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 .
In view of the appeal brief filed on 6/11/26, PROSECUTION IS HEREBY REOPENED. New grounds of rejection are set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/TSE CHEN/ Supervisory Patent Examiner, Art Unit 3791
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 9, 14 and associated dependent claims are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “substantially” in claim 1 and “approximately” in claim 9 are relative terms which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant’s disclosure [0081] merely describes all possible shapes in “substantially” language without means of determining the metes and bounds. Similarly, there is no range/threshold disclosed for “approximately”.
Regarding claim 14, “the sheath has a wall thickness that impacts the permeability of the sheath to oxygen” is indefinite as any wall thickness may have some kind of impact to permeability of oxygen. Examiner suggests the claim to be amended to “wherein the sheath has a wall thickness that is between approximately 10 micrometers and 400 micrometers] which has written description support for the intended permeability.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 2, 4-5, 7-10, 12-14, 16-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Bremer”, US Publication 20170055906, in view of “Slate”, US Patent 5605152.
Regarding claim 1, Bremer discloses an analyte sensing system for sensing an analyte within blood, bodily fluid, or tissue of a patient [0003, 0010+, 0179+: “continuous health monitoring using an analyte sensor” where “the analyte can be, for example, glucose” measured “within blood, bodily fluid, or tissue of a patient”].
The analyte sensing system comprises a sensor assembly including an energy source that generates energy [0034, 0181+, 0198+: “laser source 125” that “emits light at a wavelength of substantially 405 nm” functioning as “optical excitation source” that generates energy for interrogating the sensor; FIG. 3A illustrating laser source 125 as component of controller 120; 0603+: “excitation sources and optics 4304” including “single stage laser diodes that emit 405 nm light” functioning as energy source generating optical energy].
The sensor includes an energy guide that receives the energy from the energy source, the energy guide including a guide distal end [0067+, 0188+: waveguides 119 that function as optical pathways “transmit sensor readings from regions 117A-C and oxygen reference 116 through sensor subassembly 110A to controller 120” where waveguides include distal ends positioned adjacent to oxygen sensing polymer regions; FIG. 2B illustrating “four flexible waveguides 119 along the vertical dimension” extending to sensing regions at distal end; 0264+, 0607+: “waveguide 4330” as “energy guide” with “guide distal end” positioned at “target materials 4340a, 4340b”].
The sensor includes a sheath/layer that is coupled to the energy guide near the guide distal end, the sheath/layer being substantially [broadly interpreted in view of 112b above] cylindrical-shaped to define at least a portion of a reaction chamber therewithin that extends distally away from the guide distal end, the sheath/layer having a sheath/layer distal end [0286+: “enzymatic reaction layer 1968” with “enzymatic hydrogel reaction region 1960” where “the enzymatic hydrogel reaction region 1960 is formed such that a portion of the oxygen sensing polymer in the oxygen sensing polymer region 1958 will be contiguous with the enzymatic hydrogel in the enzymatic hydrogel reaction region 1960, such that the oxygen sensing polymer in the oxygen sensing polymer region 1958 will define part of the geometric boundary for the enzymatic hydrogel reaction region 1960”; 0273+: “enzymatic hydrogel cavity 1902” and “oxygen sensing polymer cavity 1904” forming reaction chamber within sensor structure adjacent to waveguides 1910].
The sensor includes a sensing polymer that is positioned near the guide distal end of the energy guide, the energy guide guiding the energy from the energy source toward the sensing polymer, the sensing polymer being configured to sense one of oxygen and the analyte, the sensing polymer defining a chamber proximal end of the reaction chamber [0188+: “The oxygen sensing polymer 115 forms a band or channel along the width dimension of the middle layer 112”; FIG. 2B showing oxygen sensing polymer 115 positioned adjacent to waveguides 119 at distal end; 0418+: “oxygen sensing polymer regions 3840 and 3845 comprise an oxygen detecting dye… the dye is a porphyrin dye…” configured to sense oxygen where “luminescent dye emits a measurable signal dependent on the amount of oxygen present”; 0289+: “surface 1972, which forms the base of the enzymatic hydrogel reaction region 1960 and the remainder of the enzymatic hydrogel reaction region 1960… are created by shaping the oxygen sensing polymer” such that “the oxygen sensing polymer in the oxygen sensing polymer region 1958 and the enzymatic hydrogel in the enzymatic hydrogel reaction region 1960 are in physical contact with each other” where oxygen sensing polymer defines chamber proximal boundary].
