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 .
Preliminary Amendments
Applicant’s preliminary amendment filed on January 15, 2026 is acknowledged. Claims 1-31 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-27 and 31, in the reply filed on January 15, 2026 is acknowledged.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1-6, 18-19, 21-22, and 25-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Boutelle (US 2018/0136247).
Regarding claim 1, Boutelle teaches a (¶179: the sensor comprises a hydrogel layer; ¶233: the sensing reagent) sensing composition comprising a pyruvate-responsive enzyme (¶192: pyruvate oxidase for detection of pyruvate), thiamine pyrophosphate (TPP) (¶193: when the enzyme is pyruvate oxidase, the hydrogel comprises TPP), a stabilizing agent (¶179: the hydrogel contains albumin; here, the albumin is the same agent as an enzyme-stabilizing agent disclosed in the specification, PGpub ¶10, and thus it must have the same property of being an enzyme stabilizing agent), and a redox mediator (¶195: a mediator molecule).
The optional limitation “optionally flavin adenine dinucleotide (FAD)” is not required in the prior art.
Regarding claim 2, Boutelle teaches wherein the pyruvate-responsive enzyme comprises pyruvate oxidase (¶192).
Regarding claim 3, Boutelle teaches wherein the pyruvate oxidase and TPP are present in the composition in a weight ratio of about 500:1 to about 1:1 (¶254: 0.06 mg/ml to 18 mg/ml pyruvate oxidase (POX); ¶256: 0.5 to 20 mM TPP; based on the MW of TPP, 460.77 g/mol, the calculated weight of POX and TPP in 1 ml are, e.g., 10 mg POX, and 1 mM TPP = 0.46mg, leading a weight ratio of about 22:1).
Regarding claim 4, Boutelle teaches wherein the pyruvate oxidase and TPP are present in the composition in a weight ratio of about 50:1 to about 1:1 (¶254: 0.06 mg/ml to 18 mg/ml pyruvate oxidase (POX); ¶256: 0.5 to 20 mM TPP; based on the MW of TPP, 460.77 g/mol, the calculated weight of POX and TPP in 1 ml are, e.g., 10 mg POX, and 1 mM TPP = 0.46mg, leading a weight ratio of about 22:1).
Regarding claim 5, Boutelle teaches wherein the stabilizing agent is an albumin (¶179).
Regarding claim 6, Boutelle teaches the sensing composition further comprising a pH buffer (¶233: buffer; ¶236: any suitable pH).
Regarding claim 18, Boutelle teaches a sensing electrode comprising a working electrode (¶157: working electrode) comprising a pyruvate sensing layer (¶157: hydrogel layer) comprising the sensing composition of claim 1 (as described in claim 1).
Regarding claim 19, Boutelle teaches wherein the pyruvate sensing layer is continuous (¶157: hydrogel layer, which is deemed to be continuous).
Regarding claim 21, Boutelle teaches the sensing electrode further comprising a membrane (¶209: a third layer) overcoating at least the pyruvate sensing layer (¶224: the hydrogel of the working electrode is covered in the third layer).
Regarding claim 22, Boutelle teaches wherein the membrane is permeable to pyruvate (¶219: the third layer is considered to extend the dynamic range and increases the sensitivity of the sensor; thus it must be permeable to pyruvate, the analyte, to allow the analyte reaching the hydrogel sensing layer).
Regarding claim 25, Boutelle teaches a system (Fig. 28; ¶330: analysis system) for sensing pyruvate (¶327: analysis of pyruvate), comprising an electrode (¶157: working electrode) comprising the sensing composition of claim 1 (as described in claim 1); and
a circuit (¶329: the microfluidic circuit) configured for electrochemical detection of pyruvate at the electrode (Fig. 27; ¶327: analysis of pyruvate based on the calibration curve for the pyruvate sensor; ¶329: the circuit is used to create a calibration curve; thus it must be connected to the working electrode for sensing; further, this limitation is functional limitation in apparatus claims. MPEP 2114 (II). It does not differentiate the claimed apparatus from a prior art apparatus because the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)).
