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 .
Status of Claims
Claims 1-6, 9, 12, 14, 15 and 29-31 are currently pending. Claims 1, 2, 4-6, 9, 12, 14, 15, 29 and 30 have been amended by Applicants’ amendment filed 01-15-2026. No claims have been canceled by Applicants’ amendment filed 01-15-2026. Claim 31 has been added by Applicants’ amendment filed 01-15-2026.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1-6, 9, 12, 14, 15 and 29-31 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed December 29, 2020 claims the benefit of US Provisional Patent Application 62/954,793, filed on December 30, 2019.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, instant Application 17/136,178, filed December 29, 2020, wherein the as-filed Specification and original claims fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific analyte sensor recited in independent claim 1 does not have support for; “a polyelectrolyte prepolymer” and a “hydrophobic stabilizing layer disposed over the hydrophilic sensing layer”. Therefore, the priority date for the presently claimed invention is December 29, 2020, the filing date of the claims for US Patent Application 17/136,178 comprising the recited limitations.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claim 1 of the instant application.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) the provisional application provides sufficient support for amended claim 1, such as at paragraphs [0050] and [0056]) (Applicant Remarks, pg. 5, last full paragraph through pg. 6, first partial paragraph).
Regarding (a), the as-filed Specification, the original claims and/or in US provisional patent application 62/954793 do not teach a “polyelectrolyte prepolymer” and/or a “hydrophobic stabilizing layer.” Therefore, the priority date for the presently claimed invention is December 29, 2020. Applicant is invited to indicate where the terms can be found in the as-filed Specification and/or the original claims.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed January 15, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
Maintained Objections/Rejections
Claim Interpretation: the term “a hydrophilic sensing layer made from a polyelectrolyte prepolymer” such as recited in claim 1 is interpreted to refer to any prepolymer possessing one or more ionized or ionizable functional groups along their backbone that can be used in any way to produce a polymer layer that is hydrophilic to any degree by any methods and/or through any number of steps, wherein polyelectrolyte polymers include, for example, DNA, proteins, synthetic polymers, alginate, PAA< PSS, PEI, etc.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 is maintained, and claim 31 is newly rejected, under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
The rejection of claims 1 and 6 is maintained, and claim 5 is newly rejected, as being indefinite for the recitation of the term “polyelectrolyte prepolymer” such as recited in claim 1, lines 5-6 because the as-filed Specification and claims do not teach a “polyelectrolyte prepolymer,” such that the identity of a “polyelectrolyte prepolymer” is unclear. The as-filed Specification teaches the terms “polyelectrolyte;” “ethylenically unsaturated polyelectrolyte prepolymer;” “ethylenically unsaturated polyelectrolyte;” and “prepolymer” (paragraphs [0022]; [0050]; and [0056]) and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “configured to react with an analyte” such as recited in claim 1, line 6 because it is unclear which component is configured to react with an analyte, including: (i) whether the sensing layer is “configured to react with an analyte”; or (ii) whether the enzyme is “configured to react with an analyte” and, thus, the metes and bounds of the claim cannot be determined.
Claims 1, 4, 9, 14, 15, 29 and 30 are indefinite for the recitation of the term “hydrophobic stabilizing layer” such as recited in claim 1, line 9 because the as-filed Specification and original claims do not teach a “hydrophobic stabilizing layer” that is disposed over the sensing layer and, thus, the metes and bounds of the claim cannot be determined.
Claim 12 is indefinite for the recitation of the term “wherein the analyte sensor comprises a wire” such as recited in claim 12, lines 1-2 because claim 12 depends from instant claim 1, wherein claim 1, lines 1-3 recites an analyte sensor comprising: a working electrode, and a multilayered membrane disposed over the working electrode, such that claim 1 does not recite the term “analyte sensor” in the body of the claim and, thus, the term is not given patentable weight. Moreover, claim 1 already recites the components, such that dependent claim 12 cannot recite that the analyte sensor comprises something entirely different and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “the analyte sensor of claim 1, further comprising a wire” or “the analyte sensor of claim 1, wherein the working electrode comprises a silver wire.”
Claims 14 and 15 are indefinite for the recitation of the term “wherein the hydrophobic stabilizing layer is made from polymerizing ethylenically unsaturated monomers” such as recited in claim 14, lines 1-2 because the as-filed Specification does not teach that the hydrophobic stabilizing layer is made from polymerizing ethylenically unsaturated monomers. Instead, the as-filed Specification teaches that the membrane layers are covalently attached via polymerization of their ethylenically unsaturated monomers (see, paragraph [0035] and [0056]; and Fig. 4) and, thus, the metes and bounds of the claim cannot be determined.
Claim 14 is indefinite for the recitation of the term “wherein the hydrophobic stabilizing layer is made from polymerizing ethylenically unsaturated monomers that comprise…and acrylate” such as recited in claim 14, lines 1-5 because the as-filed Specification does not teach the limitations as recited in claim 14. The as-filed Specification teaches disposing a sensing layer on a surface by treating the sensing layer with a coupling agent and attaching ethylenically unsaturated functional groups that are chemically reacted with an outer layer comprises of an ethylenically unsaturated prepolymer (see, paragraph [0022]), such that the functional groups recited in claim 14 belong to the hydrophilic sensing layer (and, not to the hydrophobic stabilizing layer) and, thus, the metes and bounds of the claim cannot be determined.
Claim 15 is indefinite for the recitation of the term “wherein the hydrophobic stabilizing layer is made from polymerizing ethylenically unsaturated monomers that comprise a component selected from…and 2-allyloxyethanol” such as recited in claim 15, lines 1-7 because the as-filed Specification does not teach the limitations as recited in claim 14. The as-filed Specification teaches that the ethylenically unsaturated monomer attached to the sensing layer is comprised of hydroxy, methacrylate, acrylate, vinyl, and ester end groups; and alkyl and ether main chain groups including, more specifically, allyl alcohol, 2-allyloxyethanol, 2-hydroxyethyl methacrylate…allyl methacrylate, methacrylic acid, acrylic acid (see, paragraphs [0027] and [0051]), such that the ethylenically unsaturated monomers recited in claim 15 belong to the hydrophilic sensing layer (and, not to the hydrophobic stabilizing layer) and, thus, the metes and bounds of the claim cannot be determined.
Claims 29 and 30 are indefinite for the recitation of the term “configured to limit the flux of the analyte” such as recited in claim 29, line 2 because the original claims and as-filed Specification do not teach that the stabilizing layer is configured to limit the flux of an analyte through the multilayered membrane. Instead, the claims as originally filed recite a flux limiting layer (which comprises a silicone prepolymer); that the membrane is configured to reduce flux of an analyte to the sensing layer; and to reduce flux of an interferent; while the as-filed Specification teaches that the membrane controls the flux of an analyte, where the term “limit” means to set a boundary or cap on something (to keep within a certain range), while the term “reduce” means to make something smally or less in quantity or size as evidenced by Content Authority (pg. 1, last partial paragraph; and pg. 2, first partial paragraph) and, thus, the metes and bounds of the claim cannot be determined.
Claim 31 is indefinite for the recitation of the term “wherein the enzyme is covalently incorporated into the hydrophilic sensing layer” as recited in claim 31, lines 1-2 because the as-filed Specification and the claims as originally filed do not teach this limitation and, thus, the metes and bounds of the claim cannot be determined.
