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 .
Status of the Claims
The Amendment filed January 2, 2026 has been entered. Claims 1-2, 4, and 9 have been amended; and claims 10-20 have been withdrawn. Claims 1-9 are currently examined herein.
Status of the Rejection
Applicant’s amendments to the Claims have overcome each objection and 112(b) rejections previously set forth in the Non-Final Office Action mailed October 3, 2025.
New grounds of rejection under 35 U.S.C. § 112(b) are necessitated by the amendment as outlined below.
All 35 U.S.C. § 102 and 35 U.S.C. § 103 rejections from the previous office action are withdrawn in view of the amendment.
New grounds of rejection under 35 U.S.C. § 103 are necessitated by the amendment as outlined below.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Regarding claim 2, claim 2 recites “the operational amplifier”, while claim 1 recites at least two sequencing units, each comprising … an electronic circuit… comprising an operation amplifier”, thus each of the at least two sequencing units comprises an operational amplifier (OA). It is unclear if “the operational amplifier” in claim 2 refers to each OA or a specific (then which) OA. Thus, the scope of claim 2 is indefinite. Claim 3 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 2.
Regarding claim 3, claim 3 recites “the memory unit”, while claim 1 recites at least two sequencing units, each comprising …a memory unit”, thus each of the at least two sequencing units comprises a memory unit. It is unclear if “the memory unit” in claim 3 refers to each memory unit or a specific (then which) memory unit. Thus, the scope of claim 3 is indefinite.
Regarding claim 4, claim 4 recites “the sequencing cell” and “the operational amplifier”, while claim 1 recites at least two sequencing units, each comprising a sequencing cell…; an electronic circuit… comprising an operation amplifier”, thus each of the at least two sequencing units comprises a sequencing cell and an operational amplifier (OA). It is unclear if “the sequencing cell” and “the operational amplifier” in claim 4 refers to, respectively, the sequencing cell and the OA of each of the at least two sequencing units, or the sequencing cell and the OA of a specific (then which) sequencing unit. Thus, the scope of claim 4 is indefinite. Claim 5 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 4.
Regarding claim 5, claim 5 recites “the memory unit”, while claim 1 recites at least two sequencing units, each comprising …a memory unit”, thus each of the at least two sequencing units comprises a memory unit. It is unclear if “the memory unit” in claim 5 refers to each memory unit or a specific (then which) memory unit. Thus, the scope of claim 5 is indefinite.
Regarding claim 6, claim 6 recites “the memory unit” and “the sequencing cell”, while claim 1 recites at least two sequencing units, each comprising a sequencing cell…; a memory unit”, thus each of the at least two sequencing units comprises a sequencing cell and a memory unit. It is unclear if “the memory unit” and “the sequencing cell” in claim 6 refers to, respectively, the memory unit and the sequencing cell of each of the at least two sequencing units, or the memory unit and the sequencing cell of a specific sequencing unit. Thus, the scope of claim 6 is indefinite.
Regarding claim 7, claim 7 recites “the sequencing cell”, while claim 1 recites at least two sequencing units, each comprising a sequencing cell”, thus each of the at least two sequencing units comprises a sequencing cell. It is unclear if “the sequencing cell” in claim 7 refers to each sequencing cell or a specific (then which) sequencing cell. Thus, the scope of claim 7 is indefinite.
Regarding claim 8, claim 8 recites “the nanopore”, while claim 1 recites at least two sequencing units, each comprising a sequencing cell comprising a nanopore”, thus each of the at least two sequencing units comprises a nanopore. It is unclear if “the nanopore” in claim 8 refers to each nanopore or a specific (then which) nanopore. Thus, the scope of claim 8 is indefinite.
Regarding claim 9, claim 9 recites “the sequencing cell”, while claim 1 recites at least two sequencing units, each comprising a sequencing cell”, thus each of the at least two sequencing units comprises a sequencing cell. It is unclear if “the sequencing cell” in claim 9 refers to each sequencing cell or a specific (then which) sequencing cell. Thus, the scope of claim 9 is indefinite.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 4, and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Fernandez-Gomez et al. (US20170091381A1; hereinafter FG), and in view of Wang et al. (CN112994680A, English translation).
