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 .
Claims Pending
Applicant’s previous cancellation of claims 4-5, 7, 9, 11, 15, 17-19, 21-23, and 29-34 is acknowledged.
Claims 1-3, 6, 8, 10, 12-14, 16, 20, 24-28, and 35-38 are currently pending.
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the “wearable device” (Claims 24 and 38) must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-3, 6, 8, 10, 12-14, 16, 20, 24-28, and 35-38 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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.
Claim 1 recites the limitation “determining a change in target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor, thereby detecting the target molecule using the electrochemical sensor”, which fails to effectively define the metes and bounds of the claim as it is unclear as to the quantity of cyclic voltammograms present. For example, the claim also recites “generating one or more cyclic voltammograms”, which indicates one or more cyclic voltammograms. However, the above limitation states “from the cyclic voltammograms”, which indicates that there would be at least two. Additionally, for a determination of a “change”, it would typically be expected that there would be more than one voltammogram. How many cyclic voltammograms are present? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as -determining a change in target peak-to-peak separation, ΔEP,T, from the one or more cyclic voltammograms generated from the electrochemical sensor, thereby detecting the target molecule using the electrochemical sensor-.
Claims 25 and 26 recite the limitation “determining a change in target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor to detect the target molecule in the sample.”, which fails to effectively define the metes and bounds of the claim as it is unclear as to the quantity of cyclic voltammograms present. For example, the claim also recites “generating one or more cyclic voltammograms”, which indicates one or more cyclic voltammograms. However, the above limitation states “from the cyclic voltammograms”, which indicates that there would be at least two. Additionally, for a determination of a “change”, it would typically be expected that there would be more than one voltammogram. How many cyclic voltammograms are present? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as -determining a change in target peak-to-peak separation, ΔEP,T, from the one or more cyclic voltammograms generated from the electrochemical sensor to detect the target molecule in the sample-.
Claims 1, 25, and 26 recite the limitation “determining a change in target peak-to-peak separation, ΔEP,T,”, which fails to effectively define the metes and bounds of the claim, as it is unclear as to what is being referred to by the phrase “ΔEP,T”. Does “ΔEP,T” refer to the entire phrase of “a change in target peak-to-peak separation” or “target peak-to-peak separation”? As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, “ΔEP,T” will be interpreted as target peak-to-peak separation.
The term “”substantially” in claim 10 is a relative term which renders the claim indefinite. The term “substantially” 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. The applicant has failed to effectively define the metes and bounds of the claim as it is unclear as to how resistant to drift the electrochemical sensor must be to be considered “substantially resistant to drift” is. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as any amount of drift resistance.
The term “”substantially” in claim 14 is a relative term which renders the claim indefinite. The term “substantially” 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. The applicant has failed to effectively define the metes and bounds of the claim as it is unclear how unprocessed a sample must be to be considered “substantially unprocessed”. As such, the claim is indefinite as the applicant has failed to effectively define the metes and bounds of the claim. For examination purposes, this will be interpreted as a sample.
Claims 2-3, 6, 8, 10, 12-14, 16, 20, 24, 27-28, and 35-38 are dependent on the above independent claims, and as such are also rejected.
Claim Rejections - 35 USC § 103
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 claims are generally directed towards a method of detecting the presence of a target molecule using an electrochemical sensor. The method involves contacting a sample that comprises the target molecule with an electrochemical sensor, generating one or more cyclic voltammograms, and determining peak to peak separation from the voltammograms.
Claim(s) 1-3, 6, 8, 10, 12-14, and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai (US Pub. No. 20150177181) hereinafter Lai, and further in view of Leach (US Pat. No. 10976279) hereinafter Leach.