Claims 2 and 3 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 12 is maintained, and claims 9, 14 and 15 are newly rejected, under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 9 recites (in part): “wherein the hydrophobic stabilizing layer comprises silicone” in lines 1-2 because claim 9 is a substantial duplicate of instant claim 4. Thus, claim 9 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 12 recites (in part): “wherein the analyte sensor comprises a wire” in lines 1-2 because claim 12 depends from claim 1, wherein claim 1 does not recite the presence of an analyte sensor in the body of the claim. Moreover, claim 1 already recites that the product comprises a working electrode, and a multilayered membrane disposed over the working electrode, such that it is improper for claim 12 to recite that the product comprises something different from the independent claim. Thus, claim 12 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 14 and 15 recite (in part): “[T]he analyte sensor of claim 9” in line 1, such that claims 14 and 15 depend from duplicate claim 9. Thus, claims 14 and 15 are improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a) – New Matter
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 is maintained, and claim 31 is newly 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art (hereafter the Artisan), that the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application". Claim 1 recites in part: “a hydrophilic sensing layer made from a polyelectrolyte prepolymer” in lines 5-6; and “a hydrophobic stabilizing layer disposed over the hydrophilic sensing layer” in lines 9-10.
Applicant does not specifically indicate where support can be found for these claim limitations, but point generally to the Specification and newly present claims. However, support was not found for this limitation in the as-filed Specification and original claims.
Upon review of the instant as-filed Specification and original claims, support was not found for an inner sensing layer made from a polyelectrolyte prepolymer and an enzyme, and an outer stabilizing layer, wherein the inner sensing layer and the outer stabilizing layer of the multilayered membrane are covalently attached to each other via covalent bonds at their interface as recited in instant claim 1.
The instant as-filed Specification, filed December 29, 2020 teaches, for example; “[T]he membrane is formed by covalently attaching an outer layer comprised of ethylenically unsaturated prepolymer to an inner layer comprised of an ethylenically unsaturated polyelectrolyte and an enzyme” (paragraph [0021]); and “disposing a sensing layer on a surface, treating the sensing layer with a coupling agent and attaching ethylenically unsaturated functional groups, and applying another layer over the sensing layer. The membrane being prepared from a composition reaction mixture of a polyelectrolyte mixed with an enzyme and a crosslinker as a first layer that is functionalized with ethylenically unsaturated groups and chemically reacted with an outer layer comprised of an ethylenically unsaturated prepolymer” (paragraph [0022]); and “covalently attaching an outer layer comprises of an ethylenically unsaturated prepolymer to an inner layer comprised of an ethylenically unsaturated polyelectrolyte” (paragraph [0050]). No such corresponding teachings of a sensing layer made from a polyelectrolyte prepolymer, and/or a hydrophobic stabilizing layer is taught by the instant as-filed Specification and/or the original claims.
A claim-by-claim analysis and for dependent claim 1, and a method step by method step analysis regarding where support can be found for the broad teaching “each same functionalized oligonucleotide in a plurality of same functionalized oligonucleotides” in the originally filed specification is respectfully suggested. See MPEP § 2163 particularly § 2163.06.
Claims 1-6, 9, 12, 14, 15 and 29-31 will remain rejected until Applicant cancels all new matter.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) the as-filed Specification provides proper support for claim 1 because paragraphs [0051]; [0052] and [0057] teaches (in part): “when a hydrophilic enzyme polymer layer is formed with a methacrylate functional group creating a prepolymer, a second hydrophobic polymeric layer can be covalently attached to the enzyme layer through a polymerization reaction”; as well as, an ethylenically unsaturated prepolymer, an ethylenically unsaturated polyelectrolyte, and an enzyme (Applicant Remarks, pg. 16, entire page through pg. 17).
Regarding (a), the Examiner can find no teaching of a “polyelectrolyte prepolymer” (or, a “hydrophobic stabilizing layer”) in the as-filed Specification and claims as originally filed. The rejection is maintained.
Claim Rejections - 35 USC § 102
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 is maintained, and claim 31 is newly rejected, under 35 U.S.C. 102(a1)/(a2) as being anticipated by Wang et. al. (hereinafter “Wang”) (US Patent Application Publication No. 20170188902, published July 6, 2017; of record).
Regarding claim 1, Wang teaches devices for determining an analyte concentration (e.g., glucose), wherein the devices comprise a sensor configured to generate a signal associated with a concentration of an analyte and a sensing membrane located over the sensor; and that the sensing membrane comprises an enzyme layer, wherein the enzyme layer comprises an enzyme and a polymer comprising polyurethane and/or polyurea segments and one or more zwitterionic repeating units such that the enzyme layer protects the enzyme and prevents it from leaching from the sensing membrane into a host or deactivating (interpreting the device to be an analyte sensor; a membrane over a working electrode; an inner sensing layer comprising an enzyme; an outer stabilizing layer that forms a subsequent flux limiting layer by covalent attachment to the inner sensing layer; and the first layer comprises an oxidase enzyme, claims 1, 2, 10 and 14) (Abstract). Wang teaches a membrane system having a biointerface domain and an enzyme domain; and that if the sensor is deemed to be the point of reference and the biointerface domain is positioned farther from the sensor than the enzyme domain, then the biointerface domain is more distal to the sensor than the enzyme domain (interpreting the enzyme domain to be the inner sensing layer; and the biointerface domain as the outer stabilizing layer, claim 1) (paragraph [0057]). Wang teaches an optional electrode domain 42, also referred to as the electrode layer, can be provided, in addition to the biointerface domain and the enzyme domain; however, in other embodiments, the functionality of the electrode domain can be incorporated into the biointerface domain so as to provide a unitary domain that includes the functionality of the biointerface domain, diffusion resistance domain, enzyme domain, and electrode domain (interpreted as the inner sensing layer; or part of the outer stabilizing layer, claim 1) (paragraph [0288]). Wang teaches that the terms "electrochemically reactive surface" and "electroactive surface" broadly refer without limitation to the surface of an electrode where an electrochemical reaction takes place, such as in a working electrode, H202 (hydrogen peroxide) produced by an enzyme-catalyzed reaction of an analyte being detected reacts and thereby creates a measurable electric current, where in the detection of glucose, glucose oxidase produces H202 as a byproduct, such that the H202 reacts with the surface of the working electrode to produce two protons (2H+), two electrons (2e-), and one molecule of oxygen (02), which produces the electric current being detected; and that in the case of the counter electrode, a reducible species, for example, 02 is reduced at the electrode surface in order to balance the current being generated by the working electrode (interpreted as a working electrode; releases H2O2 – hydrogen peroxide; releases O2 a reactive oxygen species; glucose sensor that detects glucose; generates a reactive oxygen species in response to glucose; and the enzyme is glucose oxidase, claims 1-3) (paragraph [0060]). Wang teaches that Figure 2A includes working electrode of the sensor 38, electrode layer 42, enzyme layer 44, diffusion resistance layer 46, and biointerface layer 48 (paragraph [0114]). Wang teaches in Figure 2B is a cross-sectional view through one embodiment of the sensor, illustrating another embodiment of the membrane system 32, wherein the membrane system includes an interference reduction or blocking layer 43, an enzyme layer 44, a diffusion resistance layer 46, and a biointerface layer 48 located around the working electrode of a sensor 38 (interpreted as an electrode covered by a multilayered membranes, claim 1) (paragraph [0115]; and Fig 2B). Figures 2A and 2B are shown below:
