DETAILED ACTION
Response to Amendment
This is a final office action in response to a communication filed on May 20, 2026. Claims 18-20, 23-26, 28-30, and 32-48 are pending in the application.
Status of Objections and Rejections
All rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection are necessitated by the amendments.
Claim Objections
Claim(s) 26 is/are objected to because of the following informalities:
Claim 26, line 6: “the sensing element comprises the sensing composition of claim 1, and” is suggested to be deleted because claim 1 has been canceled
Appropriate correction is required.
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(s) 33-34 is/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 pre-AIA the applicant regards as the invention.
Claim 33 recites “the composition” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. It is suggested to be “a composition of the pyruvate sensing layer.” As a result, the recitation “the composition” in lines 1-2 is suggested to be “the composition of the pyruvate sensing layer.”
Subsequent dependent claim 34 is rejected due to its dependency on rejected base claim 33.
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) 18-19, 23-26, and 32-48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oja (US 2019/0004005) in view of Boutelle (US 2018/0136247).
Regarding claims 18, 32, and 35, Oja teaches a sensor (Fig. 13; ¶103: an analyte sensor 500) for detecting pyruvate in vivo (¶103: a sensor tail 530 positionable below the surface of the skin and in contact with the wearer’s biofluid, such as interstitial fluid; thus the sensor is in vivo; claim 6: the analyte is pyruvate) comprising:
a first portion configured to be positioned above a user’s skin (¶103); and
an implantable portion (Fig. 13; ¶103: sensor tail 530) configured to be positioned below the user’s skin such that the implantable portion is in contact with the user’s interstitial fluid to monitor the level of pyruvate in vivo (¶103), the implantable portion comprising:
a working electrode (Fig. 13; ¶104: working electrode 501);
a pyruvate sensing layer disposed on the working electrode (Fig. 13; ¶104: sensing area 509 that is on the working electrode 501), the pyruvate sensing layer comprising a pyruvate-responsive enzyme (for claim 18), wherein the pyruvate-responsive enzyme comprises pyruvate oxidase (for claim 32) (Fig. 14D; ¶132: the analyte-specific enzyme 323; ¶128: the analyte-specific enzyme is pyruvate oxidase for oxidizing pyruvate), and a redox mediator (Fig. 14D; ¶132: redox mediator 324); and
a membrane permeable to pyruvate (¶21: the outer membrane is an analyte-permeable membrane) and overcoating the pyruvate sensing layer (Fig. 14B; ¶105: an outer membrane 520 overcoating the various layers, including the sensing area 509).
Oja does not explicitly disclose the pyruvate sensing layer also comprising thiamine pyrophosphate (TPP), flavin adenine dinucleotide (FAD), and a stabilizing agent (for claim 18) or wherein the stabilizing agent is an albumin (for claim 35).
However, Boutelle discloses a pyruvate sensing layer (¶179: the sensor comprises a hydrogel layer), comprising pyruvate oxidase (¶192) for detecting pyruvate. When the enzyme is pyruvate oxidase, the hydrogel comprises MgCl2, thiamine pyrophosphate (TPP) (¶193), and 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).
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 Oja by incorporating TPP, FAD, and albumin as a stabilizing agent as taught by Boutelle because they are cofactors useful that stabilize the enzyme when the hydrogel is formed so that the space enclosing the enzyme is suitable for a properly constituted functional enzyme (¶193). 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 19, Oja teaches wherein the pyruvate sensing layer is continuous (Fig. 13; ¶104: sensing area 509, which is deemed to be continuous).
Regarding claims 23-24, Oja teaches wherein the membrane comprise poly(4-vinylpyridine) (¶93: the outer membrane is made of a highly permeable materials, such as poly(vinyl pyridine) (PVP)), wherein the membrane has reduced permeability to TPP relative to pyruvate (since the membrane comprises PVP, the same material as disclosed in the specification, PGpub ¶16, thus it would have the same property, i.e., having reduced permeability to TPP relative to pyruvate).
Regarding claim 25, Oja in view of Boutelle teaches a system (Fig. 13; ¶103) for sensing pyruvate (Fig. 13; ¶104), comprising
a sensor of claim 18 (as described in claim 18); and
a circuit configured for electrochemical detection of pyruvate at the electrode (Fig. 17; ¶159: sensor control device 102 for analyte level measurements; 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, Oja in view of Boutelle teaches a system (Fig. 13; ¶103) for sensing pyruvate (Fig. 13; ¶104) comprising
a sensor of claim 18 (as described in claim 18); and
a circuit (Fig. 17; ¶159: sensor control device 102 for analyte level measurements) configured to connect and disconnect with the working electrode (¶87: after steady-state oxidation, the working electrode was electrically disconnected for a set period of time (the accumulation time) to allow for charge accumulation, and then the working electrode was reconnected to measure the accumulated charge; 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 (here, claim 1 has been canceled; also see the composition of the pyruvate sensing layer as described in claim 18), and
the pyruvate sensing layer is configured to accumulate charge derived from pyruvate reacting with the pyruvate-responsive enzyme for a set period of time (¶87: after steady-state oxidation, the working electrode was electrically disconnected for a set period of time (the accumulation time) to allow for charge accumulation, and then the working electrode was reconnected to measure the accumulated charge; 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 claims 33-34, Oja and Boutelle discloses all limitations of claim 32. Oja fails to teach wherein the pyruvate oxidase and TPP are present in the composition in a weight ratio of about 500:1 to about 1:1 (claim 33) or wherein the pyruvate oxidase and TPP are present in the composition in a weight ratio of about 50:1 to about 1:1 (claim 34).
