DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
2. According to the Amendment, filed 06 May 2026, the status of the claims is as follows:
Claims 1 and 9 are currently amended;
Claims 11, 14, 18, 21, 24-29, 34, 35, 37, 39, 43, 45, and 47 are as originally filed;
Claims 19 and 38 are previously presented; and
Claims 2-8, 10, 12, 13, 15-17, 20-23, 30-33, 36, 40-42, 44, 46, and 48-50 are cancelled.
Response to Arguments
3. Applicant’s arguments, see Remarks, p. 6, filed 06 May 2026, with respect to the rejection of claims 1, 3, 4, 9, 11, 14, 18, 19, 21, 24-29, 34, 35, 37-39, and 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rishpon et al., U.S. Patent Application Publication No. 2009/0061524 A1 (“Rishpon”), have been fully considered, but they are not persuasive.
Applicant contends, see Remarks, p. 6, the following:
Applicant submits that there is a critical structural difference between the sensor of Rishpon and the presently claimed bienzymatic sensor. For example, Rishpon provides a electrochemical sensor comprising glucose oxidase conjugated to an antigen-antibody conjugate further attached to an immobilization layer (see Rishpon para. [0081]; and Figure 1). On the other hand, the bienzymatic sensor of the presently amended claims are drawn to a recombinantly produced manganese peroxide and a glucose oxidase distributed (e.g., dispersed) throughout a coating (e.g., not attached to an immobilization layer nor a conjugate of an antisera-antigen as is taught by Rishpon). See, for example, FIG. 1 and FIG. 61 of the instant application as filed.
Accordingly, Applicant respectfully requests reconsideration and withdrawal of the rejection under 35 U.S.C. 102.
However, respectfully, this argument is not persuasive. Based on broadest reasonable interpretation, Rishpon teaches the claimed subject matter. Rishpon teaches the enzymes distributed or dispersed throughout the coating (“immobilization layer”), as follows:
Alternatively, the immobilization layer comprises a microporous membrane, acting as a sheath which is laid on the surface of the electrode, and the antigen and the first enzyme are attached to this microporous membrane. The membrane desirably contains chemical functional groups which can interact with suitable free functional groups on the first enzyme and the antigen, and be permeable at least to the electrochemically detectable moiety, but can also be permeable to all the solutes in the electrochemical cell. …
See para. [0181]. This shows that the enzymes are attached throughout the microporous membrane of the immobilization layer. Thus, the rejection is maintained for the new grounds for rejection below.
4. Applicant’s arguments, see Remarks, p. 7, filed 06 May 2026, with respect to the rejection of claims 43 and 45 under 35 U.S.C. 103 as being unpatentable over Rishpon, as applied to claim 1, and further in view of Seed et al., WO Patent No. 2011/163231 A2 (“Seed”), have been fully considered, but they are not persuasive.
Applicant contends, see Remarks, p. 7, the following:
For the reasons already set forth above with respect to claim 1, as amended, Applicant submits that claim 1 is patentable over Rishpon. Applicant finds no teaching in Seed to overcome the deficiencies of Rishpon with respect to claim 1. For at least these reasons, Applicant submits that claim 1, as amended, is patentable over Rishpon in further view of Seed. Since claims 43 and 45 depend from claim 1, as amended, Applicant submits that claims 43 and 45 are patentable over Rishpon in further view of Seed. Accordingly, Applicant respectfully requests reconsideration and withdrawal of the rejection under 35 U.S.C. 103.
However, respectfully, this argument is not persuasive for the same reasons as that provided above for base claim 1.
Claim Rejections - 35 USC § 102
5. 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 (i.e., changing from AIA to pre-AIA ) 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.
6. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
7. Claims 1, 3, 4, 9, 11, 14, 18, 19, 21, 24-29, 34, 35, 37-39, and 47 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rishpon et al., U.S. Patent Application Publication No. 2009/0061524 A1 (“Rishpon”).
