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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 14, 2026 has been entered.
Status of Objections and Rejections
All objections and rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-5, 7-8, 10-12, and 14-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz (US 2011/0269648) in view of Macphee (US 6682648).
Regarding claim 1, Schwartz teaches a method of automatic verification of product and sample integrity and identity (Fig. 22; ¶172: method of identifying a chemical) comprising:
introducing a sample into one or more microwells (Fig. 22; ¶174: multiple analytes are exposed to the nanoscale confined spaces of the senor surface; ¶19: a delivery system enables samples to be automatically delivered to the array of sensors);
generating an electrochemical response (Fig. 22; ¶175: one or more electrical variations are measured at the sensor surface; ¶19: an electrochemical sensor; a signature change in a measurable electrical property; here, Examiner notes that the measured electrical signal is the generated electrochemical response);
measuring the electrochemical response (Fig. 22; ¶175: one or more electrical variations are measured); and
determining an identity of the sample based on the electrochemical response and a known electrochemical response (Fig. 22; ¶177: the one or more analytes are identified by respective frequency signatures in the frequency domain; ¶39: compares obtained frequency responses against a library of frequency response signatures of individual contaminants).
Schwartz further discloses the system is an electrochemical sensor system utilizing measurable electrical property (¶19). For example, to identify a target analyte, specifical chemicals interact with the nanomaterial and produce variations in electrical parameters, such as current, voltage, and impedance, which are integrated to generate an electrical signature (¶¶156-157).
Schwartz does not explicitly disclose the electrochemical response is of an electrochemical and analyte detection reagent, wherein the electrochemical reporter is a chemical that undergoes or catalyzes an oxidation and/or reduction during electrochemical reaction when placed between an anode electrode and a cathode electrode, and wherein the oxidation and/or reduction occurs in the microwell in response to one or more analytes in the sample introduced into the one or more microwells.
However, Macphee teaches an electrochemical reporter system for detecting immunoassay (Title). The reporter molecules are capable of exhibiting redox recycling at the electrode’s surface, e.g., an interdigitated array of anodes and cathodes (Fig. 2; col. 6, ll. 17-19). The electrochemical labels may be directly conjugated to the reporter substance, or generated as conjugated or unconjugated products of enzyme/substrate reactions in conjunction with ligand/receptor procedures (col. 6, ll. 33-36). These techniques that have been borrowed from the immunochemical or receptor-ligand field and adapted to provide reporter systems that are safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz by substituting the electrochemical sensor using binding with the electrochemical reporter system as taught by Macphee because the reporter system is safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38). Further, since Schwartz teaches the working electrode is at the bottom of the well (Schwartz, Fig. 6; ¶8), and Macphee teaches the reporter molecules exhibit redox recycling at the electrode’s surface (Macphee, col. 6, ll. 17-18), the combined Schwartz and Macphee would necessarily result in the oxidation and/or reduction occurs in the well in response to the analytes introduced into the well.
Regarding claim 2, Schwartz teaches wherein the electrochemical response is measured in the one or more microwells (Fig. 22; ¶175: one or more electrical variations are measured at the sensor surface; ¶172: at a nanoscale confined space of a electrochemical sensor surface).
Regarding claim 3, Schwartz teaches comparing the electrochemical response to the known electrochemical response (Fig. 22; ¶177: the one or more analytes are identified by respective frequency signatures in the frequency domain; ¶156: e.g., comparing frequency responses or signatures with a library of frequency response signatures of individual analytes that compose the mixture).
Regarding claim 4, Schwartz teaches the method further comprising:
comparing the electrochemical response to a second known electrochemical response (¶168: the device can send data on the measurement of different substances such as pesticides to a database for analysis, or can be used to print tags stating the level of measured pesticide found in the food; here the measured data stored in the database is deemed to be the second known electrochemical response for subsequent comparison); and
determining an integrity and identity of the product and sample based on the electrochemical response and the second known electrochemical response (¶70: the electrochemical sensor may receive, e.g., analog information based on the electrical signals from the sensing module and translate this information into database entries; may print the name and amount of contaminants found in a food sample on a tag; here the received newly measured electrochemical response would be used for determination of the information based on the comparison to the entries of the database).
Regarding claim 5, Schwartz teaches producing immunoassay results with electrochemical responses (Fig. 22; ¶175: one or more electrical variations are measured at the sensor surface; ¶19: an electrochemical sensor; produces a signature change in a measurable electrical property; ¶121: biochemical assays).
Regarding claim 7, Schwartz teaches passing the product and sample integrity and identity to allow additional data to be added (¶168: the device can send data on the measurement of different substances to a database).
