DETAILED ACTION
Status of the Claims
1. Claims 1-20 are pending.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/09/2025 has been entered.
Status of the Rejections
2. Rejection of claims 1-18 are being modified in view of applicant’s amendments.
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 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.
3. Claim(s) 1-11 and 18-20 is/are rejected under 35 U.S.C. 103(a)as being obvious over Choi et al. (US 2019/0041378) in view of Strobel et al. (Phys.Chem. Chem. Phys., 2011, 13, 9973-9977).
Claim 1. Choi et al. teach a molecular complex configured to bridge a nanogap between a complementary pair of electrodes (biomolecule complex bridges nanogap between pair of electrodes; [0044]), the molecular complex comprising:
a biomolecule having first end and a second end (biomolecules has first and second ends; [0044), wherein at least one of the first end or the second ends of the biomolecule comprises a terminal 3' thiol modification (biomolecule has thiol groups [0047]; since biomolecule binds to Au from both ends/terminal i.e. 3’ and 5’ (see Figs 2a-2f), thus biomolecule comprises terminal 3’ thiol modification);
a first nanoparticle to couple with the first end of the biomolecule (Au island; [0044] see figs 2a-2f);
a second nanoparticle to couple with the second end of the biomolecule to form the molecular complex (Au island; see figs 2a-2f and [0044]); and
wherein the molecular complex is configured to be assembled in the nanogap between the complementary pair of electrodes ([0047], the complex is attach at the tips of the electrode which would form the complex between the nanogap the electrodes).
Choi et al. teach biomolecules are bonded to the nanoparticles using electrical charge or other binding approach [0066] but do not teach nanoparticles include a stabilized compound resulting from a reaction of a citrate compound on the surface of the nanoparticles with (bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt (BSPP).
However, Strobel et al. teach method making DNA-coated gold nanoparticles comprising the steps of modifying (reads on reacting) citrate-stabilized gold nanoparticles (reads on citrate on the surface of the nanoparticles) with phosphine (bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt for at least 12 hours to form phosphine coated gold nanoparticles (reads on stabilized compound nanoparticles) and combining with thiolated dsDNA (page 9974, col.1, paragraph 2 over to col. 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention in view of Strobel et al. teaching to use citrate-stabilized nanoparticles stabilized with BSPP in the Choi et al. assembly because BSPP/phosphine-based nanoparticles are more stable and thereby provide stabilized DNA-nanoparticle.
Claim 2. Choi et al. teach the biomolecule comprises a double stranded nucleic acid (dsDNA) having a thiolated end and wherein the first nanoparticle couples to the biomolecule through the thiolated end of the biomolecule (DNA having SH end couple to nanoparticle; [0044][0082], DNA is double stranded).
Claim 3. Choi et al. teach the biomolecule comprises one of a single strand or a double-stranded nucleic acid (the biomolecule is DNA; [0044]).
Claim 4. Choi et al. teach the molecular complex is conductive (biomolecule is bridge in the nanogap through which electronic current or voltage signals are detected; [0054]).
Claim 5. Choi et al. in view of Strobel et al. teach the first and the second nanoparticles are stabilized to prevent nanoparticle aggregation (the nanoparticles are stabilized with BSPP (see claim 1 rejection above), and BSPP charge prevents nanoparticle aggregation; see applicant PGPUB [0068]).
Claims 6 and 8. Choi et al. tach method for making a molecular complex configured to bridge a nanogap between a complementary pair of electrodes (biomolecule complex bridges nanogap between pair of electrodes; [0044]), the method comprising:
forming a nucleic acid having a first and a second functionalized ends (DNA has thiol groups on each terminal [0044];
forming a plurality of nanoparticles, the plurality of nanoparticles comprising a first nanoparticle and a second nanoparticle (Au islands; [0044];
conjugating the first functionalized end of the nucleic acid with the first nanoparticle; and conjugating the second functionalized end of the nucleic acid with the second nanoparticle; wherein the nucleic acid comprises two complementary single stranded nucleic acids with terminal 3' thiol modification to conjugate separately with each of the first and the second nanoparticles (DNA has thiol groups on each terminal [0047][0082]; since biomolecule binds to Au from both ends/terminal i.e. 3’ and 5’ (see Figs 2a-2f), thus biomolecule comprises terminal 3’ thiol modification), and
wherein the molecular complex is configured to be assembled in the nanogap between the complementary pair of electrodes ([0044], the complex is attach at the tips of the electrode which would form the complex between the nanogap the electrodes).
Choi et al. teach biomolecules are bonded to the nanoparticles using electrical charge or other binding approach [0066] but do not teach nanoparticles include a stabilized compound resulting from a reaction of a citrate compound on the surface of the nanoparticles with (bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt (BSPP).
However, Strobel et al. teach method making DNA-coated gold nanoparticles comprising the steps of modifying (reads on reacting) citrate-stabilized gold nanoparticles (reads on citrate on the surface of the nanoparticles) with phosphine (bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt for at least 12 hours to form phosphine coated gold nanoparticles (reads on stabilized compound nanoparticles) and combining with thiolated dsDNA (page 9974, col.1, paragraph 2 over to col. 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention in view of Strobel et al. teaching to use citrate-stabilized nanoparticles stabilized with BSPP in the Choi et al. method because BSPP/phosphine-based nanoparticles are more stable and thereby would provide stabilized DNA-nanoparticle.
Claim 7. Choi et al. teach the biomolecule comprises one of a single strand or a double-stranded nucleic acid (the biomolecule is DNA; [0044]).