Regarding claim 1, FG teaches a device for sequencing polynucleotides (a system for detecting a state of a nanopore and adaptively processing nanopore state data as shown in Fig.25, and the system comprises a nanopore cell 2502, measurement circuitry 2504, local event detector 2506, adaptive analyzer 2512 and a state memory 2508 [para. 0125, 0127-0129]; The biochip may be a DNA sequencing biochip [para. 0125]; thus the system is configured for performing the intended use of sequencing polynucleotides), comprising a sequencing unit (the biochip shown in Fig.25 is deemed as a sequencing unit) comprising:
a sequencing cell (nanopore cell 2502 in Fig.25) comprising a nanopore for sensing a polynucleotide (the nanopore cell 2502 may be nanopore cell 200 in Fig.2 [para. 0127], and Fig.2 shows the sequencing cell comprising a nanopore 206 for performing nucleotide sequencing with the Nano-SBS technique [para. 0043]);
an electronic circuit (measurement circuitry 2504 in Fig.25 [para. 0128]) configured to measure an electrical response in the sequencing cell (Measurement circuitry 2504 detects electrical measurements of nanopore cell 2502 [para. 0128]; thus, the disclosed electronic circuit is configured to perform the claimed functions of measuring an electrical response in the sequencing cell); and
a memory unit (state memory 2508 in Fiog.25) configured to store a state of the sequencing cell ( state memory 2508 stores one or more reference measurement values corresponding to one or more nanopore states [e.g., measurement values corresponding to an open-channel state of a nanopore] [para. 0131]; thus the state memory 2508 is configured to perform the claimed functions of storing a state of the sequencing cell).
FG is silent to wherein the electronic circuit comprises an operational amplifier, and the device comprises at least two sequencing units.
Wang teaches a nanopore device for DNA sequencing as shown in Fig.1 [para. n0026-n0027]. Fig.3 shows a sensor circuit 60 which is a nanopore sensor (corresponding to the claimed sequencing cell) is operably connected to a corresponding electronic circuit 301, wherein each sequencing cell of a plurality of sequencing cells is connected to a negative input terminal of an operational amplifier (AMP in Fig.3) via a gate (a multiplexing switch matrix 20 in Fig.3), and at least one voltage source Vbias is operably connected to a positive input terminal of the AMP of each electronic circuit 301 [para. n0029, n0032]. Thus, Wang teaches a DNA sequencing device comprising a plurality of sequencing unit (each sensor unit 60 and its corresponding electronic circuit 301 in Fig.3 is deemed as a sequencing unit), wherein each electronic circuit comprises an operational amplifier (OA), in each sequencing unit the sequencing cell is operably connected to a negative input terminal of the OA via a gate.
FG and Wang are considered analogous art to the claimed invention because they are in the same field of nanopore-based DNA sequencing devices. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the measurement circuit 2504 of FG with the measurement circuit 30 comprising an OA, wherein the sequencing cell is operably connected to a negative input terminal of the OA via a gate, as taught by Wang, since the measurement circuit with an OA would amplify the electrical signal collected by the nanopore sensor which may specifically be a weak current signal [para. n0041 in Wang].
With the above modification, modified FG teaches the sequencing unit comprising a sequencing cell comprising a nanopore for sensing a polynucleotide; an electronic circuit configured to measure an electrical response in the sequencing cell, the electronic circuit comprising an operational amplifier; and a memory unit configured to store a state of the sequencing cell.
Given the teachings of Wang regarding a plurality of sequencing units (see Fig.3), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to duplicate the sequencing unit of modified FG to provide a plurality of sequencing units, since it would allow to select the nanopore with the best quality from multiple nanopores for sequencing [para. n0022 in Wang]. Furthermore, it has been held that mere duplication of parts has no patentable significance unless a new and unexpected result is produced. See MPEP § 2144.04(VI)(B).
