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 4/7/2025 has been considered by the examiner.
Claim Objection
Claims 1, 4-5, 19, 23, 25, and 37 are objected to because of the following informalities:
Claim 1: please amend “an electrochemical sensor working electrode” to -- an electrochemical sensor comprising a working electrode--.
Claims 4-5: please amend “the amount of analyte” to -- the amount of the analyte--.
Claim 19: please amend “a time-current relationship” to -- a time-current relationship.--.
Claim 23: please amend “the rate of transport” to -- the rate of electron transport --.
Claim 25: please amend “having regard to” to – with regard to --; “the proximity” to – [[the]] a proximity--.
Claim 37: please amend “An electrochemical sensor apparatus or system” to -- An electrochemical sensor, apparatus, or system--; “about the working electrode” to – [[about]] contacting the working 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 2-10, 19, 21, 23-25 and 37 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 measured current value(s)”, while claim 1 recites “a current value”. It is unclear if the measured current value(s) is/are the same as the current value recited in claim 1. Thus, the scope of claim 2 is indefinite. Claims 3-4 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 2.
Regarding claim 5, claim 5 recites “the measured current value(s)”, while claim 1 recites “a current value”. It is unclear if the measured current value(s) is/are the same as the current value recited in claim 1. Furthermore, “the surface” in “the surface of the working electrode” lacks antecedent basis. Thus, the scope of claim 5 is indefinite.
Regarding claim 6, claim 6 recites “the measured current value(s)”, while claim 1 recites “a current value”. It is unclear if the measured current value(s) is/are the same as the current value recited in claim 1. Thus, the scope of claim 6 is indefinite. Claims 7-9 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 6.
Regarding claim 8, claim 8 recites “the fraction”, which lacks antecedent basis. Thus, the scope of claim 8 is indefinite. Claim 9 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 8.
Regarding claim 10, claim 10 recites “a substantially fixed frequency”, wherein “substantially fixed” is a relative term which also renders the claim indefinite. The term “substantially fixed” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In this instant claim, it is unclear what is the variation of the frequency is considered as a substantially fixed frequency.
Regarding claim 19, claim 19 recites “the measured current value(s)”, while claim 1 recites “a current value”. It is unclear if the measured current value(s) is/are the same as the current value recited in claim 1. Thus, the scope of claim 19 is indefinite. Claims 21, 23-25 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 19.
Regarding claim 21, claim 21 recites “the change in current over time” and “the rate of electron transport”, which lack antecedent basis. Thus, the scope of claim 21 is indefinite. Claims 23-24 are further rejected by virtue of their dependence upon and because they fail to cure the deficiencies of indefinite claim 21.
Regarding claim 23, claim 23 recites “the accessibility”, which lacks antecedent basis. Thus, the scope of claim 23 is indefinite. Claim 24 is further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of indefinite claim 23.
Regarding claim 24, claim 24 recites “the reporter”, which lacks antecedent basis. Thus, the scope of claim 24 is indefinite.
Regarding claim 37, claim 37 recites “the electrode surface” and “the surface”, which lack antecedent basis. It is also unclear if “the surface” refers to the electrode surface or the surface of the working electrode. It is unclear if “the measured current value(s)” is/are the same as the current value recited in claim 37. Thus, the scope of claim 37 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 1-6, 10, 18-19, 21, 23-24, 26, 32 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Larson et al. (US20210140956A1), and further in view of Abeykoon et al. (Continuous square wave voltammetry for high information content interrogation of conformation switching sensors, ACS Meas. Sci. Au., 2023, 3, 1-9. Published on Oct. 5, 2022).
Regarding claim 1, Larson teaches a method for determining an amount of an analyte in a fluid (a method for determining analyte concentration in a biofluid by electrochemical aptamer-based biosensing device [para. 0006; Fig.1]), the method comprising:
providing an electrochemical sensor comprising a working electrode (providing an electrochemical aptamer-based sensor comprising a working electrode 130 as shown in Fig.1 [para. 0036]), the working electrode having associated therewith a plurality of analyte recognition elements (aptamer sequence 140 that is selected to interact with a target analyte molecule 160 [para. 0036; Fig.1]) each of which has a redox-active species associated therewith (a redox moiety 150 in Fig.1 [para. 0036]),
applying a potential to the working electrode according to a periodic waveform (When the device interrogates the sensing element using, e.g., square wave voltammetry [SWV], the sensing element produces a first electrical signal, eTA [para. 0036]; SWV applies a potential to the working electrode according to a periodic waveform).
