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 .
Response to Arguments
Applicant’s remarks and amendments with respect to the rejection of claim 1 under 35 U.S.C. 103 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Applicant’s remarks and amendments with respect to the rejections of claim 1 under 35 U.S.C. 103 have been fully considered.
Applicant’s arguments with respect to Nejime are moot because the new ground of rejection does not rely Nejime for any teaching or matter specifically challenged in the argument.
Applicant’s arguments with respect to Hoss have been fully considered but are not persuasive. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, the instant application, Wilkins, and Hoss are all directed to electrochemical sensors comprising multiple layers for sensing glucose and Hoss discloses a sensing layer containing glucose oxidase (para. [0076, 0088]), a sensing layer comprising periodate oxidized horseradish peroxidase (HRP) (para. [0097-0098]), and temperature independent membranes having analyte permeability and temperature coefficients to provide a temperature independent analyte sensor (para. [0022, 0027, 0031-0035]). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wilkins such that the glucose monitoring device is temperature independent within an operating temperature range, in view of the teachings of Hoss, for the obvious advantage of improving the performance of one or more sensor components by including a membrane structure including a plurality of membrane layers configured to generate signals that are substantially temperature independent over a range of temperatures (Hoss, para. [0022, 0027, 0035]).
Applicant’s remarks and amendments with respect to the rejections of claims 37-38, 40-42, 44, 47-49, 52-62, 64-65, 69, and 71-74 under 35 U.S.C. 103 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “a computing device configured to receive measurements from the glucose monitoring device and control the insulin administration system” in claim 74.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
The computing device is defined, in para. [0111-113], as one or more user devices 102 including a smart device, such as a smart watch, smart phone, tablet, computer.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 (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.
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.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Wilkins (US 5431160 A), in view of Nguyen (Nguyen et al., Combined cross-linked enzyme aggregates of horseradish peroxidase and glucose oxidase for catalyzing cascade chemical reactions, Enzyme and Microbial Technology, Volume 100, 2019, pages 52-59, ISSN 0141-0229, https://doi.org/10.1016/j.enzmictec.2017.02.007.), and further in view of Hoss (US 20120028283 A1).
Regarding claim 1, Wilkins discloses a glucose monitoring device (fig. 1, col. 2 lines 23-25, present invention provides an improved arrangement for an implantable electrochemical sensor such as a glucose sensor) comprising: a reference electrode (fig. 1, col. 3 lines 68, reference electrode 41); a working electrode (col. 4 line 15, working electrode 49), wherein the working electrode is disposed in the vicinity of the reference electrode (see fig. 1); an enzymatic layer comprising glucose oxidase (fig. 1, col. 4 lines 30-37, inner chamber 25 is filled with the enzyme material such as glucose oxidase; indicated by the numeral 51), wherein the glucose oxidase is capable of catalyzing a first reaction of glucose and oxygen to generate one or more oxidized species (col. 2 lines 53-55, glucose oxidase reacts with the incoming glucose to deplete oxygen, and produce hydrogen peroxide); a first permeability-selective layer (fig. 1, hydrophobic inner membrane 21) for reducing or blocking the diffusion of glucose to the enzymatic layer (col. 4 lines 22-27, hydrophobic inner membrane 21 operates through molecular diffusion and is of any suitable well known material to enable the passage therethrough into the chamber 25 of only small molecules including limited amounts of glucose which may be present in bodily fluids) an oxygen-replenishing layer comprising one or more enzymes (col. 4 lines 45-50, The central chamber is filled with a catalase enzyme material generally indicated by the numeral 53. The catalase enzyme material is also immobilized and bonded, i.e., fixed, to very fine particles of graphite in the same manner as the glucose oxidase), wherein at least one enzyme in the oxygen-replenishing layer is capable of catalyzing a second reaction consuming at least one oxidized species from the first reaction in the enzymatic layer and generating oxygen (col. 5 lines 28-32, as is well known in the art, the catalase enzyme serves to decompose hydrogen peroxide generated by the oxidation of the glucose occurring in the inner chamber 25. This prolongs the useful life of the glucose oxidase); and an outer protective layer (col. 3 lines 30-31 & col. 4 lines 18-22, outer membrane 17 made of any suitable well-known hydrophilic material spans the extent of one end of the housing 11; outer membrane 17 is of any suitable well-known material to permit the passage of bodily fluids therethrough into the chamber 23. Membrane 17 prevents the entry of large proteins or other large molecules or particulate matter into the chamber 23); wherein the enzymatic layer is in closer proximity to the working electrode than the oxygen-replenishing layer (see fig. 1). Wilkins does not expressly disclose wherein the rate of the first reaction of the glucose oxidase in the enzymatic layer and the rate of the second reaction of the oxygen-generating enzyme in the oxygen-replenishing layer are substantially the same such that the glucose monitoring device is temperature independent within an operating temperature range.
