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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/19/2024 and 9/25/2025 has been considered by the examiner.
Election/Restrictions
Applicant's election of Group I, Claims 1-3, 5, 7-11, 13-15, 17-18, and 20-21, without traverse in the reply filed on 02/10/2026 is acknowledged.
Claim Objection
Claims 1, 3, 5, 9-11, 14-15 and 21 are objected to because of the following informalities:
Claim 1: please amend “an electrolytic solution” in Ln 7 to – [[an]] the electrolytic solution--; “the inlet” to –the solution inlet--; “the outlet” to –the solution outlet--; “an analyte” in Ln 16 to –[[an]] the analyte--; “a captured analyte” to –[[a]] the captured analyte--.
Claim 3: please amend “the surface of” to – the portion of the surface of --; “the electrode” to -- the working electrode--.
Claim 5: please amend “analytespecific ligand” to – analyte specific ligand—by adding a space between “analyte” and “specific”.
Claim 9: please amend “flow (F)” to – the flow (F)--.
Claim 10: please amend “the inner volume” to – [[the]] an inner volume--.
Claims 11 and 14: please amend “the inlet” to – the solution inlet--; “the outlet” to – the solution outlet--.
Claim 15: please amend “electrolytic solution” to –the electrolytic solution--.
Claim 21: please amend “one chamber for the working electrode” to – one connecting the working electrode--; “one chamber for the counter electrode” to -- the other for connecting the counter electrode--.
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.
Claims 7, 10, and 15 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 7, claim 7 recites “ranges from 20 pm to 20 mm”, and it is unclear if pm refers to µm, thus it is unclear what is the range of the average distance. Therefore, the scope of claim 7 is indefinite.
Regarding claim 10, claim 10 recites “wherein the inner volume of the housing not occupied by the working electrode is 5%-75%”, and the inner volume is a dimensionless percentage value. It is unclear if the claimed limitation refers to a ratio between an inner volume of the housing not occupied by the working electrode and an inner volume of the housing. Thus, the scope of claim 10 is indefinite.
Regarding claim 15, claim 15 recites “an electrochemical pH gradient that is at least 1- 20 pm large”, and it is unclear if pm refers to µm or mm. Furthermore, a pH gradient describes the change of pH over distance. The unit “pm” seems to be a distance instead of a unit for pH gradient. Therefore, the scope of claim 15 is indefinite.
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 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.
Claims 1-3, 7, 9 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Del Castillo (Gustav F-D. Del Castillo, Polyelectrolyte brush electrodes for protein capture and release (PhD thesis of Chalmers University of Technology, 2020; hereinafter DC). Q-Sense (QEM 401 Operator Manual, November 2008) is an evidence for claim 7. Molino et al. (Fibronectin and Bovine Serum Albumin Adsorption and Conformational Dynamics on Inherently Conducting Polymers: A QCM-D Study, Langmuir, 2012, 28, 8433-8445) and Q-Sense are evidence for claims 9 and 17.
Regarding claim 1, DC teaches a device (in-situ electrochemical cell as shown in Figure 4.4B on page 84); and the limitation “for separating an analyte from other components in an electrolytic solution” is an intended use limitation [see MPEP 2111.02]. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, DC teaches the in-situ electrochemical cell for electrochemically catch and release of proteins by triggering the pH change at the interface of the polyelectrolyte brush (section 5.5 on pages 110-114), and Fig.5.14 on page 113 shows the electrochemical catch and release of proteins from PMMA brushes monitored in-situ by QCMD (see section 5.5.2), and the in-situ electrochemical cell as shown in Fig.4.4B is QCMD flow cell designed for in-situ electrochemical measurements (QEM 401 by Q-Sense), wherein the working electrode functionalized with polyelectrolyte brushes was made of gold (section 4.5 on pages 83-84). Thus, the disclosed in-situ electrochemical cell is configured to perform the intended use of separating an analyte (proteins) from other components in an electrolytic solution by electrochemically catching the proteins by the PMMA brushes and then releasing the captured proteins. The device comprising:
a housing provided with a solution inlet and a solution outlet (Fig.4.4B shows a housing provided with “flow in” [deemed as solution inlet] and “flow out” [deemed as solution outlet]),
