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 .
Office Action: Notice
Any objection or rejection of record in the previous Office Action, mailed 8/27/2025,
which is not addressed in this action has been withdrawn in light of Applicants' amendments
and/or arguments. This action is FINAL.
Election/Restrictions
Applicant’s election without traverse of Group II in the reply filed on July 29, 2025 is acknowledged. Claims 1-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Group 1, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/29/2025. Thus, claims 14-19 are under examination (7/29/2025).
Claim Status
Claims 1-13 have been withdrawn (11/10/2025). Claims 14-15, 17-19 have been amended (11/10/2025). No new matter was added. Claims 14-20 are under examination (11/20/2025).
Priority
Claims 14-20 receive a priority date of 4/24/2019, the effective filing date of PCT/JP2019/017336.
Objections Withdrawn
Specification:
The objections to the specification due to the use of a trademark is withdrawn in view of Applicant’s amendments.
Claims:
The objection to claims 17 in request to spell out an acronym in entirety when first used, is withdrawn due to Applicant’s amendments.
Claim Interpretations
The application of broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) limited by the description in the specification under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, of independent claim 14 is no longer invoked due to the Applicant’s amendments of claim 14 removing “configured to” language.
Rejections Withdrawn
Claim Rejections - 35 USC § 112(a)
The rejections of claims 14-19 under U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in view of Applicant’s removal of functional language “configured to” without sufficient structure to perform the recited function in independent claim 14.
Claim Rejections - 35 USC § 112(b)
The rejections of claims 14-19 under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, 2nd paragraph, are withdrawn in view of Applicant’s amendments of claims 14, 17, and 19.
Rejections Maintained
Claim Rejections - 35 USC § 102
Claims 14-19 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Huff et al., (WO 2017/004463 A1, published 1/5/2017).
Regarding claim 14, Huff teaches methods, devices, and systems for analyte analysis using a nanopore via a first and a second binding member that each specifically bind to an analyte in a biological sample and further includes detecting and/or counting a cleavable tag attached to the second binding member and correlating the presence and/or the number of tags to presence and/or concentration of the analyte (Abstract). Further, Huff teaches that the previously described electrochemical method includes a technique where detection electrodes are formed by sputter deposition, where an ion beam bombards a block of metal and vaporizes metal atoms, which are then deposited on a wafer material in the form of a thin film (Paragraph 296, lines 1-3). Further, Huff teaches that a microfluidics device used in conjunction with a nanopore device is depicted (Figures 1A-1B) incorporates fluid droplets which can be analyzed in the nanopore device and includes a tag (i.e., a cleaved tag or an aptamer) that is to be counted using the nanopore device separated by a first chamber or tank and a second chamber or tank (Paragraph 333, lines 1-5), where one or both droplets may be droplets containing analyte to be detected or counted (or cleaved tag or dissociated aptamer) or conductive or electrolytic solution (i.e., buffer not containing an analyte) for analysis via the nanopore (Paragraph 341, lines 1-2). Huff also teaches that upon contact with the capillary channel, the droplets move into the capillary channel via any suitable means, such as, capillary action and can be facilitated by the capillary channel via diffusion, Brownian motion, convection, pumping, applied pressure, gravity-driven flow, density gradients, temperature gradients, chemical gradients, pressure gradients (positive or negative), pneumatic pressure, gas-producing chemical reactions, centrifugal flow, capillary pressure, wicking, electric field-mediated, electrode-mediated, electrophoresis, dielectrophoresis, magnetophoresis, magnetic fields, magnetically driven flow, optical force, chemotaxis, phototaxis, surface tension gradient driven flow, Marangoni stresses, thermo-capillary convection, surface energy gradients, acoustophoresis, surface acoustic waves, electroosmotic flow, thermophoresis, electrowetting, opto-electrowetting, or combinations thereof (Paragraph 340, lines 1-5).
Regarding claims 15-16, Huff teaches that the previously described methods may include one or more (or alternately two or more) specific binding members or electrodes to detect one or more (or alternately two or more) target analytes in the sample in a multiplexing assay where each of the one or more (or alternately two or more) specific binding members binds to a different target analyte and each specific binding member is labeled with a different tag and/or aptamer (Paragraph 252, lines 1-5). Huff teaches that the previously described electrochemical method includes application of an electric field, such as a voltage across the nanopore- enabled layer leads to the eventual formation of a nanopore, which can be readily detected, i.e., as a dielectric breakdown in a current trace (Figure 40; Paragraph 403, lines 15-20).
