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 .
Applicant' s arguments, filed 4/16/2026, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Applicants have amended their claims, filed 4/16/2026.
Claims 1-3, 5-6, 8-9, 17, 20, 22, 24, 26, 28, 31, 35, 38, and 55 are the current claims hereby under examination, with claim 57 having been canceled.
Objections
Claims 20, 28, and 35 are objected to because of the following informalities:
In claim 20, lines 1-2: “at least some of microstructures” should be “at least some of the microstructures”;
In claim 28, line 22, “at least some of the microstructures at least one of” is missing a predicate and should be amended, for example, to recite “at least some of the microstructures are configured to perform at least one of the following,” although the precise correction should reflect Applicant’s intended scope; and
In claim 35, lines 1-2: “wherein the coating at least one of” is missing a predicate, such as “wherein the coating is configured to at least one of”, although the precise correction should reflect Applicant’s intended grammar.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 55 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 55 recites “wherein the one or more sensors are connected to different groups of plate microstructures” (lines 1-2), but neither claim 55 nor claim 1 previously introduces “one or more sensors.” Claim 1 recites electrodes, electrical connections, electrical response signals, and plate microstructures, but does not identify any component as a sensor. It is therefore unclear whether “the one or more sensors” refers to the electrodes on the plate microstructures, external sensing or recording circuitry, components connected to the conductive tracks, or some other unrecited structure. The Examiner interprets “the one or more sensors” as one or more sensing or recording components configured to measure electrical response signals received through the plate microstructures for purposes of examination.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 5-6, 8-9, 17, 20, 22, 24, 26, 28, 31, 35, and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 9, 11-12, and 14 of U.S. Patent No. US12048558B2, hereinafter referred to as Reference 1, and in view of Gill et al. (US 20140170299 A1), hereinafter referred to as Gill, and further in view of Negi et al. (US 20170007813 A1), hereinafter referred to as Negi.
The analysis as follows (please note the bolded and underlined portions of the entries under the Instant Application, IA, are those portions of the IA claims that the claims of Patent US12048558B2, Reference 1, does not have or are different from in some form):
Claim Element (Instant Application, IA)
Reference 1 (US12048558B2)
Analysis
Claim 1: An electrode arrangement for use with a system for performing measurements on a biological subject, the electrode arrangement including:
a) a substrate; and
b) a plurality of plate microstructures extending from a surface of the substrate,
the plurality of plate microstructures being configured to breach the stratum corneum of the biological subject
and wherein each of the plurality of plate microstructures include a substantially planar face having an electrode thereon
to allow electrical stimulatory signals to be applied to and electrical response signals to be received from the biological subject via the plurality of plate microstructures,
wherein each of the plurality of plate microstructures includes a conductive material, wherein the electrode of each of the plurality of plate microstructures is defined, at least in part, by an insulating coating extending over only a part of a surface of the microstructure, so that an uncoated part of the microstructure acts as the electrode,
wherein at least some of the plurality of plate microstructures are arranged in groups,
wherein each group is a pair of spaced apart microstructures having electrodes in opposition, and wherein at least some of the electrical stimulatory signals are applied between microstructures in the pair;
wherein the substrate includes electrical connections to allow the electrical stimulatory signals to be applied to, and the electrical response signals received from, respective plate microstructures in the pair;
Claim 1: “A system for performing fluid level measurements on a biological subject, the system including:”
Claim 1, Element (a): “at least one substrate”
Claim 1, Element (a): “a plurality of microstructures”
Claim 1, Element (a): “microstructures configured to breach a stratum corneum of the biological subject”
Claim 1, Element (a): “at least some microstructures including an electrode...”
Claim 1, Element (c): “a signal generator operatively connected... to apply an electrical stimulatory signal”
Claim 1, Element (b): “at least one sensor... configured to measure electrical response signals between microstructures”
Claim 1, Element (a): “microstructures are conductive”
Claim 1, Element (a): “include an insulating layer extending over an end of the microstructure proximate the substrate so that at least a tip portion of the microstructure is uncoated and acts as the electrode”
Claim 2, Element (b, c, d, e): “pairs of microstructures are orthogonally arranged... arranged in rows... orthogonally arranged relative to pairs...”
Claim 1, Element (b): “wherein microstructures in the at least one microstructure pair each have respective electrodes in opposition from one microstructure and another microstructure, and wherein the electrical stimulatory signal generates an electric field between the respective electrodes”
Both the IA and Reference 1 describe a system for use with a biological subject, but the IA focuses on an electrode arrangement, while Reference 1 focuses on a broader system.
Both the IA and Reference 1 mention a substrate and microstructures extending from the substrate.
IA specifies “plate” microstructures, whereas Reference 1 does not include this detail. However, Gill, who investigates a similar art of making coated microstructures that can be adapted with biosensors including electrodes, has microstructures that have a plate form (Gill, FIG. 3D). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reference 1 in view of Gill to specify that the microstructures are plate microstructures. As shown in Gill, the planar microstructures can be cut from a metal sheet using a laser (Gill, ¶[0051]), which has the benefit of a fast and easy manufacturing process.
Both claims describe microstructures configured to breach the stratum corneum, showing similar functionality.
Both claims discuss electrodes associated with microstructures and signal application/measurement. Reference 1 includes additional details regarding the signal generator and sensor for applying and measuring signals, whereas the IA recites electrodes that allow electrical stimulatory signals and electrical response signals.
Both claims disclose conductive microstructures having an insulating layer that leaves an uncoated electrode portion.
Both claims discuss grouping electrodes into pairs that are in opposition such that signals are applied between the paired microstructures.
IA specifies “the substrate includes electrical connections”, whereas Reference 1 does not include this detail. However, Negi teaches lead lines extending from electrically active sites on the microneedles down to the surface of the substrate and across the substrate to base contacts, through which electrical signals travel, and further teaches that the active sites can be used for neural recording and stimulation (Negi, ¶[0047], ¶[0059]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reference 1 in view of Negi to provide electrical connections on the substrate for applying stimulatory signals to, and receiving response signals from, respective microstructures in the pair.
and wherein the electrical connections are conductive tracks provided on the surface of the substrate; an insulating layer is provided on the surface of the substrate to cover the conductive tracks, so that the conductive tracks do not make electrical contact with skin of the biological subject;
IA specifies “electrical connections” are “tracks” located on the surface of the substrate and covered by an insulating layer to electrically insulate against the skin, whereas Reference 1 does not include this detail. Negi teaches that conductive traces run along the microneedles and across the surface of the substrate, and that an insulating coating is applied over those traces such that the traces are covered and not exposed to the environment (Negi, FIGS. 10H-10I, ¶[0062]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reference 1 in view of Negi to provide the electrical connections as traces on the surface of the substrate covered by insulation so that the traces do not make electrical contact with the subject’s skin.
and the electrical connections include multiple stimulation and response connections allowing different measurements to be performed via different electrical connections.
IA specifies “multiple stimulation and response connections allowing different measurements to be performed via different electrical connections”, whereas Reference 1 does not include this detail. Negi teaches multiple electrically active sites that are independently addressable, connected by respective lead lines to base contacts, and usable for both neural recording and stimulation; Negi further teaches simultaneous recording from multiple tissue locations and simultaneous oxygen measurement and electrical recording (Negi, ¶[0034], ¶[0042]-¶[0047], ¶[0057]-¶[0059]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Reference 1 in view of Negi to provide multiple stimulation and response connections so that different measurements can be performed via different independently addressable electrical connections. This would have enabled selective stimulation and simultaneous or sequential measurements from different sites, thereby improving spatial resolution and measurement versatility.
Claim 3: "An electrode arrangement according to claim 1, wherein the insulating coating extending over at least one of:
(a) a proximal end of the microstructure;
(b) at least half of a length of the microstructure;
(c) 60 μm, 90 μm or 150 μm of a proximal end of the microstructure; and
(e) at least part of a tip portion of the microstructure."
Claim 1, Element (a): "microstructures are conductive and include an insulating layer extending over an end of the microstructure"
Claim 11: “A system according to claim 1, the insulating layer extending over at least one of:
b) about 90 μm of a proximal end of the microstructure; and,
a) at least half of a length of the microstructure;
b) about 90 μm of a proximal end of the microstructure; and,
c) at least part of a tip portion of the microstructure.”
Both the IA and the combination of Reference 1 and Gill mention conductive microstructures with an insulation extending over a portion of the microstructure.
The IA states the insulation is a coating, while Reference 1 uses the language of “layer”. However, the specification of Reference 1 indicates that the word layer is synonymous with coating as it states “this allows the blade to be partially covered with an insulative coating” (Reference 1, ¶[0328]).
Claim 3 of the IA provides a combination of limitations. Where the IA provides additional optional limitations regarding insulation locations as indicated. However, Reference 1 only needs to teach one of these limitation options, to which claim 11 of Reference 1 includes some of those options.
Claim 5: "An electrode arrangement according to claim 1, wherein
the electrical response signals are measured between the microstructures in the group"
Claim 1, Element (b): “the at least one microstructure pair”
Claim 1, Element (c): "at least one sensor...configured to measure electrical response signals between microstructures in the pair"
Both IA and the combination of Reference 1 and Gill mention applying electrical stimulation signals and measuring response signals between microstructures with the language differing between “arranged in groups” vs “pairs”, and groups at least include a pair.
Claim 6: "An electrode arrangement according to claim 5, wherein one of:
(a) the group is the pair of the microstructures including spaced apart plate microstructures having planar electrodes in opposition; and
(b) the group is a pair of the microstructures including spaced apart plate microstructures having planar electrodes in opposition and at least one of: (i) at least some pairs of the microstructures are angularly offset;
(ii) at least some pairs of the microstructures are orthogonally arranged;
(iii) adjacent pairs of the microstructures are orthogonally arranged;
(iv) pairs the of microstructures are arranged in rows, and the pairs of microstructures in one row are angularly offset relative to pairs of microstructures in other rows;
(v) pairs of the microstructures are arranged in rows, and the pairs of the microstructures in one row are orthogonally arranged relative to pairs of the microstructures in other rows."
see above, IA claim 5 vs Reference 1 Claim 1
Claim 1, Element (b): “microstructures in the at least one microstructure pair each have respective electrodes in opposition from one microstructure and another microstructure”
Claim 2:
“a) at least some pairs of microstructures are angularly offset;
b) at least some pairs of microstructures are orthogonally arranged;
c)adjacent pairs of microstructures are orthogonally arranged;
d) pairs of microstructures are arranged in rows, and the pairs of microstructures in one row are angularly offset relative to pairs of microstructures in other rows;
e) pairs of microstructures are arranged in rows, and the pairs of microstructures in one row are orthogonally arranged relative to pairs of microstructures in other rows.”