However, Nguyen discloses the rate of the first reaction of the glucose oxidase in the enzymatic layer (Abstract, page 53, 2.1 Materials, “glucose oxidase”, “reaction rate”) and the rate of the second reaction of the oxygen-generating enzyme in the oxygen-replenishing layer (Abstract, page 53, 2.1 Materials, “horseradish peroxidase”, “catalase”, “reaction rate”) are substantially the same (page 52, Introduction, “In the cascade reaction, if both reactions have similar reaction rates, then the overall reaction rate is determined by how fast the intermediate hydrogen peroxide can reach HRP [6,7]” & page 53, Introduction, “to optimize the reaction rate of the cascade reaction, combi-CLEA with different ratios of GOx and HRP was prepared by using the millifluidic reactor set-up” & page 54, 3.2 Formation of combi-CLEA of GOx and HRP, “the ratio of the two enzymes is an important parameter that determines the overall reaction rate of the cascade reaction … determine the optimal ratio of the two enzymes … optimal ratio is equivalent to an activity ratio of 1.1, suggesting that GOx and HRP in the CLEA had similar activities as free enzymes”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wilkins such that the rate of the first reaction of the glucose oxidase in the enzymatic layer and the rate of the second reaction of the oxygen-generating enzyme in the oxygen-replenishing layer are substantially the same, in view of the teachings of Nguyen, as such a modification would have been the result of routine optimization to optimize the reaction rate of the cascade reaction by determining the optimal ratio of glucose oxidase and horseradish peroxidase/catalase to provide similar reaction rates/activity ratios for glucose detection.
Wilkins and Nguyen do not disclose such that the glucose monitoring device is temperature independent within an operating temperature range.
However, Hoss directed to electrochemical analyte monitoring systems having a sensing layer 13, and a membrane structure 14, 15, glucose oxidase and horseradish peroxidase (HRP) (fig. 1, para. [0076, 0097-0098]) discloses the glucose monitoring device is temperature independent within an operating temperature range (para. [0022, 0027, 0035], the membrane structure includes a plurality of membrane layers, where the membrane structure as a whole has an analyte permeability that is substantially temperature independent; as such, in certain embodiments, the analyte sensor is configured to generate signals that are substantially temperature independent over a range of temperatures; the analyte sensor may generate signals that are substantially temperature independent over a range of temperatures, where the range of temperatures is from 0.degree. C. to 50.degree. C., such as from 15.degree. C. to 45.degree. C., including from 25.degree. C. to 45.degree. C.oHodsdlasjkh\).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Wilkins, as modified by Nguyen hereinabove, such that the glucose monitoring device is temperature independent within an operating temperature range, in view of the teachings of Hoss, the obvious advantage of improving the performance of one or more sensor components by including a membrane structure including a plurality of membrane layers configured to generate signals that are substantially temperature independent over a range of temperatures (Hoss, para. [0022, 0027, 0035]).
Claims 37, 44, 49, 56-57, and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos (US 20140262775 A1) in view of Liu (US 20090099434 A1), and further in view of Takahara (US 20120152763 A1).