PNG
media_image1.png
302
398
media_image1.png
Greyscale
PNG
media_image2.png
304
400
media_image2.png
Greyscale
Wang teaches that the sensing membrane can be deposited on the electroactive surfaces of the electrode material using known thin or thick film techniques (for example, spraying, electro-depositing, dipping, or the like) (interpreted as the sensing layer disposed over the working electrode, claim 1) (paragraph [0120]). Wang teaches that the enzyme layer further comprises a base polymer and enzyme stabilizing and/or immobilizing polymer, wherein the enzyme stabilizing and/or immobilizing polymer comprises a polymer chain having both hydrophilic and hydrophobic regions and one or more zwitterionic repeating units; and wherein the base polymer is selected from silicone, epoxide, polyolefin, polystylene, polyoxymethylene, polysiloxane, polyether, polyacrylic, polymethacrylic, polyester, polycarbonate, polyamide, poly(ether ketone), poly(ether imide ), polyurethane, and polyurethane urea (interpreted as a hydrophilic sensing layer comprising an enzyme, claim 1) (paragraph [0025]). Wang teaches that one or more domains of the sensing membranes can be formed from materials such as silicone, polytetrafluoroethylene, polyethylene-co tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene (PP), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), polymethylmethacrylate (PMMA), polyether ether ketone (PEEK), polyurethanes, polyurethane ureas, cellulosic polymers, poly (ethylene oxide), poly(propylene oxide) (paragraph [0119]). Wang teaches that the term “host” refers broadly and without limitation to animals, such as humans, and plants (interpreted as animals and humans, claims ) (paragraph [0061]). Wang teaches that the term “sensor session” refers to the period of time the sensor is applied to (e.g., implanted in) the host or is being used to obtain sensor values (interpreted as implantation into an animal including a human, claims 12 and 13) (paragraph [0091]). Wang teaches that the membrane system includes a plurality of domains, for example, an electrode domain, an interference domain, an enzyme domain, a resistance domain, and a bio-interface domain, wherein the membrane system can be deposited on the exposed electroactive surfaces using known thin film techniques (interpreted as a multilayer membrane disposed over an electrode; and a bio-interface domain as a biocompatible layer, claims 1 and 10) (paragraph [0092], lines 1-6). Wang teaches that the enzyme layer is formed of an enzyme layer polymer and an active enzyme, wherein the enzyme layer polymer comprises polyurethane and/or polyurea segments and one or more zwitterionic repeating units, wherein the enzyme layer coatings are formed of a polyurethane urea having carboxyl betaine groups incorporated in the polymer and non-ionic hydrophilic polyethylene oxide segments, wherein the polyurethane urea polymer is dissolved in organic or non-organic solvent system according to a pre-determined coating formulation, and is crosslinked with an isocyanate crosslinker and cured at moderate temperature of about 50°C (interpreting polyurethane urea polymer as a polyelectrolyte polymer; interpreting polyethylene oxide as PEG; and forming a flux limiting layer, claims 1 and 15) (paragraph [0093]). Wang teaches that the membrane system can comprise one electrode layer, one enzyme layer, and two biointerface layers; and in other embodiments the membrane system can comprise one electrode layer, two enzyme layers, and one bio-interface layer; and the biointerface layer can be configured to function as the diffusion resistance domain and control the flux of the analyte (e.g., glucose) to the underlying membrane layers (interpreted as an outer stabilizing layer and a flux limiting layer; a multilayered membrane configured to reduce flux including of at least one interferent (analyte); and biocompatible layer disposed over the multilayered membrane, claims 1, 29 and 30) (paragraph [0118]). Wang teaches that the materials preferred for forming the biointerface domain 48 can be resistant to the effects of these oxidative species and have thus been termed biodurable; the biointerface domain controls the flux of oxygen and other analytes (for example, glucose) to the underlying enzyme domain, wherein the functionality of the diffusion resistance domain is built-into the biointerface domain such that a separate diffusion resistance domain is not required (interpreted as a subsequent flux limiting layer; a multilayered membrane configured to reduce flux including of at least one interferent including an oxidative species, and/or am analyte such as glucose or oxygen; glucose sensor; reactive oxygen species; and biocompatible layer disposed over the multilayered membrane, claims 1 and 10) (paragraph [0182]). Wang teaches that the glucose sensor can be configured for transcutaneous or short-term subcutaneous implantation, and can have a thickness of about 0.5 microns to about 8 microns (interpreted as implantation of the glucose sensor into animals including humans, claims 12 and 13) (paragraph [0186], lines 11-14). Wang teaches that the diffusion resistance domain can comprise a combination of a base polymer (e.g., polyurethane) and one or more hydrophilic polymers (e.g., PVA, PEG, polyacrylamide, acetates, PEO, PEA, PVP, and copolymers, blends, and/or variations thereof), such that any of a variety of combination of polymers can be used to yield a blend with desired glucose, oxygen, and interference permeability properties, wherein the diffusion resistance domain can be formed from a blend of a silicone polycarbonate-urethane base polymer and a PVP hydrophilic polymer (interpreted as a ethylenically unsaturated silicone prepolymer, claims 9 and 15) (paragraph [0194]). Wang teaches that the method can employ other interactions such as hydrogen bonding or covalent linkages (interpreted as covalent bonds, claims 1 and 6) (paragraph [0262], lines 1-3). Wang teaches that the interference blocking ability provided by the alternating polycationic layers and polyanionic layers can be adjusted and/or controlled by creating covalent cross-links between the polycationic layers and polyanionic layers, wherein cross-linking can have a substantial effect on mechanical properties and structure of the film, which in tum can affect the film's interference blocking ability (interpreted as covalent bonds formed by crosslinking, claim 1) (paragraph [0263], lines 1-8). Wang teaches that one major advantage to photo-cross-linking is that it offers the possibility of patterning, such that photo-crosslinking is performed to modify the film structure and thus to adjust the interference domain's interference blocking ability, wherein blocking ability can correspond to, but is not limited to, the ability to reduce transport of a certain interfering species or to the selectivity for the transport of a desired species (e.g., H202) over an interfering species (interpreted as crosslinking to form covalent bonds; and flux limiting, claim 1) (paragraph [0263], lines 18-26). Wang teaches that the polymerization groups is selected from alkene, alkyne, epoxide, lactone, amine, hydroxyl, isocyanate, carboxylic acid, anhydride, silane, halide, and carbodiimide (interpreted as the polyelectrolyte polymer comprises amines, claim 7) (paragraph [0019]). Wang teaches that polymers with domains or segments that are functionalized to permit cross-linking can be made by methods known in the art including polyurethaneurea polymers with aromatic or aliphatic segments having electrophilic functional groups (e.g., carbonyl, aldehyde, anhydride, ester, amide, isocyano, epoxy, allyl, or halo groups) can be crosslinked with a crosslinking agent that has multiple nucleophilic groups (e.g., hydroxyl, amine, urea, urethane, or thio groups) (interpreted as the polyelectrolyte polymer comprises amines, claim 14) (paragraph [0135]). Wang teaches that the properties of the biointerface polymer can be tuned by using different segments, different segment lengths, functionalizations on certain segments, crosslinking segments and the like, wherein the biointerface polymer can be biocompatible segmented block polyurethane copolymers (interpreted as biocompatible) (paragraph [0170]). Wang teaches that the wetting property of the membrane (and by extension the extent of sensor drift exhibited by the sensor) can be adjusted and/or controlled by creating covalent cross-links between surface-active group containing