DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The amendment filed December 29, 2025 has been entered. Claims 3-4 have been cancelled, and claims 1, 2, 5, 11, and 12 have been amended. Claims 22-25 are new. Claims 1-2, 5-16, and 22-25 are pending in this application, with claims 6-10 and 13-16 withdrawn. The amendments to the Specification and Claims have overcome the objections and most of the rejections under 35 U.S.C. § 112(b) previously submitted in the Non Final Office action mailed September 4, 2025.
Response to Arguments
Applicant's arguments filed December 29, 2025 have been fully considered but they are not persuasive. Applicant’s arguments regarding Sharma and Huang are moot since the rejection below does not rely on those references. Applicant has amended claim 1 to include limitations previously recited in claims 3 and 4 along with additional amendments.
Applicant alleges that Pushpala’s teaching of a sensing layer 160 cannot be applied to both working and reference electrodes. Applicant further alleges “Pushpala does not distinguish between the working and reference electrodes in the manner required by current claim 1…Pushpala’s broad teaching…is too vague to teach or suggest the specific functions of the working and reference (or pseudoreference) microneedles required by amended claim 1” (Remarks pg. 16, paragraphs 2-3).
Contrary to Applicant’s allegation, Pushpala teaches that the filament 120 can serve as either working and reference electrode (“Each filament 120 in the array of filaments 110…can be paired with a filament 120 serving as a reference electrode configured to normalize a signal detected in response to analyte sensing…filaments characterized by different variations of filament composition (e.g., composition of layers and/or coatings). The sensing layer 160 can be different depending on its intended use, as explicitly taught by Pushpala (“The sensing layer 160 functions to enable transduction of an ionic concentration to an electronic voltage, to enable measurement of analyte/ion concentrations characterizing body chemistry…further, the sensing layer 160 serves as a reference electrode for ion concentration measurement,” par. 30). One of ordinary skill in the art would be able to combine the layers as taught by Pushpala to achieve desired working electrode and reference electrode functions.
Applicant further alleges that Pushpala and Feldman fail to teach a carbon pseudocounter electrode (Remarks pg. 20, paragraph 2). However, Feldman does teach a counter electrode comprising carbon (counter electrode 807; “counter electrode (C) 213 may be made using a conductive material…Materials include….carbon,” par. 43), which will to function to “increase the reliability of the signal” as generally known in the art (“Conventionally…the bias potential Vbias applied between the working and reference electrodes is set at a constant value…The counter electrode acts as a negative feedback circuit to maintain the desired voltage at the reference electrode,” Simpson par. 46).
Regarding claims 11-12 and the dependent claims, Applicant relies on the same arguments. Since the arguments were not persuasive, the claims are still rejected using previously cited prior art.
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 1-2, 5, 11 and 22-24 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.
Claim 1 recites “a substrate of said patch” in line 17 and “a polymeric substrate” in line 21. It is unclear whether these substrates refer to the same substrate. To expedite prosecution, they will be interpreted as the same substrate. The claim should be amended for clarity (e.g., “[[attaching]] embedding the at least one microneedle or needle configured as the reference electrode or the pseudoreference electrode to a polymeric substrate of said patch…before embedding in the [[a]] polymeric substrate). Claims 2, 5, and 2-24 are rejected by virtue of dependency.
It is noted that including “and/or” in claim 1 renders some of the limitations optional. For example, under the broadest reasonable interpretation, the claim can be interpreted as comprising the step of “coating said working electrode for ion sensing by coating the coating to improve the conductivity with a ion-to-electron transducer layer, and coating the ion-to-electron transducer layer with an ion-selective membrane,” and the remaining limitations following the phrase “and/or” can all be interpreted as not necessarily required. To expedite prosecution, the claim will be interpreted as encompassing two embodiments: the combination of a working and pseudoreference electrodes for (bio)molecule sensing and, alternatively, the combination of a working and reference electrode for ion sensing.
