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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/01/2024 and 8/5/2026 has been considered by the examiner.
Election/Restrictions
Applicant's election of Group I, Claims 1, 3-4, 6-8 and 11, without traverse in the reply filed on 08/05/2026 is acknowledged.
Claim Objection
Claims 1, 3-4, 6-8 and 11 are objected to because of the following informalities:
Claim 1: please amend “the cell” (two places) to – the electrochemical cell--.
Claims 3-4, 6-8 and 11: please amend “The cell of claim” to -- The electrochemical cell of claim--.
Claims 6 and 11: please amend “the cell” (two places) to – the electrochemical cell--.
Appropriate correction is required.
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.
Claim 11 is 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 11, claim 11 recites “the application of an alternating current”, which lacks antecedent basis. Therefore, the scope of claim 11 is indefinite.
Claim Rejections - 35 USC § 103
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 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 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.
Claims 1, 3-4, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Graham et al. (US20230227902A1), and in view of Qian et al. (US20120097539A1) and Forrest et al. (US20130068165A1). Graham, Qian, and Forrest have been provided in Restriction/Election mailed on 5/5/2026.
Regarding claim 1, Graham teaches an electrochemical cell (an electrochemical cell as shown in Fig.5A) comprising:
a nanopore embedded in a membrane that separates the cell into cis and trans chambers connected by the nanopore (Fig.5A shows a nanopore embedded in a membrane that separate the cell into cis and trans chambers connected by the nanopore [para. 0084, 0104, 0134]), wherein the cis and trans chambers each contain an electrode ( a voltage potential applied in the same direction relative to the nanopore [para. 0038]; A voltage of 20 mV is applied across the nanopore [para. 0082]; thus it must have an electrode in each of the cis and trans chambers in order to apply the voltage. This limitation will be further rejected in view of Qian in the following), a solution comprising ferrocyanide ion, ferricyanide ion, and a buffer composition (150 mM potassium ferricyanide, 150 mM potassium ferrocyanide, and 25 mM potassium phosphate pH 8 [para. 0413]).
Graham does not explicitly teach: (a) wherein the cis and trans chambers each contain an electrode, and (b) inlet and an outlet ports operably connected to the cell, wherein the ports comprise a metal, wherein the metal exhibits a current density of less than or equal to 10−3 mA/cm2 when polarized to a potential of about 0.3 V versus a Ag/AgCl reference electrode in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM HEPES, pH 7.4, or in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM MES at pH 6.2-6.8.
Qian teaches an electrochemical cell which is a nanopore-based nanoparticle (such as DNA) translocation device as shown in Fig.1A, wherein the cell comprises a first reservoir (cis chamber) having a first reservoir electrode, a second reservoir (trans chamber) having a second reservoir electrode, at least one nanopore providing fluid communication between the first and second reservoirs (abstract), inlet port 116 and outlet port 118 connected to the cell (see Fig.1A).
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 cell in Graham by providing an electrode in each of the cis and trans chamber, inlet and outlet ports connected to the cell, as taught by Qian, since it would allow to apply a voltage across the nanopore through the electrodes, and introduce and extract DNA in and out of the cell [para. 0005, 0051 in Qian].
Modified Graham is silent to wherein the ports comprise a metal, wherein the metal exhibits a current density of less than or equal to 10−3 mA/cm2 when polarized to a potential of about 0.3 V versus a Ag/AgCl reference electrode in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM HEPES, pH 7.4, or in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM MES at pH 6.2-6.8.
Forrest teaches fluid inlet and outlet ports (each fluid passage 44 disposed in the metal plate 26 in Fig.2 interconnecting the underneath fluidic device as shown in Fig.2 [para. 0021]), wherein the metal plate 26 may be constructed from a variety of materials, including iron-nickel-cobalt alloys, titanium, or other metal having a sufficiently low and/or uniform coefficient of thermal expansion [para. 0022]. Thus, Forrest teaches fluidic inlet and outlet ports comprising a metal.
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 inlet and outlet ports in Modified Graham to have the inlet and outlet ports comprising a metal, as taught by Forrest, since Forrest teaches it would be suitable to have the inlet/outlet ports made of a metal such as titanium or iron-nickel-cobalt alloys [para. 0022].