polymers, functional-group containing polymers, polymers with zwitterionic groups (or precursors or derivatives thereof), and combinations thereof (interpreted as the inner layer covalently attached to the outer layer, claim 1) (paragraph [0133]). Wang teaches that methods employ interactions such as hydrogen bonding or covalent linkages (interpreted as the inner layer covalently attached to the outer layer, claim 1) (paragraph [0262], lines 1-3). Wang teaches that the biointerface layer can further comprise a domain comprising a surface modifying polymer added to a base polymer, wherein the surface modifying polymer comprises a polymer chain having both hydrophilic and hydrophobic regions and wherein one or more zwitterionic compounds are covalently bonded to an internal region of the polymer, wherein the base polymer can be selected from silicone, epoxies, polyolefins, polystyrene, polyoxymethylene, polysiloxanes, polyethers, polyacrylics, polymethacrylic, polyesters, polycarbonates, polyamide, poly(ether ketone), poly(ether imide), polyurethane, and polyurethane urea (interpreted as the inner layer covalently attached to the outer layer, claim 1) (paragraph [0180]). Wang teaches the biointerface polymer can comprise reactive groups that can be available for further functionalization, such as unsaturated functional groups like alkynes can be used to attach various moieties attached to dipolar groups likes azides to form covalent linkages such as by Huisgen cycloaddition chemistry or click chemistry (interpreted as the inner layer covalently attached to the outer layer, claim 1) (paragraph [0184], lines 1-7). Wang teaches in Figure 11A is a schematic view of a portion of an interference domain that comprises a plurality of polycationic and polyanionic layers; while Figure 11B illustrates one embodiment of a layer-by-layer deposition method, which employs alternating adsorption of polycations and polyanions to create a structure illustrated in Figure 11A (paragraphs [0043]-[0044]). Wang teaches that Figures 11A and 11B illustrate that the interference domain can be prepared using a layer-by-layer deposition technique, wherein a substrate (e.g., the sensor or membrane layer atop the sensor, such as the resistance or enzyme layer) is dipped first in a bath of one polyelectrolyte, then in a bath of an oppositely charged polyelectrolyte; where optionally, the substrate can be dipped in a bath of rinsing solution before or after the substrate is dipped into the polyelectrolyte bath, such that during each dip a small amount of polyelectrolyte is adsorbed and the surface charge is reversed, thereby allowing a gradual and controlled build-up of electrostatically cross-linked films (or hydrogen bonded films) of alternating polycation polyanion layers; and methods employ other interactions such as covalent linkages (interpreted as the inner layer and outer layer attached via covalent bonds at their interface, claim 1) (paragraphs [0261]-[0262]). Figures 11A and 11B are shown below:
PNG
media_image3.png
152
334
media_image3.png
Greyscale
Figure 11A
PNG
media_image4.png
178
1191
media_image4.png
Greyscale
Figure 11B
Wang teaches that the interference blocking ability provided by the alternating polycationic layer(s) and polyanionic layer(s) can be adjusted and/or controlled by creating covalent cross-links between the polycationic layer(s) and polyanionic layer(s), wherein cross-linking can have a substantial effect on mechanical properties and structure of the film, which in tum can affect the film's interference blocking ability, such that crosslinking can be performed between deposition of adjacent polycationic or polyanionic layers in replacement of, or in addition to, a post-deposition cross-linking process (interpreted as the inner layer covalently attached to the outer layer, claim 1) (paragraph [0263]).
Regarding claim 2, Wang teaches that the terms "electrochemically reactive surface" and "electroactive surface" broadly refer without limitation to the surface of an electrode where an electrochemical reaction takes place, such as in a working electrode, H202 (hydrogen peroxide) produced by an enzyme-catalyzed reaction of an analyte being detected reacts and thereby creates a measurable electric current, where in the detection of glucose, glucose oxidase produces H202 as a by-product, such that the H202 reacts with the surface of the working electrode to produce two protons (2H+), two electrons (2e-), and one molecule of oxygen (02), which produces the electric current being detected; and that in the case of the counter electrode, a reducible species, for example, 02 is reduced at the electrode surface in order to balance the current being generated by the working electrode (interpreted as a working electrode; releases H2O2 – hydrogen peroxide upon contacting glucose analyte; O2 is a reactive oxygen species; glucose sensor that detects glucose; generates a reactive oxygen species in response to glucose; and the enzyme is glucose oxidase, claims 1-3) (paragraph [0060]).
Regarding claim 3, the enzyme layer protects the enzyme and prevents it from deactivating by dynamic changes in its environment, wherein the enzyme can be selected from the group consisting of glucose oxidase, cholesterol oxidase, amino acid oxidase, glucose dehydrogenase, alcohol oxidase, galactose oxidase, uricase, and lactate oxidase (interpreted as the enzyme is an oxidase, claim 3) (paragraph [0010]).
Regarding claim 4, Wang teaches that the biointerface polymer can comprise a polyurethane copolymer such as polyether-urethane-urea, polycarbonate-urethane, polyether-urethane, silicone-polyether-urethane, silicone-polycarbonate-urethane, polyester-urethane, polyurethane-urea, and the like (interpreted as carbon-silicon bonds, claim 4) (paragraph [0155]). Wang teaches that the soft segments used in the preparation of the biointerface polymer can be a polyfunctional aliphatic polyol, a polyfunctional aliphatic or aromatic amine, or the like that can be useful for creating permeability of the analyte (e.g., glucose) therethrough, and can include polyoxazoline, poly(ethylene glycol) (PEG), polyacrylamide, polyimine, polypropylene oxide (PPO), PEG co-PPO diol, silicone-co-PEG diol, Silicone-co-PPO diol, polyethylacrylate (PEA), polyvinylpyrrolidone (PVP), and variations thereof (e.g., PVP vinyl acetate) (interpreted as covalent bonds comprising silicone or silicon, claim 4) (paragraph [0161]).
Regarding claim 5, Wang teaches that the electrode domain is formed entirely from a hydrophilic polymers including polyacrylic acid; and aziridine (interpreted as a polyelectrolyte synthesized from a precursor having a carboxylic acid moiety; and a prepolymer comprising polyacrylic acid and/or aziridine, claims 4 and 5) (paragraphs [0178], lines 1-3; and [0295]).
Regarding claim 6, Wang teaches one or more zwitterionic repeating units derived from a monomer; the polymerization of betaine containing monomers; and that the term "polymerization group", means a functional group that permits polymerization of the monomer with itself to from a homopolymer or together with different monomers to form a copolymer (interpreted as comprising polymerized monomeric units, claim 6) (paragraphs [0013]-[0017]; [0074]; and [0149], lines 1-4). Wang teaches that the enzyme layer comprises an enzyme layer polymer, which is a polyzwitterion, wherein a repeating unit of the polymer chain is a zwitterionic moiety (interpreted as comprising polymerized monomeric units, claim 6) (paragraph [0199], lines 1-4).
Regarding claim 9, Wang teaches that the biointerface polymer can comprise a polyurethane copolymer such as polyether-urethane-urea, polycarbonate-urethane, polyether-urethane, silicone polyether-urethane, silicone-polycarbonate-urethane, polyester-urethane, polyurethane-urea, and the like (interpreted as encompassing a flux limiting layer that comprises silicone, claim 9) (paragraph [0155]).
Regarding claim 12, Wang teaches that the sensor is formed from a wire or is in a form of a wire such as, for example, the sensor can include an elongated conductive body, such as a bare elongated conductive core (e.g., a metal wire) or an elongated conductive core coated with one, two, three, four, five, or more layers of material, each of which may or may not be conductive, wherein the elongated sensor can be long and thin, yet flexible and strong; and that a conductive wire electrode is employed as a core, such that to such a clad electrode, one or two additional conducting layers can be added (e.g., with intervening insulating layers provided for electrical isolation) (interpreted as the working electrode is a wire, claim 12) (paragraph [0080]).
