DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Priority
This is a U.S. application filed on 05/26/2022 which claims priority to U.S. Provisional Application 63/249,367, filed on 09/28/2021 and to U.S. Provisional Application No. 63/194,005, filed on 05/27/2021.
Claim Status
Claims 1, 4 and 38 are currently amended, and the Applicant notes that no new matter is added.
Claims 2-3, 9-10, 19-20 and 45 are previously presented. Claims 5-8, 11-17 and 39-43 are original. Claims 18, 21-37 and 44 are cancelled.
Thus, claims 1-17, 19-20, 38-43 and 45 are pending and are under examination.
Withdrawn Rejections
The previous rejection of claim 1 under 35 U.S.C. 112(b), regarding improper Markush grouping of alternatives, is withdrawn in light of Applicant’s amendments of the claim.
The previous rejection of claims 1-15, 17, 19-20 and 45 under 35 U.S.C. 103, regarding obviousness as being unpatentable over Groves et al. (US 20200132600 A1) in view of Domenyuk et al. (US 2019/0078093 A1) and Burden et al. (US 2021/0123055 A1), is withdrawn in light of Applicant’s amendments of claims.
The previous rejection of claim 16 under 35 U.S.C. 103, regarding obviousness as being unpatentable over Groves et al. (US 20200132600 A1), Domenyuk et al. (US 2019/0078093 A1) and Burden et al. (US 2021/0123055 A1) as applied to claim 1 above, and further in view of Bernard et al. (US 2014/0243224 A1), is withdrawn in light of Applicant’s amendments of claims.
The previous rejection of claims 38-43 under 35 U.S.C. 103, regarding obviousness as being unpatentable over Domenyuk et al. (US 2019/0078093 A1) in view of Thubagere Jagadeesh et al. (US 2021/0095333 A1), Kozlov et al. (Biopolymers. 2004 Apr 5;73(5):621-30) and Burden et al. (US 2021/0123055 A1), is withdrawn in light of Applicant’s amendments of claims.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 102
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.
The Applicant’s amendments have significantly changed the scope of the claims because it changed the focus of the invention by limiting claim 1 to antibodies “and wherein the immobilized affinity binders are antibody molecules or portions of antibody molecules ” and necessitated a newly raised 102 rejection as follows.
Claims 1-15, 17, 19-20, 38, 43 and 45 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Schwartz et al. (US 2012/0258870 A1).
Regarding claim 1, the claim recites:
“A method for detecting an analyte molecule present in a biological sample, the method comprising:
providing a sample comprising analyte molecules, wherein the analyte molecules
comprise proteins, peptides, peptide fragments, DNA, RNA, or any combinations thereof;
contacting the sample with a pool of supramolecular structures in solution to form analyte
molecule-supramolecular structure complexes in solution, an individual analyte molecule-supramolecular structure complex comprising:
a core structure comprising a plurality of nucleic acid strands;
an affinity binder linked to the core structure; and
an analyte molecule of the analyte molecules bound to the affinity binder,
wherein different supramolecular structures of the pool of supramolecular
structures comprise different affinity binders with different binding affinity for
other analyte molecules of the analyte molecules.,_ and wherein the different
supramolecular structures of the pool have same core structures with respective
same nucleic acid strands;
providing an array comprising a plurality of binding sites on a substrate, wherein the binding sites comprise respective immobilized affinity binders, wherein the immobilized affinity binders of a first binding site of the plurality of binding sites having a binding affinity for a different analyte molecule than the immobilized affinity binders of a second binding site of the plurality of binding sites, wherein an individual binding site comprises a plurality of immobilized affinity binders, and wherein the immobilized affinity binders are antibody molecules or portions of antibody molecules;
contacting the analyte molecule-supramolecular structure complexes with the array; and
detecting binding of the analyte molecule-supramolecular structure complexes to the
immobilized affinity binders of the binding sites of the array”