Claim 1 also recites limitations that seem redundant. For example, “coating the reference electrode or the pseudoreference electrode with an external polymeric film” in lines 22-23, “coating the reference membrane film with said external polymeric film” in lines 33-34, and “coating said pseudoreference electrode…with said external polymeric film” in lines 35-36. It seems the latter two limitations are merely reiterating the first limitation rather than reciting additional coating steps of the external polymeric film, and this interpretation will be followed to expedite prosecution. Applicant should amend the claims to clearly set forth the steps of the claim and indicate which steps comprise alternative sub-steps or options.
Claim 11 recites “wherein the method of preparing said working electrode for ion sensing comprises coating the microneedle or needle configured to function as the reference electrode.” It seems that preparing the working electrode should instead coat the microneedle configured to function as the working electrode rather than the reference electrode. Claim 11 also recites “a polymer-based coating for ion detection, sealing and avoiding detachment.” Claim 11 further recites “adding next the ion-to-electron transducer layer” and “adding then an ion-selective membrane”. It is unclear whether the ion-to-electron transducer layer or ion-selective membrane constitute the polymer-based coating for ion detection. It seems that the polymer-based coating for ion detection should be different from a polymer-based coating for sealing and avoiding detachment as Applicant discloses an external coating for sealing separate from the ion sensing layer (“For the working electrode…coating of the ion-selective membrane…an external coating is needed for the final sealing,” pg. 36, lines 28-32). To expedite prosecution, the polymer-based layer for ion detection will be interpreted as one of the ion-to-electron transducer layer or ion-selective membrane. It is suggested to delete “ion detection” in lines 10-11 since the ion-to-electron transducer layer and ion-selective membrane are already recited in the claim.
Claim 24 recites “the wearable patch of claim 1.” However, the preamble of claim 1 recites a method. It seems claim 24 should depend from claim 5, which is an apparatus claim. Additionally, the claim recites “an original diameter of the microneedle is incremented as much as 100 µm in total”. It is unclear what is being claimed. Is claim 24 reciting a step of providing a plurality of microneedles of increasing size up to a diameter of 100 microns on the wearable patch or is the claim scope simply encompassing microneedles with a diameter of up to 100 microns? To expedite prosecution, the latter interpretation will be followed. It is suggested to delete the word “incremented” from the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-2, 5, 22, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Pushpala (US 2014/0275897) in view of Feldman (US 20090259118), Connolly (US 2012/0190956), and Wang (US 2017/0325724). Simpson (US 2005/0161346) is relied on as an evidentiary reference.
Regarding claim 1 (see interpretation under the 112b rejections above), Pushpala teaches a method of modifying the external surfaces of at least two solid microneedles to be arranged in a wearable patch (Figs. 1A-1B) configured for ion and/or molecule on-body transdermal sensing (“the microsensor 100 is configured to penetrate the user's stratum corneum (e.g., an outer skin layer) in order to sense analytes characterizing the user's body chemistry in the user's interstitial (extracellular) fluid,” par. 20), the method comprises:
providing at least one microneedle configured to function as a working electrode for ion sensing or (bio)molecule sensing (filament 120; “one protrusion as a substrate core for a filament 120,” par. 27), coating said at least one microneedle configured as the working electrode with a coating to improve conductivity of the microneedle configured as the working electrode (“conductive layer 140 can include…any other suitable conductive or semiconducting material,” par. 28), and attaching the at least one microneedle to said patch (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate,” par. 27);