a working electrode (QCM sensor in Fig.4.4B is a working electrode functionalized with polyelectrolyte brushes [section 4.5 on pages 83-84]) arranged in the housing in a space between the solution inlet and the solution outlet (see Fig. 4.4B), and arranged such that the electrolytic solution arranged to flow (F) from the solution inlet to the solution outlet contacts at least a portion of the working electrode (Fig.4.4B shows the electrolytic solution arranged to flow from “Flow in” to “Flow out” contacts at least a portion of the working electrode [QCM sensor] disposed on the bottom of the flow cell [section 4.5 on pages 83-84]),
a counter electrode (see “Counter electrode” in Fig.4.4B) arranged in the housing in a space between the solution inlet and the solution outlet at a distance from the working electrode (see Fig.4.4B), and arranged such that it is in electrical connection with the working electrode via the electrolytic solution arranged to flow from the solution inlet to the solution outlet (the counter and working electrodes are separated by a small and uniform distance [section 4.5 on page 83]; Fig.3.16 shows the typical three-electrode set-up with working, counter and reference electrodes immersed in the electrolyte [section 3.6.1 on pages 63-64], and Fig.4.4B shows the three-electrode set-up with working [QCM sensor], counter and reference electrodes which are in electrical connection via the electrolytic solution arranged to flow from “Flow in” to “Flow out”),
wherein at least a portion of a surface of the working electrode is provided with a polyelectrolytic coating (the working electrode is functionalized with polyelectrolyte brushes [section 4.5 on page 84]; PMMA brushes in Fig.5.14), the polyelectrolytic coating being arranged to upon application of a potential difference between the working electrode and the counter electrode switch between a first and second state (Fig.5.13 shows the PMMA brushes are electrochemically switched from high to low pH upon application of a potential difference between the working and counter electrodes [section 5.5.1]), wherein in the first state the analyte is captured in said polyelectrolytic coating and in the second state the captured analyte is released from said polyelectrolytic coating (Fig.5.14 shows electrochemical catch and release of proteins from PMMA brushes; When a positive potential is applied in a phosphate buffer with pH 7.4 that contains 5 mM hydroquinone in addition to 0.3 g/L BSA, the surface pH rapidly
decreases due to oxidation of hydroquinone . This in turn causes spontaneous
immobilization of proteins to the neutral brush [crosses in Figure 5.14 A], verified
by a control experiment where there was no protein present [circles in
Figure 5.14 A]. Upon releasing the potential, the pH immediately returns to its
initial neutral value, returning the brush to its charged state followed by release of protein due to repulsion [section 5.5.2 on page 114]; thus the PMMA brushes are configured to perform the claimed functions of capturing the analyte in the first state and releasing the captured analyte in the second state).
Regarding claim 2, DC teaches the device of claim 1, and the limitation “wherein the analyte is selected from a protein, a lipid particle, an oligonucleotide, a carbohydrate, or any combination thereof” further limits the sample but fails to further limit the apparatus. A claim is only limited by positively recited elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims." See MPEP 2115. Since the claim further limits the analyte (material worked upon) but fails to limit the device (by a structure being claimed), the limitations of the claim have no patentable weight.
Examiner further notes that DC does teach wherein the analyte is a protein (BSA protein in Fig.5.14 [section 5.5.2]).
Regarding claim 3, DC teaches the device of claim 1, wherein the polyelectrolytic coating arranged on the surface of the working electrode comprises a pH-responsive polymer (PMMA polyelectrolyte brushes are switched from high to low pH [section 5.5.1 and Fig.5.13]; When a positive potential is applied in a phosphate buffer with pH 7.4 that contains 5 mM hydroquinone in addition to 0.3 g/L BSA, the surface pH rapidly decreases due to oxidation of hydroquinone . This in turn causes spontaneous immobilization of proteins to the neutral brush (crosses in Figure 5.14 A), verified by a control experiment where there was no protein present (circles in
Figure 5.14 A). Upon releasing the potential, the pH immediately returns to its
initial neutral value, returning the brush to its charged state followed by release
of protein due to repulsion [section 5.5.2]) covalently bound to the surface of the electrode through a monolayer of aryl bonds (aryl monolayer prepared on gold by exposure of the gold surface to an aqueous solution of diazonium salt and ascorbic acid [Scheme 4.3 on page 74]; As a coupling agent the diazonium salt is power as it can interface molecules with almost any conductive electrode and material. The covalent carbon anchor bond to the substrate is stronger and more stable than the siloxane bond and the thiol-gold bond [section 4.1.3 on page 74-75]).
