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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/6/2026 has been entered.
Claims 1, 6, 8, 13-26 are pending. Claims 13-25 are withdrawn. Claims 1, 6, 8, 26 have been considered on the merits. All arguments and amendments have been considered.
Claim Interpretation
The claims are drawn to a system for detecting an analyte comprising a test strip, having an electrode and counter electrode, and a coating on the electrodes including reagents. The analyte is claimed to be creatinine and urea. As previously addressed, the limitations of blood being usable in claims 1, 8, and claim 26 do not provide a structural component to the system and the use of a material or article worked upon by a structure does not impart patentability to the claims, i.e., directed as blood being “usable” in the claimed system. The claims are drawn to a system for detection of an analyte however the claims do not require a step of detecting creatinine or urea per se but rather reagents to produce NH3 and NAD+. The “wherein” phrase “wherein the NAD+ is amplified by the enzyme cycling system, in that NAD+ is created by reaction with Diaphorase, which are collectively creatinine reactions and measure creatinine in a sample on the test strip, wherein the creatinine reactions are immune to oxygen and oxygen is not present in the creatinine reactions so both venous and capillary blood is usable”, does not impart structure to the claimed system, are taken to be results of the enzymatic reactions when combining the reagents, and thus does not impart patentability to the claims. The same is true for the newly added limitation of “wherein the test strip further includes an electrode for AC impedance detection to detect hematocrit and adjust detected levels of the first and second analyte based on techniques that include a usage of phase angle shift”. The only structural component added by the amendment appears to be an additional electrode, having an intended use. However, as seen below the newly added limitation is not clear and will be further discussed below.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 6, 8, 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, the amendment “…“wherein the test strip further includes an electrode for AC impedance detection to detect hematocrit and adjust detected levels of the first and second analyte based on techniques that include a usage of phase angle shift” introduces new matter, which is not described in the specification as originally filed. Applicants’ specification discloses “[0030] In many embodiments, gold or carbon sensors (electrodes) may be used. Alternatively, platinum, silver chloride, or other types of electrodes may be used. An advantage of gold sensors is having less background signal while maintaining the same slope. Using gold sensors would also be advantageous for methods to measure hematocrit by AC impedance based on techniques that include the usage of phase angle shift in order to detect hematocrit. Additionally, disclosing “[0033] In some embodiments, single analyte test strips are designed to have the same location with at least four associated electrodes. The electrode 60 that appears as an “h” is used for strip detection by the analyzer. The remaining assays will have at least three electrodes—one for sample fill detection, and the other two as a counter electrode and a working electrode. These assays are not limited to a set number of electrodes, for it is foreseen in some embodiments that more electrodes may be added for purposes of determining and correcting for hematocrit or other interfering substances”. However, the specification does not disclose an electrode which adjusts detected levels of the first and second analyte and which does so based on techniques that include usage of phase angle shift. There is no explicit or implicit support for this limitation. At best, the specification discloses that gold sensors can be advantageous for methods of measuring hematocrit by AC impedance based on techniques that include the usage of phase angle shift, and in some assays more electrodes can be added for determining hematocrit. It is not clear and there is no support for an electrode which adjusts detected levels of the first and second analyte and which does so based on techniques that include usage of phase angle shift with regards to applicant' s invention. Therefore, the amendment changes the scope of the claims and applicants invention for which no support is provided. This is a new matter rejection.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6, 8, 26 are 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.
The amendment to claims 1, 8, and 26 drawn to “…wherein the test strip further includes an electrode for AC impedance detection to detect hematocrit and adjust detected levels of the first and second analyte based on techniques that include a usage of phase angle shift” fails to distinctly claim applicants’ invention. It is not clear if and how the electrode, and any electrode is detecting hematocrit using AC impedance, adjusting detecting levels and doing so using phase angle shift. The specification does not disclose such an electrode. Further, it is not clear if applicant is intending to add an additional electrode to the test strip and if these claimed functions are inherent to said electrode.
