DETAILED ACTION
This action is pursuant to the claims filed on 04/10/2025. Claims 1-6, 11-13, 15-16, 19, 21-24, 27, and 29-30 are pending. A first action on the merits of claims 1-6, 11-13, 15-16, 19, 21-24, 27, and 29-30 is as follows.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/10/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6, 11-13, 15-16, 19, 21-24, 27, and 29-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-2 recites the limitation "optionally". The phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For examination purposes, this limitation following “optionally” will be interpreted as being a part of the scope of the claim. Claims 2-6, 11-13, 15-16, 19, 21-24, 27, and 29-30 inherit this deficiency.
Claim 19 recites the limitation "optionally". The phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For examination purposes, this limitation following “optionally” will be interpreted as being a part of the scope of the claim.
Claim 22 recites “providing the electrode or the cellular electrode array of claim 1”. There is no antecedent basis for “the cellular electrode array” in the claim. It is unclear if applicant is attempting to reference “the cellular electrode array of claim 2” or “the electrode of claim 1”. Claims 23-24, 27, 29 inherit this deficiency. For examination purposes, this will be interpreted as “the cellular electrode array of claim 2”.
Claim 30 recites “providing the cellular electrode array of claim 1”. There is no antecedent basis for “the cellular electrode array” in the claim. It is unclear if applicant is attempting to reference “the cellular electrode array of claim 2” or “the electrode of claim 1”. For examination purposes, this will be interpreted as “the cellular electrode array of claim 2”.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-6, 12, 16, 19, 21-24, 27, 29, and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fan (U.S. PGPub No. 2023/0147961) in view of Cullen (U.S. PGPub No. 2019/0126043).
Regarding claim 1, Fan teaches An electrode comprising: at least one neuronal cell grafted to the outer surface of the electrically conducting material (Fig 1E neuronal soma 112); and a biological electrical connection between the grafted neuronal cell and a target neuronal cell in a biological tissue in which the electrode is positioned, wherein substantially all electrical connection between the electrode and the biological tissue is through the biological electrical connection (0004] and Figs 1A-E).
Fan fails to teach an electrically conducting material having an outer surface, wherein the outer surface is optionally formed of an outer material that is different from a core material of the electrically conducting material.
In related prior art, Cullen teaches a similar device comprising an electrically conducting material having an outer surface, wherein the outer surface is optionally formed of an outer material that is different from a core material of the electrically conducting material (Fig 1 outer surface of hydrogel sheath 104 with extracellular matrix core 102). Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Fan in view of Cullen to incorporate the conducting outer surface with a different material inner core. Doing so would be obvious to one of ordinary skill in the art as the use of a hydrogel sheath with an extracellular matrix core is well-known in the art in neural interfacing to produce the predictable result of a biocompatible and conductive neural device for contacting native neural tissue.
Regarding claim 2, Fan/Cullen further teach A cellular electrode array comprising: a plurality of electrodes of claim 1 (Fig 1A-C defines a plurality of the electrodes of claim 1); and a flexible polymer substrate having a top surface (Cullen [0182] [0193] disclosing use of PDMS substrate); an array of wells disposed in the flexible polymer substrate (Fig 1b microwell array 104), each well having: an inner-facing surface that defines a well volume (see Fig 1E microwell 110 with volume), the inner facing surface comprising a bottom surface and side wall surfaces that extend from the bottom surface to the flexible polymer substrate top surface (see Fig 1E); the electrically conducting material forming a conductive contact, optionally a polymer conductive contact, at least partially covering the well inner-facing surface (Fig 1E microelectrode array 116 with transition microelectrode 108; [0004] transition microelectrodes are formed as soft polymers); a well depth corresponding to a distance between the flexible polymer substrate top surface and the well bottom surface (see Fig 1E); a hydrogel disposed in each well ([0010]); wherein each well is configured to receive a neuronal cell to form the grafted neuronal cell to electrically connect to a neuronal cell in the biological tissue (Fig 1e neuronal soma 112), and the hydrogel is configured to provide directed growth of sprouted axons and dendrites from the neuronal cell in a direction toward the flexible polymer substrate top surface (see Fig 1E and 1C, top surface interpreted to be bottom of Fig 1E similar to top surface 20 of applicant’s Fig 1A). Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Cullen in view of Fan to incorporate a cellular electrode array with a flexible polymer substrate comprising a microwell array as taught by Fan to arrive at the device of claim 2. Doing so would advantageously allow for increased integration of neural electrodes with living neurons to further “explore human brain functions and treat neurological disease, enabling an advancement of neuroscience, medical practice, and a variety of other future technologies” ([0004]).
Regarding claim 3, in view of the combination of claim 2 above, Fan further teaches at least one neuronal cell in each of the wells, including an average of between 1 and 5 neuronal cells per well (Fig 1 [0103] disclosing one or more neurons; Fan [0060] disclosing a single neuron in each well).
Regarding claim 4, in view of the combination of claim 2 above, Fan/Cullen further teaches wherein the conductive polymer contact is positioned at the well bottom surface (Fig 1E microelectrode array 116 with transition microelectrode 108 at bottom of well surface; [0004] transition microelectrodes are formed as soft polymers).