Regarding claim 7, DC teaches the device of claim 1, wherein an average distance between the working electrode and the counter electrode ranges from 20 µm to 20 mm (the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense [section 4.5 on page 83]. As evidenced by Q-Sense, the distance from counter electrode CE to working electrode WE of QEM-401 is 0.8 mm [section 3 on page 19 in Q-Sense]).
Regarding claim 9, DC teaches the device of claim 1, wherein 70-100% of the working electrode overlaps with the counter electrode, as seen in a plane orthogonal to a direction of flow of the electrolytic solution from the solution inlet towards the solution outlet (DC teaches wherein the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense [section 4.5 on page 83]. As evidenced by Q-Sense, the counter electrode of QEM-401 is a platinum disk [section 3 on page 19 in Q-Sense]. As evidenced by Molino, the diameter of the working electrode of QEM-401 is 10 mm [section 2.2 in Molino], and Fig.1 of Molino shows both the working electrode and the counter electrode of QEM-401 are cylindrical disks. Fig.1 of Molino further shows that the area of the counter electrode is larger than that of the working electrode, and 100% of the working electrode overlaps with the counter electrode, as seen in a plane orthogonal to a direction of flow of the electrolytic solution from the solution inlet [see In-flow in Fig.1 of Molino] towards the solution outlet [see Out-flow in Fig.1 of Molino]. Thus, 100% of the working electrode overlaps with the counter electrode in the disclosed QEM-401 device, as seen in a plane orthogonal to a direction of flow of the electrolytic solution from the solution inlet towards the solution outlet).
Regarding claim 17, DC teaches the device of claim 1, further comprising a reference electrode arranged in the housing (see Reference electrode in Fig. 4.4B) and arranged for electrical connection through the electrolyte solution with the working electrode and the counter electrode (Fig.3.16 shows the typical three-electrode set-up with working, counter and reference electrodes immersed in the electrolyte [section 3.6.1 on pages 63-64], and Fig.4.4B shows the three-electrode set-up with working [QCM sensor], counter and reference electrodes which are in electrical connection via the electrolytic solution flowing through the QCM-401 cell), wherein the reference electrode is arranged at an average distance of 1-50 mm from the counter electrode and at an average distance of 1-50 mm from the working electrode (DC teaches wherein the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense [section 4.5 on page 83]. As evidenced by Q-Sense, the distance from the reference electrode to the working electrode of QEM-401 is 4 mm, and distance from the counter electrode CE to the working electrode WE is 0.8 mm [section 3 on page 19 in Q-Sense]. As evidenced by Molino, Fig.1 of Molino shows the configuration of QEM-401 device wherein the counter electrode is disposed between the working electrode and the reference electrode along the height direction, and the distance between the WE and the CE is 0.8 mm. Thus, the distance from the reference electrode to the counter electrode is equal to the distance from the reference electrode to the working electrode - the distance from the counter electrode to the working electrode, which is 4 mm-0.8 mm=3.2 mm. Thus, in the disclosed QEM 401 device, the reference electrode is arranged at an average distance of 3.2 mm from the counter electrode and at an average distance of 4 mm from the working electrode).
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.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over DC, as applied to claim 1 above.
Regarding claim 8, DC teaches the device of claim 1, and is silent to wherein an average thickness of the polyelectrolytic coating provided on the working electrode is 10-50 nm.
But DC does teach the thickness of the polyelectrolyte brushes influence the volume of the polyelectrolyte brushes and thus the number of enzymes that can be immobilized (section 5.3.1 on page 102). Thus, the average thickness of the polyelectrolyte brushes is a result effective variable since it affects the volume of the polyelectrolyte brushes and accordingly the number of enzymes that can be immobilized by the polyelectrolyte brushes.
As the volume of the polyelectrolyte brushes and the number of enzymes that can be immobilized by the polyelectrolyte brushes are variables that can be modified, among others, by adjusting the average thickness of the polyelectrolytic coating (polyelectrolyte brushes) provided on the working electrode, the precise average thickness of the polyelectrolytic coating would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed average thickness of the polyelectrolytic coating provided on the working electrode in a range from 10 nm to 50 nm cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the average thickness of the polyelectrolytic coating in DC to obtain an average thickness of the polyelectrolytic coating being in a range from 10 nm to 50 nm in order to obtain the desired volume of the polyelectrolyte brushes and accordingly the desired number of enzymes/proteins/analytes that can be immobilized/captured by the polyelectrolyte brushes. “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Claims 5, 10-11 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over DC, as applied to claims 1 and 3 above, and further in view of Del Castillo et al. (WO2021107836A1, hereinafter DC’836). DC’836 was provided in IDS filed on 4/19/2024.