Regarding claim 1, Schwartz teaches a method for detecting an analyte molecule present in a biological sample by providing a sample comprising analyte molecules that comprise proteins, peptides, peptide fragments, DNA, RNA or any combinations (Abstract; [0190-0191]). Schwartz further teaches contacting a sample with a pool of supramolecular structures in solution with capture antibodies (Abstract’s figure; Sheet 63 of 88, figure 61). And Schwartz teaches the formation of an analyte molecule-supramolecular complexes in solution (Sheet 45 of 88, Figure 43, “Sandwich Immune complex”). Schwartz further teaches that an individual analyte molecule-supramolecular structure complex comprises a core structure comprising a plurality of nucleic acid strands, an affinity binder linked to the core structure and an analyte molecule bound to the affinity binder (Sheet 43 of 88, Figure 41; sheet 56 of 88, Figure 54; Sheet 60 of 88, Figure 88; Sheet 61 of 88, Figure 59). And Schwartz teaches that different supramolecular structures of the pool of supramolecular structures comprise different affinity binders with different binding affinity for analyte molecules (Sheet 44 of 88, Figure 42). Schwartz also teaches that the different supramolecular structures of the pool have the same core structures with the same nucleic acid strands (Sheet 39 of 88, Figure 37; [0076]). Schwartz further teaches providing an array comprising a plurality of binding sites on a substrate ([1132-1133]; [0080]; [0082]; page 139, claim 13; “vii) the targets or target types comprises cells and/or cell types comprising one or more distinct binding sites, distinct markers, or distinct biomarkers”). And Schwartz teaches that the binding sites comprise immobilized affinity binders such as an antibody ([0033]; [0203]). Schwartz further teaches that the immobilized affinity binders of a first binding site of the plurality of binding sites have a binding affinity for a different analyte molecule than the immobilized affinity binders of a second binding site of the plurality of binding sites ([0839]; [1148]; page 138, claim 9, “The panel development system of claim 1, wherein the plurality of binding moieties in said first panel comprises between 2-40 different binding moieties among the plurality of binding moieties”). And Schwartz teaches that an individual binding site comprises a plurality of immobilized affinity binders ([1107]; [1152]). Schwartz further teaches that the immobilized affinity binders are antibody molecules or portions of antibody molecules ([0033]; [0203]).
Schwartz also teaches contacting the analyte molecule-supramolecular structure complexes with the array (Sheet 43 of 88, Figure 41, “B”). Schwartz further teaches detecting the binding of the analyte molecule-supramolecular structure complexes to the immobilized affinity binders of the binding sites of the array (Sheet 43 of 88, Figure 41, “D” and “E”).
Regarding claim 2, Schwartz teaches identifying an individual analyte molecule of the individual analyte molecule-supramolecular structure complex that was bound to an individual binding site of an array ([0171]; [0216]; [1135]; [1149]). Regarding claim 3, Schwartz further teaches that identifying comprises generating a detectable signal from a supramolecular structure of the individual analyte molecule-supramolecular structure complex and associating the detectable signal with the individual binding site ([0150]; [1178]; page 139; claim 15). And regarding claim 4, Schwartz teaches that the detectable signal is an optical, magnetic, or electrical signal indicative of the presence of the individual analyte molecule-supramolecular structure complex at the individual binding site [0150].
Regarding claim 5, Schwartz teaches that the identifying comprises: amplifying an initiator of the supramolecular structure and detecting the amplification [0210]. And regarding claim 6, Schwartz teaches that the initiator is a nucleic acid [0210]. And regarding claim 7, Schwartz teaches the identifying comprises: amplifying an initiator immobilized on the individual binding site and detecting the amplifying [0210]. Regarding claim 8, Schwartz further teaches the initiator is a nucleic acid [0210].
Regarding claim 9, Schwartz teaches that the affinity binder and the immobilized affinity binders are aptamers, antibody molecules or portions of antibody molecules (Sheet 43 of 88, Figure 41; sheet 56 of 88, Figure 54; Sheet 61 of 88, Figure 59; sheet 60 of 88, Figure 88; [0033]; [0203]).