The sensor includes a transduction matrix that is retained substantially within the reaction chamber [0295+: “enzymatic hydrogel reaction region 1960” containing “enzymatic hydrogel” that functions as transduction matrix, where “the enzymatic hydrogel reaction region 1960 can now be filled with the enzymatic hydrogel… The enzymatic hydrogel is then crosslinked” and retained within geometrically defined reaction chamber; e.g., enzymatic hydrogel cavity 1902 filled with enzymatic hydrogel 113 containing enzymes that reacts with interstitial glucose that enters in glucose inlet 114 functioning as transduction matrix retained within reaction chamber defined by sensor structure].
However, Bremer does not explicitly disclose: (1) the sheath/layer being cylindrical-shaped; (2) the sheath/layer being “oxygen permeable, and the sheath/layer being impermeable to the analyte being sensed” with these exact material selectivity characteristics; (3) “the oxygen that permeates through the sheath/layer and into the transduction matrix that is retained within the reaction chamber follows a first diffusion path within the transduction matrix”; and (4) “the analyte permeates into the transduction matrix that is retained within the reaction chamber through the sheath/layer distal end, the analyte following a second diffusion path within the transduction matrix that is different than the first diffusion path.”
Slate discloses an analogous sheath structure that is cylindrical-shaped, oxygen permeable while being impermeable to glucose, with oxygen and glucose following distinct diffusion paths into the reaction chamber. Specifically, Skate teaches a compact semipermeable probe housing 26 designed for differential diffusion of glucose and oxygen [col.3, lines 48+] … comprising a generally cylindrical sleeve 34 having a proximal end appropriately attached to the cable sheath 32 [col.3, lines 58+]. The sleeve 34 is constructed from a selected semipermeable material to permit diffusion passage of oxygen substantially in the absence of glucose [col.3, lines 60+]. FIG. 2 shows cylindrical sleeve 34 forming reaction chamber with enzyme optrode 22 and reference optrode 24 positioned therein. Slate further discloses that the opposite or distal end of the sleeve 34 is closed by a disk-shaped membrane 36 of an appropriate material chosen for diffusion passage of glucose… comprising a selected hydrogel material permeable to both glucose and oxygen [col.3, lines 66+: distal membrane 36 functioning as glucose inlet at sheath distal end]. Slate explicitly teaches differential diffusion creating distinct pathways: “the overall surface area of the disk-shaped membrane 36 is substantially less than the total surface area provided by the oxygen permeable sleeve 34, whereby the proportional diffusion ingress of oxygen exceeds the diffusion ingress of glucose” [col.4, lines 4+: differential surface area creates first diffusion path for oxygen through larger cylindrical sleeve surface and second diffusion path for glucose through smaller distal 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 the geometrically defined sensing regions/layers of Bremer with the explicit teachings of Slate as both are directed toward optical glucose sensors utilizing enzymatic oxygen depletion measurements for continuous glucose monitoring. An ordinary artisan would have been motivated to make the modification to enhance the base device of Bremer with the teachings of Slate that includes the cylindrical sheath with differential oxygen and glucose diffusion paths – ensuring reliable maintenance of oxygen excess within the enzymatic reaction chamber of Bremer regardless of variations in tissue oxygen and glucose concentrations, as Slate demonstrates this configuration successfully achieves “a stoichiometric excess of oxygen within the probe housing” [col.1, lines45+; col.3, lines 48+, lines 66+: oxygen permeates through the cylindrical sheath walls following a first diffusion path with relatively large surface area, while glucose would enter through the smaller distal membrane following a second, distinct diffusion path, thereby maintaining the required oxygen excess for accurate glucose measurements]. In essence, the combination would predictably improve the Bremer’s sensor by providing a well-defined semipermeable housing that maintains excess oxygen at the reaction site, while retaining Bremer’s optical interrogation and signal processing.
Regarding claim 2, Bremer discloses the analyte sensing system of claim 1 wherein the sensing polymer is coated onto the guide distal end of the energy guide [0292+: “forming the surface 1972 in the oxygen sensing polymer in the oxygen sensing polymer layer 1958, ensures that the oxygen sensing polymer in the oxygen sensing polymer region 1958 and the enzymatic hydrogel in the enzymatic hydrogel reaction region 1960 are in physical contact with each other” where oxygen sensing polymer is positioned adjacent to and coating the waveguide at its distal end; 0065+, 0286+: oxygen sensing polymer 1958 positioned in direct contact with “exposed waveguide core” where “the oxygen sensing polymer that contacts the exposed waveguide core” is located at guide distal end].