Regarding claim 14, Wang teaches that the polymerization groups is selected from alkene, alkyne, epoxide, lactone, amine, hydroxyl, isocyanate, carboxylic acid, anhydride, silane, halide, and carbodiimide (interpreted as the polyelectrolyte polymer comprises amines, claim 14) (paragraph [0019]). Wang teaches that the biointerface polymer is crosslinked, wherein polyurethaneurea polymers with aromatic or aliphatic segments having electrophilic functional groups (e.g., carbonyl, aldehyde, anhydride, ester, amide, isocyanate, epoxy, allyl, or halo groups) can be crosslinked with a crosslinking agent that has multiple nucleophilic groups (e.g., hydroxyl, amine, urea, urethane, or thio groups) (interpreted as hydroxy, claim 14) (paragraph [0177]). Wang teaches a base polymer including biocompatible segmented block polyurethan copolymers comprising hard and soft segments can be used, wherein soft segments used in the preparation of the polyurethane may be a polyfunctional aliphatic polyol, a polyfunctional aliphatic or aromatic amine, or the like that may be useful for creating permeability of the analyte (e.g. glucose) therethrough, and can include, polyvinyl acetate (PVA), poly(ethylene glycol) (PEG), polyacrylamide, acetates, polyethylene oxide (PEO), polyethylacrylate (PEA), polyvinylpyrrolidone (PVP), poly(2-oxazoline (POX), and variations thereof (e.g. PVP vinyl acetate) (interpreted as ethylene oxide, claim 14) (paragraph [0237]).
Regarding claim 15, Wang teaches that the outermost layers of the interference domain can both be polycation layers, with polyanion layers present on as interior layers, wherein the polyanionic material can be any biocompatible polyanionic polymer including any polymer having a carboxylic acid group attached as pendent group such as polymethacrylic acid and polyacrylic acid (interpreting the outer stabilizing layer to comprise acrylic acid and methacrylic acid, claim 15) (paragraphs [0256], lines 6-8; and [0259]).
Regarding claims 29 and 30, Wang teaches that the biointerface layer can be configured to function as the diffusion resistance domain and control the flux of the analyte (e.g., glucose) to the underlying membrane layers (interpreting the biointerface layer as an outer stabilizing membrane that limits flux of the analyte/reactive oxygen species, claims 29 and 30) (paragraph [0118], lines 8-11). Wang teaches that the biointerface domain controls the flux of oxygen and other analytes (e.g., glucose) to the underlying enzyme domain, wherein the functionality of the diffusion resistance domain is built-into the biointerface domain (interpreting the biointerface layer as an outer stabilizing membrane that limits flux of the analyte/reactive oxygen species, claims 29 and 30) (paragraph [0182], lines 17-21).
Regarding claim 31, Wang teaches that zwitterionic repeating units can be a betaine such as a carboxyl, sulfo, or phosphor betaine compound, precursor or derivative, wherein these segments or moieties can be incorporated into the enzyme layer polymer, whether in the hard segment, the soft segment, or both, for example up to about 55 wt. % of the enzyme layer polymer (interpreted as the enzyme being covalently incorporated into the sensing layer, claim 31) (paragraph [0224]).
Wang meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Wang does not teach a hydrophilic sensing layer and a hydrophobic stabilizing layer (Applicant Remarks, pg. 18, second full paragraph through pg. 19, first full paragraph, lines 1-3); and (b) one skilled in the art would have no reason to modify Wang to provide a multilayered membrane where a hydrophilic sensing layer and a hydrophobic stabilizing layer are covalently attached to each other via covalent bonds at their interface, such as recited in amended claim 1 (Applicant Remarks, pg. 19, second full paragraph, lines 4-7).
Regarding (a), although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). Moreover, as noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
MPEP 2123(I) states:
“The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)) (underline added).
Additionally, instant claim 1 uses the term “comprising”, which is open-ended and does not exclude additional, unrecited elements or method steps, including an interface layer and/or additional layers of a multilayered membrane. Applicant’s assertion that Wang does not teach a hydrophilic sensing layer and a hydrophobic stabilizing layer and/or that the layers are covalently attached at the interface, is not found persuasive. As an initial matter, instant claim 1 is very broadly recited, such that no specific working electrode, hydrophilic sensing layer made from a polyelectrolyte prepolymer, enzyme, and/or hydrophilic stabilizing layer are recited in instant claim 1. Moreover, Wang teaches that the each of the polymer membranes can incorporate one or more hydrophilic and/or hydrophobic segments (where the term “one or more” includes all segments). As Applicant is clearly aware, a hydrophobic polymer membrane or hydrophilic polymer membrane can be made up of both hydrophobic and hydrophilic polymer segments.
Regarding covalent attachment of the polymer membranes at the interface, Wang teaches that adjacent polymer layers can be crosslinked. Given that the functional groups available for crosslinking of the adjacent polymer membranes extend from the backbone of the polymer, it is clear that covalent attachments form at the interface of the adjacent polymer membranes. To that end -
Wang teaches:
Figures 2A and 2B
Figure 2A includes working electrode of the sensor 38, electrode layer 42, enzyme layer 44, diffusion resistance layer 46, and biointerface layer 48 (paragraph [0114]).
Figure 2B illustrates membrane system 32, including an interference reduction layer 43, an enzyme layer 44, a diffusion resistance layer 46, and a biointerface layer 48 located around the working electrode of a sensor 38 (interpreted as an electrode covered by a multilayered membranes, claim 1) (paragraph [0115]; and Fig 2B). Figures 2A and 2B is shown below:
PNG
media_image1.png
302
398
media_image1.png
Greyscale
PNG
media_image2.png
304
400
media_image2.png
Greyscale
The sensing membrane can be deposited on the electroactive surfaces of the electrode material using known thin or thick film techniques (for example, spraying, electro-depositing, dipping, or the like) (interpreted as the sensing layer disposed over the working electrode, claim 1) (paragraph [0120]).
The enzyme layer further comprises a base polymer and enzyme stabilizing and/or immobilizing polymer, which comprises a polymer chain having both hydrophilic and hydrophobic regions and one or more zwitterionic repeating units; and wherein the base polymer is selected from silicone, epoxide, polyolefin, polystylene, polyoxymethylene, polysiloxane, polyether, polyacrylic, polymethacrylic, polyester, polycarbonate, polyamide, poly(ether ketone), poly(ether imide ), polyurethane, and polyurethane urea (interpreting the enzyme stabilizing polymer as a hydrophobic stabilizing layer that can include silicone, claim 1) (paragraph [0025]).
One or more domains of the sensing membranes can be formed from materials such as silicone, polytetrafluoroethylene, polyethylene-co tetrafluoroethylene, polyolefin, polyester, polycarbonate, biostable polytetrafluoroethylene, homopolymers, copolymers, terpolymers of polyurethanes, polypropylene (PP), polyvinylchloride (PVC), polyvinylidene fluoride (PVDF), polybutylene terephthalate (PBT), polymethylmethacrylate (PMMA), polyether ether ketone (PEEK), polyurethanes, polyurethane ureas, cellulosic polymers, poly(ethylene oxide), poly(propylene oxide) (interpreted as materials for forming the sensing layer comprising an enzyme, and the stabilizing layer, claim 1) (paragraph [0119]).
The biointerface polymer can comprise reactive groups that can be available for further functionalization, such as unsaturated functional groups like alkynes can be used to attach various moieties attached to dipolar groups likes azides to form covalent linkages such as by Huisgen cycloaddition chemistry or click chemistry (interpreted as the inner layer covalently attached to the outer layer, claim 1).
Crosslinking can be performed between deposition of adjacent polycationic or polyanionic layers in replacement of, or in addition to, a post-deposition cross-linking process (interpreted as the inner layer covalently attached to the outer layer at their interface, claim 1).
Thus, Wang teaches all of the limitations of instant claim 1. The claims remain rejected.
Regarding (b), Applicant’s assertion that one skilled in the art would have no reason to modify Wang to provide a multilayered membrane where a hydrophilic sensing layer and a hydrophobic stabilizing layer are covalently attached to each other via covalent bonds at their interface, such as recited in amended claim 1, is not found persuasive. The Examiner contends that Wang anticipates all of the limitations recited in claim 1. There is no need to modify Wang to provide the multilayered membrane as recited in amended claim 1. The claims remain rejected.