As to Claim 1, Rishpon teaches the following:
A bienzymatic electrochemical sensor (“exemplary system”, not labeled) for the measurement of glucose concentration (see “The present invention relates to electrochemical biosensors and, more particularly, to low-cost, separation-free and accurate electrochemical biosensors and uses thereof for qualitatively and quantitatively determining the presence of biological analytes such as antibodies in a liquid sample such as sera and blood.” in para. [0001]) comprising
one or more electrodes (“three screen-printed electrodes (SPEs)”, not labeled) (see “FIGS. 4a-c present a schematic illustration of membrane-based electrochemical cell comprising three screen-printed electrodes (SPEs); a working electrode in the center, surrounded by a crescent-shaped counter electrode and a dot-shaped reference electrode printed with carbon ink on an insulating plate (a), …” in para. [0084]; and see fig. 4a-c),
a coating (“immobilization layer”, not labeled) that surrounds the one or more electrodes (see “FIG. 1 is a schematic illustration of an exemplary system according to the present invention wherein glucose oxidase (GOX), serving as the first enzyme of the enzymatic cascade, and an antigen are attached to an immobilization layer (marked by a wavy line) which coats the working electrode, and …” in para. [0081]; and fig. 1), and
two enzymes (“first enzyme” and “second enzyme”) distributed within the coating (see “Preferably, the first enzyme is glucose oxidase (GOX, EC 1.1.3.4). … According to preferred embodiments of the present invention, the second enzyme is a peroxidase.” in para. [0138]-[0139]; and see “Alternatively, the immobilization layer comprises a microporous membrane, acting as a sheath which is laid on the surface of the electrode, and the antigen and the first enzyme are attached to this microporous membrane. The membrane desirably contains chemical functional groups which can interact with suitable free functional groups on the first enzyme and the antigen, and be permeable at least to the electrochemically detectable moiety, but can also be permeable to all the solutes in the electrochemical cell. In general, the membrane serves as a trap for the small molecules which are involved in the enzymatic cascade, such as the hydrogen peroxide, the secondary substrate and the electrochemically detectable moiety; hence it affects a local increase in the concentration of these compounds in the proximity of the working electrode by lowering their diffusion rate away from it. The proximity of electrochemically detectable moiety is a crucial prerequisite for the sensitivity and function of the system presented herein.” in para. [0181]), wherein:
the two enzymes consist of recombinantly produced manganese peroxidase (see “Exemplary peroxidases include, without limitation, horseradish peroxidase (HRP, EC 1.11.1.7), Japanese radish peroxidase, myeloperoxidase, lactoperoxidase, verdoperoxidase, guaiacol peroxidase, thiocyanate peroxidase, eosinophil peroxidase, extensin peroxidase, heme peroxidase, MPO, oxyperoxidase, protoheme peroxidase, pyrocatechol peroxidase, scopoletin peroxidase, L-ascorbate peroxidase, catalase, TPNH peroxidase, NADP peroxidase, nicotinamide adenine dinucleotide phosphate peroxidase, TPN peroxidase, triphosphopyridine nucleotide peroxidase, NADPH2 peroxidase, NADH peroxidase, iodide peroxidase, cytochrome-c peroxidase, manganese peroxidase and fatty-acid peroxidase.” in para. [0141]) and glucose oxidase (see “Preferably, the first enzyme is glucose oxidase (GOX, EC 1.1.3.4).” in para. [0138]; and see “Exemplary hydrogen peroxide producing enzymes include, without limitation, glucose oxidase (GOX, EC 1.1.3.4), glucose oxyhydrase, corylophyline, penatin, glucose aerodehydrogenase, microcid, .beta.-D-glucose oxidase, D-glucose oxidase, D-glucose-1-oxidase, .beta.-D-glucose:quinone oxidoreductase, glucose oxyhydrase, deoxin-1, nucleoside oxidase, NAD(P)H oxidase, hexose oxidase, L-sorbose oxidase and pyranose oxidase.” in para. [0137]); and
the one or more electrodes comprises a screen-printed electrode (see “In order to produce a low-cost and disposable system, the working electrode is preferably a conductive carbon electrode such as, for example, a graphite electrode, a carbon ink electrode and a screen printed electrode. More preferably, the systems presented herein are based on the screen printed electrode technique, using carbon ink which is printed on an insulating electrode plate, including the working electrode.” in para. [0144]).