Regarding claim 37, Papadimitrakopoulos discloses a glucose monitoring device (fig. 1, Abstract, a device that functions as a glucose sensor) comprising: a reference electrode (fig. 1, para. [0042], reference electrode 202); a working electrode (fig. 1, para. [0042], working electrode 102), wherein the working electrode is disposed in a vicinity of the reference electrode (fig. 1, para. [0019, 0042], the working electrode being disposed in the vicinity of the reference and counter electrode; opposed to the working electrode is a reference electrode 202); an enzymatic layer comprising glucose oxidase (para. [0059, electrically conducting membrane 106 is in operative communication with an enzyme layer 110; enzyme layer 110 comprises glucose oxidase) and a polymeric mediator for facilitating electron transfer between the glucose oxidase and the working electrode (fig. 1, para. [0042, 0045, 0050-051, 0059], an electrically conducting membrane 106; the working electrode 102 is in operative communication with an electrically conducting membrane 106; electrically conducting membrane 106 can comprise an electrically insulating organic polymer that is filled with electrically conducting filler; electrically conducting membrane 106 can comprise conducting polymers; electrically conducting membrane 106 is in operative communication with an enzyme layer 110; the enzyme layer 110 may comprise a conductive polymer if desired); a first permeability-selective layer for reducing or blocking the diffusion of glucose to the enzymatic layer (para. [0064], semi-permeable membrane 114; to regulate the amount of glucose with respect to oxygen and ensure better sensor linearity, the immobilized glucose oxidase (GO.sub.x) enzyme layer 110 is in operative communication with a semi-permeable membrane 114); and an outer protective layer (para. [0070, 0078-0079], the second layer of hydrogel 122; to immobilize and locally deliver various tissue response modifying (TRM) agents that control and suppress inflammation of the surrounding tissue, while at the same time permitting passage of glucose and O.sub.2, a hydrogel coating can be incorporated on the surface of the sensor that contacts the surface of the tissue 106; surface of the second layer of hydrogel 122 generally contacts the tissue 126 of a living being the first layer of hydrogel 118 and/or the second layer of hydrogel 122 can comprise a variety of enzymes to eliminate endogenous species).
Papadimitrakopoulos does not expressly disclose the polymeric mediator comprises a backbone material, one or more redox mediator moieties, and one or more functional groups for improving the hydrophilicity of the polymeric mediator, wherein the one or more redox mediator moieties are attached to the backbone material, optionally the redox mediator moieties are attached through one or more linkers, and wherein the one or more functional groups are attached to the backbone material, optionally the functional groups are attached to the backbone material through one or more linkers.
However, Liu directed to an electrochemical sensor having a redox polymer (para. [0081-0082]) discloses wherein the polymeric mediator comprises a backbone material, one or more redox mediator moieties (para. [0081], suitable redox polymers for use with the electrochemical analyte sensors may comprise, inter alia, a transition metal complex, a cross-linker and a polymeric backbone), and one or more functional groups (“reactive group”/ “functional groups”, para. [0057, 0073, 0077]), wherein the one or more redox mediator moieties are attached to the backbone material, optionally the redox mediator moieties are attached through one or more linkers through one or more linkers (para. [0081, 0086], one or more transition metal complexes coupled to a polymeric backbone, as described above) in a crosslinked film disposed on an electrode. A transition metal complex can be bound to the polymer backbone though covalent, coordinative or ionic bonds, where covalent and coordinative binding are preferred), and wherein the one or more functional groups are attached to the backbone material, optionally the functional groups are attached to the backbone material through one or more linkers through one or more linkers (“linkage”, para. [0077], Table II). Liu further disclose the redox polymer transfers electrons between the working electrode and an analyte (para. [0082]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos such that the polymeric mediator comprises a backbone material, one or more redox mediator moieties, and one or more functional groups for improving the hydrophilicity of the polymeric mediator, wherein the one or more redox mediator moieties are attached to the backbone material, optionally the redox mediator moieties are attached through one or more linkers, and wherein the one or more functional groups are attached to the backbone material, optionally the functional groups are attached to the backbone material through one or more linkers, in view of the teachings of Liu, in order to transfer electrons between the working electrode and an analyte by incorporating into the electrically conducting membrane of Papadimitrakopoulos a suitable redox polymer comprising a transition metal complex, a cross-linker and a polymeric backbone (Liu, para. [0082]).
Papadimitrakopoulos and Liu do not expressly disclose the one or more functional groups for improving the hydrophilicity of the polymeric mediator.