providing at least one microneedle configured to function as a reference electrode for ion sensing or as a pseudoreference electrode for (bio)molecule sensing (another one of the filaments 120, Fig. 2A; “a filament 120 serving as a reference electrode,” par. 44), coating said at least one microneedle configured as the reference electrode or the pseudoreference electrode with a layer to improve the conductivity of the microneedle (conductive layer 140) and additionally serving as a reference electrode or pseudoreference electrode (“metalizing the filament substrate by sputtering a layer of any appropriate conductive material (e.g., gold, platinum, doped silicon, nickel, silver,” par. 51; “sensing layer 160 can additionally or alternatively be composed of any appropriate conductive material (e.g., sulfur-containing polythiophenes, silver chloride, etc.)…further, the sensing layer 160 serves as a reference electrode,” par 30), and attaching the at least one microneedle toa polymeric substrate of the patch (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate…The substrate 130 can be composed of…an insulating or non-conductive material (e.g., glass, ceramic, polymer, etc.),” par. 27);
coating the reference electrode or the pseudoreference electrode film with an external polymeric film, wherein said external polymeric film is a polyurethane film (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E; “the adhesion coating 180 is composed of any one or more of: a polyurethane,” par. 34; “Any filament 120 of the microsensor 100 can further comprise any other appropriate functional layer or coating…biocompatible layer 185 can include a polymer (e.g., urethane, parylene, teflon, fluorinated polymer, etc.),” par. 25);
the method further including one of the following:
coating said working electrode for ion sensing by coating the coating to improve the conductivity with a ion-to-electron transducer layer (“sensing layer 160 functions to enable transduction of an ionic concentration to an electronic voltage,” par. 30; par. 68), and coating the ion-to-electron transducer layer with an ion-selective membrane (“selective coating 170 comprises at least one complementary molecule 171 (e.g., ionophore…distributed within a polymer matrix 172,” par. 31), and coating said reference electrode for ion sensing by coating the coating to improve the conductivity with a reference membrane film (“the sensing layer 160…can further comprise a controlled ion coating…that functions to form a portion of a reference electrode for ion concentration measurements,” par. 30), and coating the reference membrane film with said external polymeric film (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E); or
coating said working electrode for (bio)molecule sensing by coating the coating to improve the conductivity (conductive layer 140) with a mediator layer (“the concentration of the mediator species can be amperometrically detected via oxidation or reduction at a surface of the conductive layer 140 or the sensing layer 160… molecular or other species (e.g., iron hexacyanoferrate) serve as a layer of transduction,” par. 32), and coating the mediator layer with an enzyme film (“the selective coating 170 can be replaced by or may further comprise a layer of immobilized enzyme,” par. 32), and coating the enzyme layer with an additional external film for different purposes (“the layer of immobilized enzymes can be covered by one or more membranes, which functions to control the diffusion rate and/or concentrations of analyte…can also function to provide mechanical stability,” par. 33), and coating said pseudoreference electrode for (bio)molecule sensing by coating the coating to improve the conductivity with said external polymeric film (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E).
Pushpala teaches all limitations of Claim 1 except for the reference electrode comprising an Ag/AgCl layer as the conductive layer, the Ag/AgCl layer comprising an ink that is cured in an oven. Pushpala teaches any conductive material may be used and suggests silver or silver chloride (“conductive layer 140 can include…any other suitable conductive or semiconducting material,” par. 28; “sensing layer 160 can additionally or alternatively be composed of any appropriate conductive material (e.g.,…silver chloride, etc.),” par 30; “metalizing the filament substrate by sputtering a layer of any appropriate conductive material (e.g., gold, platinum, doped silicon, nickel, silver,” par. 51). Feldman teaches an analogous microneedle array (Fig. 8A) comprising a reference electrode made using Ag/AgCl (“reference electrode 806 may be constructed of Ag/AgCl,” par. 71; Fig. 8A).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala by creating conductive layer 140 out of Ag/AgCl, as taught by Feldman. Since Pushpala suggests that any other suitable conductive material may be used (par. 28), one would be motivated to use other known conductive materials for reference electrodes, and Ag/AgCl is one such material. The substitution of one known reference electrode material for another should yield predictable results.