As to Claim 9, Rishpon teaches the following:
wherein the coating comprises manganese peroxidase, polythiophene, glucose oxidase, bovine serum albumin (BSA), and glutaraldehyde (see para. [0141] and [0246]).
As to Claim 11, Rishpon teaches the following:
wherein the coating further comprises a conductive polymer, an anti-fouling polymer, or a combination thereof (see “According to further features in preferred embodiments, the immobilization layer includes a polymer attached to the surface of the working electrode and a cross-linking agent attached to the polymer.” in para. [0052]; and “According to still further features in preferred embodiments, the polymer is selected from the group consisting of polyethyleneimine, chitosan, polyethylene oxide, polyvinylalcohol, polyvinyl acetate, polyacrylamide, poly(vinylpyrrolidone), poly(2-vinylpyridine), poly(4-vinylpyridine), poly(4-vinyl-N-butylpyridinium) bromide and poly(vinylbenzyltrimethyl)ammonium hydroxide. Preferably the polymer is polyethyleneimine.” in para. [0053]).
As to Claim 14, Rishpon teaches the following:
wherein the conductive polymer is sulfonated tetrafluoroethylene (Nafion™) (see “According to still further features in preferred embodiments, the polymer is selected from the group consisting of polyethyleneimine, chitosan, polyethylene oxide, polyvinylalcohol, polyvinyl acetate, polyacrylamide, poly(vinylpyrrolidone), poly(2-vinylpyridine), poly(4-vinylpyridine), poly(4-vinyl-N-butylpyridinium) bromide and poly(vinylbenzyltrimethyl)ammonium hydroxide. Preferably the polymer is polyethyleneimine.” in para. [0053]).
As to Claim 18, Rishpon teaches the following:
wherein the coating further comprises a nanoparticle (see “According to preferred embodiments, the conductive element comprises graphite, carbon ink, gold, platinum, silver, copper, nickel, chromium, and palladium, and more preferably, the conductive element comprises graphite and carbon ink.” in para. [0192]).
As to Claim 19, Rishpon teaches the following:
wherein the nanoparticle comprises graphene, carbon nanotubes, borophene, gold, or platinum (see “According to preferred embodiments, the conductive element comprises graphite, carbon ink, gold, platinum, silver, copper, nickel, chromium, and palladium, and more preferably, the conductive element comprises graphite and carbon ink.” in para. [0192]).
As to Claim 21, Rishpon teaches the following:
wherein the coating is less than about 1.5 mm thick (see para. [0150]).
As to Claim 24, Rishpon teaches the following:
wherein the one or more electrodes comprises a counter electrode, a working electrode, a reference electrode, or a combination thereof (see para. [0084]).
As to Claim 25, Rishpon teaches the following:
wherein the counter electrode comprises platinum and carbon (see para. [0192] and [0278]).
As to Claim 26, Rishpon teaches the following:
wherein the working electrode comprises gold and carbon (see para. [0192] and [0278]).
As to Claim 27, Rishpon teaches the following:
wherein the reference electrode comprises silver (Ag), silver/silver chloride (Ag/AgCl), or saturated calomel electrode (SCE) (see para. [0192] and [0278]).
As to Claim 28, Rishpon teaches the following:
wherein the sensor is an amperometric sensor and/or a voltammetric sensor (see para. [0014]).
As to Claim 29, Rishpon teaches the following:
wherein the electrochemical sensor can detect glucose in a fluid sample (see para. [0081]).
As to Claim 34, Rishpon teaches the following:
wherein the coating allows partitioning of glucose directly from a fluid sample, partitions a biocompatible interface between the sensor and the fluid sample, prevents electrode fouling, and/or provides selectivity for glucose (see para. [0081]).
As to Claim 35, Rishpon teaches the following:
wherein the electrodes are present in a microfluidic device in communication with a microfluid channel (see para. [0146] and [0181]).
As to Claim 37, Rishpon teaches the following:
wherein the sensor is miniaturized (see para. [0146]).