Regarding claim 4, modified FG teaches the device of claim 1, wherein the sequencing cell is operably connected to a negative input terminal of the operational amplifier via a gate (as outlined in the rejection of claim 1 above, the sequencing cell is operably connected to a negative input terminal of the operational amplifier via a gate [see Fig.3 in Wang]).
Regarding claim 6, modified FG teaches the device of claim 1, and FG teaches wherein outputs of the memory unit depend in part on the stored state of the sequencing cell (the stored report status identifier [e.g., stored in state memory 2508 of FIG. 25] tracks whether an electrical measurement value that corresponds to a threaded state has been already reported [e.g., reported to adaptive analyzer 2512] for a current bright period of a current cycle of a reference AC voltage source signal of a nanopore cell. In some embodiments, at 2608, the stored report status identifier is obtained to determine whether the report status identifier indicates that an electrical measurement sample value that corresponds to a detected threaded state of the nanopore has been already reported. If the report status identifier indicates that a previous electrical measurement sample value has been already reported, a subsequent electrical measurement sample value corresponding to the same threaded nanopore state may not need to be reported [para. 0143]. Thus, outputs of the memory unit [report status identifiers] depend in part on the stored state of the sequencing cell).
Regarding claim 7, modified FG teaches the device of claim 1, and FG teaches wherein the stored state of the sequencing cell is associated with a previous electrical response in the sequencing cell (the stored report status identifier [e.g., stored in state memory 2508 of FIG. 25] tracks whether an electrical measurement value that corresponds to a threaded state has been already reported [e.g., reported to adaptive analyzer 2512] for a current bright period of a current cycle of a reference AC voltage source signal of a nanopore cell. In some embodiments, at 2608, the stored report status identifier is obtained to determine whether the report status identifier indicates that an electrical measurement sample value that corresponds to a detected threaded state of the nanopore has been already reported. If the report status identifier indicates that a previous electrical measurement sample value has been already reported, a subsequent electrical measurement sample value corresponding to the same threaded nanopore state may not need to be reported [para. 0143]. Thus, the stored state of the sequencing cell is associated with a previous electrical response in the sequencing cell [a previous electrical measurement sample value]. Furthermore, as outlined in the rejection of claim 1 above, the memory unit is configured to store the state of the sequencing cell, thus is configured to store the state of the sequencing cell which is associated with a previous electrical response in the sequencing cell).
Regarding claim 8, modified FG teaches the device of claim 1, and FG is silent to wherein the nanopore of cell 200 is an opening in a protein or nucleic acid structure deposited in a lipid or polymer membrane, or wherein the nanopore is an opening in a solid-state structure.
Wang does teach there are two types of nanopores currently used for DNA sequencing: biological nanopores (composed of certain protein molecules embedded in a phospholipid membrane) and solid nanopores (comprising various silicon-based materials, SiNx, carbon nanotubes, graphene, glass nanotubes and the like) [para. n0028].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the nanopore which is an opening in a protein structure deposited in a lipid membrane, or wherein the nanopore is an opening in a solid-state structure, as taught by Wang, since Wang teaches the two types of nanopores currently used for DNA sequencing [para. n0028].
Regarding claim 9, modified FG teaches the device of claim 1, wherein the electrical response in the sequencing cell is modulated by: nucleotides in the polynucleotide near a sensing zone of the nanopore (FG teaches Fig.2 shows nucleotide sequencing wherein the electrical response in the sequencing cell [current in y-axis of Fig.2] is modulated by nucleotides in the polynucleotide such as A, C, G, T near a sensing zone of the nanopore. In the alternative, Wang teaches because the four bases adenine (a), guanine (G), cytosine (C) and thymine (T) constituting DeoxyriboNucleic Acid (DNA) have different molecular structures and volume sizes, when single-stranded DNA (ssdna) passes through the nanopore 102 under the driving of an electric field, the current caused by the difference of different bases varies in amplitude when passing through the nanopore 102, thereby obtaining the sequence information of the detected DNA [para. n0027]).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over FG and Wang, as applied to claim 1 above, and further in view of Yanagawa et al. (US 20190369080A1).