Regarding claim 10, Schwartz teaches that binding of the analyte molecule-supramolecular structure complex to an immobilized affinity binder at an individual binding site comprises binding of the affinity binder of the supramolecular structure to a first portion of the analyte molecule and binding of an immobilized affinity binder of the individual binding site to second portion of the analyte molecule (Sheet 43 of 88, Figure 41, “C”: Capture, “D”: Biotinylated detector; Sheet 44 of 88, Figure 43, “C”: Molecular Probe for capture, Molecular Probe for detection)
Regarding claim 11, Schwartz teaches that the immobilized affinity binders are linked to each individual binding site via nucleic acid capture molecules (Sheet 43 of 88, Figure 41, “C”: Capture, “D”: Biotinylated detector; Sheet 44 of 88, Figure 43, “C”: Molecular Probe for capture, Molecular Probe for detection).
Regarding claim 12, Schwartz teaches that each individual binding site comprises a plurality of nucleic acid capture molecules (Sheet 43 of 88, Figure 41, “C”: Capture, “D”: Biotinylated detector; Sheet 44 of 88, Figure 43, “C”: Molecular Probe for capture, Molecular Probe for detection).
Regarding claim 13, Schwartz teaches that the plurality of nucleic acid capture molecules at an individual binding site all have the same nucleic acid sequence (Sheet 50 of 88, Figure 48, C: HyLK3’-coated microparticle).
Regarding claim 14, Schwartz teaches that the plurality of nucleic acid capture molecules are coupled to an immobilized supramolecular structure (Sheet 51 of 88, Figure 49, C, D and E).
Regarding claim 15, Schwartz teaches that each individual binding site comprises a plurality of immobilized affinity binders all having affinity for a same analyte molecule of the analyte molecules (Sheet 53 of 88, Figure 51, A, B and C)
Regarding claim 17, Schwartz teaches that each supramolecular structure of the pool is a nanostructure [0642].
Regarding claim 19, Schwartz teaches that each supramolecular structure of the pool is arranged into a pre-defined shape and/or have a prescribed molecular weight (Figure 14, E: Conjugate; Sheet 21 of 88, D: Lanes 3, 4 and 5).
Regarding claim 20, Schwartz teaches removing analyte molecule-supramolecular structure complexes not bound to binding sites of the array after contacting the sample with the array ([0286]“After washing to remove unbound sample,”]).
Regarding claim 38, the claim recites:
“A method for detecting an antigen molecule present in a biological sample, the method comprising:
providing a plurality of supramolecular structures, wherein an individual supramolecular
structure of the plurality of supramolecular structures comprises:
a core structure comprising a plurality of nucleic acid strands;
an antibody having binding affinity for an antigen molecule and coupled
to a nucleic acid capture strand; and
a complementary strand hybridized to the nucleic acid capture strand,
wherein the complementary strand is linked to the core structure and forms a
duplex structure with the nucleic acid capture strand, thereby coupling the
antibody to the core structure, wherein the plurality of supramolecular structures
comprise different antibodies relative to one another with respective different
binding affinities and wherein core structures of the plurality of supramolecular
structures have the same nucleic acid strands relative to one another;
contacting the plurality of supramolecular structures with a biological sample comprising
the antigen molecule such that the antigen molecule binds to the antibody of the individual supramolecular structure to form a complex in solution, wherein the antigen molecule is a
protein, peptide, or peptide fragment;
contacting the complex with a bead carrying a capture antibody having binding
specificity for the antigen molecule to form a sandwich structure, wherein the antibody of the
supramolecular structure and the capture antibody bind to different locations on the antigen
molecule;
displacing the nucleic acid capture strand duplexed to the complementary strand using a
displacing strand to release the core structure linked to the complementary strand into solution,
wherein the released core structure is not coupled to the antibody of the individual
supramolecular structure; and
detecting the core structure”.