Both the IA and the combination of the modified Ref 1 Reference 1 and Gill have electrodes in opposition with corresponding limitations.
Claim 8: “An electrode arrangement according to claim 1, wherein at least one of:
a) a spacing between the electrodes in each group are at least one of: i) less than 10 mm; ii) less than 1 mm; iii) 0.1 mm; and, iv) more than 10 µm; and
b) a spacing between groups of microstructures is at least one of: i) less than 50 mm; ii) more than 20 mm; iii) less than 20 mm; iv) less than 10 mm; v) more than 10 mm; vi) less than 1 mm; vii) more than 1 mm; viii) 0.5 mm; and, ix) more than 0.2 mm.”
Claim 3: “A system according to claim 1, wherein:
a) a spacing between the plurality of microstructures is at least one of: i) less than 1 mm; ii) about 0.5 mm; iii) about 0.2 mm; iv) about 0.1 mm; and, v) more than 10 μm; and,
b) a spacing between pairs of microstructures is at least one of: i) less than 1 mm; ii) about 0.5 mm; and, iii) more than 0.2 mm.”
Both IA and the combination of modified Reference 1 and Gill as shown in the sections for the IA claims 1 and, as well as claim 3 of the Reference 1
Where according to Claim 1 of the Reference 1, the microstructures contain electrodes, thus the spacing of the microstructures is also the spacing of the electrodes. The IA has an extra optional electrode spacing of “less than 10 mm”.
There is also a difference in language between “groups” and “pairs”, where groups at least include a pair.
Claim 8 of the IA provides a combination of optional electrode/microstructure spacings as limitations with more options as indicated. However, the modified Reference 1 only needs to teach one, to which claim 3 of Reference 1 includes some of those options.
Claim 9: "An electrode arrangement according to claim 1, wherein at least one of:
(a) the electrodes are configured to be operatively connected to at least one of: (i) at least one sensor operatively configured to measure electrical response signals from at least one of the microstructures; and, (ii) a signal generator configured to apply an electrical stimulatory signals to the at least one of the microstructures; and
(b) the electrodes are configured to be connected to one or more switches for selectively connecting at least one of the at least one sensor and the at least one signal generator to the electrodes."
Claim 1, Element (c): “microstructures including an electrode”
Claim 1, Element (c): "at least one sensor operatively connected to the at least one microstructure pair, the at least one sensor being configured to measure electrical response signals";
Claim 1, Element (c): "a signal generator operatively connected...to apply an electrical stimulatory signal";
Claim 9: "one or more switches for selectively connecting at least one sensor and signal generator to the microstructures"
Both IA and the combination of the modified Reference 1 and Gill describe connections for applying and measuring signals through electrodes and sensors. The Reference 1 also mentions the use of switches, similar to the IA.
Claim 17: "A system according to claim 1, wherein at least some of the microstructures include at least one of:
(a) a shoulder that is configured to abut against the stratum corneum to control a depth of penetration; and
(b) a shaft extending from the shoulder to a tip, the shaft being configured to control a position of the tip in the subject."
Claim 1, Element (a): "wherein at least some of the microstructures include a shoulder that is configured to abut against the stratum corneum to control a depth of penetration"
Claim 6, Element (a): “a shaft extending from a shoulder to the tip, the shaft being configured to control a position of the tip in the subject”
Both IA and the combination of the modified Reference 1 and Gill mention a shoulder feature on the microstructures to control penetration depth. Both also mentions a shaft extending from the shoulder.
Claim 20: "An electrode arrangement according to claim 1, wherein at least some of microstructures include at least part of an active sensor."
Claim 1, Element (c): "at least one sensor operatively connected"
Both IA and the combination of the modified Reference 1 and Gill mention a sensor associated with the microstructures. However, IA specifies an "active sensor," which implies functionality beyond what is explicitly described in Reference 1. However, Gill describes both passive and active sensors as potentially being part of the microstructures, where “heat, electricity, light or other energy forms may be precisely transmitted to directly stimulate, damage, or heal a specific tissue or for diagnostic purposes”, showing the sensors to be active sensors (Gill, ¶[0114]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Reference 1 in view of Gill to specify that the sensor may be an active sensor. As previously stated, this has the benefits of being able to “directly stimulate, damage, or heal a specific tissue or for diagnostic purposes” (Gill, ¶[0114]).
Claim 22: "A system according to claim 1, wherein the plurality of electrodes at least one of:
(a) extends over a length of a distal portion of the microstructure;
(b) extends over a length of a portion of the microstructure spaced from a tip;
(c) is positioned proximate an end of the microstructure;
(d) is positioned proximate the tip of the microstructure;
(e) extends over at least 25% of a length of the microstructure;
(f) extends over less than 50% of a length of the microstructure;
(g) extends over 60 µm, 90 µm or 150 µm of the microstructure;
(h) is configured to be positioned in a viable epidermis of the subject in use; and
(i) has a surface area of at least one of: i) less than 200,000 μm2; ii) about 22,500 μm2; iii) at least 10 mm2; iv) at least 1 mm2; v) at least 100,000 μm2; vi) at least 10,000 μm2; vii) at least 7,500 μm2; viii) at least 5,000 μm2; ix) at least 2,000 μm2; x) at least 1,000 μm2; xi) at least 500 μm2; xii) at least 100 μm2; and xiii) at least 10 μm2."
Claim 12: "A system according to claim 1, wherein at least one planar electrode has at least one of:
b) extends over a length of a distal portion of the microstructure;
c) extends over a length of a portion of the microstructure spaced from the tip;
d) is positioned proximate a distal end of the microstructure;
e) is positioned proximate a tip of the microstructure;
f) extends over at least 25% of a length of the microstructure;
g) extends over less than 50% of a length of the microstructure;
h) extends over about 60 μm of the microstructure; and,
i) is configured to be positioned in a viable epidermis of the subject in use.
a) has a surface area of at least one of: i) less than 200,000 μm.2; ii) about 22,500 μm; iii) at least 2,000 μm;
Where electrodes of both are described as either planer or being part of a planar structure.
Both IA and the combination of the modified Reference 1 and Gill describe the positioning and surface area of electrodes. Claim 3 of the IA provides a combination of limitations. Where the IA provides more details on the specific positioning and extent of coverage in optional elements (c), (g), and (i) as shown. However, the modified Reference 1 only needs to teach one of these limitation options, to which claim 11 of Reference 1 includes some of those options.
Claim 24: "An electrode arrangement according to claim 1, wherein the plurality of electrodes at least one of:
(a) has a width that is at least one of:
i) less than 50000 μm;
ii) less than 40000 μm;
iii) less than 30000 μm;
iv) less than 20000 μm;
v) less than 10000 μm;
vi) less than 1000 μm;
vii) at least 500 μm;
viii) at least 200 μm;
ix) at least 100 μm;
x) at least 75 μm;
xi) at least 50 μm;
xii) at least 20 μm;
xiii) at least 10 μm; and
xiv) at least 1 μm;
(b) has a height that is at least one of:
i) up to 2500 μm
ii) at least 500 μm;
iii) at least 200 μm;
iv) at least 100 μm;
v) at least 75 μm;
vi) at least 50 μm;
vii) at least 20 μm;
viii) at least 10 μm; and,
ix) at least 1 μm."
Claim 4: A system according to claim 1…wherein at least some of the plurality of microstructures at least one of:
c) have a maximum width that is at least one of:
i) about the same order of magnitude to the length;
ii) greater than the length;
iii) about the same as the length;
iv) less than 300 μm;
v) about 150 μm; and,
vi) greater than 50 μm; and,
b) have a length that is at least one of:
i) less than 300 μm;
ii) about 150 μm;
iii) greater than 100 μm; and,
iv) greater than 50 μm;
Where the microstructure acts as an electrode according to claim 1 of the modified Reference 1.
The term maximum in modified Reference 1 does not alter the limitations in a meaningful way as compared to the IA.
Both the IA and the combination of the modified Reference 1 and Gill have optional width limitations covering an infinite range, and thus cover the same structural dimensions.
The modified Reference 1 optional height/length (height/ length are used interchangeably) limitations cover an infinite range, and thus covers the same structural dimensions as in the IA.
Claim 26: "An electrode arrangement according to claim 1, wherein at least one of:
(a) the microstructure electrodes interact with one or more analytes of interest such that the electrical response signal is dependent on a presence, absence, level or concentration of the analytes of interest; and
(b) analytes interact with the coating on the microstructures to change electrical properties of the coating, thereby allowing the analytes to be detected."
Claim 1: “the microstructure… acts as the electrode… configured to measure electrical response signals…being at least partially indicative of a bioimpedance”
Claim 14: “A system according to claim 1, wherein at least some of the plurality of microstructures are coated with a coating and wherein the coating… includes at least one of:
i) a permeable membrane…
v) zwitterions;
vi) peptides;
vii) hydrogels; and,
viii) self-assembled monolayer.”
The IA response signal is dependent on an interaction with analytes of interest, but the modified Reference 1 does not specify the response signal being dependent on analytes. Gill, who also effectively includes microstructure electrodes, shows that the “microneedle devices also may be adapted to use the one or more microneedles as a sensor to detect analytes”, depicting that the microstructure electrodes interact with analytes of interest to detect their presence (Gill, ¶[0114]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Reference 1 in view of Gill to have the microstructure electrodes’ response signal be dependent on analytes of interest (through their presence, absence, level or concentration). This would have the benefit of providing a specific, sensitive, real-time detection of analytes through measurable changes in the electrical properties, greatly enhancing the device’s diagnostic abilities for things such as glucose monitoring.
The IA specifies a coating that interacts with analytes, but the modified Reference 1 only lists optional coatings which are commonly used to detect electrical changes due to analytes without specifying their purpose. However, Gill discusses analyte detection with potentiometric and amperometric transducers where “the microneedle coating may release a diagnostic agent and the microneedle detects a reaction product following reaction of the diagnostic agent with an analyte” (Gill, ¶[0114]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Reference 1 in view of Gill to specifically state that the listed coatings could be used to detect changes in their electrical properties due to their interactions with analytes. This would have the benefit of providing a specific, sensitive, real-time detection of analytes through measurable changes in the electrical properties, greatly enhancing the device’s diagnostic abilities for things such as glucose monitoring.