Regarding claim 8, Schwartz teaches applying a current and voltage to the one or more microwells (¶67: to send an electrical pulse across the two conductors; the electrical pulse can be a voltage waveform or an electrical current waveform).
The designation “to prevent generation of electrochemical response” does not further limit the method as claimed because it is the intended result of the step “applying a current and voltage to the one or more microwells.” Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. In method claims, it is the overall method steps that are given patentable weight not the intended result thereof because the intended result does not materially alter the overall method. Here, this designation is not given patentable weight when it simply expresses the intended result of a process step positively recited. MPEP 2111.04.
Regarding claim 10, Schwartz and Macphee disclose all limitations of claim 1. Schwartz does not disclose introducing the electrochemical reporter into the one or more microwells, wherein the electrochemical reporter bind to the one or more microwells.
However, Macphee teaches an electrochemical reporter system for detecting immunoassay (Title). The reporter molecules are capable of exhibiting redox recycling at the electrode’s surface, e.g., an interdigitated array of anodes and cathodes (col. 6, ll. 17-19). These techniques that have been borrowed from the immunochemical or receptor-ligand field and adapted to provide reporter systems that are safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz by substituting the electrochemical sensor using binding with the electrochemical reporter system utilizing reporter molecules undergoing redox reactions at the electrode’s surface as taught by Macphee because the reporter system is safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38). Here, Schwartz teaches the working electrode is at the bottom of the well (Schwartz, Fig. 6; ¶8), and Macphee teaches the reporter molecules exhibit redox recycling at the electrode’s surface (Macphee, col. 6, ll. 17-18), wherein reactions may take place in solution or when specific components are anchored to solid supports for ready separation of bound ligands (col. 6, ll. 51-53). As a result, it would be obvious to one of ordinary skill in the art to combined Schwartz and Macphee, i.e., using the electrochemical reporter in the well and bound to the well, and arrive the claimed subject matter. Choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is prima facie obvious. MPEP 2141(III)(E).
Regarding claim 11, Schwartz and Macphee disclose all limitations of claim 1, including introducing signal generating reagents (Schwartz, Fig. 6; ¶8; Macphee, col. 6, ll. 17-18), wherein the electrochemical response is generated when the signal generating reagents are converted into electrochemical response (Macphee, col. 6, ll. 54-55: use of labeled recognition molecules to directly indicate the presence of a substance of interest; e.g., col. 8, ll. 52-53: p-aminophenol produced indicative of the concentration of antibody)
Regarding claim 12, Schwartz and Macphee disclose all limitations of claim 1, including wherein the electrochemical reporter changes in response to exposure to the sample (¶Macphee, col. 8, ll. 45-46: a sample of body fluid containing the analyte; ll. 52-55: the quantity of p-aminophenol produced is indicative of the concentration of antibody in the specimen).
Regarding claim 14, Schwartz teaches calibrating the one or more microwells based on the electrochemical response in the one or more microwells and the known electrochemical response (¶119: sensor arrays include partitioning the sensors for self-calibration).
Regarding claims 15-16, Schwartz and Macphee disclose all limitations of claim 1. Schwartz does not disclose wherein after determining product and sample integrity and identity further conducting one or more additional analyses (claim 15) or wherein the one or more additional analyses comprises an optical immunoassay (claim 16).
However, Macphee teaches a mix-and-match immunoassay format (Fig. 1), including both optical and electrochemical reporter system (Col. 5, ll. 33-35).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz and Macphee by incorporating optical immunoassay after the electrochemical immunoassay as suggested because two methods would be able to be used for comparison (Macphee, Fig. 2-9) or used for collaboration of each other. Here, the claimed limitations are obvious because all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results. MPEP 2143(I)(A).
Regarding claim 17, Schwartz teaches wherein the sample comprises whole blood (¶87: example DNA binding layer; ¶89: it is possible that entire blood panel could be tested at once using the system to improve diagnostic capabilities).
Regarding claims 18-19, Schwartz teaches a method of automatic verification of product and sample integrity and identity (Fig. 22; ¶172: method of identifying a chemical) comprising:
introducing a sample into one or more microwells (Fig. 22; ¶174: multiple analytes are exposed to the nanoscale confined spaces of the senor surface; ¶19: a delivery system enables samples to be automatically delivered to the array of sensors);
generating an electrochemical response (Fig. 22; ¶175: one or more electrical variations are measured at the sensor surface; ¶19: an electrochemical sensor; a signature change in a measurable electrical property; here, Examiner notes that the measured electrical signal is the generated electrochemical response);
measuring the electrochemical response (Fig. 22; ¶175: one or more electrical variations are measured at the sensor surface); and
determining an identity of the sample based on the electrochemical response and a known electrochemical response (Fig. 22; ¶177: the one or more analytes are identified by respective frequency signatures in the frequency domain; ¶39: compares obtained frequency responses against a library of frequency response signatures of individual contaminants).