The limitation “wherein the metal exhibits a current density of less than or equal to 10−3 mA/cm2 when polarized to a potential of about 0.3 V versus a Ag/AgCl reference electrode in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM HEPES, pH 7.4, or in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM MES at pH 6.2-6.8” is found to be an inherent characteristic of the disclosed metal. Since the prior art does disclose that the inlet and outlet ports are made of a metal, such as titanium or iron-nickel-cobalt alloys. Since the disclosed metal is substantially the same as the claimed metal, it is contended that the disclosed metal is capable of exhibiting a current density of less than or equal to 10−3 mA/cm2 when polarized to a potential of about 0.3 V versus a Ag/AgCl reference electrode in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM HEPES, pH 7.4, or in a buffer solution of 1 M NH4Cl, 800 mM urea, 100 mM MES at pH 6.2-6.8.
Regarding claim 3, modified Graham teaches the electrochemical cell of claim 1, wherein the metal contains less than 10% iron, less than 8% iron, less than 6% iron, or less than 5% iron (as outlined in the rejection of claim 1 above, Forrest teaches wherein the metal is titanium or iron-nickel-cobalt alloys [para. 0022]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to choose titanium as the metal. Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person if ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(E)). Titanium does not contain iron).
Regarding claim 4, modified Graham teaches the electrochemical cell of claim 1, wherein the metal is a nickel alloy (as outlined in the rejection of claim 1 above, Forrest teaches wherein the metal is titanium or iron-nickel-cobalt alloys [para. 0022]. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to choose iron-nickel-cobalt alloy as the metal. Choosing from a finite number of identified, predictable solutions, with a reasonable expectation for success, is likely to be obvious to a person if ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143 (I)(E)). iron-nickel-cobalt alloy is a nickel alloy).
Regarding claim 11, modified Graham teaches the electrochemical cell of claim 1, and “wherein the application of an alternating current (AC) to the cell with a voltage range of 450 mV to 1200 mV resulting in no visible formation of Prussian Blue in the cell for at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, or at least 10 hours” is a functional limitation of the disclosed electrochemical cell. Since the disclosed electrochemical cell comprising substantially the same elements or components as that of the applicant, it is contended that the electrochemical cell of the prior art is capable of performing the claimed function of resulting in no visible formation of Prussian Blue in the cell for at least 1 hour, at least 2 hours, at least 4 hours, at least 6 hours, at least 8 hours, or at least 10 hours when an alternating current (AC) with a voltage range of 450 mV to 1200 mV is applied to the electrochemical cell.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Graham, Qian and Forrest, as applied to claim 1 above, and further in view of Barrall et al. (US20170369944A1).
Regarding claim 6, modified Graham teaches the electrochemical cell of claim 1, and is silent to wherein the electrochemical cell encloses a solution volume of between about 0.1 and about 1000 femtoliters.
Barrall teaches an electrochemical cell comprising a nanopore embedded in a membrane as shown in Fig. 5. The architecture of the nanopore based sequencing chip described herein comprises an array of wells (e.g., FIG. 5) having various volume capacities, including nanoliter (nL), picoliter (pL), femtoliter (fL), attoliter (aL), zeptoliter (zL) and yocoliter (yL) capacities. For example, the volume of electrolyte 108 (e.g., FIG. 1) or salt solution 506 (e.g., FIG. 5) is provided in a nL, pL, fL, aL, zL, or yL scale. In one embodiment of the present invention, the volume of the electrolyte or salt solution formed by the wells (e.g., well 505 in FIG. 5) of the present invention, or the volume of electrolyte or salt solution used in methods described herein may be provided in a nanoliter (nL), picoliter (pL), femtoliter (fL), attoliter (aL), zeptoliter (zL), or yocoliter (yL) scale [para. 0061]. The disclosed volume of a femtoliter (fL) scale overlaps with the claimed volume range of about 0.1 and about 1000 femtoliters.
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 electrochemical cell in modified Graham to enclose a solution volume of a femtoliter scale, as taught by Barrall, which teaches the suitable volume capacities for the nanopore based electrochemical cell for DNA sequencing [para. 0061].