Regarding claim 1, Lai discloses A method of detecting a target molecule using an electrochemical sensor comprising biomolecular receptor-bound redox reporters (Abstract) (Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”), the method comprising:
contacting the electrochemical sensor 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 (Claim 9, “A method of detecting the presence or absence of an ion in a sample, comprising: contacting the electrochemical sensor of claim 1 with a sample…”)(Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Claim 3, “The sensor of claim 1, wherein the ion sensing probe is selected from the group consisting of nucleic acids, aptamers, and polypeptides.) (Par. 31, “A sensor as described herein further includes an ion sensing probe. Generally, an ion sensing probe is covalently attached to the working electrodes….”) (Par. 32, “An ion sensing probe can be a nucleic acid. Nucleic acids are well known in the art and include DNA molecules and RNA molecules as well as DNA or RNA molecules containing one or more nucleotide analogs…”)(Par. 34, “ion sensing probe alternatively can be an aptamer. Aptamers also are well known in the art and include nucleic acids (e.g., oligonucleotides) and polypeptides…”).
Lai fails to explicitly disclose generating one or more cyclic voltammograms from the electrochemical sensor using cyclic voltammetry (CV). (Examiner's Note: Lai fails to explicitly disclose the generation of the cyclic voltammogram).
However, Lai does teach in an example generating one or more scans from the electrochemical sensor using cyclic voltammetry (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan. An E.sub.1/2 of -0.26 V (vs. Ag/AgCl) was determined from the CV scan recorded at 1 V/s in the absence of Hg.sup.2+, this value is comparable to that shown in ACV (FIG. 9)…”).
Lai teaches the use of multiple electrochemical techniques to generate voltammograms (Par. 46, “Four electrochemical techniques, including ACV, CV, SWV and DPV were used in sensor interrogation”) (Par. 52, “Voltammograms were then collected using all four techniques.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai with an exemplary embodiment of Lai to include generating one or more cyclic voltammograms from the electrochemical sensor using cyclic voltammetry (CV) as differing electrochemical measurement types are known in the art (Lai (Par. 7, 40) and it would have yielded the predictable result of explicitly providing a visual representation of the data.
Lai fails to explicitly disclose determining a change in target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor, thereby detecting the target molecule using the electrochemical sensor. (Examiner's Note: The claim does not explicitly indicate a level of specificity for the detection)
However, Lai does teach in an example determining a target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor, thereby detecting the target molecule using the electrochemical sensor (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan….”).
Leach teaches a change in peak-to peak separation (Claim 1, “readings from the cyclic voltammetry scan; identifying positions of at least two peaks in the set of readings, wherein a first peak is a reference peak corresponding to adsorption or desorption of hydrogen and a second peak is due to oxide formation or reduction…”) thereby detecting the target molecule using the electrochemical sensor (Claim 1, “and determining the concentration of the electrolyte of the electrochemical sensor by applying a correlation to a voltage difference between the identified positions of the at least two peaks”)(Claim 2, “scanning the working electrode of the electrochemical sensor using the cyclic voltammetry scan at the plurality of electrolyte concentrations; identifying the at least two peaks at each electrolyte concentration; generating a variable set of readings from the cyclic voltammetry scan comprising differences in the positions of the first peak and the second peak; and determining the correlation by plotting the variable set of readings and the plurality of electrolyte concentrations.”) (Abstract).
Lai and Leach are considered to be analogous art to the claimed invention as they are involved with analyte detection.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai with that of Lai and Leach to include determining a change in target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms generated from the electrochemical sensor, thereby detecting the target molecule using the electrochemical sensor through the combination of references as it would have yielded the predictable result of explicitly providing a detection concentration and allow for the correction of sensor errors and improve accuracy (Leach (Col. 9, lines 31-38)).
Regarding claim 2, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does teach in an example the determining step comprises comparing the ΔEP,T to a no target peak-to-peak separation, ΔEP,NT, determined from one or more cyclic voltammograms generated from the electrochemical sensor in the absence of the target molecule (Lai (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan. An E.sub.1/2 of -0.26 V (vs. Ag/AgCl) was determined from the CV scan recorded at 1 V/s in the absence of Hg.sup.2+, this value is comparable to that shown in ACV (FIG. 9)…”(comparison with absence))); or, the determining step comprises correlating at least two currents with corresponding peak potentials and calculating a separation between the peak potentials.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with an example of Lai to include the determining step comprises comparing the ΔEP,T to a no target peak-to-peak separation, ΔEP,NT, determined from one or more cyclic voltammograms generated from the electrochemical sensor in the absence of the target molecule; or, the determining step comprises correlating at least two currents with corresponding peak potentials and calculating a separation between the peak potentials through the combination of examples as it would have yielded the predictable result of allowing for the visualization of the impact of the target on measurements (Lai (Par. 56)).