Regarding claim 4, Bremer discloses the analyte sensing system of claim 1 wherein the sensing polymer is hydrophobic and wherein the transduction matrix is hydrophilic [0601+: oxygen sensing polymer immobilized in “hydrophobic oxygen permeable polymer”; 0460+, 0577+: transduction matrix comprising “PEGylated albumin-enzyme complexes” with “hydrophilic polymer decoration” where “the nanostructure may be decorated with one or more hydrophilic polymers selected from the group consisting of PEG”; 0473+, 0546+: “enzymatic hydrogel” as “hydrogel particle… a matrix of polymer that retains water within the matrix” indicating hydrophilic character].
Regarding claim 5, Bremer discloses the analyte sensing system of claim 1 wherein the sensing polymer is an oxygen sensing polymer that is configured to sense the oxygen within the transduction matrix [0419+: “oxygen sensing polymer… comprise an oxygen detecting dye… the dye is a luminescent dye…”; 0292+: oxygen sensing polymer 1958 is “in physical contact with” and senses oxygen in “enzymatic hydrogel in the enzymatic hydrogel reaction region 1960”].
Regarding claim 7, Bremer discloses the analyte sensing system of claim 1 wherein the sheath is formed via one of a three-dimensional extrusion technique and a three-dimensional molding technique [0302+: sensor manufacturing where “embossing can be used to produce precise internal structures… inserts can be used to form specific cavities… the polymer of the particular layer will pass around the outside of the insert… when the layer is solidified, such as through curing, and the insert is removed, the oxygen conduit cavity will remain in the solidified layer” describing three-dimensional molding technique using inserts and curing to form sensor structures including sheath-like layers defining reaction chambers; 0264+: “lamination” of polymer layers to form sensor structure with reaction chambers].
Regarding claim 8, Bremer in view of Slate discloses the analyte sensing system of claim 1 wherein the sheath has a concentric unibody design. Slate explicitly teaches a “cylindrical sleeve 34” that forms a unitary, concentric structure around the reaction chamber [col. 3, lines 58+; e.g., FIG. 2-3]. This concentric unibody cylindrical design of Slate would be combined with Bremer’s layered sensor structure as previously described to yield the claimed unibody sheath configuration.
Regarding claim 9, Bremer discloses the analyte sensing system of claim 1 wherein the substantially cylindrical shape of the sheath defines a chamber diameter of the reaction chamber, the chamber diameter being between approximately 100 nanometers and 500 micrometers [0614+: “The three contiguous glucose reaction volumes inside the enzymatic hydrogel each have a dimension of approximately 0.1 mm×0.1 mm×0.1 mm, respectively”; 0422+: “sensor tip dimensions of approximately 0.05mm × 0.3mm × 1.5mm”].
Regarding claim 10, Bremer in view of Slate discloses the analyte sensing system of claim 1 wherein the sheath is formed from one or more of fluorinated ethylene propylene (FEP), paraformaldehyde (PFA), polytetrafluoroethylene (PTFE), polyimide, polyether block amide (PEBA), polyvinylchloride (PVC), polydimethylsiloxane, polyurethane, polycarbonate, poly(1-trimethylsilyl-1-propyne) (PTMSP), ethylene vinyl alcohol (EVOH), sulfonated tetrafluoroethylene-based fluoropolymer-copolymer, and modified cellulose. Slate explicitly teaches appropriate sheath materials: “preferred sleeve material comprises a pliable silicone base material such as that marketed by Dow Corning Corporation of Midland, Mich. under the name Silastic™” [col.3, lines 58+; PDMS].
Regarding claim 12, Bremer discloses the analyte sensing system of claim 1 wherein the transduction matrix is comprised of a hydrogel and one or more enzymes that are configured to react with the oxygen and the analyte; and wherein a reaction between the one or more enzymes with the oxygen and the analyte consumes at least a portion of the oxygen and the analyte that is present within the transduction matrix [0295+: “enzymatic hydrogel” as transduction matrix where “the enzymatic hydrogel reaction region 1960 can now be filled with the enzymatic hydrogel”; 0415+: enzymatic hydrogel containing “GOx can convert glucose and oxygen into gluconolactone and H2O2” where reaction consumes both glucose and oxygen; paragraph 0309+: explicitly stating “The oxygen sensing polymer cavity 1904 and the enzymatic hydrogel cavity 1902 can be accessible from the surface of the middle layer 1804 through the glucose inlet cavity 1906”; 0188+, 0614+: “glucose interacts with the oxygen sensing polymer in the presence of the hydrogel in the enzymatic hydrogel channel 113, and diffuses along the continuous oxygen sensing polymer band 115” where enzymatic reaction “consumes oxygen in proportion to the amount of glucose in each reaction volume”].
