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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 10, 2026 has been entered.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-9 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.
Applicant has argued that the combination of Liu et al., in view of Umehara et al., relied upon in the previous Office Action (November 10, 2025) do not meet the limitations of the instant claims. Specifically, Applicant has argued that reference to Liu et al., do not teach a transient potential change induced by a collision event of a charged biomolecule at a nanoelectrode. After reviewing reference to Liu et al., the Examiner has found Applicant’s arguments to be persuasive. However, as detailed below, claims 1-9 now stand rejected under 35 U.S.C. 103 as being obvious over the combination of Pandey et al., (ACS Nano 2016, 10, 11237-11248) in view of Umehara et al. Because reference to Pandey et al., is newly cited, the Examiner will not argue the merits of its teachings here, but will instead rely on the rejection detailed below. With respect to reference to Umehara et al., the Examiner notes that the reference is cited for teaching label-free biosensing wherein the surface charge of proteins are detected utilizing a nanopipette. Umehara et al., teach that utilizing a nanopipette to detect biomolecules provides the advantage of a sensing mechanism that is fast, compact, and easily multiplexed compared to optical methods. Umehara et al., also teach that the system may be useful for detecting proteins related to different cancer types, thereby providing sufficient motivation to combine the references. Therefore, based on the teachings of the prior art, the Examiner contends that the limitations of the instant claims are taught by the combination of Pandey et al., in view of Umehara et al., as detailed below.
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.
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.
Claim(s) 1, 2, 4, and 6-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Panday et al., (ACS Nano 2016, 10, 11237-11248) in view of Umehara et al., (PNAS vol 106, No. 12, March 24, 2009).
Regarding claim 1, Panday et al., teach ionic current and potential detection of nanoparticles by a multifunctional nanopipette comprising providing a solution comprising nanoparticles (Figure 1a), contacting the solution with a system comprising a nanopipette sensor having a nanoelectrode barrel filled with a carbon nanoelectrode (Introduction page 11238, left column, Figures 1A and C). Panday et al., also teach measuring transient electrical potential changes induced by translocation of the nanoparticles through the nanopipette sensor (Simultaneous Ionic Current and potential Measurements of GNP Motion, pages 11240-11246), and detecting surface charges of the nanoparticles (Introduction page 11238 right column, Simultaneous Ionic Current and potential Measurements of GNP Motion, pages 11240-11246). The Examiner notes that claim 1 does not require a biomolecule colliding with the nanoelectrode, as the limitation “collision event of the individual charged biomolecule at the nanoelectrode” does not require a collision with the nanoelectrode. Given this interpretation, collisions that occur between the nanoparticles themselves, the nanoparticles and the electrode, or the nanoparticle with the barrel of the nanopipette sensor reads on the claim. Panday et al., do not teach detecting an individual biomolecule.
Umehara et al., teach label-free biosensing wherein the surface charge of proteins are detected utilizing a nanopipette (Abstract, Sensing the Specific Binding of Cancer Biomarker Proteins to the Immobilized lgG Molecules, page 4613, Discussion, pages 4613-4614). Umehara et al., teach that it is advantageous to utilize a nanopipette to detect surface charges on biomolecules as a means of providing a sensing mechanism that is fast, compact, and easily multiplexed biosensing platform compared to optical methods (Discussion, page4614, right column second full paragraph). Umehara et al., also teach that the nanopipette being suitable for detecting proteins related to various cancers (Sensing the Specific Binding of Cancer Biomarker Proteins to the Immobilized lgG Molecules, page 4613).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Panday et al., wherein the nanopipette sensor is utilized to detect biomolecules in order to provide a fast, complex, and easily multiplexed biosensing platform for detecting cancer related proteins as taught by Umehara et al.
Regarding claim 2, Panday et al., do not teach detecting a protein having a molecular weight ranging from 5kDa to 500kDa.
Umehara et al., teach label-free biosensing wherein the surface charge of proteins are detected utilizing a nanopipette (Abstract, Sensing the Specific Binding of Cancer Biomarker Proteins to the Immobilized lgG Molecules, page 4613, Discussion, pages 4613-4614) wherein VEGF (molecular weight ranges from 38 to 44 kDa) is detected (Sensing the Specific Binding of Cancer Biomarker Proteins to the Immobilized lgG Molecules, page 4613). Umehara et al., teach that it is advantageous to detect VEGF as a means of detecting proteins related to colorectal cancer (Sensing the Specific Binding of Cancer Biomarker Proteins to the Immobilized lgG Molecules, page 4613).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Panday et al., wherein VEGF having a molecular weight ranging from 38 to 44 kDa is detected in order to detect proteins related to colorectal cancer as taught by Umehara et al.
Regarding claim 4, Panday et al., teach an electrode made of carbon (Pyrolytic Carbon Nanoelectrode Fabrication, page 11247).
Regarding claim 6, Panday et al., teach the electrode having a surface area ranging from 0.30 µm to 1.33 µm (Multifunctional Nanopipette Fabrication and Characterization, page 11240 left column).
Regarding claim 7, Panday et al., teach a double barrel nanopipette sensor having first and second compartments, and a double barrel nanopipette connecting the first and second compartments wherein one barrel is filled with a carbon nanoelectrode and the other barrel having a nanopore (Introduction page 11238, left column, Figure 1).
Regarding claim 8, Panday et al., teach the electrode having a diameter around 70 ɳm (Multifunctional Nanopipette Fabrication and Characterization, page 11239).
Regarding claim 9, Panday et al., teach measuring translocation of nanoparticles (Simultaneous Ionic Current and potential Measurements of GNP Motion, pages 11240-11246).
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Panday et al., (ACS Nano 2016, 10, 11237-11248) in view of Umehara et al., (PNAS vol 106, No. 12, March 24, 2009) as applied to claim 1 above, and further in view of Karhanek et al., (US 2015/0198559).
Regarding claim 3, Panday et al., in view of Umehara et al., do not teach obtaining a sample from a subject and diluting the sample.
Karhanek et al., teach a nanopipette biosensor for detecting analytes wherein a sample is obtained from a subject, and diluted prior to detection (paragraphs 0014, 0046, 0078). Karhanek et al, teach that it is advantageous to obtain a sample from a subject as a means of performing sensitive, real-time, and cost effective proteome analysis in a clinical setting (paragraph 0031).
Therefore, it would have been obvious to one of ordinary skill in the art at the time the invention was made to modify Panday et al., in view of Umehara et al., wherein a sample is obtained from a subject and diluted as a means of performing sensitive, real-time, and cost effective proteome analysis in a clinical setting as taught by Karhanek et al.
Conclusion
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/DWAN A GERIDO/Examiner, Art Unit 1797 /LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797