Regarding claim 3, modified Lai fails to explicitly disclose the limitations of the claim.
However, Leach further teaches determining a concentration of the target molecule in the sample by comparing the ΔEP,T to a standard curve;
determining the ΔEP,T from at least a first cyclic voltammogram and at least a second cyclic voltammogram generated from the electrochemical sensor;
determining a concentration of the target molecule in the sample via the change in the target peak-to-peak separation ΔEP,T (Leach (Claim 1, “readings from the cyclic voltammetry scan; identifying positions of at least two peaks in the set of readings…” “… determining the concentration of the electrolyte of the electrochemical sensor by applying a correlation to a voltage difference between the identified positions of the at least two peaks”)(Claim 2, “scanning the working electrode of the electrochemical sensor using the cyclic voltammetry scan at the plurality of electrolyte concentrations…” “… determining the correlation by plotting the variable set of readings and the plurality of electrolyte concentrations.”) (Abstract)); or,
determining the change in the target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms with about 900 milliseconds, about 800 milliseconds, about 700 milliseconds, about 600 milliseconds, about 500 milliseconds, about 400 milliseconds, about 300 milliseconds, about 200 milliseconds, about 100 milliseconds, or less of contacting the electrochemical sensor with the sample.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with that of Leach to include determining a concentration of the target molecule in the sample by comparing the ΔEP,T to a standard curve; determining the ΔEP,T from at least a first cyclic voltammogram and at least a second cyclic voltammogram generated from the electrochemical sensor; determining a concentration of the target molecule in the sample via the change in the target peak-to-peak separation ΔEP,T; or, determining the change in the target peak-to-peak separation, ΔEP,T, from the cyclic voltammograms with about 900 milliseconds, about 800 milliseconds, about 700 milliseconds, about 600 milliseconds, about 500 milliseconds, about 400 milliseconds, about 300 milliseconds, about 200 milliseconds, about 100 milliseconds, or less of contacting the electrochemical sensor with the sample through the combination of references as it would have yielded the predictable result of explicitly providing a detection concentration of the target and allow for the correction of sensor errors and improve accuracy (Leach (Col. 9, lines 31-38)).
Regarding claim 6, modified Lai further discloses wherein the biomolecular receptor comprises an aptamer (Lai (Par. 3, “wherein the ion sensing probe is selected from the group consisting of nucleic acids, aptamers, and polypeptides.”) (Par. 34)); or, the biomolecular receptor comprises a deoxyribonucleic acid (DNA) molecule (Lai (Claim 3, “wherein the ion sensing probe is selected from the group consisting of nucleic acids, aptamers, and polypeptides.”)).
Regarding claim 8, modified Lai further discloses wherein the redox reporters comprise methylene blue (MB) (Lai (Claim 4, “wherein the redox indicator is methylene blue”)).
Regarding claim 10, modified Lai further discloses wherein the electrochemical sensor is substantially resistant to drift (Par. 47,48 (sensor regeneration and cleaning)).
Regarding claim 12, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does further teach in an example comprising generating the cyclic voltammograms from the electrochemical sensor using a voltage scanning rate of about 5 V s·1 or more (Lai (Par. 56, “Best signal attenuation was seen at scan rates between 10 and 200 V/s.”). (Examiner's Note: “about” is defined as within 25% (Par. 38 of applicant’s spec.))
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with that of Lai to include comprising generating the cyclic voltammograms from the electrochemical sensor using a voltage scanning rate of about 5 V s·1 or more as differing scanning rates are known in the art (Lai (Par. 56)) and it would have yielded the predictable result of providing the optimal scanning rate (Lai (Par. 56)).