Regarding the Ag/AgCl ink and curing the ink in an oven, Connolly teaches an analogous microelectrode for in vivo sensing (“a wound sensor comprising at least one electrode,” Abstract; “the electrodes 10a, 10b take the form of microelectrodes,” par. 76). Connolly teaches that an Ag/AgCl electrode can be formed using an Ag/AgCl ink, which is then heated at 80°C (“the silver/silver chloride ink patterns in the shape of the electrodes 10a, 10b, is then heated at 80°C for 30 minutes in order to cure the ink and form the electrodes 10a, 10b,” par. 88). Wang teaches an analogous sensor device comprising a reference electrode printed from Ag/AgCl ink and cured in an oven (“pseudo reference, and counter electrodes patterned from Ag/AgCl ink…Each printed layer was cured in oven after printing. The Ag/AgCl ink was cured at 90° C. for 10 min,” par. 164).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala in view of Feldman by creating the Ag/AgCl layer of the reference or pseudoreference electrode by applying Ag/AgCl ink on the microneedle and curing the ink in an oven. Since Feldman merely teaches “the reference electrode 806 may be constructed of Ag/AgCl or other suitable material” (par. 71) without explicitly teaching the method of construction, one would be motivated to use known methods of constructing an Ag/AgCl electrode such as using Ag/AgCl ink that is then cured, as taught by Connolly and Wang. As this method was already known in the art of in vivo sensors, such a modification could be carried out with a reasonable expectation of success. Thus, Pushpala in view of Feldman, Wang, and Connolly teaches or suggests all limitations of claim 1.
Regarding claim 2, Pushpala does not teach a microneedle configured to function as a pseudocounter electrode. Feldman further teaches providing at least one microneedle configured to function as a pseudocounter electrode (counter electrode 807), coating said at least one microneedle with a carbon layer (“counter electrode (C) 213 may be made using a conductive material…Materials include….carbon,” par. 43).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala by creating a counter electrode with a carbon layer, as taught by Feldman. Since Pushpala teaches amperometric detection, one may be further motivated to provide a counter electrode to support a more stable amperometric measurement, which is found in conventional amperometric sensing systems, as evidenced by Feldman and Simpson (“Conventionally…the bias potential Vbias) applied between the working and reference electrodes is set at a constant value…The counter electrode acts as a negative feedback circuit to maintain the desired voltage at the reference electrode,” Simpson par. 46).
Furthermore, Pushpala, Feldman, Wang, and Connolly in combination would teach that the carbon pseudocounter electrode would be coated with a coating to improve the conductivity of the microneedle and providing a constant long-term electrochemical potential (Pushpala’s conductive layer 140; “The counter electrode acts as a negative feedback circuit to maintain the desired voltage at the reference electrode,” Simpson par. 46) attached to the same substrate (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate,” Pushpala par. 27) and coating the coating to improve the conductivity with an external polymeric film, being a polyurethane film (“the adhesion coating 180 is composed of any one or more of: a polyurethane,” Pushpala par. 34; “Any filament 120 of the microsensor 100 can further comprise any other appropriate functional layer or coating…biocompatible layer 185 can include a polymer (e.g., urethane, parylene, teflon, fluorinated polymer, etc.),” Pushpala par. 25).
Regarding claim 5, Pushpala further teaches a wearable patch configured for ion and/or (bio)molecule on-body transdermal sensing (microsensor 100, Fig. 1A), comprising at least two microneedles modified according to claim 1 (see rejection of claim 1 above), wherein the patch is configured to be applied for any electrochemical technique and for any analyte (“The microsensor 100 can be configured to sense analytes/ions characterizing a user's body chemistry using a potentiometric measurement (e.g., for analytes including potassium, sodium calcium, alcohol, cortisol, hormones, etc.), using an amperometric measurement (e.g., for analytes including glucose, lactic acid, creatinine, etc.), using a conductometric measurement, or using any other suitable measurement.,” par. 137), and wherein the patch is configured to be connected to a device adapted to process sensed electrochemical values (electronics module 115, Fig. 1B; “sensed analytes result in a signal (e.g., voltage, current, resistance, capacitance, impedance, gravimetric, etc.) detectable by the electronics module 115,” par. 21).
