to heating or cooling, or chemical reactions, such as to yield species that can be qualitatively or quantitatively processed (interpreted as analyzing released oligos to confirm yield, claim 38) (col 1, lines 39-43). Bent teaches that a barcode can be added to a fragment of a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) sample before, during, and/or after sequencing of the sample, such that barcodes can allow for identification and/or quantification of individual sequencing-reads (interpreted as analyzing released oligos to confirm yield; and sequence fidelity, claim 38) (col 12, lines 65-67; and col 13, lines 1-2).
Regarding claim 39, Bent teaches that Figure 32 shows a process in which fluorescent probes were used to examine the effects of exonuclease treatment (interpreted as hybridizing a fluorescent probe to a portion of the oligonucleotides; and assess oligonucleotide density and distribution, claim 39) (col 12, lines 17-20; and Figure 32).
Regarding claim 40, Bent teaches that beads can be provided as a population or plurality of beads having a relatively monodisperse size distribution; and providing relatively consistent amounts of reagents within partitions, maintaining relatively consistent bead characteristics, such as size; and that a support used in a method of the present disclosure can be, such as a well, matrix, rod, container, or beads, can have any useful features and characteristics, such as any useful size, fluidity, solidity, density, porosity, and composition (interpreted as sorting or filtering the population of solid supports based on size gates to select beads having a uniform density of oligonucleotides, claim 40) (col 17, lines 43-46; and col 53, lines 39-43).
Bent does not specifically exemplify using CDI, cyanogen bromide, tresyl chloride, or divinyl sulfone (claim 36, in part).
Bent meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 for
the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 6, 7, 25 and 36-40 are rejected under 35 U.S.C. 103 as being unpatentable over Bent et al. (hereinafter “Bent”) (US Patent No. 10745742, issued August 18, 2020; filed December 21, 2018; effective filing date November 15, 2017) in view of Stephanie Lopina (hereinafter “Lopina”) (Thesis, Massachusetts Institute of Technology, 1996, 1-167) as evidenced by Biosynthesis (Biosynthesis, 2015, 1-11).
The teachings of Bent as applied to claims 6, 7, 25 and 37-40 are described supra.
Bent does not specifically exemplify using CDI, cyanogen bromide, tresyl chloride, or divinyl sulfone (claim 36, in part).
Regarding claim 36 (in part), Lopina teaches that appropriate ligands were covalently coupled to poly(ethylene oxide) substrates producing materials that elicit a desired cellular response, wherein hydroxyl groups on the PEO chains provided the site for attaching ligands, such that the hydroxyls are first activated, providing a leaving group which will then couple to the desired ligand (interpreted as a functional group is a hydroxyl group, claim 36) (pg. 70, first full paragraph). Lopina teaches that activated supports have long been used to immobilize antibodies for immunoaffinity chromatography (Shaltiel, 1976; Hjerten, 1981); that various activation agents have been used including N-hydroxy-succinimide (NHS) (Cuatrecasas, 1972), hydrazide (O'Shannessey, 1990), carbonyldiimidazole (CDI) (Bethel, 1979), 1,4-butanedioldiglydicyl ether (BDGE) (Sundberg, 1974); divinyl sulphone (DVS) (Porath, 1975); cyanogen bromide (CNBr) (March, 1974), tosyl chloride (Nilsson, 1984); and tresyl chloride (Nilsson, 1981; Nilsson, 1984), where it’s reactivity makes tresyl chloride attractive for use in substrate activation (Crossland, 1971) (interpreted as CDI, CNBr, tresyl chloride, and divinyl sulfone, claim 36) (pg. 70, second full paragraph), wherein CDI activation of a solid support is known in the art for the conjugation of oligonucleotides as evidenced by Biosynthesis (pg. 4, Figure 1). Lopina teaches that PEO hydrogels provide a pure poly(ethylene oxide) surface for derivatization, offering the most biologically inert scaffold possible, such that through radiation crosslinking of star PEO and linear/oligomer mixtures, PEO hydrogels with a range of ligand tether lengths and hydroxyl concentrations are possible (interpreted as PEO heterobifunctional spacers, claims 6 and 36) (pg. 77, first full paragraph).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of derivatizing hydrogels as exemplified by Lopina, it would have been prima facie obvious before the effective filing date of the claimed invention to modify the method for the production of supports such as gel beads comprising differential functionalization for the attachment of tags, barcode molecules, UMI, capture sequences, and/or primers as disclosed by Bent to include activating agents such as CDI, CNBr, tresyl chloride, and divinyl sulfone as taught by Lopina with a reasonable expectation of success in activating, functionalizing, and/or derivatizing polymer supports including hydrogel beads; and/or for the efficient attachment of nucleic acid molecules such as oligonucleotides to supports including hydrogel beads.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Conclusion
Claims 6, 7, 25 and 36-40 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684