Regarding claim 13, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does further teach in an example wherein the voltage scanning rate is between about 5 V s·1 and about 10 V s·1 (Lai (Par. 56, “Best signal attenuation was seen at scan rates between 10 and 200 V/s.”). (Examiner's Note: “about” is defined as within 25% (Par. 38 of applicant’s spec.))
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with that of Lai to include wherein the voltage scanning rate is between about 5 V s·1 and about 10 V s·1 for the reasoning as indicated in claim 12 above, and because in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a primary facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Regarding claim 14, modified Lai further discloses wherein; the sample is substantially unprocessed; or, the sample comprises an environmental sample (Lai (Par. 9 (environmental sample)).
Regarding claim 16, modified Lai further discloses wherein; the target molecule comprises a therapeutic agent (Lai (Par. 5 (ions)); the target molecule comprises a metabolite; or, the target molecule comprises a biomolecule.
Claim(s) 25-28 and 35-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai in view of Tarasov (US Pub. No. 20190376926) hereinafter Tarasov, and further in view of Leach.
Regarding claim 25, Lai discloses a system (Abstract) (Par. 3 (sensors and methods of using)), comprising:
at least one electrochemical sensor comprising biomolecular receptor-bound redox reporters (Abstract) (Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Par. 5, “one aspect, an electrochemical sensor for detecting the presence or absence of ions is provided…”); and,
perform at least:
generating 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 (Claim 9, “A method of detecting the presence or absence of an ion in a sample, comprising: contacting the electrochemical sensor of claim 1 with a sample…”)(Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Claim 3, “The sensor of claim 1, wherein the ion sensing probe is selected from the group consisting of nucleic acids, aptamers, and polypeptides.) (Par. 31, “A sensor as described herein further includes an ion sensing probe. Generally, an ion sensing probe is covalently attached to the working electrodes….”) (Par. 32, “An ion sensing probe can be a nucleic acid. Nucleic acids are well known in the art and include DNA molecules and RNA molecules as well as DNA or RNA molecules containing one or more nucleotide analogs…”)(Par. 34, “ion sensing probe alternatively can be an aptamer. Aptamers also are well known in the art and include nucleic acids (e.g., oligonucleotides) and polypeptides…”).
Lai fails to explicitly disclose 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.
However, Tarasov teaches at least one controller operably connected to the electrochemical sensor (Par. 163, “The analyte detector 110 may further comprise at least one controller 117. The controller 117 may be connected to the field-effect transistor 114 and to the electrochemical measurement device 116 and may be configured for controlling at least one transistor measurement by using the field-effect transistor 114 and for controlling at least one electrochemical measurement by using the electrochemical measurement device 116”), 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 (Par. 163, “The controller 117, as an example, may be or may comprise at least one computer or processor, e.g., for timing and/or triggering the measurements and/or for reading out and/or evaluating measurement results.”) (Par. 91 (controller)) (Par. 100-107 (computer program and processor implementation)).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai with that of Tarasov to include 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 through the combination of references as it would have yielded the predictable result of allowing for the system to be controlled and implemented through a computational device.
Modified Lai fails to explicitly disclose generating one or more cyclic voltammograms from the electrochemical sensor using cyclic voltammetry (CV). (Examiner's Note: Lai fails to explicitly disclose the generation of the cyclic voltammogram)
However, Lai does teach in an example generating one or more scans from the electrochemical sensor using cyclic voltammetry (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan. An E.sub.1/2 of -0.26 V (vs. Ag/AgCl) was determined from the CV scan recorded at 1 V/s in the absence of Hg.sup.2+, this value is comparable to that shown in ACV (FIG. 9)…”).
Lai teaches the use of multiple electrochemical techniques to generate voltammograms (Par. 46, “Four electrochemical techniques, including ACV, CV, SWV and DPV were used in sensor interrogation”) (Par. 52, “Voltammograms were then collected using all four techniques.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai and Tarasov with an exemplary embodiment of Lai to include generating one or more cyclic voltammograms from the electrochemical sensor using cyclic voltammetry as differing electrochemical measurements are known in the art (Lai (Par. 7, 40) and it would have yielded the predictable result of explicitly providing a visual representation of the data.