Regarding claim 17, Huff teaches that the previously described method includes an array of electrodes where a series of individually controllable electrodes where the single electrode may serve as a reference or a grounding electrode, while the array of electrodes may be individually controllable (for example, the array of electrodes may be actuation electrodes that can be actuated independently) (Figure 2F; Paragraph 342, lines 1-15). Further, Huff teaches that
when a nanopore is to be created in the membrane, a voltage is applied to the salt solution in the cis and trans chamber or tank and conductance through the membrane measured and prior to the creation of a nanopore, there is no or minimal current measured across the membrane and following creation of a nanopore, the current measured across the membrane increases dependent on sufficient time allotments (Paragraph 302, lines 1-10). Huff also teaches that various types of nanopores may be used for analyzing the tags/aptamer, including, among others, biological nanopores that employ a biological pore or channel embedded in a membrane or, the nanopore is a solid state nanopore produced using controlled dielectric breakdown (Paragraph 278, lines 1-5). Huff also teaches that upon contact with the capillary channel, the droplets move into the capillary channel via any suitable means, such as, capillary action and can be facilitated by the capillary channel via diffusion, Brownian motion, convection, pumping, applied pressure, gravity-driven flow, density gradients, temperature gradients, chemical gradients, pressure gradients (positive or negative), pneumatic pressure, gas-producing chemical reactions, centrifugal flow, capillary pressure, wicking, electric field-mediated, electrode-mediated, electrophoresis, dielectrophoresis, magnetophoresis, magnetic fields, magnetically driven flow, optical force, chemotaxis, phototaxis, surface tension gradient driven flow, Marangoni stresses, thermo-capillary convection, surface energy gradients, acoustophoresis, surface acoustic waves, electroosmotic flow, thermophoresis, electrowetting (EWOD), opto-electrowetting, or combinations thereof (Paragraph 340, lines 1-5).
Regarding claim 18, Huff teaches methods, devices, and systems for analyte analysis using a nanopore via a first and a second binding member that each specifically bind to an analyte in a biological sample and further includes detecting and/or counting a cleavable tag attached to the second binding member and correlating the presence and/or the number of tags to presence and/or concentration of the analyte (Abstract). Further, Huff teaches that the previously described electrochemical method includes a technique where detection electrodes are formed by sputter deposition, where an ion beam bombards a block of metal and vaporizes metal atoms, which are then deposited on a wafer material in the form of a thin film (Paragraph 296, lines 1-3). Further, Huff teaches that a microfluidics device used in conjunction with a nanopore device is depicted (Figures 1A-1B) incorporates fluid droplets which can be analyzed in the nanopore device and includes a tag (i.e., a cleaved tag or an aptamer) that is to be counted using the nanopore device separated by a first chamber or tank and a second chamber or tank (Paragraph 333, lines 1-5), where one or both droplets may be droplets containing analyte to be detected or counted (or cleaved tag or dissociated aptamer) or conductive or electrolytic solution (i.e., buffer not containing an analyte) for analysis via the nanopore (Paragraph 341, lines 1-2).
Regarding claim 19, Huff teaches that the previously described electrochemical method includes a proximal portion and a distal portion where the nanopore layer is disposed in the distal portion and the array of electrodes in the proximal portion is configured to generate a droplet, where the array is configured to position the droplet across the nanopore layer such that the droplet is split by the nanopore layer into a first portion and a second portion, wherein at least two electrodes of the array of electrodes are positioned across the nanopore layer, where the two electrodes form an anode and a cathode and operate to drive current through a nanopore in the nanopore layer when a liquid droplet is positioned across the nanopore layer (Paragraph 9, lines 5-15).
Huff teaches each and every limitation of claims 14-19, and therefore Huff anticipates claims 14-19.
Applicant’s Response: The Applicant asserts that Huff does not disclose the specific structural arrangement required by claim 14, including an insulating inorganic thin film separating first and second liquid tanks, a plurality of first electrodes arranged in the first liquid tank, and a second electrode disposed in the second liquid tank configured for electrowetting-based droplet conveyance. The Applicant further argues that Huff’s teachings of electrowetting merely lists it as a possible droplet-movement mechanism in a capillary channel and fails to teach or suggest the claimed electrode configuration or droplet conveyance system.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive, as discussed below.