Regarding claim 22, Pushpala teaches pairs of reference and working electrodes or pairs of pseudoreference and working electrodes of different dimensions to reach two different biological fluids (“the microsensor 100 is configured to…sense analytes characterizing the user's body chemistry in the user's interstitial (extracellular) fluid; however, the microsensor 100 can alternatively be configured to penetrate deeper layers of a user's skin in order to sense analytes within…the user's blood,” par. 20; “Having filaments 120 of different lengths can additionally or alternatively function to allow measurement of different ions/analytes at different depths of penetration,” par. 23). Pushpala also teaches each filament can be paired with a reference electrode filament (“Each filament 120 in the array of filaments 110…can be paired with a filament 120 serving as a reference electrode configured to normalize a signal detected in response to analyte sensing,” par. 44).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala in view of Feldman, Wang, and Connolly to comprise different pairs of filaments at different lengths to measure in both blood and interstitial fluid. One would be motivated to do so because Pushpala suggests measuring at different depths with filaments of different lengths and measuring in both blood and interstitial fluid (pars. 20, 23)
Regarding claim 24 (see interpretation under the 112(b) rejection above), Pushpala teaches an original diameter of the microneedle is as much as 100 µm in total (“an array of columnar protrusions S211b at the first surface of the substrate…width (e.g., 75-200 µm),” par. 46).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Pushpala in view of Feldman, Wang, and Connolly, as applied to claim 22 above, and further in view of Sjöstedt (WO 2019/121324).
Regarding claim 23, Pushpala teaches one pair of reference and working electrodes, or one pair of pseudoreference and working electrodes, has a length of less than 1000 µm (“a filament 120 in the array of filaments 120 can have a length from 0-1000 [µm],” par. 23). Pushpala doesn’t explicitly teach another pair of reference and working electrodes, or another pair of pseudoreference and working electrodes, has a length higher than 1500 µm, but does teach that longer filaments may be used to sense in blood (“microsensor 100 can alternatively be configured to penetrate deeper layers of a user's skin in order to sense analytes within…the user's blood,” par. 20).
Sjöstedt teaches an analogous skin patch comprising microneedles (Fig. 1). Sjöstedt teaches that for sampling of blood may require longer microneedles and the length of the microneedles may be from 50-3000 µm (pg. 6, lines 13-16).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala in view of Feldman, Wang, and Connolly to comprise a pair of filaments with length longer than 1500 microns to measure in blood. One would be motivated to do so because Pushpala suggests measuring at different depths with filaments of different lengths and measuring in both blood and interstitial fluid (“microsensor 100 can alternatively be configured to penetrate deeper layers of a user's skin in order to sense analytes within…the user's blood,” par. 20; “Having filaments 120 of different lengths can additionally or alternatively function to allow measurement of different ions/analytes at different depths of penetration,” par. 23). Sjöstedt teaches sampling blood requires longer microneedles, thus one may further be motivated to use microneedles at the longer end of the range of 50-3000 µm in order to sense blood analytes (pg. 6, lines 13-16).
Claims 11-12 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Pushpala (US 2014/0275897) in view of Feldman (US 20090259118).
Regarding claim 11 (see interpretation under the 112b rejection above), Pushpala teaches a method of modifying the external surfaces of at least two solid microneedles to be arranged in a wearable patch (Figs. 1A-1B) configured for potentiometric detection of ions through on-body transdermal and painless sensing in interstitial fluid and/or blood (“the microsensor 100 is configured to…sense analytes characterizing the user's body chemistry in the user's interstitial (extracellular) fluid… using a potentiometric measurement,” par. 20), wherein the method comprises:
providing at least one microneedle chemically and/or physically configured to function as a working electrode selective for one ion (filament 120; “one protrusion as a substrate core for a filament 120,” par. 27), attaching the at least one microneedle configured to function as the working electrode to a polymeric substrate (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate…The substrate 130 can be composed of…an insulating or non-conductive material (e.g., glass, ceramic, polymer, etc.),” par. 27) and covering the (micro)needle- substrate architecture for the working electrode for ion detection with a polymer-based coating for ion detection (sensing layer 160 or selective layer 170), sealing and avoiding detachment before, during and after skin penetration as well as providing biocompatibility (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E; “adhesion coating 180 can further function to bond the layers, coatings, and/or substrates, and can prevent delamination between the layers, coatings, and/or substrates…preferably maintains contact between layers, coatings, and/or substrates of the filament 120 over the lifetime usage of the microsensor 100,” par. 34), and