As to Claim 38, Rishpon teaches the following:
A microfluidic device comprising the electrochemical sensor of claim 1 (see para. [0146]).
As to Claim 39, Rishpon teaches the following:
A method for electrochemical detection of glucose in a sample (see “The systems and methods disclosed are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade reaction (enzyme-channeling) upon detecting an analyte, and therefore can be used to determine the titer level of an antibody analyte in a liquid sample such as artificial media, serum or blood both qualitatively and quantitatively, in a one-step and separation free immunoassay.” in Abstract) comprising:
exposing a fluid sample obtained from a subject to the electrochemical sensor of claim 1 (see “The present invention is of novel immunoassay systems (immunosensors) which are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade (enzyme-channeling), upon detecting an analyte, and which include an antigen immobilized to a working electrode in the system and hence can be used to determine the titer level of an antibody analyte in a liquid sample such as serum or blood both qualitatively and quantitatively, serving as an efficient analytical and diagnostic tool for detecting an immune response in a subject.” in para. [0096]), and
detecting the current generated from the oxidation of H2O2 during said exposing, wherein current corresponds to the concentration of glucose in the fluid sample (see “Hence, according to one aspect of the present invention, there is provided a system for detecting an antibody in a liquid sample, which comprises an electrochemical cell having components which are common to other similar systems, such as a reference electrode, a counter electrode, an electrolytic solution and a current detecting unit, as defined hereinbelow, and a working electrode having immobilized proximally thereon an antigen and a first enzyme of an enzymatic cascade.” in para. [0108]).
As to Claim 47, Rishpon teaches the following:
A method of monitoring a subject having or at risk of having diabetes (see “The systems and methods disclosed are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade reaction (enzyme-channeling) upon detecting an analyte, and therefore can be used to determine the titer level of an antibody analyte in a liquid sample such as artificial media, serum or blood both qualitatively and quantitatively, in a one-step and separation free immunoassay.” in Abstract), the method comprising:
exposing a fluid sample obtained from a subject to the electrochemical sensor of claim 1 (see “The present invention is of novel immunoassay systems (immunosensors) which are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade (enzyme-channeling), upon detecting an analyte, and which include an antigen immobilized to a working electrode in the system and hence can be used to determine the titer level of an antibody analyte in a liquid sample such as serum or blood both qualitatively and quantitatively, serving as an efficient analytical and diagnostic tool for detecting an immune response in a subject.” in para. [0096]),
detecting the current generated from the oxidation of H2O2 during said exposing, wherein current correlates to the concentration of glucose in the fluid sample, thereby monitoring the subject having or at risk of having diabetes (see “Hence, according to one aspect of the present invention, there is provided a system for detecting an antibody in a liquid sample, which comprises an electrochemical cell having components which are common to other similar systems, such as a reference electrode, a counter electrode, an electrolytic solution and a current detecting unit, as defined hereinbelow, and a working electrode having immobilized proximally thereon an antigen and a first enzyme of an enzymatic cascade.” in para. [0108]).
Claim Rejections - 35 USC § 103
8. 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.
9. 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.
10. Claims 43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Rishpon, as applied to claim 1 above, and further in view of Seed et al., WO Patent No. 2011/163231 A2 (“Seed”).
As to Claim 43, Rishpon teaches the subject matter of claim 1 above. In addition, Rishpon teaches the following:
exposing a fluid sample obtained from a subject to the electrochemical sensor of claim 1 (see “The present invention is of novel immunoassay systems (immunosensors) which are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade (enzyme-channeling), upon detecting an analyte, and which include an antigen immobilized to a working electrode in the system and hence can be used to determine the titer level of an antibody analyte in a liquid sample such as serum or blood both qualitatively and quantitatively, serving as an efficient analytical and diagnostic tool for detecting an immune response in a subject.” in para. [0096]),
detecting the current generated from the oxidation of H2O2 during said exposing, wherein current corresponds to the concentration of glucose in the fluid sample (see “Hence, according to one aspect of the present invention, there is provided a system for detecting an antibody in a liquid sample, which comprises an electrochemical cell having components which are common to other similar systems, such as a reference electrode, a counter electrode, an electrolytic solution and a current detecting unit, as defined hereinbelow, and a working electrode having immobilized proximally thereon an antigen and a first enzyme of an enzymatic cascade.” in para. [0108]),
…
Rishpon does not teach the following:
A method of treating a subject afflicted with or at risk of diabetes, the method comprising:
..
treating the subject for diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl.