Regarding claim 26, Boutelle teaches a system (Fig. 28; ¶330: analysis system) for sensing pyruvate (¶327: analysis of pyruvate) comprising
a working electrode (¶157: working electrode),
a sensing element (¶208: a hydrogel layer; ¶209: the second layer is the hydrogel layer) disposed on at least a portion of the working electrode (¶210: prior to application of the hydrogel layer, the working electrode is coated in a first layer), and
a circuit (¶329: the microfluidic circuit) configured to connect and disconnect with the working electrode (¶329: the circuit is used to create a calibration curve; thus it must be connected to the working electrode for sensing; further, this limitation is functional limitation in apparatus claims. MPEP 2114 (II). It does not differentiate the claimed apparatus from a prior art apparatus because the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)),
wherein
the sensing element comprises the sensing composition of claim 1 (as described in claim 1), and
the sensing element is configured to accumulate charge (Fig. 5; ¶304: relating electrical current and analyte concentration as a function of time) derived from pyruvate reacting with the pyruvate oxidase for a set period of time (¶284: a complete reaction in a short period of time; further, this limitation is functional limitation in apparatus claims. MPEP 2114 (II). It does not differentiate the claimed apparatus from a prior art apparatus because the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim(s) 7-17, 23-24, 27, and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boutelle in view of Oja (US 2019/0004005).
Regarding claims 7-13, Boutelle discloses all limitations of claim 1, but fails to teach wherein the redox mediator comprises a polymer and an electron transfer agent (claim 7) or wherein the polymer comprises poly(4-vinylpyridine) (claim 8) or wherein the polymer comprises a polymer repeat unit comprising at least one pendant pyridyl group (claim 9) or wherein the electron transfer agent comprises a transition metal complex (claim 10) or wherein the transition metal complex comprises osmium (claim 11) or wherein the transition metal complex is an osmium transition metal complex comprising one or more ligands, wherein at least one ligand comprises a nitrogen-containing heterocycle (claim 12) or wherein the redox mediator comprises an osmium complex bonded to a poly(4-vinylpyridine)-based polymer (claim 13).
However, Oja teaches sensing an analyte by providing the working electrode with an analyte-specific enzyme and redox mediator (¶7). The redox mediator is an immobilized redox polymer (¶11), including a redox species and a polymer (¶12). The redox species is osmium (Os) and the polymer is poly(vinylpyridine) (PVP) (¶12), and thus the redox polymer is an Os-containing poly(vinylpyridine) (¶13). Thus, Oja teaches the redox mediator comprises a polymer (¶12: PVP) and an electron transfer agent (¶119: Formula I: the electron transfer agent is the osmium (Os)-containing poly(vinylpyridine) redox polymer). Here, the polymer is poly(vinylpyridine) (¶119), and it has polymer repeat units forming the polymer backbone and pendant pyridinyl group (¶119: Formula I). The electron transfer agent comprises a transition metal complex (¶121), e.g. an osmium transition metal complex, which contains a nitrogen-containing heterocycle as the ligand (¶119: Formula I; ¶125).
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 Boutelle by substituting its mediator with the osmium (Os)-containing poly(vinylpyridine) redox polymer as taught by Oja because it would give superior detection at low analyte concentrations (¶179). 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 claims 14-16, Boutelle discloses all limitations of claim 1, but fails to teach the sensing composition further comprising a cross linking agent (claim 14) or wherein the cross linking agent is a polyepoxide (claim 15) or wherein the cross linking agent is a polyethylene glycol diglycidylether (PEGDGE) (claim 16).