However, Takahara directed to a reagent layer (4) of a sensor (1) containing as a mediator a quinone compound having a hydrophilic functional group and acts as the electrochemically active region (Abstract, para. [0103]) discloses one or more functional groups for improving the hydrophilicity of the polymeric mediator (para. [0014, 0121], “hydrophilic functional group … better solubility in water”; “sulfonic acid group (sulfo group, --SO.sub.3H), a carboxylic acid group (carboxyl group, --COOH), and a phosphoric acid group (--PO.sub.4H.sub.2). Sulfonic acid groups, carboxylic acid groups, and phosphoric acid groups also include salts of these”). Furthermore, Takahara disclose that a quinone compound having a hydrophilic functional group is expected to have better solubility in water than a quinone compound that has no hydrophilic functional group and as a result, it is anticipated that there will be an increase in response current and measurement will take less time (para. [0014]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu hereinabove, to further comprise the one or more functional groups for improving the hydrophilicity of the polymeric mediator, in view of the teachings of Takahara, as such a modification would have been merely a substitution of the functional group of Papadimitrakopoulos and Liu for the hydrophilic functional group of Takahara to provide a better solubility in water, increase response current, and reduce measurement time.
Regarding claim 44, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37, wherein the backbone material comprises polyethylenimine (PEI), polyallylamine, cellulose, cellulose acetate, chitosan, poly(acrylic acid), poly(lactic acid), carbon nanofibers, carbon nanotubes, or metal nanofibers, or combinations thereof (para. [0050], examples of electrically conducting fillers are carbon nanotubes, carbon black, carbon nanoparticles, nanorods, intrinsically electrically conducting polymer powders, metal powders, electrically conducting ceramic powders, or the like, or a combination comprising at least one of the foregoing electrically conducting fillers).
Regarding claim 49, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37, wherein the one or more redox mediator moieties of the polymeric mediator comprise ferrocene, transition metal complexes, or organic molecules, or combinations thereof (para. [0051], the electrically conducting membrane 106 can comprise conducting polymers that are copolymers of (3,4-dihydroxy-L-phenylalanine), hydroxyquinones, ferrocene and ferrocene derivatives, ferricyanide, tetrathiafulvalene-tetracyanoquinodimethane, osmium salts, phenothiazine, phenoxazine, porporphorins, flavins, pyroloquinoline quinines, or the like, or a combination comprising at least one of the foregoing copolymers).
Regarding claim 56, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37, wherein the first permeability-selective layer is disposed between the enzymatic layer and the outer protective layer (see fig. 1, para. [0042], an enzyme layer 110, a semi-permeable membrane 114, a first layer of a first hydrogel 118 and a second layer of the second hydrogel 122).
Regarding claim 57, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 56, wherein the first permeability- selective layer is in direct contact with one or both of the enzymatic layer and the outer protective layer (see fig. 1, para. [0064, 0071], the immobilized glucose oxidase (GO.sub.x) enzyme layer 110 is in physical communication with a semi-permeable membrane 114; the first layer of hydrogel 118 is in physical communication with the semi-permeable membrane 114, while the second layer of hydrogel 122 is in physical communication with the first layer of hydrogel 118).
Regarding claim 69, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37. Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, does not disclose wherein the glucose monitoring device is an implantable continuous glucose monitoring device.
However, Liu discloses wherein the glucose monitoring device is an implantable continuous glucose monitoring device (para. [0026, 0103], sensor may be in the form of a subcutaneously implantable continuous in vivo sensor; embodiments relate to the continuous and/or automatic in vivo monitoring of the level of one or more analytes using a continuous analyte monitoring system that includes an analyte sensor at least a portion of which is to be positioned beneath a skin surface of a user for a period of time and/or the discrete monitoring of one or more analytes using an in vitro blood glucose ("BG") meter and an analyte test strip).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the glucose monitoring device is an implantable continuous glucose monitoring device, in view of the teachings of Liu, for the obvious advantage of providing a subcutaneously implantable continuous in vivo sensor for continuous and/or automatic in vivo monitoring of the level of one or more analytes using a continuous analyte monitoring system (Liu, para. [0026, 0103]).
Claims 38 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, as applied to claim 37 above, and further in view of Guy (US 20200008717 A1).
Regarding claim 38, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37, and a hydrogel matrix comprising one or more materials selected from the group consisting of cellulose acetate, chitosan, poly(2-hydroxyethyl methacrylate) (pHEMA), polyethylene glycol diamine, 3,6,9-Trioxaundecanedioic acid, sodium citrate, polyvinyl alcohol and polyethylenimine (PEI), and combinations thereof (para. [0074-0075], examples of the first and second hydrogels are crosslinked polyhydroxyethylmethacrylate, polyethylene oxide, polyacrylic acid, polyvinylpyrrole, chitosan, collagen, or the like, or a combination comprising at least one of the foregoing hydrogels; the first layer of the first hydrogel 118 and the second layer of the second hydrogel 122 both comprise polyvinylalcohol (PVA)) and further that the enzyme layer 110 may comprise a conductive polymer if desired and in another embodiment, the electrically conducting membrane 106 and the enzyme layer 110 are electropolymerized concurrently (para. [0059, 0062]).
Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, does not disclose the glucose oxidase and the polymeric mediator are present in a hydrogel matrix comprising one or more materials selected from the group consisting of cellulose acetate, chitosan, poly(2-hydroxyethyl methacrylate)(pHEMA), polyethylene glycol diamine, 3,6,9-Trioxaundecanedioic acid, sodium citrate, polyvinyl alcohol and polyethylenimine(PEI), and combinations thereof.
However, Guy directed to systems for non-invasive monitoring of substances, such as glucose, discloses wherein the glucose oxidase and the polymeric mediator are present in a hydrogel matrix (para. [0041], the enzyme glucose oxidase is entrapped in the hydrogel reservoirs; the enzyme is mixed with the hydrogel while in the liquefied state; the hydrogel is allowed to set to a semi-solid state, which typically corresponds to the set volume being about 2/3 of the initial volume. This state of the hydrogel facilitates both glucose diffusion through the gel and effective electron transfer during electrochemical sensing) comprising one or more materials selected from the group consisting of cellulose acetate, chitosan, poly(2-hydroxyethyl methacrylate)(pHEMA), polyethylene glycol diamine, 3,6,9-Trioxaundecanedioic acid, sodium citrate, polyvinyl alcohol and polyethylenimine(PEI), and combinations thereof (para. [0084], hydrogel (based on a polymers such as agarose, chitosan, ethyl cellulose, or methyl cellulose) used to encase the enzyme).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the glucose oxidase and the polymeric mediator are present in a hydrogel matrix comprising one or more materials selected from the group consisting of cellulose acetate, chitosan, poly(2-hydroxyethyl methacrylate)(pHEMA), polyethylene glycol diamine, 3,6,9-Trioxaundecanedioic acid, sodium citrate, polyvinyl alcohol and polyethylenimine(PEI), and combinations thereof, in view of the teachings of Guy, as such a modification would have been merely a substitution of the electrically conducting membrane and enzyme layer of Papadimitrakopoulos for the hydrogel encasing the glucose oxidase enzyme such that the hydrogel layer facilitates both glucose diffusion through the gel and effective electron transfer during electrochemical sensing (Guy, para. [0041, 0084]).
Regarding claim 40, Papadimitrakopoulos, as modified by Liu, Takahara, and Guy hereinabove, further discloses the glucose monitoring device of claim 38, wherein the hydrogel matrix comprises two or more crosslinked materials (para. [0074], examples of the first and second hydrogels are crosslinked polyhydroxyethylmethacrylate, polyethylene oxide, polyacrylic acid, polyvinylpyrrole, chitosan, collagen, or the like, or a combination comprising at least one of the foregoing hydrogels).
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, further in view of Guy, as applied to claim 38 above, and further in view of Crane (US 20130040404 A1).
Regarding claim 41, Papadimitrakopoulos, as modified by Liu, Takahara, and Guy hereinabove, further discloses the glucose monitoring device of claim 38. Papadimitrakopoulos, as modified by Liu, Takahara, and Guy hereinabove, does not disclose the hydrogel matrix further comprises one or more polymeric materials that render the hydrogel matrix with a negative charge.
However, Crane directed to a barrier layer for glucose sensor, discloses the hydrogel matrix further comprises one or more polymeric materials that render the hydrogel matrix with a negative charge (para. [0010, 0055], a hydrophilic and/or negatively charged polymer is present within the pores of the membrane. This is typically achieved via in situ polymerisation, within the pores of the membrane, of a monomer mixture comprising one or more hydrophilic monomers and/or one or more negatively charged monomers; In an alternative embodiment, the negatively charged material is heparin. This has the advantage that the negative charge carried on the heparin molecule repels proteins, but has the added benefit of being antithrombogenic; Heparin can be incorporated into a hydrogel or grafted to, or polymerised with, a membrane (e.g., microporous membrane or dialysis membrane)).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu, Takahara, and Guy hereinabove, such that the hydrogel matrix further comprises one or more polymeric materials that render the hydrogel matrix with a negative charge, in view of the teachings of Crane, for the obvious advantage of repelling proteins.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, further in view of Crane, as applied to claim 41 above, and further in view of McShane (US 20190000361 A1).