Regarding claim 13, Bremer discloses the analyte sensing system of claim 12 wherein the transduction matrix further includes a catalyst that is configured to initiate the reaction between the oxygen and the analyte [0415+: enzymatic reactions where “GOx can convert glucose and oxygen into gluconolactone and H2O2” and “H2O2 can then be converted back to oxygen and water in the presence of water and CAT [catalase]” where catalase functions as catalyst enzyme; 0489+: e.g., “CAT-albumin nanoparticle”].
Regarding claim 14, Bremer in view of Slate discloses the analyte sensing system of claim 1 wherein the sheath has a wall thickness that impacts the permeability of the sheath to oxygen [see 112b above]; and wherein the wall thickness of the sheath is between approximately 10 micrometers and 400 micrometers. Bremer describes sensor layer thicknesses in the relevant dimensional range [0390+: sensor features with dimensions including “thickness ‘T’ ranging between approximately 100 μm to approximately 400 μm” for structural elements; 0630+ “thickness of about 50 μm” for waveguide cores]. Slate also teaches that sheath wall thickness affects oxygen permeability: the cylindrical sleeve 34 must have appropriate thickness to provide structural integrity while maintaining sufficient oxygen permeability [col.3, lines 60+: “pliable silicone base material” sleeve with sufficient oxygen permeability].
Regarding claim 16, Bremer discloses the analyte sensing system of claim 1 wherein the sensor further includes a buffer layer that is positioned about the energy guide, the buffer layer being formed from one or more polymeric materials [0624+: “cladding material 4332 having a cladding index of refraction n3… the cladding material 4332 surrounding the core material 4336 to form the excitation path 4330a, the emission path 4330b, and the transmission path 4330c” where cladding functions as buffer layer positioned about waveguide core; 0619+: “The core 4336 can have a fourth index of refraction, n4, that is close to but greater than the index of refraction of the cladding 4332 (e.g., n3<n4) so that light is maintained within and directed along the waveguide by undergoing total internal reflection at the boundary between the cladding 4332 and the core 4336”; 0620+: cladding 4332 as “acrylate” polymeric material functioning as buffer layer surrounding waveguide core].
Regarding claim 17, Bremer discloses the analyte sensing system of claim 1 wherein the energy source is a light source [e.g., 125] that generates light energy; and wherein the energy guide [e.g. 119] is an optical fiber.
Regarding claim 18, Bremer in view of Slate discloses the analyte sensing system of claim 1 wherein the sensor is a first sensor channel; and wherein the analyte sensing system further includes a second sensing channel [Bremer, 0190+: multiple waveguide channels where “four flexible waveguides 119 along the vertical dimension of middle layer 112 transmit sensor readings from regions 117A-C and oxygen reference 116” indicating multiple sensing channels; 0621+: “sensor 4300 can include a plurality of measurement waveguides in a sensor waveguide system 4330” where multiple channels interrogate different target material regions].
The second sensing channel includes a second energy guide that receives the energy from the energy source, the second energy guide including a second guide distal end [0190+: plurality of waveguides 119 where each waveguide functions as energy guide receiving energy from common laser source 125].
The second sensing channel includes a second sheath that is coupled to the second energy guide near the second guide distal end, the second sheath defining at least a portion of a second reaction chamber, the second sheath being oxygen permeable, and the second sheath being impermeable to the analyte being sensed. [Bremer in view of Slate where Bremer describes middle layer 1804 with multiple reaction regions 117A-C and reference region 116, and Slate teaches oxygen-permeable, glucose-impermeable cylindrical sheath structure 34 that would be applied to each sensing channel as previously described].
The second sensing channel includes a second sensing polymer that is positioned near the second guide distal end of the second energy guide, the second energy guide guiding the energy from the energy source toward the second sensing polymer, the second sensing polymer being configured to sense one of the oxygen and the analyte [Bremer, oxygen sensing polymer 115 extending across multiple regions 117A-C where oxygen sensing polymer band 115 is sampled at different distances from glucose inlet 114 by different waveguides 119, with each waveguide having its own portion of oxygen sensing polymer functioning as second sensing polymer].