For examination purposes, the limitations are given their broadest reasonable interpretation in light of the specification, and applicants specification teaches that a gold sensor/electrode would be advantageous for the claimed function, thus a reference which teaches a gold electrode would be one which would be capable of functioning as claimed. However, applicant is reminded that the limitations of “…for AC impedance detection to detect hematocrit and adjust detected levels of the first and second analyte based on techniques that include a usage of phase angle shift” does not impart structure to the claimed system, and are taken to be an inherent function of the electrode, and thus does not impart patentability to the claims.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 6, 8, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hughes et al. (US2016/0327562 A1) in view of Hughes et al. (US2017/0284954), Shull (US2004/0126833A1), Yamaguchi et al. (Clinica Chimica Acta. 352: 165-173, 2005), JP2003279525(IDS), Yamaguchi et al. (Biosci. Biotech. Biochem, p. 2052-2059, 2002) supported by Gambhir (Appl. BIochem, 2001, IDS) in further view of Winarta et al. (US20070131548).
Hughes teaches a system for the electrochemical detection of analyte levels (a ketone and glucose) comprising a test strip including a first electrode and a first counter electrode located proximate to a sample reception area for detecting a first analyte, i.e. ketones, and a second electrode and counter electrode located proximate to a second sample reception area and a coating on one of the electrodes to detect a second analyte (abstract, 0003, 0004). The coating of the system is disclosed to comprise a ferricyanide as the mediator and a dehydrogenase enzyme, diaphorase, a buffer and a surfactant (0003-0005). Hughes teaches the system to be used for electrochemical detection of ketone and glucose levels. Regarding claim 26, the coating may include hydroxybutyrate, hydroxybutyrate dehydrogenase, a mediator and NAD (0003, 0004, 0023-0026)
Hughes teaches the enzymatic reaction pathway; it can be seen that NAD+ with a dehydrogenase enzyme produces NADH. The NADH with mediator and diaphorase produces NAD+ (0025).
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Regarding claim 8, the system of Hughes comprises an analyzer, i.e., a microprocessor for receiving the test strip and having software or firmware as a form of instructions containing in or on a non-transitory computer-readable storage medium including ROM and RAM which may be read and executed by the processors (0034).
Hughes differ from the claimed invention in that they do not teach the reagents (creatinine iminohydrolase, deamido NAD+, ATP, NAD synthetase/Mg2+, glucose, glucose dehydrogenase, the claimed mediators and diaphorase) for detecting the analyte creatinine as claimed in claims 1, 8, and 26.
Regarding the mediators of claims 1, 8, and 26, Hughes (US’954) teaches a system for the electrochemical detection of an analyte comprising a test strip including an electrode and counter electrode located proximate to a sample reception area and a coating including a reagent coating for the analyte, specifically for creatinine. The reagent comprises a surfactant, binder and a mediator, wherein the mediator for use in creatinine electrochemical reactions with a dehydrogenase is selected from meldora blue, phenazine methosulfate, 2,6-diclorophenol indophenol, potassium ferricyanide, and nile blue (0005-0008, 0029). The system also comprises an analyzer for receiving the test strip including instructions for stored on a non-transitory medium for applying a current to the test strip and responsively determining an amount of creatinine (0006, 0007). Hughes additionally teaches that the reactions are not dependent on oxygen and can test both venous and capillary blood (0020). Regarding the newly added limitations to claims 1, 8, 26, drawn to test strip further includes an electrode for AC impedance detection to detect hematocrit and adjust detected levels of the first and second analyte based on techniques that include a usage of phase angle shift, Hughes also discloses that gold sensors/electrodes can be used to measure hematocrit by AC impedance based on techniques that include a usage of phase angle shift (0042) and that additional electrodes can be added to test strips for determining hematocrit (0045). Thus, these additional electrodes are taken to be one which can detect hematocrit and adjust analyst levels as claimed.