Modified Lai fails to explicitly disclose 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 (Examiner's Note: The claim does not explicitly indicate a level of specificity for the detection).
However, Lai does teach in an example determining 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 (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan….”).
Leach teaches a change in peak-to peak separation (Claim 1, “readings from the cyclic voltammetry scan; identifying positions of at least two peaks in the set of readings, wherein a first peak is a reference peak corresponding to adsorption or desorption of hydrogen and a second peak is due to oxide formation or reduction…”) to detect the target molecule using the electrochemical sensor (Claim 1, “and determining the concentration of the electrolyte of the electrochemical sensor by applying a correlation to a voltage difference between the identified positions of the at least two peaks”)(Claim 2, “scanning the working electrode of the electrochemical sensor using the cyclic voltammetry scan at the plurality of electrolyte concentrations; identifying the at least two peaks at each electrolyte concentration; generating a variable set of readings from the cyclic voltammetry scan comprising differences in the positions of the first peak and the second peak; and determining the correlation by plotting the variable set of readings and the plurality of electrolyte concentrations.”) (Abstract).
Lai, Leach, and Tarasov are considered to be analogous art to the claimed invention as they are involved with analyte detection.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai and Tarasov with that of Lai and Leach to include 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 through the combination of references as it would have yielded the predictable result of explicitly providing a detection concentration and allow for the correction of sensor errors and improve accuracy (Leach (Col. 9, lines 31-38)).
Regarding claim 26, Lai discloses perform at least:
generating from an electrochemical sensor comprising biomolecular receptor-bound redox reporters (Abstract) (Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Par. 5, “one aspect, an electrochemical sensor for detecting the presence or absence of ions is provided…”) 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 (Claim 9, “A method of detecting the presence or absence of an ion in a sample, comprising: contacting the electrochemical sensor of claim 1 with a sample…”)(Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Claim 3, “The sensor of claim 1, wherein the ion sensing probe is selected from the group consisting of nucleic acids, aptamers, and polypeptides.) (Par. 31, “A sensor as described herein further includes an ion sensing probe. Generally, an ion sensing probe is covalently attached to the working electrodes….”) (Par. 32, “An ion sensing probe can be a nucleic acid. Nucleic acids are well known in the art and include DNA molecules and RNA molecules as well as DNA or RNA molecules containing one or more nucleotide analogs…”)(Par. 34, “ion sensing probe alternatively can be an aptamer. Aptamers also are well known in the art and include nucleic acids (e.g., oligonucleotides) and polypeptides…”).
Lai fails to explicitly disclose a computer readable media comprising non-transitory computer executable instructions which, when executed by at least electronic processor.
However, Tarasov teaches A computer readable media comprising non-transitory computer executable instructions which, when executed by at least electronic processor (Par. 163, “The analyte detector 110 may further comprise at least one controller 117. The controller 117 may be connected to the field-effect transistor 114 and to the electrochemical measurement device 116 and may be configured for controlling at least one transistor measurement by using the field-effect transistor 114 and for controlling at least one electrochemical measurement by using the electrochemical measurement device 116”) (Par. 163, “The controller 117, as an example, may be or may comprise at least one computer or processor, e.g., for timing and/or triggering the measurements and/or for reading out and/or evaluating measurement results.”) (Par. 91 (controller)) (Par. 100-107 (computer program and processor implementation)).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai with that of Tarasov to include a computer readable media comprising non-transitory computer executable instructions which, when executed by at least electronic processor through the combination of references as it would have yielded the predictable result of allowing for the method to be controlled through a computational device.
Modified Lai fails to explicitly disclose generating one or more cyclic voltammograms from an electrochemical sensor comprising biomolecular receptor-bound redox reporters using cyclic voltammetry (CV) (Examiner's Note: Lai fails to explicitly disclose the generation of the cyclic voltammogram).