The second sensing channel includes a second transduction matrix that is retained substantially within the second reaction chamber [Bremer, 0614+: enzymatic hydrogel 113 extending across multiple reaction regions 117A-C where glucose diffuses progressively through first, second, and third reaction volumes with each region having transduction matrix as discussed above].
Alternatively, it would have been obvious to duplicate the first channel structure of claim 1 to form a second sensing channel of claim 18 in order to expand dynamic range and provide redundancy.
Regarding claim 19, Bremer in view of Slate discloses the analyte sensing system according to claim 1, including all limitations previously described for claim 1, wherein the sensor is a first sensor channel; and wherein the analyte sensing system further includes a reference channel [Bremer, 0615+: four oxygen sensing polymer volumes are each interrogated… i.e., each of the three reaction volumes in the target material 4340a reference material 4340b and to measure the oxygen concentration remaining in the enzymatic hydrogel, all three reaction volumes of the enzymatic hydrogel are in physical contact with an adjacent oxygen sensing polymer layer operating as a reference volume for oxygen measurements].
The reference channel includes a reference energy guide that receives the energy from the energy source, the reference energy guide including a guide distal end [Bremer, e.g., FIG. 2B showing separate waveguide 119 extending to oxygen reference 116 region].
The reference channel includes a reference sheath that is coupled to the reference energy guide near the guide distal end [Bremer in view of Slate, where Bremer describes structural layers defining reference region structurally separated from working regions 117A-C and Slate teaches oxygen-permeable sheath structure 34 that would be applied to reference channel as previously described for claim 1).
The reference channel includes a reference sensing polymer that is configured to sense oxygen from within the blood, bodily fluid or tissue of the patient to set a baseline level of oxygen within the blood, bodily fluid or tissue of the patient. [0615+: oxygen conduit is also in physical contact with an adjacent oxygen sensing polymer layer at reference region 116 where the three glucose reaction portions of the target material 4340a reaction volume and the reference material 4340b reaction volume are interrogated optically through separate optrodes and each of these waveguides returns the luminescent emission signal from the oxygen sensing polymer in each volume; 0191+: interstitial glucose concentration is readily calculable from a set of oxygen concentration measurements, given a reference oxygen level and three oxygen concentration measurements in the enzymatic hydrogel where reference oxygen sensing polymer at region 116 measures baseline tissue oxygen concentration independent of glucose reaction].
Bremer and Slate are combinable as previously described for claim 1. The combination would yield the claimed reference channel configuration with reference energy guide, reference sheath, and reference sensing polymer for baseline oxygen measurements.
Regarding claim 20, Bremer in view of Slate discloses an analyte sensing system for sensing an analyte within blood, bodily fluid, or tissue of a patient, the analyte sensing system comprising a sensor assembly including an energy source that generates energy, and a sensor including an energy guide, as previously described in detail for claim 1.
The sensor includes a sheath that is coupled to the energy guide near the guide distal end, the sheath having a concentric unibody design that is substantially cylindrical-shaped to define at least a portion of a reaction chamber therewithin that extends distally away from the guide distal end, the sheath being oxygen permeable, and the sheath being impermeable to the analyte being sensed, the sheath having a sheath distal end. [Slate, col.3, lines58+: “a generally cylindrical sleeve 34” as concentric unibody structure that is “constructed from a selected semipermeable material to permit diffusion passage of oxygen substantially in the absence of glucose” where “the opposite or distal end of the sleeve 34 is closed by a disk-shaped membrane 36”; FIG. 2 illustrating cylindrical sleeve 34 as single continuous concentric piece forming unibody sheath around reaction chamber containing optrodes 22, 24). This concentric unibody cylindrical sheath design of Slate would be combined with Bremer’s sensor structure as previously described to satisfy all sheath limitations.
The sensor includes a hydrophobic oxygen sensing polymer that is coated onto the guide distal end of the energy guide, the oxygen sensing polymer being configured to sense oxygen within the reaction chamber, the oxygen sensing polymer defining a chamber proximal end of the reaction chamber, the energy guide guiding the energy from the energy source toward the oxygen sensing polymer. [Bremer, 0287+: oxygen sensing polymer 1958 positioned adjacent to and in contact with waveguide cores at distal end where the oxygen sensing polymer in the oxygen sensing polymer region 1958 will define part of the geometric boundary for the enzymatic hydrogel reaction region 1960 functioning as chamber proximal end; 0601+: oxygen sensing polymer configured to sense oxygen where polymer is “immobilized in a hydrophobic oxygen permeable polymer”; 0188+: oxygen sensing polymer 115 forms a band or channel along the width dimension of the middle layer 112 positioned adjacent to waveguides 119 at distal end].