Regarding claim 5, DC teaches the device of claim 3, and is silent to wherein the pH-responsive polymer is a polymer functionalized with a pH-responsive and analyte specific ligand.
DC’836 teaches an electrochemical catch-release system comprising pH-responsive polymers 2 covalently linked to an electrode 3 (abstract and Fig.8a), wherein the pH-responsive polymer 2 is a polyacidic polymer (claim 2) and further comprising enzymes bound to the polyelectrolyte arrangement (claim 8). Fig. 20 shows an in-situ electrochemical QCM experiment of a polyelectrolyte brush synthesized on a platinum surface, that is covalently functionalized with GOX enzymes. The brush switches reversibly in phosphate buffered saline solution containing 10 mM glucose, when a positive potential (+1.0 V and +1.2 V) is applied [para. 0073]. Thus, DC’836 teaches wherein the pH-responsive polymer is a polymer functionalized with a pH-responsive and analyte specific ligand (GOx enzyme).
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 pH-responsive polymer in DC to a polymer functionalized with a pH-responsive and analyte specific ligand, as taught by DC’836, since it would allow for an electrochemically operated polyelectrolyte brush surfaces that would operate in biologically relevant fluids [para. 00101 in DC’836].
Regarding claim 10, DC teaches the device of claim 1, and is silent to wherein the inner volume of the housing not occupied by the working electrode is 5%-75%.
DC’836 teaches an electrochemical catch-release system comprising pH-responsive polymers 2 covalently linked to an electrode 3 (abstract and Fig.8a), wherein the WE is porous (Said structure of the electrochemical catch-release system is microporous or mesoporous in size allowing a multi-scale hierarchical porous structure which would allow higher surface area and thus higher protein loading capacity [para. 0015]; polymerization of PMAA within porous carbon electrodes [para. 0027]; we used a porous scaffold with a very high internal porosity [96.5%], this is advantageous if used in flow applications, which is the case in most commercial protein purification equipment, since it dramatically lowers the pressure drop and increases mass transport throughout the electrode [para. 0106]; The electrode had a bulk density of 0.05 g/cm3, a porosity of 96.5 % and the number of pores were 24 pores/cm with a diameter of 20 mm and 25 mm in height [7.85 cm3] [para. 0083]).
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 flat WE in DC to a porous WE, as taught by DC’836, since it would allow higher surface area and thus higher protein loading capacity [para. 0015 in DC’836].
Since DC’836 teaches it is advantageous to use a porous scaffold with a very high internal porosity (96.5%) in flow applications, which is the case in most commercial protein purification equipment, since it dramatically lowers the pressure drop and increases mass transport throughout the electrode [para. 0106], part of the internal volume of the flow cell is occupied by the porous working electrode. The inner volume of the housing not occupied by the working electrode is equal to the inner volume of the housing – the volume of the working electrode exposed in the housing. Thus, the inner volume of the housing not occupied by the working electrode depends on the volume of the working electrode exposed in the housing, which further depends on the height of the working electrode. As the height of the working increases, the surface area of the working increases, and accordingly higher protein loading capacity [para. 0015]. Thus, the inner volume of the housing not occupied by the working electrode affects the volume of the working electrode exposed in the flow cell and accordingly affects the surface rea of the working electrode and protein loading capacity. Therefore, the inner volume of the housing not occupied by the working electrode is a result effect variable.
As the surface area of the working electrode and protein loading capacity are variables that can be modified, among others, by adjusting the inner volume of the housing not occupied by the working electrode, the precise inner volume of the housing not occupied by the working electrode would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed inner volume of the housing not occupied by the working electrode being 5%-75% cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the inner volume of the housing not occupied by the working electrode in modified DC to be 5%-75% in order to obtain a desired surface area of the working electrode and accordingly the desired protein loading capacity. “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 11, DC teaches the device of claim 1, and is silent to wherein the working electrode is porous and arranged in the housing such that the electrolytic solution is allowed to flow from the solution inlet through at least a portion of the working electrode to the solution outlet and wherein the working electrode has a porosity of 40% to 99%, and an electroactive surface area of the working electrode is between 100 to 10,000 m²/m³.