Claim 28: "An electrode arrangement according to claim 1, wherein at least one of:
(a) the microstructures include a material including at least one of:
i) a bioactive material;
ii) a reagent for reacting with analytes in the subject;
iii) a binding agent for binding with the analytes of interest;
iv) a material for binding one or more of the analytes of interest;
v) a probe for selectively targeting the analytes of interest;
vi) an insulator;
vii) a material to reduce biofouling;
viii) a material to attract at least one substance to the plurality of plate microstructures;
ix) a material to repel the at least one substance from the plurality of plate microstructures;
x) a material to attract at least some of the analytes to the plurality of plate microstructures; and
xi) a material to repel at least some of the analytes from the plurality of plate microstructures;
(b) the substrate includes the plurality of plate microstructures and wherein different microstructures are at least one of: i) differentially responsive to the analytes; ii) responsive to different ones of the analytes; iii) responsive to different combinations of the analytes; and iv) responsive to different concentrations of the analytes; and
(c) at least some of the microstructures at least one of: i) attract the at least one substance to the plurality of plate microstructures;
ii) repel the at least one substance from the plurality of plate microstructures;
iii) attract at least one of the analytes to the plurality of plate microstructures; and
iv) repel at least one of the analytes from the plurality of plate microstructures."
Claim 14: "A system according to claim 1… at least some of the plurality of microstructures are coated with a coating and wherein the coating at least one of:”
Claim 14: “…includes… peptides”
Claim 1: “the microstructures… include an insulating layer”
Claim 14: “…modifies surface properties to… minimize biofouling;”
Claim 14: “attracts at least one substance to the microstructures”
Claim 14: “repels at least one substance from the microstructures”
Claim 14:
b) attracts at least one substance to the microstructures;
c) repels at least one substance from the microstructures;
Where the coating on the microstructures from the modified Reference 1 is interpreted to be part of the microstructure such that the coating material is now included as part of the microstructure in relation to the IA term “the microstructures include a material”.
Where the modified Reference 1 Claim 14 has peptides which are a bioactive material.
Both the IA and the combination of the modified Reference 1 and Gill describe the material of the microstructure or its properties. Claim 28 of the IA provides a combination of optional limitations with additional limitations to the microstructure’s material/properties as shown. However, the modified Reference 1 only needs to teach one of these limitation options, to which claims 1 and 14 of Reference 1 includes some of those options.
Claim 31: "An electrode arrangement according to claim 1, wherein at least one of:
(a) at least some of the plurality of plate microstructures are uncoated;
(b) at least some of the plurality of plate microstructures are porous with an internal coating;
(c) at least some of the plurality of plate microstructures are partially coated;
(d) different of the plurality of plate microstructures have different coatings;
(e) different parts of the plurality of plate microstructures include different coatings;
(f) at least some of the plurality of plate microstructures include multiple coatings;
(g) at least some of the of the plurality of plate microstructures are coated with a selectively dissolvable coating; and
(h) at least some of the plurality of plate microstructures are coated with a selectively dissolvable coating that dissolves at least one of:
i) after a defined time period;
ii) in response to the presence of one or more reagents in the subject;
iii) in response to application of the electrical stimulatory signals;
iv) in response to a presence, absence, level or concentration of analytes; and
v) upon breaching or penetration of a functional barrier."
Claim 1: “microstructures… include an insulating layer extending over an end of the microstructure proximate the substrate so that at least a tip portion of the microstructure is uncoated”
Both IA and the combination of the modified Reference 1 and Gill describe the microstructures as being partially covered. The IA states the microstructures are coated, while Reference 1 says layer. However, the specification of Reference 1 indicates that the word layer is synonymous with coating as it states “this allows the blade to be partially covered with an insulative coating” (Reference 1, ¶[0328]). Thus, the modified Reference 1 shows a partially coated microstructure.
The IA provides more detailed options for coatings, including selectively dissolvable coatings and multiple types of coatings, which are not explicitly detailed in the modified Reference 1. However, the modified Reference 1 only needs to teach one of these limitation options, to which claims 1 of Reference 1 includes one of those options.
Claim 35: "An electrode arrangement according to claim 1,wherein the coating at least one of:
(a) interacts with analytes;
(b) undergoes a change in properties upon exposure to analytes;
(c) undergoes a shape change to selectively anchor microstructures;
(d) modifies surface properties to at least one of: i) increase hydrophilicity; ii) increase hydrophobicity; and iii) minimize biofouling;
(e) attracts at least one substance to the microstructures;
(f) repels the at least one substance from the microstructures;
(g) provides a physical structure to at least one of: i) facilitate penetration of a barrier; ii) strengthen the microstructures; and iii) anchor the microstructures in the subject;
(h) dissolves to at least one of: i) expose a microstructure of the plurality of the plate microstructures; ii) expose a further coating; and iii) expose a material;
(i) provides stimulation to the subject;
(j) contains the material;
(k) selectively releases a material;
(l) acts as a barrier to preclude the at least one substance from the microstructures; and
(m) includes at least one of: i) polyethylene; ii) polyethylene glycol; iii) polyethylene oxide; iv) zwitterions; v) peptides; vi) hydrogels; and vii) self-assembled monolayer."
Claim 14: "A system according to claim 1… at least some of the plurality of microstructures are coated with a coating and wherein the coating at least one of:
a) modifies surface properties to at least one of: i) increase hydrophilicity; ii) increase hydrophobicity; and, iii) minimize biofouling;
b) attracts at least one substance to the microstructures;
c) repels at least one substance from the microstructures;
d) acts as a barrier to preclude at least one substance from the microstructures; and,
e) includes at least one of: i) a permeable membrane; ii) polyethylene; iii) polyethylene glycol; iv) polyethylene oxide; v) zwitterions; vi) peptides; vii) hydrogels; and, viii) self-assembled monolayer."
Both IA and the combination of the modified Reference 1 and Gill describe coatings on microstructures and their properties. Claim 35 of the IA provides a combination of limitations, where the IA includes additional optional limitations (as shown) of properties and functionalities such as shape change, stimulation, and selective release, which are not explicitly described in the modified Reference 1. However, the modified Reference 1 only needs to teach one of these limitation options, to which claim 14 of the modified Reference 1 includes some of those options.
Claim 38: "A system according to claim 1, wherein the plate microstructures are at least partially tapered and have a substantially rounded rectangular cross sectional shape."
Claim 4: "A system according to claim 1, wherein at least some of the plurality of microstructures at least one of: a) are at least partially tapered and have a rounded rectangular cross sectional shape"
Both the IA and the combination of the modified Reference 1 and Gill mention tapered microstructures with a substantially rounded rectangular cross-sectional shape.
Claims 2 and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. US12048558B2, hereinafter referred to as Reference 1, and in view of Gill et al. (US 20140170299 A1), hereinafter referred to as Gill, and further in view of Negi et al. (US 20170007813 A1), hereinafter referred to as Negi, and in further view of Rajaraman et al. (US 20140303471 A1), hereinafter referred to as Rajaraman.
The analysis as follows (please note the bolded and underlined portions of the entries under the Instant Application, IA, are those portions of the IA claims that the claims of Patent US12048558B2, Reference 1, does not have or are different from in some form):
Claim Element (Instant Application, IA)
Reference 1 (US12048558B2)
Analysis
Claim 2: An electrode arrangement according to claim 1, wherein the electrode is a surface electrode coated on at least part of the microstructure.
Claim 1, Element (a): at least some microstructures including an electrode
Both the IA and the combination of the modified Reference 1, Gill, and Negi mention electrodes in combination with microstructures. However, the IA specifically mentions “a surface electrode coated on at least part of...”, whereas Reference 1 lacks this explicit coating detail. Rajaraman, who investigates a similar area of biological microdevices that incorporate electrodes, encompasses “microneedle structures and functionally coating the structures with a conductive layer” for the purpose of making them an electrode (Rajaraman, ¶[0046]).
Additionally, Gill already implies this feature where “the coating material may aid in operation of the sensor”, but does not specify that the coating is used as an electrode (Gill, ¶[0061]). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Reference 1 in view of Rajaraman to specify that one of the coatings used on the microstructures was a conductive material to use as a surface electrode. This would have the benefit of providing lower impedance, improved signal fidelity, and better signal quality and efficiency (Rajaraman, ¶[0043], ¶[0044], FIG. 9).
Claim 55: A system according to claim 1, wherein the one or more sensors are connected to different groups of plate microstructures to allow different measured response signals to be measured from different groups of microstructures.
Claim 1, Element (c): “at least one sensor operatively connected to the at least one microstructure pair, the at least one sensor being configured to measure electrical response signals between microstructures in the pair”; Claim 2: recites multiple pairs of microstructures; Claim 9: recites switches selectively connecting the sensor to one or more microstructures to allow a measurement to be performed.
Reference 1 teaches a sensor connected to a microstructure pair, multiple microstructure pairs, and selective connection of the sensor to different microstructures for performing measurements, but does not expressly teach obtaining different measured response signals from different groups of microstructures. Rajaraman teaches a plurality of individually addressable microneedle electrode arrays, each having a unique electrical contact, with external electronics configured to selectively record electrical activity from each array, and further teaches respective recordings from different arrays and multiple simultaneous recording sites (Rajaraman, [0036], [0039], [0050], [0051], claim 21). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied Rajaraman’s group-level addressing and recording arrangement to the modified Reference 1 so that different measured response signals could be obtained from different microstructure groups. This modification would have been technically feasible because Reference 1 already teaches sensor connections and selective switching among microstructures, while Rajaraman expressly demonstrates separately connected and individually addressable microneedle groups. The benefit would have been to obtain spatially distinct measurements from different groups and provide multiple simultaneous recording sites. One of ordinary skill in the art would have had a reasonable expectation of success because Rajaraman expressly demonstrates the claimed group-level addressing and recording arrangement.
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.
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.
Claims 1, 3, 5-6, 8-9, 17, 20, 22, 24, 26, 28, 31, 35, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US 2014/0170299 A1), hereinafter referred to as Gill, in view of Negi et al. (US 2017/0007813 A1), hereinafter referred to as Negi, and further in view of Hantash et al. (US 2007/0142885 A1), hereinafter referred to as Hantash.