The sensor includes a hydrophilic transduction matrix that is retained substantially within the reaction chamber, the transduction matrix including a hydrogel and one or more enzymes that are configured to react with the oxygen and the analyte. [Bremer, 0460+, 0577+: transduction matrix comprising “PEGylated albumin-enzyme complexes” with “hydrophilic polymer decoration” where “the nanostructure may be decorated with one or more hydrophilic polymers selected from the group consisting of PEG”; 0473+, 0546+: “enzymatic hydrogel” as “hydrogel particle… a matrix of polymer that retains water within the matrix” indicating hydrophilic character; 0415+: enzymatic reactions where “GOx can convert glucose and oxygen into gluconolactone and H2O2” and “H2O2 can then be converted back to oxygen and water in the presence of water and CAT [catalase]” where catalase functions as catalyst enzyme; 0489+: e.g., “CAT-albumin nanoparticle”].
Wherein the oxygen that permeates through the sheath and into the transduction matrix that is retained within the reaction chamber follows a first diffusion path within the transduction matrix; wherein the analyte permeates into the transduction matrix that is retained within the reaction chamber through the sheath distal end of the sheath, the analyte following a second diffusion path within the transduction matrix that is different than the first diffusion path [Slate, col.3, lines 58+: explicitly teaching differential diffusion paths where oxygen permeates through large surface area “cylindrical sleeve 34” while glucose enters through smaller “disk-shaped membrane 36” at “distal end of the sleeve 34” such that “the overall surface area of the disk-shaped membrane 36 is substantially less than the total surface area provided by the oxygen permeable sleeve 34, whereby the proportional diffusion ingress of oxygen exceeds the diffusion ingress of glucose,” implicitly creating first diffusion path for oxygen through cylindrical walls and second, distinct diffusion path for glucose through distal membrane]. This differential diffusion path design of Slate combined with Bremer’s transduction matrix arrangement as previously described satisfies these limitations.
Wherein a reaction between the one or more enzymes with the oxygen and the analyte consumes at least a portion of the oxygen and the analyte that is present within the transduction matrix [Bremer, 0295+: “enzymatic hydrogel” as transduction matrix where “the enzymatic hydrogel reaction region 1960 can now be filled with the enzymatic hydrogel”; 0415+: enzymatic hydrogel containing “GOx can convert glucose and oxygen into gluconolactone and H2O2” where reaction consumes both glucose and oxygen; paragraph 0309+: explicitly stating “The oxygen sensing polymer cavity 1904 and the enzymatic hydrogel cavity 1902 can be accessible from the surface of the middle layer 1804 through the glucose inlet cavity 1906”; 0188+, 0614+: “glucose interacts with the oxygen sensing polymer in the presence of the hydrogel in the enzymatic hydrogel channel 113, and diffuses along the continuous oxygen sensing polymer band 115” where enzymatic reaction “consumes oxygen in proportion to the amount of glucose in each reaction volume”].
Bremer and Slate are combinable as previously described for claim 1. The combination would yield all limitations of claim 20 including the concentric unibody cylindrical sheath design, hydrophobic oxygen sensing polymer coated on guide distal end, hydrophilic transduction matrix with hydrogel and enzymes, differential diffusion paths for oxygen and glucose, and enzymatic consumption of oxygen and glucose within the transduction matrix.
Regarding claim 21, this claim depends from claim 18 and adds the limitation that at least one of (i) the chamber proximal end is staggered relative to the second chamber proximal end, and (ii) the chamber distal end is staggered relative to the second chamber distal end. Bremer discloses a sensor with multiple sensing channels at different positions along the oxygen sensing polymer band 115, where “oxygen sensing polymer band 115” is sampled at “different distances from the glucose inlet 114” by separate waveguides 119 positioned at regions 117A, 117B, 117C [Bremer, 0188+]. This implicitly creates staggered chamber configurations where the first reaction region 117A closest to glucose inlet 114 has its chamber proximal and distal ends at different positions compared to second reaction region 117B and third reaction region 117C. Bremer explicitly teaches: “the first reaction region 117A volume close to the glucose inlet 114 will be sensitive to low concentrations of glucose…” [Bremer, 0197+] and “As the interstitial glucose concentration increases and the amount of glucose diffusing through the glucose inlet 114 increases, and more glucose is reacted in the second and third regions 117B, 117C, the oxygen consumption occurs farther within each reaction region 117B, 117C volume” [Bremer, 0193+]. This progressive arrangement of reaction regions 117A-C at different distances from glucose inlet 114 implicitly staggers the chamber proximal and distal ends relative to each other, satisfying the limitation of claim 21. The combination of Bremer and Slate as previously described yields this staggered multi-channel configuration.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Bremer in view of Slate, as applied to claim 1 above, and further in view of “Shu”, “Stimuli-responsive polymer-based systems for diagnostic applications”.