Lai does disclose an electrochemical sensor comprising biomolecular receptor-bound redox reporters (Par. 7, “In another aspect, a method of detecting the presence or absence of an ion in a sample is provided…” “…cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV).”) (Par. 6, “the redox indicator is methylene blue”) (Par. 5, “one aspect, an electrochemical sensor for detecting the presence or absence of ions is provided…”).
However, Lai does teach in an example generating one or more cyclic voltammograms from an electrochemical sensor comprising biomolecular receptor-bound redox reporters using cyclic voltammetry (CV) (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan. An E.sub.1/2 of -0.26 V (vs. Ag/AgCl) was determined from the CV scan recorded at 1 V/s in the absence of Hg.sup.2+, this value is comparable to that shown in ACV (FIG. 9)…”).
Lai teaches the use of multiple electrochemical techniques to generate voltammograms (Par. 46, “Four electrochemical techniques, including ACV, CV, SWV and DPV were used in sensor interrogation”) (Par. 52, “Voltammograms were then collected using all four techniques.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai and Tarasov with an exemplary embodiment of Lai to include generating one or more cyclic voltammograms from an electrochemical sensor comprising biomolecular receptor-bound redox reporters using cyclic voltammetry (CV) as differing electrochemical measurements are known in the art (Lai (Par. 7, 40) and it would have yielded the predictable result of explicitly providing a visual representation of the data.
Modified Lai fails to explicitly disclose 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 (Examiner's Note: The claim does not explicitly indicate a level of specificity for the detection).
However, Lai does teach in an example determining 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 (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan….”).
Leach teaches a change in peak-to peak separation (Claim 1, “readings from the cyclic voltammetry scan; identifying positions of at least two peaks in the set of readings, wherein a first peak is a reference peak corresponding to adsorption or desorption of hydrogen and a second peak is due to oxide formation or reduction…”) to detect the target molecule using the electrochemical sensor (Claim 1, “and determining the concentration of the electrolyte of the electrochemical sensor by applying a correlation to a voltage difference between the identified positions of the at least two peaks”)(Claim 2, “scanning the working electrode of the electrochemical sensor using the cyclic voltammetry scan at the plurality of electrolyte concentrations; identifying the at least two peaks at each electrolyte concentration; generating a variable set of readings from the cyclic voltammetry scan comprising differences in the positions of the first peak and the second peak; and determining the correlation by plotting the variable set of readings and the plurality of electrolyte concentrations.”) (Abstract).
Lai, Leach, and Tarasov are considered to be analogous art to the claimed invention as they are involved with analyte detection.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai and Tarasov with that of Lai and Leach to include 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 through the combination of references as it would have yielded the predictable result of explicitly providing a detection concentration and allow for the correction of sensor errors and improve accuracy (Leach (Col. 9, lines 31-38)).
Regarding claim 27, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does teach in an example comparing the ΔEP,T to a no target peak-to-peak separation, ΔEP,NT, determined from one or more cyclic voltammograms generated from the electrochemical sensor in the absence of the target molecule (Lai (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan. An E.sub.1/2 of -0.26 V (vs. Ag/AgCl) was determined from the CV scan recorded at 1 V/s in the absence of Hg.sup.2+, this value is comparable to that shown in ACV (FIG. 9)…”(comparison with absence))).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with an example of Lai to include comparing the ΔEP,T to a no target peak-to-peak separation, ΔEP,NT, determined from one or more cyclic voltammograms generated from the electrochemical sensor in the absence of the target molecule through the combination of examples as it would have yielded the predictable result of allowing for the visualization of the impact of the target on measurements (Lai (Par. 56)).
Regarding claim 28, modified Lai fails to explicitly disclose the limitations of the claim.