DC’836 teaches an electrochemical catch-release system comprising pH-responsive polymers 2 covalently linked to an electrode 3 (abstract and Fig.8a). DC’836 further teaches wherein the WE is porous and has a porosity of 40% to 99% (Said structure of the electrochemical catch-release system is microporous or mesoporous in size allowing a multi-scale hierarchical porous structure which would allow higher surface area and thus higher protein loading capacity [para. 0015]; polymerization of PMAA within porous carbon electrodes [para. 0027]; we used a porous scaffold with a very high internal porosity (96.5%), this is advantageous if used in flow applications, which is the case in most commercial protein purification equipment, since it dramatically lowers the pressure drop and increases mass transport throughout the electrode [para. 0106]; The electrode had a bulk density of 0.05 g/cm3, a porosity of 96.5 % and the number of pores were 24 pores/cm with a diameter of 20 mm and 25 mm in height [7.85 cm3] [para. 0083]).
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 flat WE in DC to a porous WE having a porosity of 96.5%, wherein the porous WE is arranged in the housing such that the electrolytic solution is allowed to flow from the solution inlet through at least a portion of the working electrode to the solution outlet, as taught by DC’836, since it would allow higher surface area and thus higher protein loading capacity [para. 0015 in DC’836], and would dramatically lower the pressure drop and increase mass transport throughout the electrode [para. 0106 in DC’836].
DC’836 further teaches the BSA protein uptake of the PMAA functionalized electrode at pH 5 was determined to be 50 mg/cm3 (static binding capacity). However, is highly likely that the binding capacity can increase even further by optimization of (1) the polymer brush synthesis within high internal surface area materials and (2) maximizing the porosity and available surface area for polymerization. In our preliminary tests, we used a porous scaffold with a very high internal porosity (96,5%), this is advantageous if used in flow applications, which is the case in most commercial protein purification equipment, since it dramatically lowers the pressure drop and increases mass transport throughout the electrode. However, high internal porosity lowers the internal surface area. The trade-off between porosity and surface area can most likely be substantially pushed towards high porosity with optimization of the polymer brush synthesis within the scaffold, because of the very high protein immobilization capacity per surface area displayed by the polymer brushes (by at least a factor 100 compared to conventional surfaces). [para. 0106]. Thus, the surface area of the porous working electrode affects the binding capacity as well as pressure drop and mass transport through the electrode, accordingly the surface area of the porous working electrode is a result effective variable.
As the binding capacity as well as pressure drop and mass transport through the working electrode are variables that can be modified, among others, by adjusting the electroactive surface area of the working electrode, the precise electroactive surface area of the working electrode would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed electroactive surface area of the working electrode being between 100 to 10,000 m2/m3 cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the electroactive surface area of the working electrode in modified DC to be 100-10,000 m2/m3 in order to obtain a desired binding capacity as well as pressure drop and mass transport through the working electrode. “[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 15, modified DC teaches the device of claim 11, and a void space within the working electrode (porous working electrode with internal porosity of 96.5% [para. 0083, 0106 in DC’836 ]); and
the limitation “configured such that electrolytic solution passing through the working electrode creates an electrochemical pH gradient that is at least 1- 20 pm large” is a functional recitation. Apparatus claims cover what a device is, not what a device does [MPEP 2114(II)]. A functional recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See MPEP 2114. In the instant case, modified DC teaches the void space within the working electrode with a porosity of 96.5%, and the disclosed porosity falls within the claimed porosity range of 40% to 99% (see claim 11 above). Since the porosity of the porous working electrode in modified DC falls within the claimed porosity range of the claimed porous working electrode, it is contended that the void space of the porous working electrode of modified DC is capable of creating the same electrochemical pH gradient of at least 1- 20 pm large when the electrolytic solution passes through the working electrode.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over DC and DC’836, as applied to claim 11 above, and further in view of Minett (Minett A., Electrochemical detection of microorganism using conducting polymers, PhD thesis of University of Wollongong, 2000). Q-Sense is used as an evidence for claim 13.
Regarding claim 13, modified DC teaches the device of claim 11, and is silent to wherein the counter electrode is porous.
DC further teaches wherein the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense (section 4.5 on page 83). As evidenced by Q-Sense, the counter electrode of QEM-401 is a platinum disk (section 3 on page 19 in Q-Sense).