Regarding Claim 1, Gill teaches an electrode arrangement for use with a system for performing measurements on a biological subject (Gill, [0114]: “The microneedle devices also may be adapted to... detect analytes, electrical activity, and optical or other signals... [with a] biosensor... potentiometric, amperometric” and can be arranged in configurations such as, [0118]: “single microneedles, individual rows of microneedles, or as two-dimensional arrays of microneedles”; showing that the microneedle arrangements can function as electrodes for measurement of a biologic subject); the electrode arrangement including: a) a substrate (Gill, [0022]: “includes an array two or more microneedles extending out of plane from a substrate”; where the microneedles function as electrodes); and b) a plurality of plate microstructures extending from a surface of the substrate (Gill, Fig. 3D: depicts a plurality of microstructures that have a plate like form referred to as “microneedles”); the plurality of plate microstructures being configured to breach the stratum corneum of the biological subject (Gill, Fig. 3D, [0104]: “The microneedle devices described herein may be used to deliver substances into and through the various biological tissues... into the skin”, where the microneedles are depicted as plate-like structures, and with particular interest in the stratum corneum as shown in [0005]; where penetrating the skin necessitates breaching the stratum corneum of the subject); and wherein each of the plurality of plate microstructures include a substantially planar face having an electrode thereon to allow electrical stimulatory signals to be applied to and electrical response signals to be received from the biological subject via the plurality of plate microstructures (Biosensors can be located on the microneedle surface, which are planar in form and serve as plate microstructures (Gill, [0114]); these biosensors may be “potentiometric, amperometric...” and are used “to detect analytes, electrical activity, and optical or other signals,” indicating that they can receive electrical response signals; it also explains that “electricity, light or other energy forms may be precisely transmitted to directly stimulate, damage, or heal a specific tissue or for diagnostic purposes”, connoting communication between the electrodes through biological tissue with electric stimulation (Gill, [0114])); wherein each of the plurality of plate microstructures includes a conductive material (Gill, [0041]: “The microneedle can be formed/constructed of different biocompatible materials, including metals, glasses, semi-conductor materials, ceramics, or polymers. Examples of suitable metals include pharmaceutical grade stainless steel, gold, titanium...”, where the metals listed are known to be conductive materials and the microneedle is the microstructure); wherein the electrode of each of the plurality of plate microstructures is defined, at least in part, by an insulating coating (Gill, [0153]: “(pre) coating the microneedles with a thin silicon dioxide layer”, where the microneedles are the microstructures and silicon dioxide is known to be a strong insulator, thus part of the electrode has an insulating coating); and wherein at least some of the plurality of plate microstructures are arranged in groups (Gill, [0048]: “The microneedles can be fabricated as, or combined to form microneedle arrays... an array may include microneedles having various lengths, base portion diameters, tip portion shapes, spacings between microneedles, drug coatings, etc”; [0118]: “Microneedles were prepared as single microneedles, individual rows of microneedles, or as two-dimensional arrays of microneedles”; demonstrating the arrangement of microneedles, i.e., microstructures, into rows and arrays corresponding to groups).
Also regarding claim 1, Gill does not expressly teach that the insulating coating extends over only a part of a surface of the microstructure, so that an uncoated part of the microstructure acts as the electrode. Rather, Gill teaches that microneedles may be coated with insulating material, stating “(pre) coating the microneedles with a thin silicon dioxide layer” (Gill, [0153]). Since silicon dioxide is a well-known electrical insulator, this disclosure supports that Gill includes microneedles, i.e., microstructures, with an insulating coating. However, Gill does not expressly disclose that the insulating coating covers only part of the microneedle surface such that an uncoated portion acts as the electrode.
Negi describes a microneedle system in which the needle is covered in an insulating coating while the conductive tip and electrically active sites remain exposed, showing that part of the microneedle surface is insulated while another part is left uncoated to function as the electrode (Negi, FIG. 2, [0044]: “An electrically insulating coating 225 covers the microneedle. However, the tip and the electrically active sites on the shaft are exposed, e.g., not covered by the insulating coating”; see also claim 12). While Gill discloses the use of insulating coatings on microneedles, it does not explain that the coating covers only a portion of the microstructure to expose a region for electrode function. Negi fills this gap by teaching a structure in which an insulating layer is selectively applied, leaving the tip and selected electrically active sites uncoated to act as electrodes.
It would have been obvious to one of ordinary skill in the art to combine Gill with Negi because both involve fabrication methods and design choices for microneedle electrodes. The partially coated structure in Negi is functionally compatible with the coated microneedles in Gill, making it technically feasible to implement a configuration where only part of the microneedle is coated, leaving the rest exposed for electrical functionality. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Gill in view of Negi to configure the insulating coating to extend over only part of a surface of the microstructure so that an uncoated part acts as the electrode. It would have been obvious because Negi expressly teaches that the insulating coating electrically isolates the intended active sites such that each active site can be independently addressed (Negi, [0045]: “A layer of insulating coating can be oriented between each of the lead lines and the electrically conductive core. Therefore, each electrically active site can be isolated so that each is independently addressable”). The benefit of this combination would have been to electrically isolate the intended electrode regions while leaving selected regions exposed for stimulation and recording, thereby permitting the exposed sites to be independently addressed as taught by Negi.
Also regarding claim 1, Gill does not fully teach that each group is a pair of spaced apart microstructures having electrodes in opposition, and wherein at least some of the electrical stimulatory signals are applied between microstructures in the pair.
Hantash expressly teaches an array of spaced apart microneedle electrodes arranged as active and return electrodes connected to opposite poles of an RF source. In particular, Hantash teaches that the RF source has a positive active terminal and a negative return terminal and that alternate interleaved rows of the array are wired to the respective terminals through common wiring buses, thereby forming interleaved arrays of positive active electrodes and negative return electrodes (Hantash, FIG. 3A, [0049]: “One of the output terminals is labeled with a plus sign (active) and the other with a minus sign (return) to indicate two poles of the RF source 110. Alternate interleaved rows of the array are wired to either the plus or the minus electrode through the common wiring buses 111 and 112”). Hantash further teaches that the spacing between the negative and positive needles is selected such that pulsing the RF source creates a treatment zone “between nearest neighbors within the array of needles” (Hantash, [0050]) and that treatment zones are created “between nearest neighbor needles” connected to opposite poles of the RF source (Hantash, FIG. 4A, [0053]). Hantash expressly refers to the selected needles as electrode pairs and teaches controlling which electrode pairs are pulsed and the timing between the pulsing of the electrode pairs (Hantash, [0056]). Hantash also teaches selecting the polarity of each individual needle for each pulse and floating or grounding selected needles to create different electrode configurations (Hantash, [0057]). Hantash further teaches creating each treatment zone by electrically connecting needles at opposite ends of a local region of skin to different poles of the RF source (Hantash, [0059]).
Gill and Hantash are directed to the common field of substrate-supported, skin-penetrating microneedle electrode arrays used to apply electrical energy to biological tissue. Gill teaches conductive plate microneedles through which electricity may be transmitted for tissue stimulation or diagnostic purposes, while Hantash teaches established wiring and control arrangements for routing electrical energy between selected, spaced apart microneedle electrodes. Hantash is therefore both within the same general field of endeavor and reasonably pertinent to the problem of applying and routing electrical signals between Gill’s spaced, skin-penetrating electrodes.
This modification would have been technically feasible because Gill already teaches spaced arrays of conductive plate microstructures through which electrical energy may be applied to biological tissue, while Hantash expressly demonstrates mounting spaced conductive microneedle electrodes on a substrate, connecting selected electrodes to opposite poles of an RF source, and applying electrical energy through the tissue between the selected electrodes (Gill, FIG. 3D, [0114]; Hantash, [0040], [0049], [0050], [0053]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Gill in view of Hantash to electrically configure selected pairs of spaced apart plate microstructures as active and return electrodes connected to opposite poles, with the electrical stimulatory signals applied through the biological tissue between the microstructures in the pair. Applying Hantash’s known active-and-return electrode-pair arrangement to Gill’s similar substrate-supported microneedle electrode array would have constituted the application of a known technique to a similar device to obtain the predictable result of applying electrical energy through a defined tissue region between selected electrodes. Hantash expressly teaches creating treatment zones between nearest-neighbor electrodes connected to opposite poles, selecting which electrode pairs are pulsed, and selecting the polarity of individual electrodes to produce different electrode configurations and treatment patterns (Hantash, [0050], [0053], [0056], [0057]).
The benefit of the modification would have been to establish a defined and selectable current path through the biological tissue between the plate electrodes, permit selection and reconfiguration of the electrodes forming each pair, and control the tissue region through which the electrical signal is applied. One of ordinary skill in the art would have had a reasonable expectation of success because Hantash expressly demonstrates the paired, opposite-polarity, and selectable-electrode arrangement using a substrate-supported array of skin-penetrating microneedle electrodes.
To the extent that “electrodes in opposition” is interpreted as additionally requiring the electrode-bearing planar faces to be physically directed toward one another, Gill FIG. 3D depicts a two-dimensional array of substantially parallel plate microstructures in which at least some adjacent plate microstructures have broad planar faces confronting one another across the space between the microstructures. Gill does not expressly identify the confronting faces as the electrode-bearing faces or electrically pair those particular microstructures. Hantash FIG. 4A depicts treatment zones extending through the tissue between nearest-neighbor electrodes connected to opposite poles, and Hantash further teaches selecting electrode geometry to create more localized electrical-field profiles within the tissue (Hantash, FIG. 4A, [0053], [0058], [0059]).
This modification would have been technically feasible because Gill already teaches spaced arrays of conductive plate microstructures having the confronting planar-face arrangement shown in FIG. 3D and used for electrical stimulation, while Hantash expressly teaches mounting conductive microneedles on a patterned circuit board, wiring selected electrodes to opposite poles, and applying electrical energy through the tissue between the electrodes (Gill, FIG. 3D, [0114]; Hantash, [0040], [0049], [0050], [0053]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected the confronting planar faces of adjacent Gill plate microstructures as the electrode-bearing faces when configuring those microstructures as the active and return pair taught by Hantash. It would have been obvious because Hantash teaches that the intended electrical path extends through the local tissue region between the paired electrodes and that electrode geometry may be selected to create more localized electrical-field profiles within the tissue (Hantash, FIG. 4A, [0053], [0058], [0059]).
The benefit of the modification would have been to define and concentrate the intended current path through the intervening tissue between the active and return electrodes, while permitting selection and reconfiguration of the plate microstructures forming each pair. One of ordinary skill in the art would have had a reasonable expectation of success because Gill already provides confronting planar faces within its plate-microstructure array, and Hantash demonstrates the paired, opposite-polarity, selectable-electrode arrangement and localization of electrical fields between electrodes using a substrate-supported array of skin-penetrating microneedle electrodes.
Also regarding claim 1, Gill does not fully teach that the substrate includes electrical connections to allow the electrical stimulatory signals to be applied to, and the electrical response signals received from, respective plate microstructures in the pair. Gill implies that connections must exist for the biosensors and electrodes to function, but does not expressly disclose substrate-based wiring.