Claim Rejections - 35 USC § 103
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30is maintained, and claim 31 is newly rejected, under 35 U.S.C. 103 as being unpatentable over Wang et. al. (hereinafter “Wang”) (US Patent Application Publication No. 20170188902, published July 6, 2017; of record) in view of Sofman et al. (hereinafter “Sofman”) (International Application WO2017087693, published May 27, 2017; of record).
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 with regard to Wang is discussed supra.
Wang does not specifically exemplify additional outer stabilizing layer components (instant claim 15, in part).
Regarding claim 15 (in part), Sofman teaches hydrogel microarray can be readily adapted to immobilize covalently or non-covalently a variety of therapeutic, prophylactic and diagnostic agents, wherein these agents can be introduced into the patterned hydrogels by forming the hydrogels in the presence of the biologically active molecules, by allowing the biologically active molecules to diffuse into the patterned hydrogels, or by otherwise introducing the biologically active molecules into the patterned hydrogels (pg. 14, lines 13-19). Sofman teaches biocompatible patterned hydrogels can be applied to, or formed on, any implantable medical device, including, but not limited to, chemical sensors or biosensors including devices for the detection of analyte concentrations in a biological sample, cell transplantation devices, drug delivery devices such as controlled drug-release systems, and electrical signal delivering or measuring devices (interpreted as implantation sensor, claim 1) (pg. 25, line 17-22). Sofman teaches that the hydrogel improves the biocompatibility of the implanted medical device, such as the biocompatibility and communication of neuro-electrodes and pacemaker leads with surrounding tissues, improves the sealing of skin to percutaneous devices, such as in-dwelling catheters or transcutaneous glucose sensors, enhances tissue integration, and provides barriers for immuno-isolation of cells in artificial organs systems; and that the patterned hydrogels can be immobilized onto (or within) a surface of an implantable or attachable medical device body (pg. 25, lines 23-31). Sofman teaches that a solution containing polymers with at least two polymerizable groups can be photo-crosslinked to form hydrogel, such that the at least two polymerizable groups can be identical or different, wherein additional crosslinkers can be optionally added to the polymer solution to provide features such as degradability; alternatively, a solution containing monomers, crosslinkers, and photo-initiators is photo-polymerized to form hydrogel microarrays. The polymerizable group on the monomer, polymer, crosslinking agent, or other precursor materials to make photo-patternable hydrogel include a methacrylate group, an acrylate group, vinyl groups, aryl azides, azido-methyl-coumarins, benzophenones, anthraquinones, certain diazo compounds, diazirines, and psoralen derivatives (interpreted as forming covalent bonds) (pg. 11, lines 11-21). Sofman teaches exemplary monomer materials include, but are not limited to, methacrylate derivatives, acrylate derivatives, ethylenes, dienes, styrenes, halogenated olefins, vinyl esters, acrylonitriles, acrylamides, n-vinylpyrrolidones, and mixtures thereof, wherein suitable methacrylate derivatives include, but are not limited to, 2-hydroxyethyl methacrylates, methyl methacrylates, methacrylic acids, n-butyl methacrylates, glycidyl methacrylates, n-propyl methacrylates, poly(ethylene glycol) monomethacrylates, and mixtures thereof; and where suitable acrylate derivatives include, but are not limited to, 2-hydroxyethyl acrylate, 2-methoxyethyl acrylate, acrylic acid, n-butyl acrylate, glycidyl acrylate, glycidyl methacrylates, n-propyl acrylate, poly(ethylene glycol) monoacrylate, and mixtures thereof (interpreted as monomers include 2-hydroxyethyl methacrylates, methacrylic acids, poly(ethylene glycol) monomethacrylates, acrylic acid, etc., claim 15) (pg. 11, lines 22-32). Sofman teaches that the patterned hydrogel is covalently attached to a solid support including glass, film, silicon, ceramic, plastic, or an appropriate polymer such as (poly)tetrafluoroethylene, or (poly)vinylidenedifluoride (interpreted as covalently attaching layers, claim 1) (pg. 5, lines 9-11). Sofman teaches exposing the precursor solution and the solid support for a period of time and under suitable conditions, wherein this exposure induces essentially complete conversion of polymerizable groups on the monomer and the crosslinking agent, or essentially complete crosslinks of polymers having at least two functional groups to form crosslinked hydrogel in patterned regions, such that the formed hydrogel is also covalently linked to the surface-treated substrate during the exposure process (interpreted as covalently binding layers, claim 1) (pg. 20, lines 17-23).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that 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 would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of biocompatible patterned hydrogels can be applied to, or formed on, any implantable medical device as exemplified by Sofman, it would have been prima facie obvious before the effective filing date of the claimed invention to modify the sensor including an implantable analyte sensor comprising at least an electrode layer, enzyme layer, and a bio-interface layer, wherein the biointerface layer of the electrode is formed primarily from a hydrophilic polymer, such as film-forming copolymers including ethyl-methacrylate and methacrylic acid monomers to detect the concentration of an analyte such as glucose in a host as taught by Wang to include biocompatible hydrogels including patterned hydrogels applied to, or formed on, any implantable medical device including chemical sensors or biosensors and/or devices for the detection of analytes, wherein suitable polymers include methacrylate derivatives such as 2-hydroxyethyl methacrylates, methyl methacrylates, methacrylic acids, n-butyl methacrylates, glycidyl methacrylates, n-propyl methacrylates, poly(ethylene glycol) monomethacrylates, and mixtures thereof, with a reasonable expectation of success in using the methacrylate monomers to produce hydrogels that improve the biocompatibility of the implanted medical device; improve the sealing of skin to percutaneous devices; and/or in producing a sensing biointerface that can enhance tissue integration of a sensor device including a glucose sensor that is transcutaneously, subcutaneously, and/or wholly implanted into a host and allows for the diffusion of biologically active molecules.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Applicant submits that Wang does not teach or suggest all features of amended independent claim 1 (Applicant Remarks, pg. 20, first and second full paragraphs).
Regarding (a), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments. Applicant did not distinctly and specifically point out the supposed errors in the Examiner’s action as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
The rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 is maintained, and claim 31 is newly rejected under 35 U.S.C. 103 as being unpatentable over Rao et al. (hereinafter “Rao”) (US Patent No. 10324058, issued June 18, 2019; effective filing date November 2, 2017) in view of Papadimitrakopoulos et. al. (hereinafter “Papadimitrakopoulos”) (US Patent Application Publication No. 20140262775, published September 18, 2014).