A claim is anticipated when a single prior art reference discloses, either expressly or inherently, each and every limitation of the claimed invention (see MPEP 2131). Further, during examination, claims are given their broadest reasonable interpretation consistent with the specification (see MPEP 2111). Huff teaches analyte analysis using a nanopore device including first and second chambers or tanks separated by a membrane or thin film, electrodes formed by sputter deposition on a thin film substrate, and droplets containing analyte or conductive solution positioned for nanopore analysis (Paragraphs 296, 333, 341). Huff further teaches arrays of individually controllable electrodes and application of voltage across cis and trans chambers to drive current through a nanopore and analyze droplets positioned across the nanopore layer (Paragraphs 302, 342), as well as droplet manipulation mechanisms including electric-field-mediated transport and electrowetting (Paragraph 340). These disclosures collectively teach the structural arrangement and functional operation recited in independent claim 14 and the dependent claims.
The Applicant’s contention that Huff merely lists electrowetting without teaching the claimed electrode configuration is unpersuasive because anticipation does not require the identical arrangement or preferred embodiment described in the specification, only that the claimed limitations are disclosed in the reference (see MPEP 2131.02). Specifically, independent claim 14 uses the open transitional phrase “comprising”, which does not exclude additional elements or variations in configuration (See MPEP 2111.03). Further, anticipation does not require the reference to disclose an identical embodiment or preferred structural arrangement, but only that the claimed elements are present in the reference as broadly interpreted (see MPEP 2111, 2131). Huff teaches electrodes arranged relative to chambers separated by a membrane and capable of electrically actuating and transporting droplets for nanopore analysis, which reasonably encompasses electrowetting-based conveyance using first and second electrodes, as claimed. Moreover, disclosure of multiple alternative droplet-movement mechanisms does not negate anticipation where one disclosed mechanism meets the claim limitations (see MPEP 2131).
Accordingly, because Huff teaches each limitation of claims 14-19, the rejection under 35 USC 102(a)(1) and 102(a)(2) is maintained.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Application No. 16/463,502
Claims 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of co-pending Application No. 16/463,502 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending claim 1 recites “A nanopore forming method that is a method of applying a voltage to a thin film to form a nanopore, comprising: applying a first modulation voltage to a thin film; comparing an amount of a change in a phase of a current carried through the thin film with respect to a phase of the first modulation voltage with a threshold; and upon detecting that the amount of the change in the phase exceeds the threshold, stopping application of the first modulation voltage.”
Co-pending claim 2 recites “The nanopore forming method according to claim 1, wherein a parameter of the first modulation voltage is determined corresponding to an impedance of the thin film.”.
Co-pending claim 3 recites “The nanopore forming method according to claim 2, wherein before application of the first modulation voltage, the impedance of the thin film is measured.”
Co-pending claim 8 recites “The nanopore forming method according to claim 1, wherein: a plurality of the thin films is provided such that the thin films are isolated from each other by a wall, and the first modulation voltage is applied to each of the plurality of thin films; an amount of a change in a phase of a current carried through each of the thin films with respect to the phase of the first modulation voltage is individually compared with the threshold; and application of the first modulation voltage is stopped on a thin film on which the amount of the change in the phase exceeds the threshold is detected.”
The difference between the present application and 17/604,881 is claims 14-16 of 17/604,881 recites a biopolymer analysis method that includes preparing an analysis device with liquid tanks, introducing droplets, conveying droplets by electrowetting, introducing an electrolyte solution, and analyzing biopolymers based on current values when the biopolymer passes through the nanopore. Claims 1-3 and 8 of the present application, 16/463,502 recite a nanopore forming method comprises applying voltage to a thin film, comparing phase changes in current with a threshold, and stopping voltage application when the threshold is exceeded. Thus, it would be obvious to one of ordinary skill in the art that the nanopore forming method of claims 1-3 and 8 of the present application, 16/463, 502, could be incorporated into a biopolymer analysis device as recited in claims 14-16 of 17/604,881. The addition of biopolymer analysis steps to the disclosed nanopore formation method would be a natural and obvious extension of the technology for its intended purpose. Thus, the subject matter of claims 1-3 and 8 of the present application, 16/463,502 would be obvious to one of ordinary skill in the art in view of the disclosure of claims 14-16 of 17/604,881.