Regarding claim 42, Papadimitrakopoulos, as modified by Liu, Takahara, Guy, and Crane hereinabove, further discloses the glucose monitoring device of claim 41. Papadimitrakopoulos, as modified by Liu, Takahara, Guy, and Crane hereinabove, does not disclose the one or more polymeric materials comprise poly(sodium 4-styrenesulfonate), poly(4-styrenesulfonic acid-co- maleic acid) sodium salt, poly(acrylic acid-co-maleic acid), or poly(vinylsulfonic acid) sodium salt, or combinations thereof.
However, McShane directed to biosensors comprising one or more encapsulated functionalized domains, discloses wherein the one or more polymeric materials comprise poly(sodium 4-styrenesulfonate), poly(4-styrenesulfonic acid-co- maleic acid) sodium salt, poly(acrylic acid-co-maleic acid), or poly(vinylsulfonic acid) sodium salt, or combinations thereof (para. [0023], the microparticles are then encapsulated in a surrounding shell comprising 15 bilayers of poly(sodium 4-styrenesulfonate) and poly(allylamine hydrochloride) (PSS-PAH), which is then crosslinked to reduce pore size, and hence, glucose diffusion. A matrix of hydrogel (e.g., calcium-crosslinked alginate) is made by dispersing the pre-made sensing capsules in a precursor solution (e.g., sodium alginate) and supplying the divalent cation crosslinker (e.g., calcium) via external or internal sources).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu, Takahara, Guy, and Crane hereinabove, such that the one or more polymeric materials comprise poly(sodium 4-styrenesulfonate), poly(4-styrenesulfonic acid-co- maleic acid) sodium salt, poly(acrylic acid-co-maleic acid), or poly(vinylsulfonic acid) sodium salt, or combinations thereof in view of the teachings of McShane for the obvious advantage of reducing pore size, and hence, glucose diffusion (McShane, para. [0023]).
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, as applied to claim 37 above, and further in view of McDonald (US 20040051083 A1).
Regarding claim 47, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37. Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, does not disclose wherein the functional groups comprise -So3-, -PO3, -NH3+, or -N(CH3)3+, or combinations thereof.
However, McDonald directed to polymer-based coatings and materials, discloses wherein the functional groups comprise -So3-, -PO3, -NH3+, or -N(CH3)3+, or combinations thereof (para. [0010], the polymer used in the polymeric composition preferably comprises a polymer having side chains along a backbone forming the polymer wherein at least two of the side chains contain an amino group (--NRH, --NH.sub.2, --NRH.sub.2.sup.+, --NH.sub.3.sup.+)).
Upon the modification of Papadimitrakopoulos to incorporate hydrophilic functional groups, as described with respect to claim 37 above, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the functional groups comprise -So3-, -PO3, -NH3+, or -N(CH3)3+, or combinations thereof, in view of the teachings of McDonald, as such a modification would have been merely a substitution of the functional groups of Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, for the -NH3+ side chain of McDonald.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, as applied to claim 37 above, and further in view of Ettlinger (US 20130203065 A1).
Regarding claim 48, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37. Papadimitrakopoulos does not disclose the one or more linkers comprises an alkylene linker, a heteroalkylene linker, a polyethylene glycol (PEG) linker, or combinations thereof.
However, Ettlinger directed to a method for electrochemical detection of binding reactions, discloses wherein the one or more linkers comprises an alkylene linker, a heteroalkylene linker, a polyethylene glycol (PEG) linker, or combinations thereof (para. [0046-0047], due to good water solubility, the marginal unspecific binding to proteins and surfaces and availability of a plurality of chain lengths and chemical functions, polyethylene glycol linkers (synonym: polyethylene oxide linker, PEG, PEO) belong to the most frequently used water-soluble linkers; preferably a 2000 Da diamino-PEG linker, is used to couple ferrocene or another suitable redox mediator to one end and the target analyte to the other end. By using PEG linkers of sufficient length, analytes not soluble in water can also be made accessible for the test).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the one or more linkers comprises an alkylene linker, a heteroalkylene linker, a polyethylene glycol (PEG) linker, or combinations thereof, in view of the teachings of Ettlinger, in order to access analytes not soluble in water for testing by incorporating the PEG linker of a sufficient length to couple ferrocene to one end and the target analyte to the other (Ettlinger, para. [0046-0047]).