Larson teaches the use of square wave voltammetry (SWV) to interrogate the sensing element [para. 0036-0037], but does not explicitly teach measuring a current value resulting from the application of the potential at one or more time points within a cycle of the periodic waveform.
Abeykoon teaches a continuous square wave voltammetry (cSWV), which utilizes the continuous collection of current to maximize the information content obtainable from a single voltammetry sweep (abstract). The left column in Fig.1 shows in traditional SWV, current is sampled at the end of the forward pulse and reverse pulse, and the current different is plotted against the potential. The right column in Fig.1 shows cSWV continuously collects current data through the applied potential waveform (see caption of Fig.1). Fig.4 shows voltammograms obtained from SWV and cSWV of aptamer-based sensors. The advantages of using cSWV is that the entire frequency response of an E-AB sensor is obtained from simply two voltammetric sweeps – one without a target and one with saturated target condition (the 2nd paragraph in Col. 1 on pg. 7).
Given the teachings of Larson regarding the use of square wave voltammetry (SWV) to interrogate the sensing element, and the teachings of Abeykoon regarding in traditional SWV, current is sampled at the end of the forward pulse and reverse pulse, the SWV in Larson must measuring a current value resulting from the application of the potential at one or more time points within a cycle of the periodic waveform (current is sampled at the end of the forward pulse and reverse pulse, as evidenced by Fig.1 in Abeykoon).
Furthermore, 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 SWV technique in Larson to the cSWV technique which continuously collects current data through the applied potential waveform, as taught by Abeykoon, since cSWV would provide the advantages over SWV that the entire frequency response of an E-AB sensor is obtained from simply two voltammetric sweeps – one without a target and one with saturated target condition (the 2nd paragraph in Col. 1 on pg. 7 and abstract in Abeykoon).
Regarding claim 2, modified Larson teaches the method of claim 1, and wherein each of the plurality of analyte recognition elements is associated with a surface of the working electrode (Larson teaches an active electrode having the plurality of active aptamer sensing elements attached thereto, wherein the electrode is capable of detecting a first signal from the active redox moiety moieties [claim 1]).
Larson does not explicitly teach wherein the measured current value(s) is/are used to determine a location or a distribution of the redox-active species in relation to the surface.
Larson does teach in the absence of the target analyte, the aptamer 140 is in a first configuration, and the redox moiety 150 is in a first position relative to the electrode 130. When the device interrogates the sensing element using, e.g., square wave voltammetry (SWV), the sensing element produces a first electrical signal, eTA [para. 0036]; With reference to FIG. 1B, the aptamer 140 is selected to interact with a target analyte 160, so that when the aptamer interacts with a target analyte molecule, the aptamer undergoes a conformation change that at least partially disrupts the first configuration, and forms a second configuration. The capture of the target analyte 160 accordingly moves the redox moiety 150 into a second position relative to the electrode 130. Now when the biofluid sensing device interrogates the sensing element, the sensing element produces a second electrical signal, eTB that is distinguishable from the first electrical signal [para. 0037]. Fig.1A shows the redox moiety 150 is in a first position relative to the electrode 130 without target analyte, and Fig.1B shows the redox moiety 150 is in the second position relative to the electrode 130 with the target analyte.
Abeykoon teaches wherein Fig.4 shows the measured current signal of an E-AB sensor and the corresponding relative location of the redox reporter in relation to the surface of the electrode with and without targets. The aptamer’s reaction to the target analyte alters a location of the redox reporter in relation to the surface of the electrode and accordingly changes the current signal.
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 method to use the measured current value(s) to determine a location of the redox-active species in relation to the electrode surface due to the correlation of the resulting current signal and the location of the redox reporter in relation to the surface of the electrode, as shown in Fig.4 of Abeykoon.
Regarding claim 3, modified Larson teaches the method of claim 2, wherein the location or the distribution is an initial location or an initial distribution (Fig.1A in Larson shows the location is an initial location of the redox reporter 150 without the target analyte).