However, Boutelle teaches the sensing reagent comprises: 0.06 mg/ml to 18 mg/ml pyruvate oxidase (POX) and 0.5 to 20 mM TPP (¶254: ¶253-254, 256). Here, 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, which overlaps the claimed ranges in claims 33-34.
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 Oja by adjusting the weight ratio of pyruvate oxidase and TPP within the claimed range because it is known in the prior art as suitable composition of the pyruvate sensing reagent. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05(I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). MPEP 2144.05(I).
Regarding claim 36, Oja teaches the sensor further comprising a pH buffer (¶174: buffer solution).
Regarding claim 37, Oja teaches wherein the redox mediator comprises a polymer and an electron transfer agent (¶11: the redox mediator is an immobilized redox polymer; ¶12: the immobilized redox polymer includes a redox species and a polymer; the polymer is PVP; ¶119: the redox species is an electron transfer agent).
Regarding claim 38, Oja teaches wherein the polymer comprises poly(4-vinylpyridine( (¶119).
Regarding claim 39, Oja teaches wherein the polymer comprises a polymer repeat unit comprising at least one pendant pyridyl group (¶119: Formula I).
Regarding claim 40, Oja teaches wherein the electron transfer agent comprises a transition metal complex (¶121).
Regarding claim 41, Oja teaches wherein the transition metal complex comprises osmium (¶119: Formula I).
Regarding claim 42, Oja teaches wherein the transition metal complex is an osmium transition metal complex (¶119: Formula I) comprising one or more ligands, wherein at least one ligand comprises a nitrogen-containing heterocycle (¶125).
Regarding claim 43, Oja teaches wherein the redox mediator comprises an osmium complex bonded to a poly(4-vinylpyridine)-based polymer (¶119: Formula I).
Regarding claim 44, Oja teaches wherein the sensor further comprising a cross linking agent (¶118: the electron transfer agent and analyte-specific enzyme are co-immobilized with a chemical crosslinker).
Regarding claim 45, Oja teaches wherein the cross linking agent is a polyepoxide (¶118: the chemical crosslinker is poly(ethylene glycol) diglycidyl ether PEGDGE).
Regarding claim 46, Oja teaches wherein the cross linking agent is poly(ethylene glycol) diglycidyl ether (PEGDGE) (¶118).
Regarding claim 47, Oja teaches wherein the pyruvate oxidase is attached to the redox mediator (Fig. 14D: electrons enzyme 323; redox polymer (mediator) 324; ¶116: immobilization of the electron transfer agent and the analyte-specific enzyme on the sensing layer).
Regarding claim 48, Oja teaches wherein the pyruvate sensing layer is configured to accumulate charge derived from pyruvate reacting with the pyruvate-responsive enzyme for a set period of time (¶87: after steady-state oxidation, the working electrode was electrically disconnected for a set period of time (the accumulation time) to allow for charge accumulation, and then the working electrode was reconnected to measure the accumulated charge; 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(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Oja in view of Boutelle, and further in view of Blauw (EP 2372355).
Regarding claim 20, Oja and Boutelle disclose all limitations of claim 18, 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 Oja and 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).
Response to Arguments
Applicant’s arguments have been considered and they are persuasive.
Applicant argues Boutelle teaches away from using in vivo sensors (Response, pp. 8-9) and modifying Boutelle by Oja would change Boutelle’s principle of operation (pp. 11-12). These arguments are unpersuasive. The instant rejection is based on Oja’s in vivo sensor, and Boutelle is relied on to teach the TPP, FAD, and album as a stabilizing agent forming the pyruvate sensing layer. Boutelle does not teach away from an in vivo sensor because it merely teaches the depletion of oxygen is potentially an issue for lactate sensor (Boutelle, ¶19). Although Boutelle discloses an alternative approach, i.e., the microdialysis using the sensor on an extracellular composition (¶20), Boutelle does not disclose that in vivo measurement for pyruvate is impossible. Instead, Oja explicitly teaches a sensor for in vivo measurement of pyruvate (Fig. 13; ¶103: sensor tail 530 positionable below the surface of the skin and in contact with the wearer’s biofluid, such as interstitial fluid).
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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.
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/C. SUN/Primary Examiner, Art Unit 1795
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