Negi, however, expressly teaches electrical connections extending from electrically active sites on microneedles to contacts on the substrate. For example, Negi teaches that “Lead lines 120 run from the microneedle to base contacts 125” (Negi, FIG. 3, [0046]) and further teaches that “the lead lines 120 run from the circular electrically active sites 215 on the shaft of the microneedle down to the surface of the substrate, and then across the surface to the base contacts 125. Electrical signals can travel from the electrically active sites, through the lead lines to the base contacts, and then through the silicon wells 130 to the bond pads 140” (Negi, FIG. 4, [0047]). Negi further teaches transistor gates on the underside of the base substrate through which each electrically active site may connect to a controller and a current source (Negi, [0055]) and teaches that the active sites may be used for neural recording and stimulation (Negi, [0059]). This makes clear that the substrate includes electrical connections that allow signals to be applied to and received from respective microneedle electrodes.
Hantash additionally teaches that the microneedle electrodes may be connected through common wiring buses or may each be individually wired to a controller and RF source (Hantash, FIGS. 3A and 3B, [0025], [0049]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Gill and Negi in view of Hantash to include electrical connections in the substrate to allow stimulatory signals to be applied to, and response signals to be received from, respective electrodes in a pair. This modification would have been technically feasible because Gill discloses microneedle electrode arrays formed on a substrate, Negi expressly discloses lead lines extending from active sites along the microneedles and across the substrate to base contacts and controller connections, and Hantash expressly discloses wiring paired microneedle electrodes to opposite poles of an RF source.
More specifically, one of ordinary skill in the art would have applied Negi’s respective lead-line and substrate-contact connections to the two Gill plate microstructures selected and wired as Hantash’s active and return pair. The electrical connections would thereby provide respective pathways to each member of the pair for delivering the stimulatory signals according to Hantash and for receiving electrical response signals according to Negi’s use of independently addressable active sites for both stimulation and neural recording.
It would have been obvious because Negi expressly teaches independently connecting the active sites through the substrate to controller and current-source circuitry so that the active sites can be used for stimulation and recording, while Hantash expressly teaches separately wiring and selecting the electrodes that form each active and return pair. The benefit of this combination would have been to permit the respective plate microstructures in the selected pair to be independently connected and addressed for Hantash’s paired stimulation and Negi’s electrical recording functions.
Also regarding claim 1, the modified Gill does not teach that the electrical connections are conductive tracks provided on the surface of the substrate; an insulating layer is provided on the surface of the substrate to cover the conductive tracks, so that the conductive tracks do not make electrical contact with skin of the biological subject.
Negi, however, teaches microneedle arrays in which electrically conductive traces are routed along the microneedles and across the surface of the substrate and are covered by an insulating coating so that only intended active sites contact the biological environment. For example, Negi describes that conductive traces extend from the microneedle active sites down the shaft and across the substrate to base contacts, and that a second insulating coating is applied over the traces and base contacts so that the traces are encapsulated beneath the insulating layer and only defined electrode sites are exposed to tissue (Negi, FIGS. 10H-10I; [0062]: “a second insulating coating 225′ can be applied to the microneedle and substrate. This insulating coating layer covers the traces and base contacts... The electrically active sites can be covered by the second insulating coating... The traces leading from the electrically active sites to the base contacts are above the first insulating layer, but below the second insulating layer. Thus, the only portions of the traces that are exposed to the neural environment are the electrically active sites”, where the traces and coating are on the side of the substrate containing the needles, thus insulating the traces and substrate from the tissue or environment that the needles penetrate; see also claim 12). This teaches conductive tracks provided on the surface of a substrate with an insulating layer over the substrate that covers the tracks such that the tracks themselves are not in electrical contact with the surrounding biological environment.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Gill, Negi, and Hantash in view of Negi to implement electrical connections as conductive tracks provided on the surface of the substrate and to provide an insulating layer on the substrate that covers those tracks so that they do not make electrical contact with the subject’s skin. This modification would have been technically feasible because Gill already discloses microneedle electrode arrays formed on a substrate for stimulation and sensing, Hantash discloses wiring microneedle electrodes to stimulation circuitry, and Negi demonstrates routing conductive traces on the substrate surface and encapsulating them beneath an insulating coating while leaving only intended electrode regions exposed.
It would have been obvious because Negi expressly teaches placing the conductive traces between first and second insulating layers such that only the electrically active sites, rather than the intervening traces, are exposed to the biological environment (Negi, [0062]). The benefit of this combination would have been to isolate the substrate tracks from the subject’s skin while maintaining exposed electrode sites for stimulation and recording, thereby providing the selective electrical isolation expressly taught by Negi.
Also regarding claim 1, the combined Gill, Negi, and Hantash do not fully teach that the electrical connections include multiple stimulation and response connections allowing different measurements to be performed via different electrical connections. Rather, the combined Gill, Negi, and Hantash teach microneedle electrode arrays used for sensing and stimulation, as shown above in claim 1, but do not expressly disclose the limitation in the same terms.
Negi teaches multiple electrically active sites on each microneedle and teaches that the sites may be independently addressable through respective electrical connections (Negi, [0044]-[0047], [0052], [0055]). Negi further teaches that multiple sites enable “bi-polar stimulation and flexibility of selecting a channel,” “simultaneous recording from a volume of tissue,” and “precise current steering” (Negi, [0034]). Negi teaches ring electrode sites connected by lead lines to substrate contacts that simultaneously examine multiple tissue depths and perform temporal correlation studies (Negi, [0057]). Negi also teaches different active sites configured as electrical recording sites, device sensors, oxygen sensors, or pH sensors and expressly teaches simultaneous oxygen-level measurement and electrical recording, while further stating that the active sites can be used for neural recording and stimulation (Negi, [0059]). Negi describes the disclosed arrangement as a “multi-channel neuromodulation electrode array” used for stimulation and recording, field steering, and three-dimensional spatial mapping (Negi, [0072]).
Hantash further teaches a wiring arrangement having multiple source electrodes in which each electrode is wired individually (Hantash, FIG. 3B, [0025]), selected electrode pairs are activated through different electrical connections to create different treatment patterns (Hantash, [0056]), and the polarity of each individual needle may be selected for each pulse, while selected needles may also be floated or grounded (Hantash, [0057]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined Gill, Negi, and Hantash to provide multiple stimulation and response connections so that different measurements can be performed via different electrical connections. This modification would have been technically feasible because Negi already discloses multiple independently addressable active sites connected through respective lead lines and substrate contacts to controller and current-source circuitry, and Hantash discloses individually wired electrodes and selectable electrode pairs. These channelized connections could be straightforwardly implemented in Gill’s microneedle arrays without altering their fundamental structure.
It would have been obvious because Negi expressly teaches that its independently addressable multichannel arrangement permits channel selection, bipolar stimulation, simultaneous recording from multiple sites, measurements at different tissue depths, different recording configurations, simultaneous electrical and oxygen measurements, current steering, and three-dimensional spatial mapping (Negi, [0034], [0057], [0059], [0072]). Hantash further teaches selecting which individually wired electrode pairs are activated and selecting the polarity of each needle to create different electrode configurations and treatment patterns (Hantash, [0056], [0057]). The benefit of the combination would have been to permit the different stimulation, recording, depth-analysis, oxygen-sensing, and pH-sensing functions expressly described by Negi to be performed using independently selected electrical channels, while also permitting the individually wired electrode pairs to be selected and reconfigured as taught by Hantash.
Regarding Claim 3, the modified Gill teaches that the insulating coating extends over at least one of: a) a proximal end of the microstructure; b) at least half of a length of the microstructure; c) 60 µm, 90 µm or 150 µm of a proximal end of the microstructure; and d) at least part of a tip portion of the microstructure (Negi, FIG. 2, ¶[0044]: “An electrically insulating coating 225 covers the microneedle. However, the tip and the electrically active sites on the shaft are exposed, e.g., not covered by the insulating coating” wherein the insulating coating covering the microneedle while leaving the distal tip and selected shaft sites exposed necessarily extends over the proximal end of the microneedle, thereby teaching alternative a); see also Negi, claim 12: “an electrically insulating coating over the microneedle array such that at least one active site from the set of electrically active sites is exposed”).
Regarding Claim 5, the modified Gill teaches that the electrical response signals are measured between the microstructures in the group (Hantash, FIG. 4A, ¶[0053]: “FIG. 4A shows the treatment zones 160 that are created between nearest neighbor needles 115 that are connected to opposite poles of the RF source 110”; ¶[0054]: “The self limiting nature of the treatment can be achieved by choosing the frequency of the RF source 110 to be a frequency for which the tissue resistivity (impedance) increases as the tissue is treated”; ¶[0017]: “The controller unit has the capability of monitoring changes in the tissue parameters, such as conductivity and temperature, and uses these measurements to determine when treatment should be terminated” wherein Hantash’s active and return needles correspond to the pair of microstructures, and monitoring the conductivity or impedance of the treatment zone formed between the pair corresponds to measuring electrical response signals between the microstructures in the group).
Regarding Claim 6, the modified Gill teaches that one of: a) the group is the pair of the microstructures including spaced apart plate microstructures having planar electrodes in opposition; and b) the group is a pair of the microstructures including spaced apart plate microstructures having planar electrodes in opposition and at least one of: i) at least some pairs of the microstructures are angularly offset; ii) at least some pairs of the microstructures are orthogonally arranged; iii) adjacent pairs of the microstructures are orthogonally arranged; iv) pairs of the microstructures are arranged in rows, and the pairs of the microstructures in one row are angularly offset relative to pairs of the microstructures in other rows; and v) pairs of the microstructures are arranged in rows, and the pairs of the microstructures in one row are orthogonally arranged relative to pairs of the microstructures in other rows because, as set forth regarding claim 1, Gill teaches spaced plate microstructures having substantially planar electrode-bearing faces (Gill, FIG. 3D, ¶[0114]), and Hantash teaches arranging selected electrode microstructures as active and return pairs connected to opposite poles and applying current through the tissue between the pair (Hantash, FIG. 4A, ¶[0053]), thereby teaching alternative a). Because claim 6 expressly recites alternatives a) and b), the teaching of alternative a) is sufficient to satisfy the claim, and the additional limitations recited in alternative b), including subalternatives i) through v), need not be separately shown by the applied prior art.