Claim 9. Choi et al. in view of Strobel et al. teach coupling the first nanoparticle to a first nanoelectrode via a surface ligand and wherein the surface ligands is selected from the group consisting of citrate, amine, tannic acid, dodecanethiol, carboxyl, polyethylene glycol (PEG), Polyvinylpyrrolidone (PVP) may be capped onto the nanoparticle (the nanoparticles comprised of citrate-stabilized nanoparticles; page 9974, col.1, paragraph 2 over to col. 2).
Claim 10, modified Choi et al. teach coupling the second nanoparticle to a second nanoelectrode and extending the molecular complex to substantially bridge a nanogap between the first and the second nanoelectrodes (biomolecule complex bridges nanogap between pair of electrodes; see Choi et al. [0044]).
Claim 11, Choi et al. in view of Strobel et al. teach method making DNA-coated gold nanoparticles comprising the step of forming citrate-stabilized gold nanoparticles with phosphine (bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt for at least 12 hours and combining with thiolated dsDNA (page 9974, col.1, paragraph 2 over to col. 2).
Claim 19. Choi et al. teach positioning of the molecular complex in the nanogap [0044] but do not explicitly teach an induction source to induce positioning of the molecular complex substantially in the gap. However, Strobel et al. teach trapping DNA-Au nanoparticles in the nanogap using dielectrophoretic field in order to achieve controlled functionalization of nanogap (see 9974, col. 2, paragraph 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention in view of Strobel to use dielectrophoretic force to place the molecular complex of Choi et al. into the nanogap because dielectrophoretic force would place the DNA-Au complex in nanogap in a controlled manner in order to properly sequence the DNA.
Claim 20. Choi et al. teach the molecular complex is attach between the tips of the electrodes ([0044]) and gap is defined between the tips, thus complex defines is equal to the nanogap as claimed.
Claim 18. Choi et al. teach positioning of the molecular complex in the nanogap [0044] but do not explicitly teach an induction source to induce positioning of the molecular complex substantially in the gap. However, Strobel et al. teach trapping DNA-Au nanoparticles in the nanogap using dielectrophoretic field in order to achieve controlled functionalization of nanogap (see 9974, col. 2, paragraph 2).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention in view of Strobel to use dielectrophoretic force to place the molecular complex of Choi et al. into the nanogap because dielectrophoretic force would place the DNA-Au complex in nanogap in a controlled manner in order to properly sequence the DNA.
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.
Claim(s) 12-17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choi et al. (US2019/0041378).
Claim 12. A molecular sensor array (molecular electronic device comprising parallel electronic sensing array [0044]), comprising:
at least one sensor having:
a first nanoelectrode and a second nanoelectrode, the first and the second nanoelectrodes separated by a nanogap, the first nanoelectrode and the second nanoelectrodes forming an electrode pair (nanogap between pair of electrodes; [0044]);
a molecular complex extended between the first nanoelectrode and the second nanoelectrode (biomolecule complex bridges nanogap between pair of electrodes; [0044]), the molecular complex further comprising:
a biomolecule having first end and a second end, wherein at least one of the first end or the second ends of the biomolecule comprises a terminal 3' thiol modification (biomolecule has thiol groups [0047]; since biomolecule binds to Au from both ends/terminal i.e. 3’ and 5’ ([0082]), thus biomolecule comprises terminal 3’ thiol modification;
a first nanoparticle to couple with the first end of the biomolecule ([0044][0052]);
a second nanoparticle to couple with the second end of the biomolecule ([0044][0052]); and
the first end of the biomolecule is conjugated to the first nanoparticle and the second end of the biomolecule is conjugated to the second nanoparticle (biomolecules is coupled to the nanoparticles using thiol group [0047]);
wherein the biomolecule is functionalized with a terminal 3' thiol modification to conjugate separately with each of the first and the second nanoparticles (biomolecule has thiol groups [0047][0082]; since biomolecule binds to Au from both ends/terminal i.e. 3’ and 5’, thus biomolecule comprises terminal 3’ thiol modification; and
wherein the molecular complex is configured to be assembled in the nanogap between the complementary pair of electrodes ([0044], the complex is attach at the tips of the electrode which would form the complex between the nanogap the electrodes).
Claim 13. Choi et al. teach the biomolecule comprises one of a single strand or a double-stranded nucleic acid (the biomolecule is DNA; [0044]).
Claim 14. Choi et al. teach the molecular complex is conductive (biomolecule is bridge in the nanogap through which electronic current or voltage signals are detected; [0054]).
Claim 15. Choi et al. in view of Strobel et al. teach the first and the second nanoparticles are stabilized to prevent nanoparticle aggregation (the nanoparticles are stabilized with BSPP (see claim 12 rejection above), and BSPP charge prevents nanoparticle aggregation; see applicant PGPUB [0068]).
Claim 16. Choi et al. teach the molecular complex defines a length substantially equal to the gap and wherein the length is selected from the group consisting of 10-15 nm, 15-25nm, 25-35 nm, 35-45 nm, 45-100 nm, 100 nm - 500 nm, 500 nm - 1 um (the nanogap is 3-10 nm; (Figs 2a-2f) and biomolecule complex bridges the gap, thus the biomolecule complex has a length substantially equal to the nanogap).
Claim 17. Choi et al. teach a passivation layer supporting the nanoelectrodes and a substrate to support the passivation layer (substrate with SiO2 insulator surface; [0013]).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-18 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.
Conclusion
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/GURPREET KAUR/
Primary Examiner
Art Unit 1759