Regarding claim 4, modified Larson teaches the method of claim 2, wherein the location or the distribution of the redox-active species is used to determine the extent to which the redox-active species mobilize toward the surface of the working electrode (as outlined in the rejection of claim 2 above, the resulting current is correlated to the location of the redox reporter in relation to the surface of the working electrode as shown in Figs.1A and 1B in Larson and Fig.4 in Abeykoon; thus, the location of the redox-active species is used to determine the extent to which the redox-active species mobilize toward the surface of the working electrode as shown in Figs.1A and 1B in Larson and Fig.4 in Abeykoon) , and in turn the amount of analyte recognized by the plurality of analyte recognition elements ( signal strength can be more accurately correlated with analyte concentration [para. 0032 in Larson ]; EAB sensor for measurements of biofluid analyte concentrations [para. 0006 in Larson ]).
Regarding claim 5, modified Larson teaches the method of claim 1, and wherein the measured current value(s) is/are used to determine the extent to which the redox-active species mobilize toward the surface of the working electrode, and in turn the amount of analyte recognized by the plurality of analyte recognition elements (Larson teach in the absence of the target analyte, the aptamer 140 is in a first configuration, and the redox moiety 150 is in a first position relative to the electrode 130. When the device interrogates the sensing element using, e.g., square wave voltammetry (SWV), the sensing element produces a first electrical signal, eTA [para. 0036]; With reference to FIG. 1B, the aptamer 140 is selected to interact with a target analyte 160, so that when the aptamer interacts with a target analyte molecule, the aptamer undergoes a conformation change that at least partially disrupts the first configuration, and forms a second configuration. The capture of the target analyte 160 accordingly moves the redox moiety 150 into a second position relative to the electrode 130. Now when the biofluid sensing device interrogates the sensing element, the sensing element produces a second electrical signal, eTB that is distinguishable from the first electrical signal [para. 0037]. Fig.1A shows the redox moiety 150 is in a first position relative to the electrode 130 without target analyte, and Fig.1B shows the redox moiety 150 is in the second position relative to the electrode 130 with the target analyte. Abeykoon teaches wherein Fig.4 shows the measured current signal of an E-AB sensor and the corresponding relative location of the redox reporter in relation to the surface of the electrode with and without targets. The aptamer’s reaction to the target analyte alters a location of the redox reporter in relation to the surface of the electrode and accordingly changes the current signal. Thus, the measured current value(s) is/are used to determine the extent to which the redox-active species mobilize toward the surface of the working electrode, as shown in Figs. 1A and 1B in Larson and Fig.4 in Abeykoon. Larson further teaches signal strength can be more accurately correlated with analyte concentration [para. 0032] and EAB sensor for measurements of biofluid analyte concentrations [para. 0006], thus the measured current values are used to determine the amount of analyte [analyte concentration] recognized by the aptamers).
Regarding claim 6, modified Larson teaches the method of claim 1, wherein the measured current value(s) are used to generate one or more current-potential relationships (voltammograms obtained from both the SWV and cSWV generate current-potential relationships as shown in Figs. 1-2 and 4 in Abeykoon).
Regarding claim 10, modified Larson teaches the method of claim 1, wherein the periodic waveform has a substantially fixed frequency (SWV at 400 Hz or 500 Hz in caption of Fig.4 in Abeykoon), the periodic waveform being superimposed on an underlying swept potential (SWV utilizes a square wave pulse waveform superimposed on a staircase step to generate a voltammetric linear sweep [the first paragraph in Col. 1 on pg. 1 in Abeykoon]) .
Regarding claim 18, modified Larson teaches the method of claim 1, wherein the periodic waveform is applied according to a square wave voltammetry method (SWV [para. 0036 in Larson]; SWV and cSWV in Figs.1 and 4 of Abeykoon; note that cSWV is still a type of SWV method).
Regarding claim 19, modified Larson teaches the method of claim 1, wherein the measured current value(s) are used to provide a time-current relationship (see current-time in Fig.1 of Abeykoon).