Regarding Claim 8, the modified Gill teaches that at least one of: a) a spacing between the electrodes in each group are at least one of: i) less than 10 mm; ii) less than 1 mm; iii) 0.1 mm; and iv) more than 10 µm; and b) a spacing between groups of microstructures is at least one of: i) less than 50 mm; ii) more than 20 mm; iii) less than 20 mm; iv) less than 10 mm; v) more than 10 mm; vi) less than 1 mm; vii) more than 1 mm; viii) 0.5 mm; and ix) more than 0.2 mm (Gill, FIG. 3D: depicts adjacent plate microstructures arranged in rows with a spacing of approximately 800 µm, wherein selecting adjacent Gill microstructures as the paired electrode microstructures discussed regarding claim 1 results in a spacing between the electrodes in each group of approximately 800 µm, which is less than 1 mm and more than 10 µm, thereby teaching alternative a), subalternatives ii) and iv); Gill, FIG. 4B: depicts a microneedle array having dimensions of approximately 7,000 µm by 7,000 µm, wherein the electrode-pair groups discussed regarding claim 1 are positioned within the approximately 7 mm by 7 mm array and therefore have a spacing between groups of less than 10 mm, thereby teaching alternative b), subalternative iv), and necessarily also subalternatives i) and iii); see also ¶[0046]).
Regarding Claim 9, the modified Gill teaches that at least one of: a) the electrodes are configured to be operatively connected to at least one of: i) at least one sensor operatively configured to measure the electrical response signals from at least one of the microstructures (Gill, ¶[0114]: “The microneedle devices also may be adapted to use the one or more microneedles as a sensor to detect analytes, electrical activity, and optical or other signals” and “Biosensors can be located on the microneedle surface, inside a hollow or porous microneedle, or inside a device in communication with the body tissue via the microneedle” wherein Gill’s biosensor located on the microneedle surface or in communication with the tissue through the microneedle is operatively connected to the microneedle electrode and is configured to detect electrical activity, thereby measuring electrical response signals received through at least one of the microstructures); and ii) a signal generator configured to apply the electrical stimulatory signals to the at least one of the microstructures; and b) the electrodes are configured to be connected to one or more switches for selectively connecting at least one of the at least one sensor and the signal generator to the electrodes. Because claim 9 requires at least one of alternatives a) and b), and alternative a) requires at least one of subalternatives i) and ii), Gill’s teaching of alternative a), subalternative i), is sufficient to satisfy the claim, and subalternative ii) and alternative b) need not be separately shown by the applied prior art.
Regarding Claim 17, the modified Gill teaches that at least some of the microstructures include at least one of: a) a shoulder that is configured to abut against the stratum corneum to control a depth of penetration; and b) a shaft extending from the shoulder to a tip, the shaft being configured to control a position of the tip in the subject (Gill, ¶[0111]: “The depth of insertion also may be controlled by the geometry of the microneedle, such as a widening of the needle” wherein the widened portion of the microneedle corresponds to a shoulder that engages the skin surface, including the stratum corneum, to limit further insertion and thereby control the depth of penetration, teaching alternative a); Gill, ¶[0015]: teaches a microneedle having “a base, a tip end, and a shaft portion therebetween”; ¶[0110]: teaches that “the microneedles are designed to have a length equal to the desired penetration depth” wherein the widened base or shoulder and the shaft extending therefrom to the tip position the tip at the desired depth in the subject, thereby additionally teaching alternative b)).
Regarding Claim 20, the modified Gill teaches that at least some of the microstructures include at least part of an active sensor (Gill, ¶[0114]: “The microneedle devices also may be adapted to use the one or more microneedles as a sensor to detect analytes, electrical activity, and optical or other signals” and “Similarly, heat, electricity, light or other energy forms may be precisely transmitted to directly stimulate, damage, or heal a specific tissue or for diagnostic purposes” wherein Gill teaches using the microneedle itself as a sensor and actively transmitting energy through the microneedle device for diagnostic purposes, such that at least some of the microneedle microstructures include at least part of an active sensor).
Regarding Claim 22, the modified Gill teaches that the plurality of electrodes at least one of: a) extends over a length of a distal portion of the microstructure; b) extends over a length of a portion of the microstructure spaced from a tip; c) is positioned proximate an end of the microstructure; d) is positioned proximate the tip of the microstructure; e) extends over at least 25% of a length of the microstructure (Gill, ¶[0114]: “Biosensors can be located on the microneedle surface, inside a hollow or porous microneedle, or inside a device in communication with the body tissue via the microneedle (solid, hollow, or porous)” and ¶[0060]: “the microneedle may be part of a sensor, and the coating material may aid in operation of the sensor” demonstrating that the electrode can be positioned in or on the microstructure or can include the microstructure itself, such that the electrode extends over the distal portion, extends over a portion spaced from the tip, is positioned proximate an end and the tip, and extends over at least 25% of the length of the microstructure); f) extends over less than 50% of a length of the microstructure; g) extends over about 60 µm, 90 µm or 150 µm of the microstructure (Gill, ¶[0046]: “In various embodiments, the microneedle may have a length of between about 50 µm and about 5000 µm” wherein Gill’s disclosed range includes microneedles having lengths of about 60 µm, 90 µm and 150 µm, and the microneedle itself may form the electrode as taught in ¶[0060], thereby teaching alternative g)); h) is configured to be positioned in a viable epidermis of the subject in use (Gill, ¶[0046]: “the microneedle, or array thereof, are designed for . . . withdrawal of biological fluid, while being inserted into the skin” showing that the microneedles, which may act as electrodes as taught in ¶[0114], are configured to penetrate the stratum corneum and be positioned in the underlying viable epidermis); and i) has a surface area of at least one of: i) less than 200,000 µm²; ii) 22,500 µm²; iii) at least 10 mm²; iv) at least 1 mm²; v) at least 100,000 µm²; vi) at least 10,000 µm²; vii) at least 7,500 µm²; viii) at least 5,000 µm²; ix) at least 2,000 µm²; x) at least 1,000 µm²; xi) at least 500 µm²; xii) at least 100 µm²; and xiii) at least 10 µm² (Gill, ¶[0114]: teaches that the microstructure can act as the electrode, and using the microstructure dimensional ranges disclosed in ¶[0046], ¶[0051] and ¶[0121], the surface area of a solid microstructure can be roughly calculated to be between 7,000 µm² and 6,250,000 µm², which encompasses subalternatives i), ii), iv), v), vi), vii), viii), ix), x), xi), xii) and xiii)). Because claim 22 recites alternatives a) through i), Gill’s teaching of alternatives a) through e), g), h) and i) is sufficient to satisfy the claim, and alternative f) need not be separately shown by the applied prior art.
Regarding Claim 24, the modified Gill teaches that the plurality of electrodes at least one of: a) has a width that is at least one of: i) less than 50,000 µm; ii) less than 40,000 µm; iii) less than 30,000 µm; iv) less than 20,000 µm; v) less than 10,000 µm; vi) less than 1,000 µm; vii) at least 500 µm; viii) at least 200 µm; ix) at least 100 µm; x) at least 75 µm; xi) at least 50 µm; xii) at least 20 µm; xiii) at least 10 µm; and xiv) at least 1 µm (Gill, ¶[0046]: “In various embodiments, the base portion of the microneedle has a width or cross-sectional dimension between about 20 µm and about 500 µm” and “For a hollow microneedle, the outer diameter or width may be between about 50 µm and about 400 µm” wherein, as discussed regarding claim 1, the microneedle may function as the electrode, and Gill’s disclosed width range satisfies the recited width alternatives); and b) has a height that is at least one of: i) up to 2,500 µm; ii) at least 500 µm; iii) at least 200 µm; iv) at least 100 µm; v) at least 75 µm; vi) at least 50 µm; vii) at least 20 µm; viii) at least 10 µm; and ix) at least 1 µm (Gill, ¶[0046]: “In various embodiments, the microneedle may have a length of between about 50 µm and about 5000 µm” wherein the length of the microneedle corresponds to the claimed height, and Gill’s disclosed length range satisfies the recited height alternatives).
Regarding Claim 26, the modified Gill teaches that at least one of: a) the electrodes interact with one or more analytes of interest such that the electrical response signal is dependent on a presence, absence, level or concentration of the analytes of interest (Gill, ¶[0114]: “The microneedle devices also may be adapted to use the one or more microneedles as a sensor to detect analytes” and teaches that the microneedle biosensor may operate using potentiometric or amperometric transduction, wherein the microstructure electrodes interact with analytes and generate electrical response signals dependent on the presence, absence, level or concentration of the analytes); and b) analytes interact with the coating on the microstructures to change electrical properties of the coating, thereby allowing the analytes to be detected (Gill, ¶[0114]: “a microneedle is coated with a drug formulation that has a sensing functionality associated with it” and “In an application for sensing based on binding to a substrate or reaction mediated by an enzyme, the substrate or enzyme can be immobilized on at least a portion of the surface of the microneedle” wherein the analyte interacts with the sensing coating through binding or an enzyme-mediated reaction, and the resulting change is detected using the disclosed potentiometric or amperometric biosensor).
Regarding Claim 28, the modified Gill teaches that at least one of: a) the microstructures include a material including at least one of: i) a bioactive material (Gill, ¶[0065]-¶[0066]: “Optionally, additional drug can be integrated into the microneedle structure” and “The drug can be a substance having biological activity” wherein the drug integrated into the microneedle structure is a bioactive material); ii) a reagent for reacting with analytes in the subject; iii) a binding agent for binding with the analytes of interest; iv) a material for binding one or more of the analytes of interest (Gill, ¶[0114]: “a microneedle is coated with a drug formulation that has a sensing functionality associated with it. In an application for sensing based on binding to a substrate or reaction mediated by an enzyme, the substrate or enzyme can be immobilized on at least a portion of the surface of the microneedle” wherein the immobilized enzyme corresponds to a reagent for reacting with analytes, and the immobilized substrate corresponds to a binding agent or material for binding analytes); v) a probe for selectively targeting the analytes of interest; vi) an insulator (Gill, ¶[0153]: “(pre) coating the microneedles with a thin silicon dioxide layer” wherein silicon dioxide is an insulating material); vii) a material to reduce biofouling; viii) a material to attract at least one substance to the plurality of plate microstructures; ix) a material to repel the at least one substance from the plurality of plate microstructures (Gill, ¶[0154]: “microneedles were (pre) coated with PLGA... to make the microneedles hydrophobic” wherein the hydrophobic PLGA is a material that repels aqueous substances from the microneedles); x) a material to attract at least some of the analytes to the plurality of plate microstructures; and xi) a material to repel at least some of the analytes from the plurality of plate microstructures; b) the substrate includes the plurality of plate microstructures and wherein different microstructures are at least one of: i) differentially responsive to the analytes; ii) responsive to different ones of the analytes; iii) responsive to different combinations of the analytes; and iv) responsive to different concentrations of the analytes; and c) at least some of the microstructures at least one of: i) attract the at least one substance to the plurality of plate microstructures; ii) repel the at least one substance from the plurality of plate microstructures (Gill, ¶[0154]: “microneedles were (pre) coated with PLGA... to make the microneedles hydrophobic” wherein the hydrophobic coating forms part of the microneedles and causes the microneedles to repel aqueous substances); iii) attract at least one of the analytes to the plurality of plate microstructures; and iv) repel at least one of the analytes from the plurality of plate microstructures. Because claim 28 recites alternatives a), b), and c), and alternative a) requires only one of subalternatives i) through xi), Gill’s teaching of alternative a), including at least subalternatives i), ii), iii), iv), vi), and ix), is sufficient to satisfy the claim, and the remaining alternatives need not be separately shown by the applied prior art.