Regarding claim 5, in view of the combination of claim 2 above, Fan/Cullen further teaches configured to operably connect flush against a tissue surface, including a tissue that corresponds to a brain surface with the operably connected mediated by synaptic connections between the neuronal cells in the wells and dendrites in the brain adjacent to the brain surface (Figs 4A-C, device is configured for the function as claimed).
Regarding claim 6, in view of the combination of claim 2 above, Fan/Cullen further teaches wherein: each well has a well depth that is between 10 µm and 2 mm (Fan [0093] wells have a depth of 20 µm); each well has a volume that is between 10 µL and 1 mL; each well has a characteristic diameter of between 1 µm and 1 mm; a well density of between 0.001 wells/µm2 (1000 wells/mm2) to 0.1 wells/µm2 (105 wells/mm2); and/or adjacent wells are separated by a separation distance of between 10 µm and 1 mm (examiner notes preceding limitations are recited in the alternative given the “and/or” recitation such that they need not be taught by the prior art in order to reject the claim).
Regarding claim 12, in view of the combination of claim 2 above, Fan/Cullen further teaches wherein the conductive polymer contact has a thickness of between 1 µm and 100 µm ([0073] transition microelectrode 108 is 50 to 250 micron in width) and/or greater than the well depth. It would have been obvious to one having ordinary skill in the art at before the effective filing date of the claimed invention to have modified Fan to incorporate the conductive polymer contact with a thickness of between 1 and 100 µm, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). One would have adjusted the conductive polymer contact thickness to optimize the recording spot to closely contact the integrated neuronal soma for well a controlled extracellular recording interface ([0073]).
Regarding claim 16, in view of the combination of claim 2 above, Fan/Cullen further teaches the neuronal cells grafted onto the conductive polymer contact ([0060-0061] disclosing culturing to secure attachment to well); wherein:the neuronal cells are selected to synaptically connect to a neural tissue during use ([0076]): and are immune compatible with a subject having the neural tissue for in vivo use or with the subject from which neural tissue is obtained for in vitro research use ([0087] neuronal cells are cultured from new born rats and used on rats, such that cells are immune compatible).
Regarding claim 19, in view of the combination of claim 2 above, Fan/Cullen further teaches wherein the top surface of the flexible polymer is an electrical conductor to ground the cellular electrode array so that during use electrical communication between the cellular electrode array and a subject is confined to the neuronal cells in the wells synaptically connected to the subject (in vivo) or to a volume of an explanted tissue (in vitro or ex vivo) (Fig 1E top surface 116 is conductive transition microelectrode to achieve claimed result): and having a device footprint of up to 1000 mm2 ([0073] array 116 is as small as 500 µm across which would equal a surface area of 0.25 mm^2, within the claimed range), and optionally with up to 10,000 unique contacts between the neuronal cells in the wells and a tissue in which the cellular electrode array is implanted (limitation is optional, as recited in the claim, thus need not be taught by the prior art).
Regarding claim 21, in view of the combination of claim 2 above, Fan/Cullen further teaches wherein the top surface comprises a surface electrode array for bulk electrical interfacing with a biological tissue (Figs 1A-C, electrode 103; also shown in Figs 4A-C).
Regarding claim 22, Fan/Cullen teaches A method of electrically interfacing with biological tissue, the method comprising the steps of: providing the electrode or the cellular electrode array of claim 1 (see rejection of claims 1-2 above).
Fan further teaches grafting a neuronal cell to the electrode or in each of the wells by providing less than 10 neuronal cells to the electrode or to each of the wells and culturing the neuronal cells to form axons and/or dendrites (Fig 1e neuronal soma 112; [0060] disclosing a single neuron in each well).); contacting the grafted neuronal cells to the biological tissue (see Fig 1A, C); electrically connecting at least a portion of the grafted neuronal cells to biological cells adjacent to the grafted neuronal cells, thereby forming electrical contacts between the biological tissue and the cellular electrode array ([0004]); and thereby electrically interfacing with the biological tissue via the grafted neuronal cells that are in electrical contact with the biological tissue ([0004] and Figs 1A-C).
Regarding claim 23, in view of the combination of claim 22 above, Fan/Cullen further teaches wherein the electrical interfacing comprises electrically actuating the biological tissue and/or measuring an electrical parameter of the biological tissue (Fan [0069]).
Regarding claim 24, in view of the combination of claim 22 above, Fan/Cullen further teaches wherein the electrically interfacing step comprises measuring current flowing to or from at least a portion of the grafted neuronal cells that are electrically connected to biological tissue ([0069]); and further comprising the steps of: selecting a portion of the wells having neuronal cells electrically connected to biological cells; and electrically interfacing the selected portion of the wells with the biological cells ([0060-0061] & [0069-0071] discloses implicit selection of wells and electrically interfacing said wells with biological cells); wherein the selected portion of wells corresponds to a spatial region having a surface area of between 1 µm2 and 5 mm2 ([0073] array 116 is as small as 500 µm across which would equal a surface area of 0.25 mm^2, within the claimed range).