Application No. 18/018,084
Claims 14-16 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 12 of co-pending Application No. 18/018,084 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons that follow. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Co-pending claim 1 recites “A biomolecule analysis method comprising: preparing a biomolecule analysis device including a thin film, a first liquid tank and a second liquid tank separated by the thin film, a first electrode disposed in the first liquid tank, and a second electrode disposed in the second liquid tank; and forming a nanopore in the thin film by applying a first voltage between the first electrode and the second electrode in a state where a nanopore forming solution is enclosed in the first liquid tank and the second liquid tank, wherein the nanopore forming solution contains ammonium ions and sulfate ions.”
Co-pending claim 2 recites “A biomolecule analysis method comprising: preparing a biomolecule analysis device including a thin film having a nanopore, a first liquid tank and a second liquid tank separated by the thin film, a first electrode disposed in the first liquid tank, and a second electrode disposed in the second liquid tank; and measuring a current flowing between the first electrode and the second electrode by applying a voltage between the first electrode and the second electrode in a state where a measurement solution is enclosed in the first liquid tank and the second liquid tank, wherein the measurement solution contains ammonium ions and sulfate ions.”
Co-pending claim 3 recites “The biomolecule analysis method according to claim 1, further comprising measuring a current flowing between the first electrode and the second electrode by applying a second voltage between the first electrode and the second electrode in a state where a measurement solution is enclosed in the first liquid tank and the second liquid tank after formation of the nanopore, wherein the measurement solution contains the ammonium ions and the sulfate ions.”
Co-pending claim 12 recites “The biomolecule analysis method according to claim 2, further comprising: introducing a biomolecule into the measurement solution when measuring the current; and analyzing the biomolecule based on a measurement result of the current.”
The difference between the present application and 17/604,881 is claims 14-16 and 18 of 17/604,881 recites a biopolymer analysis method that includes preparing an analysis device with liquid tanks, introducing droplets, conveying droplets by electrowetting, introducing an electrolyte solution, and analyzing biopolymers based on current values when the biopolymer passes through the nanopore. Claims 1-3 and 12 of the present application, 18/018,084 recite a biomolecule analysis method comprising applying voltage to thin film, comparing phase changes in current with a threshold, and stopping voltage application when the threshold is exceeded, wherein the nanopore forming solution and measurement solution contain ammonium ions and sulfate ions. Thus, it would be obvious to one of ordinary skill in the art that the nanopore forming method of claims 1-3 and 12 of the present application, 18/018,084, could be incorporated into a biopolymer analysis device with electrowetting droplet manipulations recited in claims 14-16 and 18 of 17/604,881. The addition of electrowetting-based droplet handling to the disclosed nanopore-based biomolecule analysis method would be a natural and obvious combination for improving the analytical capabilities of the device. Thus, the subject matter of claims 1-3 and 12 of the present application, 18/018,084 would be obvious to one of ordinary skill in the art in view of the disclosure of claims 14-16 and 18 of 17/604,881.
Applicant’s Response: The Applicant does not address the nonstatutory double patenting rejection.
Examiner’s Response to Traversal: Since the Applicant does not address the nonstatuatory double patenting rejection, no arguments have been considered and the rejection is maintained.
New Rejections
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 (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 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.
Claim 20 is rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Huff et al., (WO 2017/004463 A1, published 1/5/2017).
Regarding claim 20, Huff teaches that the position of the cross section at the position of the transfer electrode and capillary channel have various thickness dependent on difference in height of the substrates and resultant alignment (Figure 2E; Paragraphs 339-340). Huff further teaches that while the two capillary channels are depicted to be perpendicular to each other at the point of intersection, other configurations are also envisioned where the two channels intersect at an angle other than 90 degrees and upon contact with the capillary channel, the droplets move into the capillary channel via any suitable means, such as, capillary action and may be facilitated by additional methods/materials (i.e., electrode-mediated, electrophoresis, dielectrophoresis, magnetophoresis, magnetic fields, magnetically driven flow) or via an actuation force, such as those disclosed herein; using hydrophilic coating in the capillary; varying size (e.g. width and/or height and/or diameter and/or length) of the capillary channel) (Paragraph 340, lines 1-10). Specifically, Huff teaches that site-specific induced cleavage at aspartic acid residue in peptides and proteins applies a method of pyrolytic cleavage where samples were placed in a glass tube and subjected to 13 volts (Figure 62).
Huff teaches each and every limitation of claim 20, and therefore Huff anticipates claim 20.
Conclusions
No claim is 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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/ELIZABETH ROSE LAFAVE/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684