Claims 52-53 are rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, as applied to claim 37 above, and further in view of Ouyang (US 20200237277 A1).
Regarding claim 52, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37. Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, does not disclose wherein the enzymatic layer further comprises a second enzyme.
However, Ouyang directed to analyte sensors and sensing methods for dual detection of glucose and ethanol discloses wherein the enzymatic layer further comprises a second enzyme (fig. 6, para. [0079], second active area 414c may comprise glucose oxidase, catalase, and a second polymer). Ouyang further discloses Catalase may be present in the active area to clear hydrogen peroxide (e.g., as a catalase-hydrogen peroxide complex) such that catalase reacts with the hydrogen peroxide to form a catalase-hydrogen peroxide complex (para. [0061, 0096]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the enzymatic layer further comprises a second enzyme, in view of the teachings of Ouyang, for the obvious advantage of forming a catalase-hydrogen peroxide complex by incorporating catalase into the enzymatic layer of Papadimitrakopoulos such that catalase reacts with the hydrogen peroxide (Ouyang, para. [0061, 0069]).
Regarding claim 53, Papadimitrakopoulos, as modified by Liu, Takahara, and Ouyang hereinabove, further discloses the glucose monitoring device of claim 52, wherein the second enzyme is horseradish peroxidase or catalase (Ouyang, para. [0079], second active area 414c may comprise glucose oxidase, catalase, and a second polymer).
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, as applied to claim 37 above, and further in view of Petisce (US 20120283537 A1).
Regarding claim 54, Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, further discloses the glucose monitoring device of claim 37, wherein the first permeability-selective layer comprises one or more polymers (para. [0065-0067], semi-permeable membrane 114 comprises alternating layers of positive and negative polyion species (i.e., polymers, oligomers and/or multi-valent cations); semipermeable membrane can also comprise polystyrene sulfonate …). Papadimitrakopoulos, as modified by Liu and Takahara, does not disclose wherein the first permeability-selective layer comprises one or more polymers selected from the group consisting of a polyacetal, a polyolefin, a polyacrylic, a polycarbonate, a polystyrene, a polyester, a polyamide, polyamideimides, a polyarylate, a polyarylsulfone, a polyethersulfone, a polyphenylene sulfide, a polyvinyl chloride, a polyethylene oxide, a polysulfone, a polyimide, a polyetherimide, a polytetrafluoroethylene, a polyetherketone, a polyether etherketone, a polyether ketone ketone, a polybenzoxazole, a polyphthalide, a polyacetal, a polyanhydride, a polyvinyl ether, a polyvinyl thioether, a polyvinyl alcohol, a polyvinyl ketone, a polyvinyl halide, a polyvinyl nitrile, a polyvinyl ester, a polysulfonate, a polysulfide, a poly(allyl amine), a polythioester, a polysulfone, a polysulfonamide, a polyurea, a polyphosphazene, a polysilazane, a polyvinylchloride, a polyvinyl acetate, a humic acid, a cellulose acetate, a polythiophene, a polyphenylene diamine, a polypyrrole, a polynaphthalene a polyurethane, an ethylene propylene diene rubber, a polytetrafluoroethylene, a fluorinated ethylene propylene, a sulfonated tetrafluoroethylene based fluoropolymer-copolymer, a perfluoroalkoxyethylene, a polychlorotrifluoroethylene, a polyvinylidene fluoride, and a polysiloxane, and combinations thereof.