Minett teaches for electrochemical polymerization a three-electrode voltammetric cell is normalized used, wherein the three-electrode voltammetric cell comprising a working electrode on which the polymer is deposited, an auxiliary electrode made from platinum mesh, and a reference electrode (the 2nd paragraph on page 11 , Figure 2.1 and section 3.2.2).
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 flow cell and the platinum disk in modified DC such that the flow cell comprises a platinum mesh as the counter electrode, as taught by Minett, since Minett teaches a suitable platinum mesh, which is an alternative to the platinum disk, as the counter electrode for the three-electrode electrochemical system (the 2nd paragraph on page 11 , Figure 2.1 and section 3.2.2). Platinum mesh is porous.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over DC and DC’836, as applied to claim 11 above, and further in view of ALS (EQCMT flow cell kit, 2016).
Regarding claim 14, modified DC teaches the device of claim 11, and is silent to wherein the working electrode and the counter electrode are arranged in the housing such that the electrolytic solution arranged to flow (F) from the inlet to the outlet first passes through the working electrode and then through or past the counter electrode.
As outlined in the rejection of claim 11 above, the working electrode is porous and the electrolytic solution is allowed to flow from the solution inlet through at least a portion of the porous working electrode to the solution outlet.
ALS teaches an EQCMT flow cell as shown in the figure on page 1, wherein the counter electrode is disposed inside the solution outlet and the working electrode is disposed on top of the quartz crystal. In the configuration of the EQCMT flow cell, the working electrode and the counter electrode are arranged in the housing such that the electrolytic solution arranged to flow from the inlet to the outlet first passes through the working electrode and then through or past the counter electrode since the counter electrode is disposed inside the solution outlet (see figure on page 1).
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 flow cell such that the counter electrode is disposed inside the solution outlet, as taught by ALS, since such construction for EQCMT flow cell would be simple (the first paragraph on page 1 in ALS). With the above modification, the working electrode and the counter electrode are arranged in the housing such that the electrolytic solution arranged to flow from the inlet to the outlet first passes through the working electrode and then through or past the counter electrode, as shown in the figure on page 1 of ALS.
Claims 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over DC, as applied to claim 1 above, and further in view of Galliano et al. (Flow cell for EQCM adsorption studies application to iodide adsorption on gold, Journal of the electrochemical society, 2003, 150, B504-B511) and Srinivasan et al. (US20030127392A1).
Regarding claim 18, DC teaches the device of claim 1, and further teaches wherein the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense (section 4.5 on page 83).
DC is silent to further comprising an ion-selective membrane arranged between the working electrode and the counter electrode in the housing.
Galliano teaches a EQCM flow cell as shown in Fig.1 comprising an ion-selective membrane (semi-permeable membrane) arranged between the working electrode and the counter electrode in the housing. Fig.1 shows the counter electrode and reference electrode are disposed in the RE and CE compartment above the semi-permeable membrane, while the working electrode is disposed below the electrochemical cell, and the semi-permeable membrane is arranged between the electrochemical cell and the RE and CE compartment (section of Switch-flow cell setup on page B505).
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 flow cell in to provide an RE and CE compartment and a semi-permeable membrane disposed between the flow cell and the RE and CE compartment, wherein the CE and RE are disposed in the RE and CE compartment, as taught by Galliano, since it would reduce the volume in the flow cell and thus improve solution switch time (section of Switch-flow cell setup on page B505 in Galliano).
Modified DC is silent to wherein the semi-permeable membrane arranged between the working and counter electrodes is ion-selective.
Srinivasan teaches an eluent purifier comprising a barrier 24 disposed between the compartment of the working electrode (anode 22 in Fig.1) and the compartment of the counter electrode (cathode 16 in Fig.1), and the barrier 24 is in the form of a charged permselective membrane [para. 0014].
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 semi-permeable membrane in modified DC with a charged permselective membrane, as taught by Srinivasan, since it would substantially prevent bulk liquid flow while providing an ion transport bridge between the two compartments of the working and counter electrodes ( corresponding to the flow cell and the RE and CE compartment) [para. 0014 in Srinivasan]. The substituted charged permselective membrane is an ion-selective membrane.
Regarding claim 21, DC teaches the device of claim 1, and is silent to comprising two connected chambers, one chamber for the working electrode and one chamber for the counter electrode, separated by an ion-permeable membrane.