Bremer in view of Slate discloses the analyte sensing system of claim 1, as previously described. However, Bremer in view of Slate does not explicitly disclose wherein the sensing polymer is configured to directly sense the analyte (glucose) within the transduction matrix. Rather, Bremer teaches an oxygen sensing polymer comprising platinum-porphyrin that senses oxygen concentration within the transduction matrix, where the oxygen concentration is depleted by the enzymatic reaction with glucose [e.g., see at least claim 12 above]. This appears to represent an indirect glucose sensing mechanism, where glucose concentration is inferred from oxygen depletion measurements rather than direct glucose binding by the sensing polymer.
Shu discloses analogous sensing polymers configured to directly sense glucose within a polymer matrix through direct molecular binding interactions. Specifically, Shu teaches: “The authors first synthesized poly(N-isopropylacrylamide)-co-acrylic acid (pNIPAm-co-AAc) microgels, and then coupled aminophenylboronic acid (APBA) to pNIPAm-co-AAc microgel via a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) coupling reaction. The hydroxylated boronic acid groups in APBA (pH 4 9) could bind to glucose molecules that shifts the equilibrium towards the charged form of boronic acid. The increasing number of negatively charged APBA molecules enhances the Coulombic repulsion inside the microgel, which resulted in a swelling of the microgel layer” [page 7044, Glucose sensors section describing Sorrell et al. example]. Shu further teaches another example: “Zhou and coworkers developed a glucose sensor from fluorescent nanogels made of a AgNP core covered by a poly(4-vinylphenylboronic acid-co-2-(dimethylamino)ethyl acrylate) (p(VPBA–DMAEA)) copolymer shell. In the presence of glucose, the boronic acid binds glucose and created negative charges inside the nanogel, leading to the swelling of the hybrid nanogel” [pages 70-48-7049, Glucose sensors section]. These examples demonstrate that sensing polymers containing boronic acid functional groups can directly bind glucose molecules and transduce this binding into a measurable signal through polymer conformational changes.
Bremer, Slate, and Shu are combinable because all three references are directed toward glucose sensors for continuous glucose monitoring in patients. Both Bremer and Shu specifically teach stimuli-responsive polymer-based glucose sensors designed to provide continuous glucose measurements for diabetes management. Shu explicitly states its focus on “stimuli-responsive polymers for sensing and imaging” with particular emphasis on “biosensing” applications including glucose detection [page 7042 and Section 3]. All three references address the fundamental challenge of developing accurate, sensitive, and biocompatible glucose sensors suitable for in vivo or point-of-care applications.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Bremer in view of Slate with the teachings of Shu regarding boronic acid-based direct glucose sensing polymers. This modification would have been prompted in order to enhance the base device of Bremer with the well-known and applicable technique Shu applied to glucose sensing systems.
Replacing the oxygen sensing polymer of Bremer with a boronic acid-functionalized sensing polymer as taught by Shu would enhance the base device of Bremer by providing direct glucose sensing capability, eliminating the need for the enzymatic oxygen depletion mechanism and potentially simplifying the sensor design. Shu demonstrates that boronic acid-based glucose sensing provides “a significant spectral red-shift in the presence of 3 mg ml solution of glucose within 30 min” and notes that such sensors can “be used for point-of-care diagnostics” [pages 7044-7045]. An ordinary artisan would have recognized that incorporating Shu’s boronic acid-based direct glucose sensing polymer into Bremer’s sensor structure could provide an alternative sensing mechanism while maintaining the advantages of Bremer’s optical interrogation system and sensor architecture.
Furthermore, both Bremer and Shu teach pNIPAm-based responsive polymers, indicating technical compatibility. Bremer extensively describes pNIPAm-based microgels and their use in sensor construction [Bremer, e.g., 0460, 0524], while Shu teaches pNIPAm-based polymers functionalized with boronic acid groups for glucose sensing as discussed above. This common polymer platform would have made the combination straightforward to implement.