However, Petisce directed analyte sensor layers and methods related thereto, discloses wherein the first permeability-selective layer comprises one or more polymers selected from the group consisting of a polyacetal, a polyolefin, a polyacrylic, a polycarbonate, a polystyrene, a polyester, a polyamide, polyamideimides, a polyarylate, a polyarylsulfone, a polyethersulfone, a polyphenylene sulfide, a polyvinyl chloride, a polyethylene oxide, a polysulfone, a polyimide, a polyetherimide, a polytetrafluoroethylene, a polyetherketone, a polyether etherketone, a polyether ketone ketone, a polybenzoxazole, a polyphthalide, a polyacetal, a polyanhydride, a polyvinyl ether, a polyvinyl thioether, a polyvinyl alcohol, a polyvinyl ketone, a polyvinyl halide, a polyvinyl nitrile, a polyvinyl ester, a polysulfonate, a polysulfide, a poly(allyl amine), a polythioester, a polysulfone, a polysulfonamide, a polyurea, a polyphosphazene, a polysilazane, a polyvinylchloride, a polyvinyl acetate, a humic acid, a cellulose acetate, a polythiophene, a polyphenylene diamine, a polypyrrole, a polynaphthalene a polyurethane, an ethylene propylene diene rubber, a polytetrafluoroethylene, a fluorinated ethylene propylene, a sulfonated tetrafluoroethylene based fluoropolymer-copolymer, a perfluoroalkoxyethylene, a polychlorotrifluoroethylene, a polyvinylidene fluoride, and a polysiloxane, and combinations thereof (para. [0083-0084], the flux limiting membrane comprises a semi-permeable material that controls the flux of oxygen and glucose to the underlying layers, preferably providing oxygen in a non-rate-limiting excess; for example, non-polyurethane type layers such as vinyl polymers, polyethers, polyesters, polyamides, or thin-film, track-etched polycarbonates, inorganic polymers such as polysiloxanes and polycarbosiloxanes, natural polymers such as cellulosic and protein based materials, and mixtures or combinations thereof may be used; the analyte flux limiting membrane comprises a polyethylene oxide component).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Papadimitrakopoulos, as modified by Liu and Takahara hereinabove, such that the first permeability-selective layer comprises one or more polymers selected from the group consisting of a polyacetal, a polyolefin, a polyacrylic, a polycarbonate, a polystyrene, a polyester, a polyamide, polyamideimides, a polyarylate, a polyarylsulfone, a polyethersulfone, a polyphenylene sulfide, a polyvinyl chloride, a polyethylene oxide, a polysulfone, a polyimide, a polyetherimide, a polytetrafluoroethylene, a polyetherketone, a polyether etherketone, a polyether ketone ketone, a polybenzoxazole, a polyphthalide, a polyacetal, a polyanhydride, a polyvinyl ether, a polyvinyl thioether, a polyvinyl alcohol, a polyvinyl ketone, a polyvinyl halide, a polyvinyl nitrile, a polyvinyl ester, a polysulfonate, a polysulfide, a poly(allyl amine), a polythioester, a polysulfone, a polysulfonamide, a polyurea, a polyphosphazene, a polysilazane, a polyvinylchloride, a polyvinyl acetate, a humic acid, a cellulose acetate, a polythiophene, a polyphenylene diamine, a polypyrrole, a polynaphthalene a polyurethane, an ethylene propylene diene rubber, a polytetrafluoroethylene, a fluorinated ethylene propylene, a sulfonated tetrafluoroethylene based fluoropolymer-copolymer, a perfluoroalkoxyethylene, a polychlorotrifluoroethylene, a polyvinylidene fluoride, and a polysiloxane, and combinations thereof, in view of the teachings of Petisce, as such a modification would have been merely a substitution of the semi-permeable membrane of Papadimitrakopoulos for the flux limiting membrane of Petisce to control the flux of oxygen and glucose to the underlying layers, preferably providing oxygen in a non-rate-limiting excess (Petisce, para. [0083-0084]).
Claim 55 is rejected under 35 U.S.C. 103 as being unpatentable over Papadimitrakopoulos in view of Liu, further in view of Takahara, further in view of Petisce, as applied to claim 54 above, and further in view of Gerhardt (US 20170079568 A1).
Regarding claim 55, Papadimitrakopoulos, as modified by Liu, Takahara, and Petisce hereinabove, further discloses the glucose monitoring device of claim 54 and that the glucose oxidase (GO.sub.x) layer is coated with a semi-permeable membrane to reduce the amount of glucose entering the sensor (para. [0023]). Papadimitrakopoulos, as modified by Liu, Takahara, and Petisce hereinabove, does not disclose wherein the first permeability- selective layer comprises poly(ortho-phenylenediamine) (PoPD), poly(meta-phenylenediamine) (PmPD), or poly(para-phenylenediamine) (PpPD), or combinations thereof.
However, Gerhardt directed to a dual-sided biomorphic bioflex polymer-based microelectrode array and fabrication thereof, discloses wherein the first permeab