Therefore, before the effective filing date of the claimed invention, mediators for use in creatinine electrochemical systems were known in the art. One of ordinary skill in the art could have substituted one known mediator for another and the results would have been predictable. Thus, one could have substituted the ferricyanide of Hughes with the mediators disclosed by Hughes (‘954) with a reasonable expectation of success.
Regarding the reagents for detecting an analyte, Shull (US2004/0126833) teach a test strip for determining creatinine in a body fluid. Shull teach the reaction pathway for the enzymatic determination of creatinine.
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It can be seen from the pathway that creatinine iminohydrolase reacts with creatinine to produce ammonia NH3.
Yamaguchi teaches an enzymatic cycling method for detecting the analyte ammonia NH3 using NAD synthetase. Yamaguchi teaches that the new method of ammonia assay ensures sensitive, precise, and accurate assay of ammonia in biological samples containing substances such as urea and creatinine due to the fact that NAD synthetase is highly specific for ammonia (page 171, col. 1, paragraph 1). The method uses NAD synthetase, glucose dehydrogenase, and diaphorase (page 166, col. 2, paragraph 2). Yamaguchi further teaches that the reaction necessary for assaying ammonia using these enzymes also requires ATP, deamino-NAD, and glucose (page 166, col. 2, paragraph 2; Fig. 1). NAD synthetase requires ATP and deamino-NAD to assay ammonia by converting it into NAD (Fig. 1, page 171, col. 1, paragraph 1); glucose and the NAD produced from ammonia is required by glucose dehydrogenase and produces NADH (Fig. 1); the NADH is used by the diaphorase to produce a formazan dye that is then measured as the final product (page 166, col. 2, paragraph 2; Fig. 1). Yamaguchi teaches the presence of MgCl2 in reagent 1 (R1) (p. 167, section 2.2.)
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Further, JP525 teaches an electrode system which is highly sensitive, simple and speedy to measure NH3 using a reagent comprising diaphorase, dehydrogenase (p. 7), diamino-NAD+, ATP, NAD synthetase/Mg2+(p. 7, 9), a mediator including potassium ferricyanide, methylene blue (p. 9), a surfactant a buffer (p. 10)(abstract, p. 6-11).
Yamaguchi (2002) teach the use of Mg2+ in Reagent 1 (R1) with the enzyme NAD synthetase. Yamaguchi teaches that their NAD synthetase was prepared according to Yamaguchi (Biosci. Biotech. Biochem, 2002) which specifically teaches that metal ions such as Mg2+ are needed for NAD synthetase activity to catalyze the final conversion of deamide-NAD to NAD in the presence of ATP and ammonia (p. 2056, last parag. and Fig. 3, p. 2058, Discussion section). Therefore, it would have been obvious before the effective filing date of the claimed invention to use Mg2+ in complex NAD synthetase as it maximizes the enzymes activity.
Therefore, it would have been obvious before the effective filing date of the claimed invention to have used the reagents of Shull, Yamaguchi and JP525 in the system of Hughes for detecting an analyte, wherein the analyte is creatinine because the art collectively teaches the enzymatic reaction pathways wherein creatinine iminohydrolase reacts with creatinine to produce ammonia (NH3) and NH3 is enzymatically converted by reacting NH3 with deamino-NAD + ATP+ NAD synthetase to produce NAD+AMP+ pyrophosphate. The NAD is then amplified by an enzyme cycling system of glucose dehydrogenase and diaphorase (page 166, col. 2, paragraph 2) to produce NADH and D-gluco-δ-lactone, or HBA and HBA dehydrogenase (as taught by Hughes US’562). One would have a reasonable expectation of successfully using the NADH in step (2) of the reaction pathway of Hughes with the mediator and diaphorase to produce NAD+, thereby meeting the limitation of the NAD+ being amplified by the enzyme cycling system and creating NAD+ by reaction with diaphorase according to claim 1, 8 and 26 (using either glucose and glucose dehydrogenase or HBS and HBA dehydrogenase). The NADH with mediator and diaphorase produces NAD+ in Hughes. Therefore, one would have a reasonable expectation of successfully using the reagents of Shull and Yamaguchi in the coating of Hughes to determine creatinine given the arts enzymatic pathway systems and reagents used therefore.