This combination would yield predictable results in that the boronic acid groups on the sensing polymer would directly bind glucose molecules entering through the sheath distal end as taught by Slate, causing the sensing polymer to undergo conformational changes [swelling due to charge repulsion as taught by Shu] that could be optically interrogated using Bremer’s waveguide and optical detection system, thereby providing direct glucose sensing within the transduction matrix rather than indirect sensing through oxygen depletion.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Bremer in view of Slate, as applied to claim 10 above, and further in view of Kunze (US 2008/0194933, cited previously).
Regarding claim 11, Slate teaches the probe housing 26 is made of silicone (col.2, lines 15-17). Neither Bremer nor Slate teach explicitly the sheath is formed at least partially from fluorinated ethylene propylene (FEP). Kunze teaches an analogous optical fiber for measuring oxygen content in tissue (Abstract). Kunze teaches an oxygen-permeable, liquid-impermeable membrane 7 can be made from silicone or tetrafluoroethylene-hexafluoropropylene copolymer (FEP) (paras. 13, 16, 35).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Bremer in view of Slate such that the silicone oxygen-permeable membrane is instead made of FEP. One would be motivated to do so because both materials were known in the art to form an oxygen-permeable membrane for an oxygen-sensing optical fiber, and one could substitute one material for the other to achieve the same function of allowing oxygen through the membrane while preventing analytes from coming through.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Bremer in view of Slate, as applied to claim 1 above, and further in view of Shults (US 2009/0287074, cited previously).
Regarding claim 15, while Slate teaches that the semipermeable probe housing 26 is permeable to oxygen and impermeable to glucose, Slate does not explicitly teach or suggest the dimensions or specific properties of the semipermeable probe housing. Shults teaches an analogous analyte sensor comprising a membrane with a high oxygen solubility material in order to provide excess oxygen to glucose oxidase enzyme reaction (“the resistance domain includes a semipermeable membrane that controls the flux of oxygen and glucose to the underlying enzyme domain, preferably rendering oxygen in a non-rate-limiting excess,” par. 347; “a lower ratio of oxygen-to glucose can be sufficient to provide excess oxygen by using a high oxygen solubility domain,” par. 348). Shults further teaches that the high oxygen solubility material has an oxygen permeability of 1 Barrer to about 1000 Barrers (claim 20) and a thickness of the resistance domain may range from 0.05 microns-20 microns (par. 353). Particularly, Shults teaches the resistance domain comprises an oxygen permeability of 1-1000 Barrers (claim 20). 1 Barrer converts to 64.8 cm3*mm/ m2*day*bar (1 Barrer is 10-10 cm3*cm/ cm2*sec*cmHg; conversion to the claimed unit uses 75 cmHg=1 bar). At a resistance domain thickness of 20 microns (0.02 mm), Shults teaches an oxygen permeability of 3,240-3,240,000 (cm3*mm/ m2*day*bar)/mm which overlaps with the claimed range of 5-60,000 (cm3*mm/ m2*day*bar)/mm.
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Bremer in view of Slate to configure the probe housing to have a similar thickness and oxygen permeability as the resistance domain taught by Shults. One would be motivated to do so because Shults paragraph 347 teaches these properties allow excess oxygen to diffuse through the membrane, which is desired by Slate (“housing 26 is designed for…significantly greater proportional ingress of oxygen,” col. 3, lines 50-53). Since Slate doesn’t explicitly teach a thickness of the probe housing but indicates the dimensions may be modified to achieve the desired oxygen excess (“the specific dimensional comparison between the sleeve 34 and the membrane 36 is chosen to yield a stoichiometric excess of oxygen within the probe,” col. 2, lines 8-10), then one may be motivated to configure the probe housing to have a thickness and oxygen permeability known in the art. Slate and Shults teach silicone membranes, which further indicates that such a modification would be successful (“probe housing…formed from a material such as silicone permeable to oxygen, but substantially impermeable to glucose,” Slate col. 2, lines 14-17; Shults claim 21).
Response to Arguments
Applicant’s arguments submitted 6/11/26 with respect to the combination of Reardon and Slate have been considered but are moot because the new ground of rejection is based on Bremer and Slate.
Applicant’s arguments with respect to the rejection(s) of claim(s) 6 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Shu.
Conclusion
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TSE W. CHEN
Supervisory Patent Examiner
Art Unit 3793
Prosecution Insights