providing at least one microneedle configured to function as a reference electrode (another one of the filaments 120, Fig. 2A), coating said at least one microneedle configured to function as the reference electrode with a conductive layer (“conductive layer 140 can include…any other suitable conductive or semiconducting material,” par. 28), depositing a reference membrane (“the sensing layer 160…can further comprise a controlled ion coating…that functions to form a portion of a reference electrode for ion concentration measurements,” par. 30), attaching the at least one microneedle configured to function as the reference electrode to the same substrate of said working electrode (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate,” par. 27) and covering the (micro)needle-substrate architecture for the reference electrode with a polymer-based coating for sealing and avoiding detachment before, during and after skin penetration as well as providing biocompatibility (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E),
wherein the method of preparing said working electrode for ion sensing comprises coating the microneedle (conductive layer 140) and adding next the ion-to-electron transducer layer by either a chemical or physical procedure (“sensing layer 160 functions to enable transduction of an ionic concentration to an electronic voltage,” par. 30; par. 68), and adding then an ion-selective membrane by chemical and/or physical immobilization of each component being a polymeric core, an ion-exchanger and an ionophore (“selective coating 170 comprises at least one complementary molecule 171 (e.g., ionophore…distributed within a polymer matrix 172,” par. 31; exemplary polymer matrix, ion-exchanger, and ionophores disclosed in par. 31 – for example, the polymer core is PVC, the ion-exchanger is potassium tetrakis, and the ionophore is valinomycin).
Pushpala teaches all limitations of Claim 11 except for the reference electrode comprising an Ag/AgCl layer. Pushpala teaches any conductive material may be used (“conductive layer 140 can include…any other suitable conductive or semiconducting material,” par. 28). Feldman teaches an analogous microneedle array (Fig. 8A) comprising a reference electrode made using Ag/AgCl (“reference electrode 806 may be constructed of Ag/AgCl,” par. 71; Fig. 8A).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala by creating conductive layer 140 out of Ag/AgCl, as taught by Feldman. Since Pushpala suggests that any other suitable conductive material may be used (par. 28), one would be motivated to use other known conductive materials for reference electrodes, and Ag/AgCl is one such material. The substitution of one known reference electrode material for another should yield predictable results.
Regarding claim 12, Pushpala teaches a method of modifying the external surfaces of at least three solid microneedles to be arranged in a wearable patch (Figs. 1A-1B) configured for amperometric detection of (bio)molecules through on-body transdermal and painless sensing in interstitial fluid and/or blood (“the microsensor 100 is configured to penetrate the user's stratum corneum (e.g., an outer skin layer) in order to sense analytes characterizing the user's body chemistry in the user's interstitial (extracellular) fluid…using an amperometric measurement,” par. 20), wherein the method comprises:
providing at least one microneedle chemically and/or physically configured to function as a working electrode selective for one (bio)molecule (filament 120; “one protrusion as a substrate core for a filament 120,” par. 27), attaching the at least one microneedle to a polymeric substrate (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate…The substrate 130 can be composed of…an insulating or non-conductive material (e.g., glass, ceramic, polymer, etc.),” par. 27) and covering the (micro)needle-substrate architecture for the working electrode for (bio)molecule detection with a polymer-based coating for sealing and avoiding detachment before, during and after skin penetration as well as providing biocompatibility (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E; “adhesion coating 180 can further function to bond the layers, coatings, and/or substrates, and can prevent delamination between the layers, coatings, and/or substrates…preferably maintains contact between layers, coatings, and/or substrates of the filament 120 over the lifetime usage of the microsensor 100,” par. 34), and
providing at least one microneedle configured to function as a pseudoreference electrode (another one of the filaments 120, Fig. 2A), coating said at least one microneedle with an AgCl layer (“sensing layer 160 can additionally or alternatively be composed of any appropriate conductive material (e.g.,…silver chloride, etc.…the sensing layer 160 serves as a reference electrode ,” par. 30), attaching the at least one microneedle to the same substrate of said working electrode for (bio)molecule (“substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate,” par. 27) and covering the (micro)needle-substrate architecture for the pseudoreference electrode with a polymer-based coating for sealing and avoiding detachment before, during and after skin penetration as well as providing biocompatibility (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E).