Schwartz further discloses the system is an electrochemical sensor system utilizing measurable electrical property (¶19). For example, to identify a target analyte, specifical chemicals interact with the nanomaterial and produce variations in electrical parameters, such as current, voltage, and impedance, which are integrated to generate an electrical signature (¶¶156-157).
Schwartz does not explicitly disclose the electrochemical response is of an electrochemical and analyte detection reagent, wherein the electrochemical reporter is an enzyme (claim 18) or wherein the electrochemical reporter is an alkaline phosphate (claim 19).
However, Macphee teaches an electrochemical reporter system for detecting immunoassay (Title). The reporter molecules are capable of exhibiting redox recycling at the electrode’s surface, e.g., an interdigitated array of anodes and cathodes (Fig. 2; col. 6, ll. 17-19). The electrochemical labels may be directly conjugated to the reporter substance, or generated as conjugated or unconjugated products of enzyme/substrate reactions in conjunction with ligand/receptor procedures (col.6, ll. 33-36). Enzyme/substrates may include alkaline phosphatase/p-aminophenylphosphate (col. 6, ll. 45-46). These techniques that have been borrowed from the immunochemical or receptor-ligand field and adapted to provide reporter systems that are safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz by substituting the electrochemical sensor using binding with the electrochemical reporter system using an enzyme, e.g., an alkaline phosphate, as taught by Macphee because the reporter system is safer, environmentally friendly, more cost effective, far faster, appropriate for use in a wide range of methods and compatible with efficiently conducting large numbers of procedures (col. 3, ll. 33-38).
Claim(s) 6 and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz in view of Macphee, and further in view of Pugia (US 2018/0283998).
Regarding claims 6 and 9, Schwartz and Macphee disclose all limitation of claims 1 and 5, but fails to teach wherein the one or more microwells comprise a size exclusion filter (claim 6) or wherein the immunoassay results comprise quantitative sample enumeration (claim 9).
However, Pugia teaches a method and apparatus for analysis of small amounts of sample liquids (¶2). The apparatus includes a porous matrix 2 attached to a liquid holding area 1 (Fig. 1) for filtering the sample and reagents through the porous matrix (¶¶22, 29). The sample and reagents can be collected through the porous matrix 2 by being transferred into a microfluidic surface 7 using a hydrodynamic force (Fig. 2; ¶23). For example, the rare molecules and rare cells may be measured using immunoassay reactions for Her2nue or CK proteins (¶193). The porous matrix with captured rare cells could be removed from the microfluidic surface and then analyzed by a microscope so that the number of cells containing Her2nue or CK proteins were enumerated under the microscope (¶194).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz and Macphee by incorporating a porous matrix to filter the sample and capture the analyte using immunoassays for subsequent enumeration as taught by Pugia because the concentration of one or more different populations of target molecules is enhanced to form a concentrated sample (¶136) subject to subsequent analysis and/or enumeration. Here, applying a known technique to a known method ready for improvement to yield predictable results is prima facie obvious. MPEP 2141(III)(D).
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz in view of Macphee, and further in view of Sullivan (US 2003/0104503).
Regarding claim 13, Schwartz and Macphee disclose all limitation of claim 10 but fails to teach wherein differing concentrations of electrochemical reporters are introduced into each of the one or more microwells.
However, Sullivan teaches a voltametric or amperometric approach to detection, wherein a rate of change of voltage or current conductivity in proportion to the amount of antigen or antibody contained in the test material, using an electrochemical reporter system for detecting and quantifying enzymes and other bioagents in analytical and clinical applications (¶6). The sensor detects voltametric and/or amperometric signals that are produced in proportion to the concentration of organic (or inorganic) reporter molecules by redox (e.g. reduction-oxidation) recycling at the sensor (¶6), rendering the electrochemical reporter concentration a result-effective variable.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Schwartz by differing the concentrations of electrochemical reporters as suggested by Sullivan because the concentrations of electrochemical reporters is a result-effective variable and can be optimized through routine experimentation to achieve desirable electrochemical signal. MPEP 2144.05 (II)(B).
Response to Arguments
Applicant’s arguments has/have been considered but are moot because the arguments do not apply to any of the references being used in the current rejection. The newly cited reference, Macphee, is relied on to teach the electrochemical reporter system.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached on M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795
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