Regarding claim 38, Schwartz teaches a method for detecting an antigen molecule present in a biological sample (Abstract). Schwartz further teaches providing a plurality of supramolecular structures (Sheet 61 of 88, Figure 59). Schwartz also teaches that an individual supramolecular structure of the plurality of supramolecular structures comprises: a core structure comprising a plurality of nucleic acid strands; an antibody having binding affinity for an antigen molecule and coupled to a nucleic acid capture strand; and a complementary strand hybridized to the nucleic acid capture strand (Sheet 61 of 88, Figure 59). And Schwartz teaches that the complementary strand is linked to the core structure and forms a duplex structure with the nucleic acid capture strand, thereby coupling the antibody to the core structure (Sheet 61 of 88, Figure 59). Schwartz further teaches that the plurality of supramolecular structures comprises different antibodies relative to one another with respective different binding affinities (Sheet 61 of 88, Figure 59). And Schwartz teaches that core structures of the plurality of supramolecular structures have the same nucleic acid strands relative to one another (Sheet 61 of 88, Figure 59). Schwartz further teaches contacting the plurality of supramolecular structures with a biological sample comprising the antigen molecule such that the antigen molecule binds to the antibody of the individual supramolecular structure to form a complex in solution (Sheet 61 of 88, Figure 59). And Schwartz teaches that the antigen molecule is a protein, peptide, or peptide fragment ([0190-0191]).
Schwartz also teaches contacting the complex with a bead carrying a capture antibody having binding
specificity for the antigen molecule to form a sandwich structure (Sheet 62 of 88, Figure 60; Sheet 63 of 88, Figure 61; [0850]). And Schwartz teaches that the antibody of the supramolecular structure and the capture antibody bind to different locations on the antigen molecule [0850]. Schwartz teaches further displacing the nucleic acid capture strand duplexed to the complementary strand using a displacing strand to release the core structure linked to the complementary strand into solution (Sheet 68 of 88, figure 66; sheet 69 of 88, figure 67). And Schwartz teaches that the released core structure is not coupled to the antibody of the individual supramolecular structure (Sheet 68 of 88, figure 66; sheet 69 of 88, figure 67). Schwartz also teaches detecting the core structure [0286].
Regarding claim 43, Schwartz teaches separating a remaining portion of the sandwich structure from the released core structure before the detecting (Sheet 68 of 88, figure 66; sheet 69 of 88, figure 67; [0286]).
Regarding claim 45, Schwartz teaches that an individual binding site of the array is sized to permit single-molecule binding of the individual analyte molecule-supramolecular structure complex via the immobilized affinity binders (Sheet 43 of 88, Figure 41; Sheet 45 of 88, Figure 43; Sheet 46 of 88, Figure 44; Sheet 51 of 88, Figure 49).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art (PHOSITA) 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 16 is rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 2012/0258870 A1) as applied to claim 1 above, and further in view of Bernard et al. (US 2014/0243224 A1).
Regarding claim 16, the claim recites:
“The method of claim 1, wherein each binding site has a diameter between 20-
500 nanometers”.
Regarding claim 16, the teachings of Schwartz are previously discussed.
Regarding claim 16, Schwartz does not teach that each binding site has a diameter between 20-
500 nanometers.
Regarding claim 16, Bernard teaches that the diameter of binding sites is between 20-500 nanometers (Page 2, [0020]; page 14, [0113]).
It would have been obvious for a PHOSITA before the effective filing date of the application to modify the spacing and diameter of binding sites as suggested by Bernard and combine it with the binder method of Schwartz because Bernard noted that the spacing and diameter of binding sites allows for its applicability to nucleic acid arrays (Column 1, [0002]), and further noted that the array can be used in a method for detecting analytes such as in the method of Schwartz (Column 2, [0009]). A PHOSITA would have a reasonable expectation of success for combining the above inventions based on the methods of Burden and Schwartz being in the field of detecting analytes by binders.