wherein the method of preparing said working electrode for (bio)molecule sensing comprises coating the microneedle to improve the conductivity or a direct modification of the microneedle depending on the former material (conductive layer 140), and adding next a redox mediator layer by either a chemical or physical procedure (“the concentration of the mediator species can be amperometrically detected via oxidation or reduction at a surface of the conductive layer 140 or the sensing layer 160…In a variation of this example, the conducting surface may alternatively not be held at an electric potential, for instance, in cases wherein molecular or other species (e.g., iron hexacyanoferrate) serve as a layer of transduction,” par. 32), and immobilizing then different enzymes by either a chemical or physical procedure (“the selective coating 170 can be replaced by or may further comprise a layer of immobilized enzyme,” par. 32), and selecting an external polymeric layer according to different functions to control the analytical performance of the (bio)molecule sensor (“in variations of the sensing layer including a layer of immobilized enzymes, the layer of immobilized enzymes can be covered by one or more membranes, which functions to control the diffusion rate and/or concentrations of analyte…can also function to provide mechanical stability,” par. 33).
Pushpala teaches all limitations of Claim 12 except for the reference electrode comprising an Ag/AgCl layer and a microneedle configured to function as a pseudocounter electrode. Pushpala already teaches using AgCl as a reference electrode and further teaches any conductive material may be used (“conductive layer 140 can include…any other suitable conductive or semiconducting material,” par. 28). Feldman teaches an analogous microneedle array (Fig. 8A) comprising a reference electrode made using Ag/AgCl (“reference electrode 806 may be constructed of Ag/AgCl,” par. 71; Fig. 8A). Feldman further teaches providing at least one microneedle configured to function as a pseudocounter electrode (counter electrode 807), coating said at least one microneedle with a carbon layer (“counter electrode (C) 213 may be made using a conductive material…Materials include….carbon,” par. 43).
It would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Pushpala by creating conductive layer 140 out of Ag/AgCl to create the reference electrode and comprise a counter electrode with a carbon layer, as taught by Feldman. Since Pushpala suggests that any other suitable conductive material may be used (par. 28), one would be motivated to use other known conductive materials for reference electrodes, and Ag/AgCl is one such material. The substitution of one known reference electrode material for another should yield predictable results. Furthermore, since Pushpala teaches amperometric detection, one may be further motivated to provide a counter electrode to support a more stable amperometric measurement, which is found in conventional amperometric sensing systems, as evidenced by Feldman and Simpson (“Conventionally…the bias potential Vbias) applied between the working and reference electrodes is set at a constant value…The counter electrode acts as a negative feedback circuit to maintain the desired voltage at the reference electrode,” Simpson par. 46).
Furthermore, Pushpala and Feldman in combination would teach that the carbon pseudocounter electrode would be attached to the same substrate (Pushpala Fig. 1A; “substrate 130 can be coupled to a protrusion (e.g., as a piece separate from the substrate,” par. 27) and covering the substrate and microneedles with the polymer-based coating for sealing and avoiding detachment before, during and after skin penetration as well as providing biocompatibility (biocompatible layer 185 and/or adhesion coating 180, Fig. 2E).
Regarding claim 25, Pushpala teaches the polymer for coating the pseudoreference electrode is polyurethane (“the adhesion coating 180 is composed of any one or more of: a polyurethane,” par. 34; “Any filament 120 of the microsensor 100 can further comprise any other appropriate functional layer or coating…biocompatible layer 185 can include a polymer (e.g., urethane, parylene, teflon, fluorinated polymer, etc.),” par. 25).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ALICE L ZOU whose telephone number is (571)272-2202. The examiner can normally be reached Monday-Friday 9-6 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert (Tse) Chen can be reached at (571) 272-3672. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALICE LING ZOU/Examiner, Art Unit 3791 /TSE W CHEN/Supervisory Patent Examiner, Art Unit 3791