However, Seed teaches the following:
A method of treating a subject afflicted with or at risk of diabetes (see “The present invention provides methods for treating diabetes and associated complications by co-administration of sertraline and telenzepine.” in para. [0002]), the method comprising:
treating the subject for diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl (see “As a non-limiting example, if a subject to be treated according to the methods of the present invention has a first FPG measurement that is in the diabetic range (i.e., greater than 125 mg/dl), for example 200 mg/dl, in some instances it may be desirable for the FPG threshold level for efficacious treatment to be some value less than 100 mg/dl (i.e., in the normal range), in some instances it may be desirable for the FPG threshold level for efficacious treatment to be some value between 100 mg/dl and 125 mg/dl (i.e., in the pre- diabetic range), and in some instances it may be desirable for the FPG threshold level for efficacious treatment to be some value greater than or equal to 125 mg/dl (i.e., in the diabetic range) but less than the value of the subject's first FPG measurement (in this example, a value less than 200 mg/dl).” in para. [0062]).
Thus, it would have been obvious for one of ordinary skill in the art at the time the present application was effectively filed to modify Rishpon’s method to treat the subject for diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl, as taught by Seed, in order to properly manage a subject with a diabetic condition.
As to Claim 45, Rishpon teaches the subject matter of claim 1 above. In addition, Rishpon teaches the following:
exposing a fluid sample obtained from a subject to the electrochemical sensor of claim 1 (see “The present invention is of novel immunoassay systems (immunosensors) which are based on recording an electrochemical signal which is generated proportionally to an enzymatic cascade (enzyme-channeling), upon detecting an analyte, and which include an antigen immobilized to a working electrode in the system and hence can be used to determine the titer level of an antibody analyte in a liquid sample such as serum or blood both qualitatively and quantitatively, serving as an efficient analytical and diagnostic tool for detecting an immune response in a subject.” in para. [0096]),
detecting the current generated from the oxidation of H2O2 during said exposing, wherein current corresponds to the concentration of glucose in the fluid sample (see “Hence, according to one aspect of the present invention, there is provided a system for detecting an antibody in a liquid sample, which comprises an electrochemical cell having components which are common to other similar systems, such as a reference electrode, a counter electrode, an electrolytic solution and a current detecting unit, as defined hereinbelow, and a working electrode having immobilized proximally thereon an antigen and a first enzyme of an enzymatic cascade.” in para. [0108]), and …
Rishpon does not teach the following:
A method of diagnosing a subject with or at risk of diabetes, the method comprising:
…
diagnosing the subject as having or at risk of having diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl.
However, Seed teaches the following:
A method of diagnosing a subject with or at risk of diabetes (see “The present invention provides methods for treating diabetes and associated complications by co-administration of sertraline and telenzepine.” in para. [0002]), the method comprising:
diagnosing the subject as having or at risk of having diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl (see “A subject is identified as having pre-diabetes if the subject has a fasting blood glucose level greater than 100 mg/dl but less than or equal to 125 mg/dl, a 2 hour post- load glucose reading of greater than 140 mg/dl but less than 200mg/dl, or a HbAlc level greater than or equal to 6.0% but less than 6.5%.” in para. [0017]).
Thus, it would have been obvious for one of ordinary skill in the art at the time the present application was effectively filed to modify Rishpon’s method to diagnose the subject as having or at risk of having diabetes if the subject has a fasting blood glucose concentration is greater than 100 mg/dl, as taught by Seed, in order to properly manage a subject with a diabetic condition.
Conclusion
11. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAVIN NATNITHITHADHA whose telephone number is (571)272-4732. The examiner can normally be reached Monday - Friday 8:00 am - 8:00 am - 4:00 pm.
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/NAVIN NATNITHITHADHA/Primary Examiner, Art Unit 3791 07/20/2026
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