Regarding claim 27, in view of the combination of claim 22 above, Fan/Cullen further teaches matching a mechanical property of the cellular electrode array with a mechanical property of the biological tissue ([0076] growth of grafted axons beyond probe guide into surrounding neural tissue is a matching of mechanical property of the electrode array with the biological tissue); wherein the biological tissue is selected from the group consisting of: brain, spinal cord, peripheral nerves, a three-dimensional cell culture (including a bioartificial organ), and organotypic cultures (Fan see Fig 2, device inserted into brain [0076]).
Regarding claim 29, in view of the combination of claim 22 above, Fan/Cullen discloses substantially all the limitations of the claim(s) except for wherein at least 80% of a total electric current between the cellular electrode array and surrounding electrically connected tissue is via the grafted neuronal cells. However, it would have been obvious to one having ordinary skill in the art at before the effective filing date of the claimed invention to have provided at least 80% of a total electric current between the array and surrounding electrically connected tissue is via the grafted neuronal cells, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). One would have done so to attempt to maximize the recording and/or stimulating capability of the neural interface to further “explore human brain functions and treat neurological disease, enabling an advancement of neuroscience, medical practice, and a variety of other future technologies” (Fan [0004]).
Regarding claim 30, Fan/Cullen teaches A method of making a grafted cellular electrode array, the method comprising the steps of: providing the cellular electrode array of claim 1 (see rejection of claims 1-2 above); introducing at least one neuronal cell to at least one well (Fan [0060] disclosing a single neuron in each well); culturing the at least one neuronal cell for a time period selected to ensure: attachment the at least one neuronal cell to a bottom surface and/or a sidewall of the well, or the hydrogel scaffold ([0060-0061] disclosing culturing to secure attachment to well); sprouting axons and/or dendrites from the at least one neuronal cell, thereby grafting the neuronal cell to the well and making the grafted cellular electrode array ([0061] axons grow post-implantation to form grafted cellular electrode array interfaced with tissue).
Claim(s) 11 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fan in view of Cullen, and in further view of Guvanasen (U.S. PGPub No. 2013/0338746).
Regarding claim 11, the Fan/Cullen combination teaches the device of claim 2 as stated above.
Fan/Cullen fail to teach explicitly teach wherein the polymer substrate is conformable to a tissue surface.
In related prior art, Guvanasen teaches a similar polymer substrate that is conformable to a tissue surface (Fig 5 PDMS substrate 505; [0014] discloses conformability). Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the substrate of Fan in view of Cullen and Guvanasen to incorporate a conformable polymer substrate to arrive at claim 11. Doing so would advantageously enable the device to provide three dimensional conformance to live tissue ([0014]).
Regarding claim 13, the Fan/Cullen combination teaches the device of claim 2 as stated above.
Fan/Cullen fail to teach wherein the flexible polymer substrate comprises a plurality of polydimethylsiloxane (PDMS) layers, including a conductive PDMS layer and a non-conductive PDMS layer; wherein the non-conductive PDMS layer on the conductive PDMS layer forms an insulated conductive layer that is an electrical interconnect between the electrodes and external electronic components; wherein the conductive PDMS layer is a PDMS composite layer.
In related prior art, Guvanasen teaches a similar device wherein the flexible polymer substrate comprises a plurality of polydimethylsiloxane (PDMS) layers, including a conductive PDMS layer and a non-conductive PDMS layer ([0016] disclosing a conductive PDMS layer with a PDMS layer on top of the conductive layer); wherein the non-conductive PDMS layer on the conductive PDMS layer forms an insulated conductive layer that is an electrical interconnect between the electrodes and external electronic components ([0075]; [0048] disclosing pad form electrical interconnect between electrodes 515 and external electronics); wherein the conductive PDMS layer is a PDMS composite layer ([0040]). Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the electrical interconnection of Fan in view of Cullen and Guvanasen to incorporate a conductive PDMS layer and a non-conductive PDMS layer to form an insulated conductive layer that functions as an electrical interconnect to arrive at claim 13. Doing so advantageously provides a conductive interconnect for the neural interface without requiring solder or epoxy compounds ([0049]).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fan in view of Cullen, and in further view of Horn (U.S. PGPub No. 2021/0268268).
Regarding claim 15, the Fan/Cullen combination teaches the device of claim 2 as stated above.
Fan/Cullen fail to teach at least two non-conductive PDMS layers.
In related prior art, Horn teaches a similar device wherein the array comprises at least two non-conductive PDMS layers ([0103] disclosing one or more PDMS outer layers). Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Fan in view of Cullen and Horn to incorporate at least two non-conductive PDMS substrate layers to arrive at claim 15. The use of non-conductive PDMS as a substrate is well-known in the art due to PDMS’ biocompatibility ([0166]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Adam Z Minchella whose telephone number is (571)272-8644. The examiner can normally be reached M-Fri 7-3 EST.
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/ADAM Z MINCHELLA/Primary Examiner, Art Unit 3794