Regarding claim 2, modified FG teaches the device of claim 1, and as outlined in the rejection of claim 1 above, Wang teaches comprising at least one voltage source, Vbias, operably connected to the positive input terminal of the operational amplifier (see Fig.3 in Wang). Note that Wang also teaches the negative input terminal of the amplifier is connected to the sequencing cell (see Fig.3).
Modified FG is silent to wherein the at least one voltage source operably connected to the positive input terminal of the operational amplifier “via at least one switch”.
Yanagawa teaches an electronic circuit configured to measure an electrical response in a sequencing cell (see Fig.18 [para. 0078]), wherein the electronic circuit comprises an transimpedance amplifier 207, and one input terminal of the amplifier is operably connected to the sequencing cell via the first electrode 206, and at least one voltage source (voltage source 209, Vstby, and Vread in Fig.18) operably connected to another input terminal of the operational amplifier “via at least one switch” 1708 [para. 0079].
Given the teachings of Wang regarding at least one voltage source, Vbias, operably connected to the positive input terminal of the operational amplifier, and the negative input terminal of the OA is connected to the sequencing cell; and the teachings of Yanagawa regarding one input terminal of the amplifier is connected to the sequencing cell, and at least one voltage source (voltage source 209, Vstby and Vread in Fig.18) operably connected to another input terminal of the amplifier “via at least one switch” 1708, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the at least one voltage source and the electronic circuit in modified FG to include a modulation voltage source, standby voltage, and read voltage as the at least one voltage source, and add a switch connecting the at least one voltage source and the positive input terminal of the OA, as taught by combined Wang and Yanagawa, since it would allow to selectively apply a different voltage at different stage [para. 0080 in Yanagawa].
Allowable Subject Matter
Claims 3 and 5 would be allowable if they are rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
The following is a statement of reasons for the indication of allowable subject matter.
Regarding claim 3, as outlined in the rejection of claim 2 above, the at least one switch connects the at least one voltage source and the positive input terminal of the OA. The prior art of the record does not teach and/or suggest wherein the at least one switch is operably connected to at least some output terminals of the memory unit.
Regarding claim 5, as outlined in the rejection of claim 4 above, the gate (the multiplexing switch matrix 20 in Fig.3 of Wang) connects each sequencing cell and the corresponding electronic circuit (see Fig.3 in Wang). The prior art of the record does not teach and/or suggest wherein the gate is operably connected to at least some output terminals of the memory unit.
As allowable subject matter has been indicated, applicant's reply must either comply with all formal requirements or specifically traverse each requirement not complied with. See 37 CFR 1.111(b) and MPEP § 707.07(a).
Response to Arguments
Applicant's arguments, see Remarks Pgs. 5-8, filed 1/2/2026, with respect to the 35 U.S.C. § 102 and 35 U.S.C. § 103 rejections have been fully considered, and all 102 and 103 rejections from the previous office action have been withdrawn in view of the amended claim 1.
Applicant’s Argument #1:
Applicant argues at pages 5-8 that Chen fails to teach or suggest a device comprising at least two sequencing units that each comprises a memory unit. Chen's disclosure only suggests a device wherein all of the sequencing units connect to one computer memory. Claims 2-9 depend from amended claim 1, and are allowable for the same reasons as claim 1.
Examiner’s Response #1:
Applicant’s arguments have been fully considered, but are moot in view of the new grounds of rejection for the amended claim 1 above.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHIZHI QIAN whose telephone number is (571)272-3487. The examiner can normally be reached Monday-Thursday 8:00 am-5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan V Van can be reached on 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHIZHI QIAN/Examiner, Art Unit 1795