Regarding Claim 31, the modified Gill teaches that at least one of: a) at least some of the plurality of plate microstructures are uncoated (Gill, ¶[0088]: “the physical mask may include reservoirs, closed at one end, that can be filled with the coating liquid (see, e.g., FIG. 10B). Single microneedles or multiple microneedles of an array can be dipped into each reservoir or groove” showing that selected microneedles may be coated while other microneedles remain uncoated); b) at least some of the plurality of plate microstructures are porous with an internal coating (Gill, ¶[0019]: “at least one microneedle comprises one or more pockets therein. The coating may be located substantially only in the one or more pockets” showing a microstructure having an internal coating within one or more pockets); c) at least some of the plurality of plate microstructures are partially coated (Gill, ¶[0085]: “the coating is on 50% to 100% of the surface of the microneedle or on 75% to 100% of the surface of the microneedle” showing that the microstructure may be partially coated); d) different microstructures of the plurality of plate microstructures have different coatings (Gill, ¶[0048]: “an array may include microneedles having various lengths, base portion diameters, tip portion shapes, spacings between microneedles, drug coatings, etc.” showing that different microstructures in the array may have different coatings); e) different parts of the plurality of plate microstructures include different coatings (Gill, ¶[0091]: “the method may further include the step of applying a second coating liquid onto the solid coating or onto a second surface of the microneedle” and ¶[0092]: “one coating composition is located on one part of the microneedle (e.g., a first pocket) and a second coating composition is located on another part of the microneedle (e.g., a second pocket)” showing different coatings on different parts of the microstructure); f) at least some of the plurality of plate microstructures include multiple coatings (Gill, ¶[0091]: teaches dipping at least one microneedle into the same or a different coating liquid to apply an additional coating, showing microstructures having multiple coatings); g) at least some of the plurality of plate microstructures are coated with a selectively dissolvable coating; and h) at least some of the plurality of plate microstructures are coated with a selectively dissolvable coating that dissolves at least one of: i) after a defined time period (Gill, ¶[0064]: “the exterior coating may include a material known in the art that dissolves or biodegrades relatively slowly in vivo to provide delayed or slow release of drug” and “an exterior layer could provide for rapid (e.g., bolus) release of drug” showing a selectively dissolvable coating; ¶[0016]: “the coating may be adapted to come off of the microneedle in fifteen minutes or less following insertion into a biological tissue” showing that the coating dissolves or comes off after a defined time period); ii) in response to a presence of one or more reagents in the subject; iii) in response to application of the electrical stimulatory signals; iv) in response to a presence, absence, level or concentration of analytes; and v) upon breaching or penetration of a functional barrier (Gill, ¶[0016]: “all of the coating is adapted to come off of the microneedle following insertion into a biological tissue” showing that the coating comes off upon penetration of the biological tissue barrier). Because claim 31 recites alternatives a) through h), Gill’s teaching of alternatives a) through g), and at least subalternatives h)(i) and h)(v), is sufficient to satisfy the claim, and subalternatives h)(ii) through h)(iv) need not be separately shown by the applied prior art.
Regarding Claim 35, the modified Gill teaches that the coating at least one of: a) interacts with analytes (Gill, ¶[0114]: “In one example, the microneedle coating may release a diagnostic agent and the microneedle detects a reaction product following reaction of the diagnostic agent with an analyte in vivo” showing that the coating interacts with analytes); b) undergoes a change in properties upon exposure to analytes (Gill, ¶[0114]: teaches that “a microneedle is coated with a drug formulation that has a sensing functionality associated with it” and sensing based on binding to a substrate or a reaction mediated by an enzyme, showing that the sensing coating undergoes a detectable change upon exposure to an analyte); c) undergoes a shape change to selectively anchor microstructures; d) modifies surface properties to at least one of: i) increase hydrophilicity; ii) increase hydrophobicity (Gill, ¶[0063]: “the microneedle is first coated with a precoat material... to alter or improve the surface properties (e.g., hydrophilicity or hydrophobicity)” showing modification of the surface properties to increase hydrophilicity or hydrophobicity; see also Gill, ¶[0015]: “The coating may include a hydrogel” and ¶[0016]: teaches that the coating may comprise an amphiphilic material); and iii) minimize biofouling; e) attracts at least one substance to the microstructures (Gill, ¶[0015]: “The coating may include a hydrogel” wherein the hydrogel attracts aqueous substances); f) repels the at least one substance from the microstructures (Gill, ¶[0154]: “microneedles were (pre) coated with PLGA... to make the microneedles hydrophobic” wherein the hydrophobic coating repels aqueous substances); g) provides a physical structure to at least one of: i) facilitate penetration of a barrier; ii) strengthen the microstructures; and iii) anchor the microstructures in the subject; h) dissolves to at least one of: i) expose a microstructure of the plurality of the plate microstructures; ii) expose a further coating (Gill, ¶[0064]: “an exterior layer could provide for rapid (e.g., bolus) release of drug. An underlying layer could provide bolus or controlled release of the same or another drug” wherein dissolution or removal of the exterior coating exposes the underlying coating); and iii) expose a material; i) provides stimulation to the subject; j) contains the material (Gill, ¶[0016]: “the coating comprises drug dispersed in a matrix material” showing that the coating contains a material); k) selectively releases the material (Gill, ¶[0059]: “the coating may include a matrix material or layer that serves to modulate release of a drug, which may be dispersed therein, which may be located in an underlying layer, or both” and ¶[0016]: teaches that the matrix material provides controlled release of the drug, showing selective release of a material); l) acts as a barrier to preclude the at least one substance from the microstructures (Gill, ¶[0064]: teaches that an exterior secondary coating may alter the release kinetics of a drug from an underlying coating layer, wherein the exterior coating acts as a barrier that temporarily precludes exposure or release of the underlying substance); and m) includes at least one of: i) polyethylene; ii) polyethylene glycol; iii) polyethylene oxide; iv) zwitterions; v) peptides; vi) hydrogels; and vii) self-assembled monolayer (Gill, ¶[0080]: teaches coatings including “polyethylene glycols,” “poly(ethyleneoxide) (PEO) derivatives,” “PEG derivatives” and “PEG-PEO derivatives”; ¶[0015]: “The coating may include a hydrogel” thereby teaching at least subalternatives m)(ii), m)(iii), and m)(vi)). Because claim 35 recites alternatives a) through m), Gill’s teachings of at least alternatives a), b), d)(i), d)(ii), e), f), h)(ii), j), k), l), m)(ii), m)(iii), and m)(vi) are sufficient to satisfy the claim, and the remaining alternatives need not be separately shown by the applied prior art.
Regarding Claim 38, the modified Gill teaches that the plate microstructures are at least partially tapered and have a substantially rounded rectangular cross sectional shape (Gill, [0119] and Fig 3D: “microneedles of... constant tip angle of 55°” depicting pointed microstructures such that they are partially tapered; [0121] and Fig 3D: “The microneedles were electropolish” which reduced the thickness of each surface by 25 µm (thickness started at “75 µm” [0118]; and was reduced to “50 µm” [0121]), which effectively created rounded corners with a radius of ~12.5 µm as can be seen in Fig. 3D. This rounded corner equates to 25% of the thickness and 7% of the width of the microstructure, creating a substantially rounded rectangular cross sectional shape).
Claims 2 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Gill et al. (US 2014/0170299 A1), hereinafter referred to as Gill, in view of Negi et al. (US 2017/0007813 A1), hereinafter referred to as Negi, and further in view of Hantash et al. (US 2007/0142885 A1), hereinafter referred to as Hantash, and further in view of Rajaraman et al. (US 2014/0303471 A1), hereinafter referred to as Rajaraman.
The modified Gill teaches claim 1 as described above.
Regarding claim 2, the combined Gill, Negi, and Hantash does not fully teach that the electrode is a surface electrode coated on at least part of the microstructure. Gill implies that a coating may aid in the operation of a sensor, but does not expressly specify that the coating itself is a surface electrode (Gill, [0061]).
Rajaraman, who investigates a similar area of biological microdevices that incorporate electrodes, teaches “functionally coating the structures with a conductive layer” by transferring thin-film metal to a microneedle structure during molding (Rajaraman, [0046]). Rajaraman further teaches metallizing microneedle electrode arrays with low-impedance coatings and expressly teaches coating stainless-steel microneedle electrode arrays with a conductive silver/silver-chloride layer using sputter deposition (Rajaraman, [0043]). Thus, the conductive layer coated on the surface of Rajaraman’s microneedle structure corresponds to the claimed surface electrode coated on at least part of the microstructure.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the combined Gill, Negi, and Hantash in view of Rajaraman to specify that one of the coatings used on the microstructures was a conductive layer functioning as a surface electrode. This modification would have been technically feasible because Gill already teaches coating microneedle surfaces, and Rajaraman expressly demonstrates forming or depositing conductive layers on microneedle structures using known thin-film transfer, sputter-deposition, electrodeposition, electroplating, and related coating techniques (Rajaraman, [0043], [0046]). It would have been obvious because Rajaraman expressly teaches that metallizing the microneedle electrode arrays with low-impedance coatings enables lower noise, higher sensitivity, and higher signal fidelity (Rajaraman, [0043]). The benefit of this combination would have been to reduce electrode impedance and improve signal fidelity, as Rajaraman demonstrates that its coated microneedle electrode arrays provide nearly an order-of-magnitude impedance reduction and improved signal fidelity relative to conventional surface electrodes (Rajaraman, FIG. 9, [0044]). One of ordinary skill in the art would have had a reasonable expectation of success because Rajaraman expressly demonstrates the application and electrical operation of conductive surface coatings on microneedle electrode structures.