Regarding claim 21, modified Larson teaches the method of claim 19, and “wherein the change in current over time is a current transient dependent upon the rate of electron transport between the redox-active species and a surface of the working electrode” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the instant case, Larson teaches Fig.1A shows the redox moiety 150 is in a first position relative to the electrode 130 without target analyte, and Fig.1B shows the redox moiety 150 is in the second position relative to the electrode 130 with the target analyte. Non-specific binding to the electrode surface can interfere with redox proximity to the electrode, hindering electrical response to target analyte, for example, by preventing the redox from coming close enough to the electrode to allow electron exchange [para. 0033].
Abeykoon teaches wherein Fig.4 shows the measured current signal of an E-AB sensor and the corresponding relative location of the redox reporter in relation to the surface of the electrode with and without targets. The aptamer’s reaction to the target analyte alters a location of the redox reporter in relation to the surface of the electrode and accordingly changes the current signal.
Since the current signal depends on the location of the redox reporter in relation to the surface of the working electrode, and the redox reporter provides electron exchange when it is proximity to the electrode surface, the change in current over time is a current transient dependent upon the rate of electron transport between the redox-active species and a surface of the working electrode.
Regarding claim 23, modified Larson teaches the method of claim 21, and “wherein the rate of transport is dependent upon the accessibility of the redox-active species to the surface of the working electrode” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the alternative, as outlined in the rejection of claim 21 above, Larson teaches non-specific binding to the electrode surface can interfere with redox proximity to the electrode, hindering electrical response to target analyte, for example, by preventing the redox from coming close enough to the electrode to allow electron exchange [para. 0033]. Thus, the rate of transport is dependent upon the accessibility of the redox-active species to the surface of the working electrode.
Regarding claim 24, modified Larson teaches the method of claim 23, and “wherein the accessibility of the redox-active species to the surface of the working electrode is dependent upon proximity of the reporter to the surface of the working electrode” is an intended result of a positively recited step. The court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
In the alternative, as outlined in the rejection of claim 21 above, Larson teaches non-specific binding to the electrode surface can interfere with redox proximity to the electrode, hindering electrical response to target analyte, for example, by preventing the redox from coming close enough to the electrode to allow electron exchange [para. 0033]. Thus, the accessibility of the redox-active species to the surface of the working electrode is dependent upon proximity of the redox reporter to the surface of the working electrode.
Regarding claim 26, modified Larson teaches the method of claim 1, comprising measuring current at 2, 3 or more, different time points within a cycle of the periodic waveform (current is sampled at the end of the forward pulse and reverse pulse in SWV [caption of Fig.1 in Abeykoon]), or measuring current at 2, 3 or more, different frequencies of the periodic waveform (Fig.1 in Abeykoon shows cSWV measuring current at 2, 3 or more difference frequencies of the periodic waveform).
Regarding claim 32, modified Larson teaches the method of claim 1, wherein the periodic waveform has a first frequency (Fig.1 in Abeykoon shows the periodic waveform has a native SWV frequency of nf=100 Hz [caption of Fig.1]), and the method comprises:
applying the potential using the periodic waveform at the first frequency (the applied potential waveform at a native SWV frequency of nf=100 Hz [caption of Fig.1 in Abeykoon]) and measuring a current resulting therefrom at a time point late in the periodic wave cycle and also at one or two earlier time points (cSWV of Fig.1 in Abeykoon shows measuring a current resulting therefrom at a time point late in the periodic wave cycle [see reserve sample time points in cSWV of Fig.1] and also at one or two earlier time points [see forward sample time points in cSWV in Fig.1]).
Regarding claim 35, modified Larson teaches the method of claim 1, and Larson teaches wherein each of the plurality of analyte recognition elements is an aptamer (aptamer 140 [para. 0036]).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Larson and Abeykoon, as applied to claim 6 above, and further in view of Korri-Youssoufi et al. (US20190250120A1).
Regarding claim 7, modified Larson teaches the method of claim 6, and is silent to wherein each of the one or more current-potential relationships is a differential current-potential relationship.
Korri-Youssoufi teaches an E-AB sensor (claim 1) and further teaches the use of Cyclic Voltammetry (CV), Square Wave Voltammetry (SWV) and Differential Pulse Voltammetry (DPV) measurement techniques to interrogate the sensing element [para. 0172-0176 ].