Regarding claim 1, Rao teaches an in-situ polymerization technique for creating a glucose sensor chemistry stack, such that the analyte sensor comprises a crosslinked polymer matrix in contact with an electrode, wherein the crosslinked polymer matrix is formed by exposing ultraviolet (UV) light to a polymer matrix mixture comprising a plurality of hydroxyethyl methacrylate (HEMA) monomers, one or more diacrylate crosslinkers, one or more UV photo-initiators, and an oxidoreductase, which is covalently linked to the crosslinked polymer matrix (interpreted as comprising a multilayer membrane; glucose sensor; and hydroxyethyl-methacrylate, claims 1 and 15) (Abstract). Rao teaches that Figure 5A is a sensor embodiment comprising an adhesion promoter layer added to facilitate close attachment of various layers such as a diffusion control membrane and an enzyme layer (col 10, lines 29-32; and Figure 5A). Rao teaches that Figure 5A includes a base layer 102A to support the sensor 100, wherein the base layer 102A can be made of a material such as a metal and/or a ceramic and/or a polymeric substrate, which can be self-supporting or further supported by another material as is known in the art, wherein the base layer 102A comprises polyimide; and includes a conductive layer 104 which is disposed on and/or combined with the base layer 102A, such that the conductive layer 104 comprises one or more electrodes including a plurality of electrodes such as a working electrode, a counter electrode, and a reference electrode (interpreted as a working electrode, claim 1) (col 11, lines 52-63; and Figure 5A). Rao teaches sensor configuration 5B, comprising an interference rejection membrane 120 is disposed on one or more of the exposed electrodes of the conductive layer 104, with the analyte sensing layer 110 then being disposed on this interference rejection membrane 120, wherein the analyte sensing layer 110 is an enzyme layer; and the analyte sensing layer 110 comprises an enzyme capable of producing and/or utilizing oxygen and/or hydrogen peroxide, for example the enzyme glucose oxidase (interpreted as comprising an electrode; an analyte sensing layer/inner sensing layer comprising an enzyme; an interference rejection membrane/outer stabilizing layer; the enzyme is an oxidase; releasing hydrogen peroxide; and forming a reactive oxygen species, claims 1, 2 and 30) (col 12, lines 42-50; and Figure 5B). Figures 5A and 5B are shown below:
PNG
media_image5.png
284
652
media_image5.png
Greyscale
PNG
media_image6.png
196
724
media_image6.png
Greyscale
Figure 5A Figure 5B
Rao teaches that the analyte sensing layer 110 is coated and/or disposed next to one or more additional layers, wherein the one or more additional layers include a protein layer 116 disposed upon the analyte sensing layer 110, wherein the protein layer 116 can comprise a protein such as human serum albumin, bovine serum albumin or the like (col 13, lines 27-32). Rao teaches that an additional layer includes an analyte modulating layer 112 that is disposed above the analyte sensing layer 110 to regulate analyte access with the analyte sensing layer 110, wherein the analyte modulating membrane layer 112 can comprise a glucose limiting layer or membrane, which regulates the amount of glucose that contacts an enzyme such as glucose oxidase that is present in the analyte sensing layer (col 13, lines 41-47). Rao teaches an adhesion promoter layer 114 is disposed between the analyte modulating layer 112 and the analyte sensing layer 110 as shown in Figure 5B in order to further facilitate their contact and/or adhesion, wherein adhesion promoter layer 114 can be made from any one of a wide variety of materials known in the art to facilitate the bonding between such layers including a silane compound (interpreted as layers covalently attached to each other via covalent bonds at their interface, claim 1) (col 13, lines 48-59). Rao teaches the adhesion promoting constituent is disposed between the analyte sensing constituent and the analyte modulating constituent, wherein the adhesion promoter constituent can be made from any one of a wide variety of materials known in the art to facilitate the bonding between such constituents and can be applied by any one of a wide variety of methods known in the art, such that the adhesion promoter constituent can comprises a silane compound such as g-aminopropyl-trimethoxysilane (interpreted as layers covalently attached to each other via covalent bonds at their interface, claim 1) (col 17, lines 41-51). Rao teaches that
the analyte modulating constituent includes an agent selected for its ability to crosslink a siloxane moiety present in a proximal constituent, where the adhesion promoting constituent includes an agent selected for its ability to crosslink an amine or carboxyl moiety of a protein present in a proximal constituent (interpreting the modulating layer as the outer stabilizing layer, claim 1) (col 18, lines 66-67; and col 19, lines 1-5).
Regarding claim 2, Rao teaches that the invention utilizes an enzyme (e.g. glucose oxidase) included in a polymer matrix mixture that is applied on the surface of an electrode and subsequently exposed to UV light to form a thin crosslinked polymer matrix with the enzyme covalently linked to this matrix, such that the analyte sensing layer having GOx reacts with glucose present in the sensing environment (e.g. the body of a mammal) and generates hydrogen peroxide according to the reaction shown in Figure 4, wherein the hydrogen peroxide so generated is anodically detected at the working electrode in the conductive constituent, wherein the GOx is a Gox-Acrylate bioconjugate (interpreted as releasing hydrogen peroxide upon contacting the analyte, claim 2) (col 17, lines 1-14).
Regarding claim 3, Rao teaches that an additional layer includes an analyte modulating layer 112 that is disposed above the analyte sensing layer 110 to regulate analyte access with the analyte sensing layer 110, wherein the analyte modulating membrane layer 112 can comprise a glucose limiting layer or membrane, which regulates the amount of glucose that contacts an enzyme such as glucose oxidase that is present in the analyte sensing layer (interpreting the enzyme layer to comprise an oxidase, claim 3) (col 13, lines 41-47).
Regarding claim 4, Rao teaches that acceptable polymer coatings for use as the insulating cover layer or the insulator 102B can include, but are not limited to, non-toxic biocompatible polymers such as silicone compounds, polyimides, biocompatible solder masks, epoxy acrylate copolymers, or the like (interpreting the covalent bonds to comprise silicone, claim 4) (col 12, lines 12-16). Rao teaches that the solution by an electrically insulating cover constituent; and that examples of useful materials for generating this protective cover constituent include polymers such as polyimides, polytetrafluoro-ethylene, poly-hexafluoropropylene and silicones such as polysiloxanes (col 15, lines 21-26). Rao teaches glucose limiting membranes can be made from a wide variety of materials known to be suitable for such purposes, e.g., silicones such as polydimethyl siloxane and the like, polyurethanes, cellulose acetates, NAFION, polyester sulfonic acids (e.g. Kodak AQ), hydrogels or any other membrane known to those skilled in the art that is suitable for such purposes (interpreting the covalent bonds to comprise silicone, claim 4) (col 30, lines 12-19).
Regarding claim 6, Rao teaches that the crosslinked polymer matrix is formed in situ by exposing a polymer matrix mixture to ultraviolet (UV) light, wherein this polymer matrix mixture typically comprises a plurality of hydroxyethyl methacrylate (HEMA) monomers, one or more di-acrylate crosslinkers, one or more UV photo-initiators (interpreted as comprising polymerized monomer units, claim 6) (col 2, lines 37-41).
Regarding claim 9, Rao teaches that the analyte modulating membrane layer 112 can comprise a glucose limiting layer or membrane, which regulates the amount of glucose that contacts an enzyme such as glucose oxidase that is present in the analyte sensing layer, wherein such glucose limiting membranes can be made from a wide variety of materials known to be suitable for such purposes, e.g., silicone compounds such as polydimethyl siloxanes, polyurethanes, polyurea cellulose acetates, NAFION, polyester sulfonic 45 acids (e.g. Kodak AQ), hydrogels or any other suitable hydrophilic membranes known to those skilled in the art (interpreting the analyte modulating membrane to be the outer stabilizing layer that comprises silicone, claim 9) (col 13, lines 37-47).
Regarding claims 14 and 15, Rao teaches that the analyte modulating layer comprises hydroxyethyl methacrylate (HEMA) monomer, di-acrylate crosslinker (e.g. triethylene glycol diacrylate (TEGDA) or polyethylene glycol diacrylate (PEGDA) (interpreting the outer stabilizing layer to comprise a methacrylate, hydroxy, hydroxyethyl methacrylate, claims 14 and 15) (col 30, lines 19-23).