However, Oja teaches the sensing element includes a crosslinker besides the analyte specific enzyme and the electron transfer agent (¶78). The crosslinker is poly(ethylene glycol) diglycidyl ether (PEGDGE), so that the electron transfer agent and analyte-specific enzyme are co-immobilized onto the working electrode (¶118). Here, PEGDGE is a polyepoxide because it is a bifunctional epoxy-terminal polymer.
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 Boutelle by incorporating PEGDGE as a crosslinker into the sensing composition as taught by Oja because it would co-immobilize the electron transfer agent and analyte-specific enzyme onto the working electrode (¶118) to give superior detection at low analyte concentration (¶179). 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, Boutelle discloses all limitations of claim 2, but fails to teach wherein the pyruvate oxidase is attached to the redox mediator.
However, Oja teaches the analyte-specific enzyme is crosslinked to the electron transfer agent (¶116), and thus attached to the redox mediator.
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 Boutelle by crosslinking the enzyme and the redox mediator as taught by Oja because the immobilization of the electron transfer agent and the analyte–specific enzyme on the sensing layer, so called “electrically wired enzyme”, would enable relaying electrons between the immobilized molecules for sensing the analyte (¶116). 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 claims 23-24, Boutelle discloses all limitations of claim 22, but fails to teach wherein the membrane has reduced permeability to TPP relative to pyruvate (claim 23) or wherein the membrane comprises poly(4-vinylpyridine) (claim 24).
However, Oja teaches an outer membrane that limits diffusion of the analyte to the sensing reagent (¶91), which is made of a highly permeable materials, such as poly(vinyl pyridine) crosslinked with PEGDGE (¶93).
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 Boutelle by substituting the third layer with the outer membrane comprising poly(vinyl-pyridine) as taught by Oja because the outer membrane would provide a biocompatible interface with an in vivo environment and/or provide stability to the underlying sensing layer including the electron transfer agents and/or analyte-specific enzymes thereon (¶92). Here, the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Regarding claims 27 and 31, Boutelle discloses all limitations of claims 25 and 26 respectively, but fails to teach the system further comprising an implantable portion configured for inserting into a tissue, wherein the working electrode is disposed on the implantable portion.
However, Oja teaches a sensor 500 for accumulation mode sensing, which includes a first portion positioned above a surface of the skin and a second portion that includes a sensor tail 530 positionable below the surface of the skin, e.g., penetrating through the skin (dermis) and into the subcutaneous space and in contact with the wearer’s biofluid (Fig. 13, ¶103). The working electrode 501 is at the second portion of the sensor 500 and particularly at the bottom portion of sensor tail 530 (Fig. 13; ¶103).
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 Boutelle by incorporating an implantable portion to be inserted into a tissue for the working electrode to be exposed to the analyte in the tissue as taught by Oja because the insertion location may allow for enhanced contact with deeper locations beneath a wearer's skin ( e.g., the subcutaneous space), where greater access to the wearer's interstitial fluid may permit greater access the analyte of interest being measured (¶110). 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).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boutelle in view of Blauw (EP 2372355).
Regarding claim 20, Boutelle discloses all limitations of claim 8, but fails to teach wherein the pyruvate sensing layer is discontinuous.
However, Blauw teaches thin films that can be used as a sensing layer for sensing of chemical and biochemical analytes in a gas or liquid phase (¶1). The film can be a thin continuous or discontinuous layer without grain boundaries for sensing a predetermined analyte, having a surface in used exposed to the analyte (¶11).
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 Boutelle by substituting the continuous pyruvate sensing layer with a discontinuous one as taught by Blauw because it would be able to sensing analyte by being exposed to the analyte (¶11). Here, the substitution of one known element for another would yield nothing more than predictable results. MPEP 2141(III)(B). Since “continuous” and “discontinuous” sensing layer is only two alternatives, choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success is prima facie obvious. MPEP 2141(III)(E).
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 M-F: 8:30am - 5:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Luan Van can be reached on 571-272-8521. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C. SUN/Primary Examiner, Art Unit 1795