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 SWV with DPV, as taught by Korri-Youssoufi, which teaches DPV measurement technique as a suitable alternative to the SWV technique to interrogate the sensing element [para. 0172-0176 in Korri-Youssoufi]. The resulting current-potential relationships from the DPV measurements is a differential current-potential relationship.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Larson, and in view of Abeykoon and Arroyo et al. (US20240125729A1).
Regarding claim 37, Larson teaches an electrochemical sensor apparatus or system (an electrochemical aptamer-based sensor as shown in Fig.1) comprising:
a working electrode (gold electrode 130 in Fig.1 [para. 0036]) having associated therewith (i) an analyte recognition element (aptamer 140 in Fig.1 [para. 0036]) and (ii) an associated redox-active species (redox moiety 150 in Fig.1 [para. 0036]) spatially constrained within a layer adjacent to the electrode surface (see Fig.1), and
wherein the analyte recognition element is associated with a surface of the working electrode (see Fig.1).
Larson further teaches a method for determining an amount of an analyte in a fluid about the working electrode, the method comprising applying a potential to the working electrode according to a periodic waveform (When the device interrogates the sensing element using, e.g., square wave voltammetry [SWV], the sensing element produces a first electrical signal, eTA. The capture of the target analyte 160 accordingly moves the redox moiety 150 into a second position relative to the electrode 130. Now when the biofluid sensing device interrogates the sensing element, the sensing element produces a second electrical signal, eTB that is distinguishable from the first electrical signal. [para. 0036-0037]; “EAB sensor” means an electrochemical aptamer-based biosensor that is configured with a plurality of aptamer sensing elements that, in the presence of a target analyte in a fluid sample, produce a signal indicating analyte capture, and which signal can be added to the signals of other such sensing elements, so that a signal threshold may be reached that indicates the presence or concentration of the target analyte [para. 0021]).
Larson is silent to: a microprocessor-based controller, wherein the microprocessor-based controller is configured to perform the method for determining the amount of the analyte in a fluid about the working electrode, the method further comprising: measuring a current value resulting from the application of the potential at one or more time points within a cycle of the periodic waveform, and the measured current value(s) is/are used to determine a location or a distribution of the redox-active species in relation to the surface.
Larson teaches the use of square wave voltammetry (SWV) to interrogate the sensing element [para. 0036-0037], but does not explicitly teach measuring a current value resulting from the application of the potential at one or more time points within a cycle of the periodic waveform.
Abeykoon teaches a continuous square wave voltammetry (cSWV), which utilizes the continuous collection of current to maximize the information content obtainable from a single voltammetry sweep (abstract). The left column in Fig.1 shows in traditional SWV, current is sampled at the end of the forward pulse and reverse pulse, and the current different is plotted against the potential. The right column in Fig.1 shows cSWV continuously collects current data through the applied potential waveform (see caption of Fig.1). Fig.4 shows voltammograms obtained from SWV and cSWV of aptamer-based sensor. The advantages of using cSWV is that the entire frequency response of an E-AB sensor is obtained from simply two voltammetric sweeps – one without a target and one with saturated target condition (the 2nd paragraph in Col. 1 on pg. 7).
Given the teachings of Larson regarding the use of square wave voltammetry (SWV) to interrogate the sensing element, and the teachings of Abeykoon regarding in traditional SWV, current is sampled at the end of the forward pulse and reverse pulse, the SWV in Larson must measuring a current value resulting from the application of the potential at one or more time points within a cycle of the periodic waveform (current is sampled at the end of the forward pulse and reverse pulse, as evidenced by Fig.1 in Abeykoon).
Furthermore, 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 SWV technique in Larson to the cSWV technique which continuously collects current data through the applied potential waveform, as taught by Abeykoon, since cSWV would provide the advantages over SWV that the entire frequency response of an E-AB sensor is obtained from simply two voltammetric sweeps – one without a target and one with saturated target condition (the 2nd paragraph in Col. 1 on pg. 7 and abstract in Abeykoon).
Larson does not explicitly teach wherein the measured current value(s) is/are used to determine a location or a distribution of the redox-active species in relation to the surface.