Regarding claims 29 and 30, Rao teaches that the analyte sensor apparatus further comprises a glucose limiting membrane positioned over the crosslinked polymer matrix, wherein the glucose limiting membrane is formed by exposing ultraviolet (UV) light to a glucose limiting membrane mixture comprising a plurality of hydroxyethyl methacrylate (HEMA) monomers, one or more di-acrylate crosslinkers, one or more UV photo-initiators, ethylene glycol, and water (interpreted as the outer stabilizing layer limits the flux of analytes or reactive oxygen species through the membrane, claims 29 and 30) (col 9, lines 28-34). Rao teaches that the analyte modulating constituent is an analyte limiting membrane or diffusion control membrane (e.g. a glucose limiting membrane (GLM)) which operates to prevent or restrict the diffusion of one or more analytes, such as glucose, through the constituents, wherein the analyte modulating constituents can be formed to prevent or restrict the diffusion of one type of molecule through the constituent (e.g. glucose), while at the same time allowing or even facilitating the diffusion of other types of molecules through the constituent (e.g. 02) (interpreted as limiting reactive oxygen species, claim 30) (col 18, lines 25-37).
Regarding claim 31, Rao teaches that HEMA, TEGDA or polyethylene glycol diacrylate are coated on the sensors at a desired thickness over the enzyme layer (e.g., Gox-Acrylate layer), crosslinked via UV to form in-situ glucose-limiting membrane (GLM) on the sensor (interpreted the enzyme is covalently incorporated, claim 31) (col 8, lines 59-67; and col 9, lines 1-3).
Rao does not specifically exemplify polyacrylic acid (claim 5).
Regarding claim 5, Papadimitrakopoulos teaches devices that function as a glucose sensor (Abstract, line 1). Papadimitrakopoulos teaches that the working electrode comprises a metal upon which is disposed an electrically conducting polymer and an enzyme specific to an analyte of interest (hereinafter the "analyte"), a layer-by-layer film to fine-tune permeability to the analyte, a poly(vinyl alcohol) hydrogel layer to store and provide additional oxygen to the sensor, and a biocompatible coating that are also capable of releasing a variety of drugs, wherein the biosensor is advantageous over other comparative biosensors in that it (a) exhibits high linearity; (b) exhibits high sensitivity; (c) takes into account the contribution of exogenous interfering species; and (d) provides internal calibration routines to take into account sensor drifts based on in vivo induced effects that change the permeability of semi-permeable membrane, which also accounts for gradual decay of electrode activity (paragraph [0040]). Papadimitrakopoulos teaches examples of the first and second hydrogels are crosslinked including poly-hydroxyethyl methacrylate, polyethylene oxide, polyacrylic acid, polyvinyl pyrrole, chitosan, collagen, or the like, or a combination comprising at least one of the foregoing hydrogel (paragraph [0074]).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that 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 would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of fine-tuning permeability to the analyte in an analyte sensor as exemplified by Papadimitrakopoulos, it would have been prima facie obvious before the effective filing date of the claimed invention to modify the analyte sensor including an electrode comprising an in-situ crosslinked polymer matrix, wherein the analyte sensor comprises a conductive layer, an interference membrane, a sensing layer, an adhesion promotor layer, and an analyte modulating layer as taught by Rao to include additional monomers and/or polymers for the formation of a first and/or second hydrogel layer including polyacrylic acid as taught by Papadimitrakopoulos, with a reasonable expectation of success in the in-situ crosslinking of different polymers to fine-tune the permeability of the analyte to a membrane including in an implantable glucose biosensor, while improving sensor sensitivity and linearity.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Rao does not describe a multilayered membrane comprising a hydrophobic stabilizing layer disposed over a hydrophilic sensing layer, much less that the hydrophilic sensing layer and the hydrophobic stabilizing layer being covalently attached to each other via covalent bonds at their interface (Applicant Remarks, pg. 22, first full paragraph).
Regarding (a), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments. As noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
MPEP 2123(I) states:
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. See In re Heck, 699 F.2d 1331, 1332-33,216 USPQ 1038, 1039 (Fed. Cir. 1983); In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275,277 (CCPA 1968); Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); and Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (underline added).
MPEP 2141.02(VI) states:
"the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
Applicant’s assertion that Rao does not describe a multilayered membrane comprising a hydrophobic stabilizing layer disposed over a hydrophilic sensing layer, much less that the hydrophilic sensing layer and the hydrophobic stabilizing layer being covalently attached to each other via covalent bonds at their interface, is not found persuasive. As an initial matter, Applicant has not addressed the teachings of Papadimitrakopoulos. The Examiner agrees that Rao and Papadimitrakopoulos teach many embodiments of their inventions, which include teaching the multilayered membranes as recited in instant claim 1. For example -
Rao teaches:
Figure 5A illustrates a sensor, comprising:
A conductive layer comprising one or more electrodes, 104;
An analyte sensing layer comprising an enzyme such as glucose oxidase, 110, which is capable of utilizing oxygen and/or hydrogen peroxide, wherein the monomer mixture comprising a plurality of HEMA monomers, one or more di-acrylate crosslinkers, and an oxidoreductase, including a glucose oxidase-acrylate bioconjugate, is crosslinked and cured (interpreting the analyte sensing layer as the instant hydrophilic sensing layer comprising an enzyme).
An analyte modulating layer comprising a glucose limiting layer or membrane 112,
wherein glucose limiting membranes can be made from a wide variety of materials known to be suitable for such purposes, e.g., silicone compounds such as polydimethyl siloxanes, polyurethanes, polyurea cellulose acetates, NAFION, polyester sulfonic acids, hydrogels, etc. (interpreted as the hydrophobic stabilizing layer) (col 12, lines 12-16 and 41-50; col 13, lines 27-32 and 37-47; and Figure 5A).
Figure 5A is shown below:
PNG
media_image7.png
251
574
media_image7.png
Greyscale
The crosslinked polymer matrix exhibit a number of unexpected and desirable characteristics including enhanced adhesion resulting from the crosslinked polymer matrix and the glucose limiting membrane layers being formed in a way that creates a more homogeneous stack of sensor material layers (thereby inhibiting delamination, etc.) (interpreted as covalently attached to each other via covalent bonds at the interface, claim 1) (col 8, lines 59-67; and col 9, lines 1-3).
Papadimitrakopoulos teaches:
Figure 1 shows a glucose sensor comprising an electrode, and a glucose oxidase layer coated with a semi-permeable membrane to reduce the amount of glucose entering the sensor (interpreted as a stabilizing layer disposed over a sensing layer) (paragraph [0023]; and Figure 1).
PNG
media_image8.png
572
986
media_image8.png
Greyscale
The working electrode comprises a metal upon which is disposed an electrically conducting polymer and an enzyme specific to an analyte of interest, a layer-by-layer film to fine-tune permeability to the analyte, a poly(vinyl alcohol) hydrogel layer to store and provide additional oxygen to the sensor, and a biocompatible coating (interpreted as the sensor of claim 1) (paragraph [0040]).
The combined reference teach all of the limitations of the claims. Thus, the rejection is maintained.
Double Patenting
The provisional rejection of claims 1-6, 9, 12, 14, 15, 29 and 30 is maintained, and claim 31 is newly provisionally rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of copending US Patent Application No. 17/537,310 for the reason of record.
Response to Arguments
Applicant’s arguments filed January 15, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Applicant requests that the Office hold the rejection in abeyance (Applicant Remarks, pg. 15, third full paragraph).
Regarding (a), Applicant did not specifically indicate how the claims of the copending application recited supra are patentably distinct from the instant claims as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
New Objections/Rejections
Double Patenting Objection
Claim 9 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 4. Claim 9 recites “wherein the hydrophobic stabilizing layer comprises silicone;” while claim 4 recites “wherein the hydrophobic stabilizing layer comprises silicone.” Therefore, claim 9 does not differ in scope from claim 4.
When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
Claims 1-6, 9, 12, 14, 15 and 29-31 are rejected.
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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, Heather Calamita can be reached on (571) 272-2876. 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.
/AMY M BUNKER/Primary Examiner, Art Unit 1684