However, Leach further teaches determining a concentration of the target molecule in the sample by comparing the ΔEP,T to a standard curve;
determining the ΔEP,T from at least a first cyclic voltammogram and at least a second cyclic voltammogram generated from the electrochemical sensor; or
determining a concentration of the target molecule in the sample via the change in the target peak-to-peak separation, ΔEP,T (Leach (Claim 1, “readings from the cyclic voltammetry scan; identifying positions of at least two peaks in the set of readings…” “… determining the concentration of the electrolyte of the electrochemical sensor by applying a correlation to a voltage difference between the identified positions of the at least two peaks”)(Claim 2, “scanning the working electrode of the electrochemical sensor using the cyclic voltammetry scan at the plurality of electrolyte concentrations…” “… determining the correlation by plotting the variable set of readings and the plurality of electrolyte concentrations.”) (Abstract)).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with that of Leach to include determining a concentration of the target molecule in the sample by comparing the ΔEP,T to a standard curve; determining the ΔEP,T from at least a first cyclic voltammogram and at least a second cyclic voltammogram generated from the electrochemical sensor; determining a concentration of the target molecule in the sample via the change in the target peak-to-peak separation ΔEP,T through the combination of references as it would have yielded the predictable result of explicitly providing a detection concentration of the target, and allow for the correction of sensor errors and improve accuracy (Leach (Col. 9, lines 31-38)).
Regarding claim 35, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does further teach in an example comprising generating the cyclic voltammograms from the electrochemical sensor using a voltage scanning rate of about 5 V s·1 or more (Lai (Par. 56, “Best signal attenuation was seen at scan rates between 10 and 200 V/s.”).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with that of Lai to include comprising generating the cyclic voltammograms from the electrochemical sensor using a voltage scanning rate of about 5 V s·1 or more as differing scanning rates are known in the art (Lai (Par. 56)) and it would have yielded the predictable result of providing the optimal scanning rate (Lai (Par. 56)).
Regarding claim 36, modified Lai further discloses wherein the target molecule comprises a therapeutic agent (Lai (Par. 5 (ions)).
Lai fails to explicitly disclose generating a dose-response curve for the therapeutic agent.
However, Lai does teach in an embodiment generating a dose-response curve for the therapeutic agent (Lai (Par. 13, “FIG. 3 is a graph showing a dose-response curve obtained in ACV at 10 Hz in PBS. The Hg.sup.2+ concentrations used were 10, 50, 100, 500, 1000, 2000, and 3000 nM. The results were averaged from three different sensors. The inset shows the voltammograms collected before and after addition of various concentrations of Hg.sup.2+.”)).
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with that of Lai to include generating a dose-response curve for the therapeutic agent through the combination of embodiments as it would have yielded the predictable result of allowing for the observation of the impact of varying concentrations (Lai (Par. 13)).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai in view of Leach as applied to claim 1 above, and further in view of Lee (US Pat. No. 9841403) hereinafter Lee.
Lai and Leach teach the method of claim 1 above.
Regarding claim 20, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does disclose the target peak-to-peak separation, ΔEP,T (Lai (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan….”)).
Lee teaches continuously monitoring the change in the target peak-to-peak separation, ΔEP,T over time from multiple cyclic voltammograms generated from the electrochemical sensor (Claim 1, “…generating, using the primary data set, a first voltammogram that characterizes a response to the primary pulse at the working electrode over the first time interval; generating, using the secondary data set, a second voltammogram that characterizes a response to the secondary pulse at the working electrode over the second time interval…” “… determining the characteristic of the analyte in the environment using the difference voltammogram.”) (Claim 2, “wherein the controller is further configured to repeatedly vary the electrical potential applied between the working electrode and the reference electrode according to the binary waveform while the set of electrodes are located in the environment at a frequency defined by a repetition time interval.”).
Lai, Leach, and Lee are considered to be analogous art to the claimed invention as they are involved with analyte measurements.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with that of Lee to include continuously monitoring the change in the target peak-to-peak separation, ΔEP,T over time from multiple cyclic voltammograms generated from the electrochemical sensor through the combination of references as it would have yielded the predictable result of monitoring any changes over time.
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai in view of Leach as applied to claim 1 above, and further in view of Zakashansky (US Pub. No. 20230050906) hereinafter Zakashansky.