Regarding claim 55, the modified Gill does not fully teach that the one or more sensors are connected to different groups of plate microstructures to allow different measured response signals to be measured from different groups of microstructures.
Negi teaches one or more sensors associated with the electrically active sites of a microneedle array. In particular, Negi teaches an interdigitated electrode active site and states that such interdigitated electrodes may be used as device sensors, pH sensors for tissue health, or oxygen sensors, and that other materials may be integrated to form sensors (Negi, FIG. 8, [0059]: “Such interdigitated electrodes can be used as device sensors to monitor device performance, pH sensors for tissue health, or oxygen sensors. Other materials can also be integrated to form sensors”). Negi further teaches an integrated oxygen sensor formed on a microneedle shaft for simultaneously measuring oxygen level and performing electrical recording and teaches that the active sites may be used for neural recording and stimulation (Negi, [0059]: “an integrated oxygen sensor can be formed on a shaft of a microneedle for measurement of oxygen level and electrical recording simultaneously” and “The active sites can be used for neural recording and stimulation”). Negi therefore teaches sensing and recording components connected through respective active sites, lead lines, and substrate contacts. However, Negi does not fully teach connecting the sensors to different groups of plate microstructures so that different measured response signals are obtained from the respective groups.
Rajaraman teaches a microneedle electrode patch comprising a plurality of individually addressable microneedle electrode arrays, wherein each microneedle electrode array includes a plurality of microneedles and is connected to external electronics adapted to selectively stimulate or record electrical activity at the respective array (Rajaraman, [0036]: “a microneedle electrode patch comprises a plurality of individually addressable microneedle electrode arrays, each microneedle electrode array having a plurality of microneedles extending from an upper surface thereof” and “The microneedle electrode patch can be connected to an external electronics assembly adapted to selectively stimulate or record electrical activity at each of the plurality of microneedle electrode arrays”). Each of Rajaraman’s microneedle electrode arrays corresponds to a different group of microstructures.
Rajaraman further teaches that each group has a unique electrical contact and is independently controlled by the external electronics assembly to record the electrical response of the biological tissue (Rajaraman, [0039]: “A single microneedle electrode patch can comprise a plurality of individually addressable microneedle electrode arrays 112, each having a unique electrical contact 114 and adapted to be selectively controlled by the external electronics assembly 108”). Rajaraman additionally claims external electronics connected to the electrical contact of each microneedle electrode array and adapted to record electrical activity from each array, wherein the arrays are individually addressable (Rajaraman, claim 21).
Rajaraman expressly teaches obtaining different measured response signals from the different groups, stating that an array of plots results from individually recording the respective microneedle electrode arrays and that each plot represents a recording from a respective array on the patch (Rajaraman, FIGS. 10A and 10B, [0050]: “an array of plots resulting from individually recording each one of an array of microneedle electrodes integrated into a single microneedle electrode patch enables nerve-mapping. Each plot represents a recording from each of the microneedle electrode arrays on a microneedle electrode patch applied to the skin”). Rajaraman also teaches measuring at multiple locations along a nerve using multiple simultaneous recording sites rather than repeatedly moving a single recording electrode (Rajaraman, [0051]). Thus, Rajaraman teaches separately addressable groups of microneedles having respective electrical connections through which different measured response signals are obtained from the different groups.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Gill in view of Rajaraman to connect the sensing and recording components taught by Negi to different groups of Gill’s plate microstructures according to Rajaraman’s individually addressable group arrangement, so that different measured response signals are obtained from the respective groups. This modification would have been technically feasible because the modified Gill already includes multiple independently addressable stimulation and response connections extending from the plate microstructures through respective conductive tracks and substrate contacts, Negi expressly teaches sensing and recording components connected through active sites and respective electrical pathways, and Rajaraman expressly teaches connecting each group of microneedles through a unique electrical contact to external electronics adapted to record a respective electrical response. It would have been obvious because Rajaraman expressly teaches individually recording from the different microneedle electrode arrays to perform nerve mapping, determine the course and speed of an underlying nerve, compare effective electrodes, and obtain measurements from multiple locations simultaneously without repeatedly repositioning a single recording electrode (Rajaraman, [0040], [0050], [0051]). One of ordinary skill in the art would therefore have connected the sensing and recording components of the modified Gill to the different groups according to Rajaraman to obtain spatially distinct response signals from the respective groups and permit simultaneous comparison and analysis of those signals. The benefit of this combination would have been to provide the separate group-specific recordings expressly taught by Rajaraman, thereby enabling nerve mapping, measurements at multiple locations, comparison of effective electrode groups, and improved test repeatability without repositioning the electrode arrangement. One of ordinary skill in the art would have had a reasonable expectation of success because Rajaraman expressly demonstrates individually addressable microneedle groups having unique electrical contacts and separate recorded signals in a substrate-supported, skin-penetrating microneedle electrode patch.
Response to Arguments
35 U.S.C. §112(b)
Applicant's arguments filed 4/16/2026, page 15, regarding the previous 112(b) Rejections of claims 22, 28, and 35 under 35 U.S.C. 112(b) have been fully considered and are persuasive. The previous 112(b) rejections have been withdrawn. Separate informalities in the present wording of claims 28 and 35 are addressed by objections elsewhere in this Office Action, and claim 55 is separately rejected under 35 U.S.C. § 112(b) on a ground not previously presented as shown above.
Double Patenting Rejections
Applicant's arguments filed 4/16/2026, page 15, regarding the previous Double Patenting Rejections, have been fully considered and are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. That is, there are new grounds of rejection.
Applicant’s Argument: Applicant argues that the amendments render the nonstatutory double-patenting rejections moot and requests that, if the Examiner disagrees, the rejections be held in abeyance until the claims are otherwise in condition for allowance.
Examiner’s Response: Applicant’s arguments have been considered but are not persuasive. Amended claim 1 incorporates the limitation of former claim 57 requiring that the electrical connections include multiple stimulation and response connections allowing different measurements to be performed via different electrical connections. As set forth in the updated double-patenting analysis, this additional limitation does not patentably distinguish claim 1 from the claims of U.S. Patent No. 12,048,558 in view of the applied references.
The amendments to claims 22, 28, and 35 clarify portions of the recited language but do not substantively alter the limitations relied upon in the double-patenting analysis or otherwise render the claims patentably distinct from the claims of U.S. Patent No. 12,048,558 in view of the applied references. The remaining rejected claims have not been substantively amended. Accordingly, the nonstatutory double-patenting rejections are maintained as set forth above.
Applicant’s request to hold the rejections in abeyance is not granted. The nonstatutory double-patenting rejections remain applicable, and Applicant must either establish that the pending claims are patentably distinct from the reference patent claims or otherwise appropriately resolve the rejections.
35 U.S.C. §103
Applicant's arguments filed 4/16/2026, pages 16-19, regarding the previous 103 Rejections of claims 1-3, 5-6, 8-9, 17, 20, 22, 24, 26, 28, 31, 35, 38, 55 and 57 have been fully considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. That is, there are new grounds of rejection.
Applicant’s Argument: Applicant argues that the cited references fail to disclose, teach, or suggest every limitation of the pending claims. Applicant further argues that the prior rejection did not adequately explain why a person of ordinary skill in the art would have provided multiple stimulation and response connections allowing different measurements to be performed via different electrical connections and contends that the stated benefits of the combination were based on hindsight and were not supported by the cited references.
Examiner’s Response: Applicant’s arguments have been considered. Independent claim 1 has been amended to incorporate the additional limitations of former claim 57. In view of the amended claim language and reconsideration of the claim as a whole, the previous rejection based on Gill in view of Negi and Patolsky has been superseded by the new ground of rejection set forth above based on Gill in view of Negi and Hantash. Accordingly, Applicant’s arguments directed to the particular teachings and combination of references applied in the previous rejection do not address the presently applied rejection and are moot with respect to the present action. The replacement of the previous rejection does not constitute agreement with Applicant’s characterization of that rejection.
The present rejection identifies the particular teachings relied upon for each limitation of amended claim 1. Gill teaches the substrate-supported plate microneedle arrangement having substantially planar electrode-bearing faces for applying electrical stimulatory signals and receiving electrical response signals. Negi teaches partially insulated conductive microneedle electrodes, conductive tracks provided on the substrate beneath an insulating layer, and multiple independently addressable electrical sites and connections. Hantash teaches spaced microneedle electrodes configured as active and return pairs connected to opposite poles, with electrical signals applied through the tissue between the paired electrodes.
The reason for providing multiple independently addressable stimulation and response connections is supported by Negi. Negi teaches multiple electrically active sites supported on microneedles, with at least some or all of the active sites being independently electrically addressable and connected through respective lead lines to electrically independent base contacts and controller circuitry (Negi, ¶[0006]-¶[0008], ¶[0042]-¶[0047], claims 1, 6, and 7). Negi explains that multiple active sites improve recording reliability through temporal correlation, permit recording from multiple locations and depths, enable simultaneous recording from a volume of tissue, permit bipolar stimulation and flexible channel selection, and allow precise current steering (Negi, ¶[0032]-¶[0034], ¶[0057]-¶[0059]). Negi further teaches simultaneous oxygen measurement and electrical recording using different sensing functions integrated into the microneedle arrangement (Negi, ¶[0059]). These express teachings demonstrate that the reason for providing separate, independently addressable stimulation and response connections arises from the prior art itself rather than from Applicant’s disclosure.
A person of ordinary skill in the art therefore would have been motivated to provide Gill’s microneedle arrangement with Negi’s multiple independently addressable stimulation and response connections to obtain the selective stimulation, recording, channel-selection, and measurement capabilities expressly described by Negi.
One of ordinary skill in the art would have had a reasonable expectation of success because Negi expressly implements independently addressable electrode sites, separate conductive lead lines, electrically independent base contacts, and controller connections in a substrate-supported microneedle array, while Hantash expressly implements selectable active and return microneedle pairs connected to opposite poles. The applied references therefore demonstrate the technical compatibility and predictable operation of the proposed modifications.
Applicant’s general assertion that the references fail to teach every limitation is not persuasive because the present rejection identifies the particular teaching relied upon for each limitation of independent claim 1. Applicant has not presented separate substantive arguments directed to the additional limitations of the dependent claims. Those limitations are addressed by the particular teachings and reasoning set forth in their respective rejections. Accordingly, Applicant’s arguments do not overcome the present rejections under 35 U.S.C. § 103.
Conclusion
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/AARON MERRIAM/Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791
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