Larson does teach in the absence of the target analyte, the aptamer 140 is in a first configuration, and the redox moiety 150 is in a first position relative to the electrode 130. When the device interrogates the sensing element using, e.g., square wave voltammetry (SWV), the sensing element produces a first electrical signal, eTA [para. 0036]; With reference to FIG. 1B, the aptamer 140 is selected to interact with a target analyte 160, so that when the aptamer interacts with a target analyte molecule, the aptamer undergoes a conformation change that at least partially disrupts the first configuration, and forms a second configuration. The capture of the target analyte 160 accordingly moves the redox moiety 150 into a second position relative to the electrode 130. Now when the biofluid sensing device interrogates the sensing element, the sensing element produces a second electrical signal, eTB that is distinguishable from the first electrical signal [para. 0037]. Fig.1A shows the redox moiety 150 is in a first position relative to the electrode 130 without target analyte, and Fig.1B shows the redox moiety 150 is in the second position relative to the electrode 130 with the target analyte.
Abeykoon teaches wherein Fig.4 shows the measured current signal of an E-AB sensor and the corresponding relative location of the redox reporter in relation to the surface of the electrode with and without targets. The aptamer’s reaction to the target analyte alters a location of the redox reporter in relation to the surface of the electrode and accordingly changes the current signal.
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 method to use the measured current value(s) to determine a location of the redox-active species in relation to the electrode surface due to the correlation of the resulting current signal and the location of the redox reporter in relation to the surface of the electrode, as shown in Fig.4 of Abeykoon.
Modified Larson is silent to: a microprocessor-based controller, wherein the microprocessor-based controller is configured to perform the method for determining the amount of the analyte in a fluid about the working electrode.
Arroyo teaches methods of detecting target molecules using electrochemical sensors that comprise biomolecular receptor-bound redox reporters (abstract), wherein the electrochemical sensor is an E-AB sensor as shown in Fig.1 [para. 0003]. The system further comprises at least one controller operably connected to the electrochemical sensor, which controller comprises, or is capable of accessing, computer readable media comprising non-transitory computer executable instructions which, when executed by at least one electronic processor, perform at least: generating one or more cyclic voltammograms from the electrochemical sensor using cyclic voltammetry (CV) when the electrochemical sensor is contacted with at least one sample that comprises the target molecule such that one or more of the biomolecular receptors undergo conformational changes when the biomolecular receptors bind the target molecule; and determining a change in a target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor to detect the target molecule in the sample (claim 25).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a microprocessor-based controller configured to perform the method of modified Larson for determine an amount of an analyte in the fluid about the working electrode of the E-AB sensor, as taught by Arroyo, since it would automate the operations of the method to detect the target analyte in the sample [para. 0014 in Arroyo].
Allowable Subject Matter
Claims 8-9 and 25 would be allowable if rewritten 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 and to include all of the limitations of the base claim and any intervening claims.
Regarding claims 8-9, modified Larson teaches the method of claim 6, wherein the one or more current-potential relationships each provide a peak current (Figs. 1 and 4 in Abeykoon show the voltammograms [current-potential relationships] each provide a peak current). The prior art of the record does not teach and/or suggest wherein the peak currents are used to calculate one or more f values, each f value being indicative of the fraction of the redox-active species that is at or proximal to a surface of the working electrode (of claim 8); wherein the f value is calculated according to Equation (3) (of claim 9).
Regarding claim 25, the prior art of the record does not teach and/or suggest wherein the time-current relationship is used to determine a distribution of the redox-active species with regard to the proximity of the redox-active species to the surface of the working electrode.
Conclusion
The prior arts made of record and not relied upon are considered pertinent to applicant's disclosure: Heikenfeld et al. (US20250116626A1) teaches an E-AB sensor.
Wang et al. (US20230003725A1) teaches devices and methods for aptamer-based sensor for monitoring biomarkers (title and abstract), wherein the device comprises a processor 220 to perform various operations. Ouellet et al. (US20250251394A1) teaches E-AB sensor system comprising a processor 210 to perform various method [para. 0152]. Plaxco et al. (US20210196161A1) teaches E-AB sensor for measuring analyte comprising a non-transitory computer-readable recording media having stored thereon data and/or an encoding program that causes a computer to execute series of operations, wherein the data and/or series of operations causes the operation of an electrochemical sensing system to effect the methods [para. 0088 ].
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.
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/SHIZHI QIAN/Primary Examiner, Art Unit 1795
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