Lai and Leach teach the method of claim 1 above.
Regarding claim 24, modified Lai fails to explicitly disclose the limitations of the claim. However, Zakashansky teaches wherein the electrochemical sensor comprises a wearable device that is worn by the subject (Par. 62, “Referring now to FIGS. 1-140, the present invention features methods for the fabrication and use of a stretchable wrinkled electrode for electrochemical detection of biomarkers in body fluids, to be used in portable/wearable point-of-care health monitoring devices.”).
Lai, Leach, and Zakashansky are considered to be analogous art to the claimed invention as they are involved with analyte measurements.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the method of Lai and Leach with that of Zakashansky to include wherein the electrochemical sensor comprises a wearable device that is worn by the subject through the combination of references as it would have yielded the predictable result of making the device portable (Zakashansky (Par. 62)).
Claim(s) 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai in view of Tarasov and Leach as applied to claim 25 above, and further in view of Lee.
Lai, Tarasov, and Leach teach the system of claim 25 above
Regarding claim 37, modified Lai fails to explicitly disclose the limitations of the claim.
However, Lai does disclose the target peak-to-peak separation, ΔEP,T (Lai (Par. 56, “Although CV is most commonly used in sensor characterization, it is an equally good sensor interrogation technique (Yang and Lai, 2011, Langmuir, 27:14669-77; Lai et al., 2013, Methods, 64:267-75). At 100 V/s, a set of redox peaks with a relatively large hysteresis (i.e., peak-to-peak separation) was recorded in the absence of Hg.sup.2+ (FIG. 1C). In the presence of Hg.sup.2+, the MB redox peaks diminished substantially, accompanied by a slight change in the hysteresis. Sensor regeneration was equally successful, as evidenced by the overlapping CV scan….”)).
Lee teaches continuously monitoring the change in the target peak-to-peak separation, ΔEP,T over time from multiple cyclic voltammograms generated from the electrochemical sensor (Claim 1, “…generating, using the primary data set, a first voltammogram that characterizes a response to the primary pulse at the working electrode over the first time interval; generating, using the secondary data set, a second voltammogram that characterizes a response to the secondary pulse at the working electrode over the second time interval…” “… and determining the characteristic of the analyte in the environment using the difference voltammogram.”) (Claim 2, “wherein the controller is further configured to repeatedly vary the electrical potential applied between the working electrode and the reference electrode according to the binary waveform while the set of electrodes are located in the environment at a frequency defined by a repetition time interval.”).
Lai, Tarasov, Leach, and Lee are considered to be analogous art to the claimed invention as they are involved with analyte measurements.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with that of Lee to include continuously monitoring the change in the target peak-to-peak separation, ΔEP,T of Lai over time from multiple cyclic voltammograms generated from the electrochemical sensor through the combination of references as it would have yielded the predictable result of monitoring any changes over time.
Claim(s) 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lai in view of Tarasov and Leach as applied to claim 25 above, and further in view of Zakashansky.
Lai, Tarasov, and Leach teach the system of claim 25 above
Regarding claim 38, modified Lai fails to explicitly disclose the limitations of the claim. However, Zakashansky teaches wherein the electrochemical sensor comprises a wearable device that is worn by the subject (Par. 62, “Referring now to FIGS. 1-140, the present invention features methods for the fabrication and use of a stretchable wrinkled electrode for electrochemical detection of biomarkers in body fluids, to be used in portable/wearable point-of-care health monitoring devices.”).
Lai, Leach, Tarasov, and Zakashansky are considered to be analogous art to the claimed invention as they are involved with analyte measurements.
Therefore, it would have been obvious to a person of ordinary skill in the art to modify the system of Lai, Tarasov, and Leach with that of Zakashansky to include wherein the electrochemical sensor comprises a wearable device that is worn by the subject through the combination of references as it would have yielded the predictable result of making the device portable (Zakashansky (Par. 62)).
Conclusion
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/ARI S PADDA/Examiner, Art Unit 3791
/RENE T TOWA/Primary Examiner, Art Unit 3791