Galliano teaches a EQCM flow cell as shown in Fig.1 comprising two connected chambers, one chamber for the working electrode (the chamber of the flow cell disposed above the working electrode) and the other chamber for the counter electrode (RE and CE compartment) separated by an ion-permeable membrane (semi-permeable membrane). Fig.1 shows the counter electrode and reference electrode are disposed in the RE and CE compartment above the semi-permeable membrane, while the working electrode is disposed below the electrochemical cell, and the semi-permeable membrane is arranged between the electrochemical cell and the RE and CE compartment (section of Switch-flow cell setup on page B505).
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 flow cell to provide an RE and CE compartment and a semi-permeable membrane disposed between the flow cell and the RE and CE compartment, wherein the CE and RE are disposed in the RE and CE compartment and the working electrode faces upward the flow cell, as taught by Galliano, since it would reduce the volume in the flow cell and thus improve solution switch time (section of Switch-flow cell setup on page B505 in Galliano).
Modified DC is silent to wherein the semi-permeable membrane arranged between the two chambers is ion-selective.
Srinivasan teaches an eluent purifier comprising a barrier 24 disposed between the compartment of the working electrode (anode 22 in Fig.1) and the compartment of the counter electrode (cathode 16 in Fig.1), and the barrier 24 is in the form of a charged permselective membrane [para. 0014].
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 semi-permeable membrane in modified DC with a charged permselective membrane, as taught by Srinivasan, since it would substantially prevent bulk liquid flow while providing an ion transport bridge between the two compartments of the working and counter electrodes ( corresponding to the flow cell and the RE and CE compartment) [para. 0014 in Srinivasan]. The substituted charged permselective membrane is an ion-selective membrane.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over DC, as applied to claim 1 above, and further in view of van Dijk (van Dijk M., Does counter electrode (CE) size matter? August 16, 2021). Q-Sense and Molino are used as evidences for claim 20.
Regarding claim 20, DC teaches the device of claim 1, and further teaches wherein the in-situ cell was a QCM-D flow cell of QEM-401 by Q-Sense (section 4.5 on page 83).
As evidenced by Q-Sense, the counter electrode of QEM-401 is a platinum disk (section 3 on page 19). As further evidenced by Molino, the diameter of the working electrode of QEM-401 is 10 mm (section 2.2 in Molino); Fig.1 of Molino shows both the working electrode and the counter electrode of QEM-401 are cylindrical disks, and the surface area of the counter electrode is larger than that of the working electrode.
DC is silent to wherein an effective surface area of the counter electrode is at least two times larger than an effective surface area of the working electrode.
van Dijk teaches a three-electrode chemical cell wherein the current is passed between the working electrode (WE) and a counter electrode (CE) (page 3). Because the current flows between the WE and the CE, the total surface area of the CE (source/sink of electrons) must be larger than the area of the WE so that it will not be a limiting factor in the kinetics of the electrochemical processes under investigation (first paragraph on page 4). As general rule for accurate current measurements and an unhindered flow of electrons in the cell, the counter electrode should be three times larger than the working electrode (page 6).
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 working electrode and/or the counter electrode in DC such that an effective surface area of the counter electrode is three times larger than an effective surface area of the working electrode, since it would allow for accurate current measurements and an unhindered flow of electrons (page 6 in van Dijk).
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Briseno et al. (Studies of potential-dependent metallothionein adsorptions using a low-volume electrochemical quartz crystal microbalance flow cell, Journal of electroanalytical chemistry, 2001, 513, 16-24) teaches a QCM flow cell. Toth et al. (High-Sensitivity Dual Electrochemical QCM for Reliable Three-Electrode Measurements, Sensors, 2021, 21, 2592) teaches a dual EQCM with reference electrode disposed between the working and counter electrode. Saito et al. (Determination of current Density Suppression Ability of Poly(ethylene glycol) during Copper Electrodeposition by an Electrochemical Analysis with a Microfluidic Device and an Electrochemical Quartz Crystal Microbalance, Japanese Journal of Applied Physics, 2013, 52, 05FB03) teaches an electrochemical flow cell comprising a working electrode arranged at upstream of the flow channel, a reference electrode arrange in the middle region of the flow channel, and a counter electrode disposed at the downstream of the flow channel (see Fig.1). Aastrup et al. (US20090142789A1) teaches a QCM flow cell as shown in Fig.1.
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/SHIZHI QIAN/Examiner, Art Unit 1795
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