Regarding newly added limitations to claims 1 and 8, drawn to a second analyte being urea and the coating on the second electrode including urease, deamido NAD+, ATP, NAD synthetase/Mg2+ , glucose and glucose dehydrogenase, diaphorase and a mediator, it is known in the art that the reaction of urea with urease produces ammonia (NH3), support is provided by Gambhir who teach that the hydrolysis of urea is catalyzed by urease releasing ammonia and the oxidation of NADH to NAD (p. 250, last parag).
Therefore, before the effective filing date of the claimed invention, one of ordinary skill in the art would have a reasonable expectation of successfully using the reagents of Yamaguchi in a system to detect urease because the art teaches the assay of ammonia in biological samples containing substances such as urea and creatinine. NAD synthetase is taught to be highly specific for ammonia (page 171, col. 1, paragraph 1) and thus uses NAD synthetase, glucose dehydrogenase, and diaphorase (page 166, col. 2, paragraph 2). Yamaguchi further teaches that the reaction necessary for assaying ammonia using these enzymes also requires ATP, deamino-NAD, and glucose (page 166, col. 2, paragraph 2; Fig. 1). NAD synthetase requires ATP and deamino-NAD to assay ammonia by converting it into NAD (Fig. 1, page 171, col. 1, paragraph 1); glucose and the NAD produced from ammonia is required by glucose dehydrogenase and produces NADH (Fig. 1); the NADH is used by the diaphorase to produce a formazan dye that is then measured as the final product. Therefore, the one would have had a reasonable expectation of successfully detecting urea when using the reagents of Yamaguchi because it was known that the hydrolysis of urea by urease releases ammonia, which is then used in the enzyme cycle of Yamaguchi to create an detectable electrochemical product.
Regarding the newly added limitation of the analyzer reporting a creatinine to urea ratio, Winarta teaches an electrochemical sensor system for determining creatinine to urea ratio in blood (0002, 0015, 0016). Urea (BUN) and creatinine are commonly screened for the evaluation of kidney function and the BUN-to-creatinine ratio is also typically used to determine decreased kidney function including kidney failure and other diseases and conditions (0004, 0010-0014). The system of Winarta comprises a test strip at least one electrode and counter electrode (0019, 0021, Fig. 1, Fig. 3) and reagents including urease, a surfactant, buffer, and mediator (0024, 0025, 0026). The system includes additional electrodes having creatinine/creatine sensitive enzymes, a surfactant, buffer and mediator (0032, 0034, 0035, 0038, 0042) and thus the multiple electrode system allows one to measure the urea-to-creatinine ratio (0032, 0038).
Thus, before the effective filing date of the claimed invention, it would have been obvious to a posita to include test strips, electrodes and reagents for detecting both creatinine and urea in a system because Winarta teaches that both analytes are useful to determining kidney function, diseases and other related conditions.
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Regarding the limitations of blood being usable, the art teaches the claimed creatinine reactions and the reagents and test strips of the prior art are disclosed to be used with blood and plasma samples. Regardless of the use of blood, the limitations of claim 1 and 8 do not provide a structural component to the system and the use of a material or article worked upon by a structure does not impart patentability to the claims.
Response to Arguments
Applicant's arguments filed 7/6/2026 have been fully considered but they are not persuasive. Applicants only argument is that the prior art does not teach the adjustment added by the amendment to claims 1, 8, and 26. The new limitations have been addressed in the rejections above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651
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