Furthermore, it would have been obvious to have selected and utilized a volume of the electrochemical cell within the disclosed range, as taught by Barrall, including those amounts that overlap within the claimed range, since one of ordinary skill in the art would reasonably expect any value within the taught range to be suitable given that Barrall specifically teaches the range to be suitable for the volume capacities of the nanopore based electrochemical cell for DNA sequencing. It has been held that obviousness exists where the claimed ranges overlap or lie inside ranges disclosed by the prior art. See MPEP 2144.05 (I).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Graham, Qian and Forrest, as applied to claim 1 above, and further in view of Clarke et al. (US20140262784A1).
Regarding claim 7, modified Graham teaches the cell of claim 1, and Graham teaches 150 mM potassium ferricyanide and 150 mM potassium ferrocyanide [para. 0413], thus is silent to wherein the ferrocyanide and ferricyanide ions are at a total concentration of between about 25 mM and 250 mM.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." MPEP § 2144.05(II)(A). Therefore, it would have been obvious to one skilled in the art to use ferrocyanide and ferricyanide ions at a total concentration of between about 25 mM and 250 mM. Furthermore, the total concentration limitation is further rejected in view of Clarke as outlined in the following.
Clarke teaches an electrochemical cell comprising a nanopore embedded in a membrane for DNA sequencing as shown in Fig.3, and further teaches the solution comprising 625 mM sodium chloride, 25 mM potassium ferricyanide, 75 mM potassium ferrocyanide, 100 mM HEPES, pH 8.0 (buffer 1) [para. 0334 ]. Thus, Clarke teaches wherein the ferrocyanide and ferricyanide ions are at a total concentration of between about 25 mM and 250 mM (25 mM+75 mM=100 mM).
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 ferrocyanide and ferricyanide ions in modified Graham to have a total concentration of 100 mM, as taught by Clarke, which teaches the suitable alternative concentration of the ferrocyanide and ferricyanide ions used in the solution for DNA sequencing in a nanopore based electrochemical cell [para. 0334].
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Graham, Qian and Forrest, as applied to claim 1 above, and further in view of Bayley et al. (US20220162692A1).
Regarding claim 8, modified Graham teaches the cell of claim 1, and is silent to wherein the buffer composition comprises one or more of the following components: ammonium acetate at a concentration of from about 0 mM to about 1500 mM; and ammonium chloride at a concentration of less than 2000 mM, or less than 1000 mM.
Bayley teaches an electrochemical cell comprising a nanopore embedded in a membrane for DNA sequencing as shown in Fig.3 [para. 0044], wherein the buffer composition comprises ammonium acetate at a concentration of from about 0 mM to about 1500 mM ( In some aspects the plurality of nucleic acids are mixed together in solution or suspension. In some aspects the mixing is performed in phosphate buffer, Tris-HCl buffer, TAE, TBE buffer, ammonium acetate buffer or triethylammonium acetate. In some aspects the mixing is performed in 0.1 M phosphate buffer, 0.1 M Tris-HCl buffer, 1×TAE, 1×TBE buffer, 0.1 M ammonium acetate buffer or 0.1 M triethylammonium acetate [para. 0171]). Thus, Bayley teaches wherein the buffer composition comprises 0.1 M ammonium acetate buffer.
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 potassium phosphate buffer in modified Graham to 0.1 M ammonium acetate, as taught by Bayley, which teaches 0.1 M ammonium acetate buffer would be a suitable alternative buffer to the phosphate buffer for the sequence of nucleic acid in nanopore based electrochemical cell [para. 0171; Fig.3].
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Shinoda et al. (US20110020855A1) teaches a tube 1002 made of a metal such as nickel or nickel alloy. Davis et al. (US20150153302A1) teaches nanopore based electrochemical cell wherein the buffer comprises sodium glutamate, potassium glutamate, tetramethylammonium chloride, tetraethylammonium chloride, ammonium chloride, ferrocyanide, ferricyanide, potassium acetate, etc. [para.0183].
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/Primary Examiner, Art Unit 1795