It would have been obvious for a PHOSITA to use the array of Bernard with the binders of Schwartz because the detection of molecular analyte will be further enhanced with the above combinations.
Claims 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 2012/0258870 A1) as applied to claim 38 above, and further in view of Domenyuk et al. (US 2019/0078093 A1).
Regarding claim 39, the claim recites:
“The method of claim 38, wherein the core structure is a box origami formed
from nucleic acids”.
Regarding claims 39-40, the previous teachings of Schwartz are previously discussed.
Regarding claim 39, Schwartz does not teach that the core structure is a box origami formed from nucleic acids. And regarding claim 40, Schwartz does not teach that the origami is coupled to a plurality of fluorophores that fluoresce at a particular wavelength, and that detecting the core structure comprises detecting fluorescence at the particular wavelength.
Regarding claim 39, Domenyuk teaches that the core structure is a box origami formed from nucleic acids [0245]. And regarding claim 40, Domenyuk teaches that the origami is coupled to a plurality of fluorophores that fluoresce at a particular wavelength, and wherein detecting the core structure comprises detecting fluorescence at the particular wavelength ([0192]: “On UV light absorption, the fluorochrome emits its own light at a longer wavelength (fluorescence), thus allowing localization of the primary complexes”; [0244], [0245]; Sheet 2 of 100, Figure 1B).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the nucleic acids box origami of Domenyuk with the binder’s method of Schwartz because Domenyuk teaches that DNA scaffolds onto which assemblies are made are modifications that improve in vivo stability, specificity, affinity and avidity [0244-0245]. A PHOSITA would have had a reasonable expectation of success for combining the above inventions based on the methods and discussions of Domenyuk and Schwartz being in the field of detecting analytes by affinity binders.
Claims 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (US 2012/0258870 A1) as applied to claim 38 above, and further in view of Thubagere Jagadeesh et al. (US 2021/0095333 A1).
Regarding claim 41, the claim recites:
“The method of claim 38, wherein the capture strand comprises a toehold region
that does not bind to the complementary strand but that does bind to the displacing strand”.
Regarding claims 41-41, the previous teachings of Schwartz are previously discussed.
Regarding claim 41, Schwartz does not teach that the capture strand comprises a toehold region that does not bind to the complementary strand but that does bind to the displacing strand. And regarding claim 42, Schwartz does not teach that the complementary strand comprises a toehold region that does not bind to the capture strand but that does bind to the displacing strand.
Regarding claim 41, Thubagere Jagadeesh teaches that a first oligonucleotide of a capture strand comprises a toehold region that does not bind to the second nucleotide of a complementary strand but that does bind to a third oligonucleotide of a displacing strand [0009].
Regarding claim 42, Thubagere Jagadeesh teaches that a second oligonucleotide strand of a complementary strand comprises a toehold region that does not bind to the first oligonucleotide strand of a capture strand but that does bind to the third oligonucleotide of a displacing strand ([0009]; [0036]; [0064]).
It would have been obvious for a PHOSITA before the effective filing date of the application to combine the multiple complementary nucleic acid strands of Thubagere Jagadeesh with the binder’s method of Schwartz to use in diagnostic applications because Thubagere Jagadeesh invention can detect an analyte at very low concentrations (Column 1, [0004] and [0005]). A PHOSITA would have had a reasonable expectation of success in combining the above inventions based on the methods and discussions of Thubagere Jagadeesh and Schwartz being in the field of detecting analytes by affinity binders.
It would have been obvious for a PHOSITA to combine the oligo displacement technique of Thubagere Jagadeesh with the binders of Schwartz to make an easy and cost-effective test that detect an analyte with no cross-reactivity.
Response to Arguments
Applicant’s arguments with respect to claims 1-17, 19-20, 38-43 and 45 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Furthermore, Applicant's amendment necessitated the new grounds of rejection presented in this Office action.
Conclusion
No claims are allowed.
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.
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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/OMAR RAMADAN/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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