# US 9,517,020 B2 · IL-1 receptor antagonist-coated electrode and uses thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,517,020 B2 - Document ID: US9517020B2 - Status: Granted - Kind: B2 - Application number: 14/236,853 - Filed: 2012-07-23 - Published: 2014-09-04 - Granted: 2016-12-13 - Earliest claimed: 2011-08-04 - Assignees: Ramot at Tel-Aviv University Ltd. - Applicants: Yosi Shacham-Diamand; Matti Mintz; Aryeh Taub - Inventors: Yosi Shacham-Diamand; Matti Mintz; Aryeh Taub - Web page: https://patentgrep.com/patent/US9517020B2 ## CPC - A61B 5/388: Nerve conduction study, e.g. detecting action potential of peripheral nerves - A61B 5/293: Invasive - A61B 5/6868: {Brain} - A61L 27/28: Materials for coating prostheses - A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)} - A61N 1/0534: {Electrodes for deep brain stimulation} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) ## Abstract The present invention provides an electrode designed for implantation into the central nervous system (CNS) of a mammal, wherein said electrode is substantially coated with interleukin-1 receptor antagonist (IL-1ra) or a coating composition comprising it, and the IL-1ra actively inhibits scarring on or around the surface of the electrode when implanted into the CNS. The electrode of the invention may be used for brain recording and/or stimulation, and can thus be used for treatment of a brain dysfunction, a brain disease or disorder, or a brain injury, as well as for brain computer interface, brain machine interface, or electrotherapy. ## Claims ### Claim 1 An electrode designed for implantation into the central nervous system (CNS) of a mammal, said electrode comprising: (i) a sole electrical lead coated with an insulator forming a passivation layer, or multiple electrical leads each being either coated with an insulator forming a passivation layer or imprinted on a carrier and coated with an insulator forming a passivation layer; (ii) an adhesive layer consisting of an upper adhesive layer and optionally a lower adhesive layer; and (iii) interleukin-1 receptor antagonist (IL-1ra), wherein said lower adhesive layer, when present, is covalently linked to the surface of said passivation layer; said upper adhesive layer is covalently linked to said lower adhesive layer, when present, or to the surface of said passivation layer; and the IL-1ra is covalently linked to said upper adhesive layer and actively inhibits scarring on or around the surface of said electrode when implanted into the CNS. ### Claim 2 (depends on 1) The electrode according to claim 1, comprising the multiple electrode leads imprinted on the carrier, wherein said carrier is coated with said insulator. ### Claim 3 (depends on 1) The electrode according to claim 1, wherein: (i) said insulator is a silicon-based insulator, metal oxide, or polymer; (ii) said lower adhesive layer, when present, comprises amino functional alkoxysilane, mercapto functional alkoxysilane, aminoalkanethiol, carboxyalkanethiol, carboxyalkyldisulfide, succinimidyl ester, or ferrocenylalkanethiol; (iii) said upper adhesive layer comprises succinaldehyde, glutaraldehyde, adipaldehyde, heptanedial, octanedial, cyanoacrylate type adhesives, fibrin glue, gelatin-resorcin aldehyde type adhesives, or polyelectrolyte multilayers of hyaluronic acid and chitosan, coupled with surface-immobilized cell-adhesive arginine-glycine-aspartic acid peptide; (iv) said carrier is a silicon-based insulator, metal oxide, or polymer; or (v) each one of said electrical leads is made of a material selected from the group consisting of a metal, preferably a noble metal, a metal alloy, a metalloid, and a conducting ceramic material. ### Claim 4 (depends on 3) The electrode according to claim 3, wherein: (i) said silicon-based insulator is silicon nitride, silicon dioxide, or silicon oxynitride; said metal oxide is aluminum oxide, tantalum oxide, or hafnium oxide; and said polymer is a polyimide, or a plastic; (ii) said metal is gold, platinum, iridium, osmium, silver, palladium, rhodium or ruthenium, mercury, polonium, copper, bismuth, technetium, rhenium, or antimony; (iii) said metal alloy is selected from the group consisting of nitrides of refractory metals, metal borides, metal carbides, metal silicides, beryllides, metal selenides, metal phosphides, metal chromides, mixtures of the aforesaid, ternary alloys of the aforesaid with other elements, non-toxic nickel alloys, and quaternary alloys; (iv) said metalloid is boron, silicon, germanium, arsenic, antimony, tellurium, or polonium; or (v) said conducting ceramic material is a metal nitride, a metal carbide, a metal boride, a metal silicide, a metal beryllide, a metal selenide, a metal phosphide, a metal chromate, a metal-silicon nitride, a metal-silicon carbide, a metal-silicon boride, or a mixture thereof. ### Claim 5 (depends on 3) The electrode according to claim 3, wherein: (i) said amino functional alkoxysilane has the formula H2N—(C1-C8)alkylene-Si(OR1)3 or H2N—(C1-C8)alkylene-SiR2(OR1)2; (ii) said mercapto functional alkoxysilane has the formula HS—(C1-C8)alkylene-Si(OR1)3 or HS—(C1-C8)alkylene-SiR2(OR1)2; (iii) said aminoalkanethiol has the formula H2N—(C1-C8)alkylene-SH; (iv) said carboxyalkanethiol has the formula HOOC—(C1-C8)alkylene-SH; (v) said hydroxyalkanethiol has the formula HO—(C1-C8)alkylene-SH; (vi) said carboxyalkyldisulfide has the formula HOOC—(C1-C8)alkylene-S—S—(C1-C8)alkylene-COOH; or (vii) said ferrocenylalkanethiols has the formula ferrocenyl-(C1-C8)alkylene-SH, wherein R1 each independently is (C1-C4)alkyl; and R2 each independently is (C1-C4)alkyl or H. ### Claim 6 (depends on 3) The electrode according to claim 3, wherein said insulator is silicon nitride; said lower adhesive layer comprises 3-aminopropyltrimethoxysilane; said upper adhesive layer comprises glutaraldehyde; or said electrical lead each is made of titanium-nitride. ### Claim 7 (depends on 3) The electrode according to claim 3, wherein said metal is a noble metal. ### Claim 8 (depends on 1) The electrode according to claim 1, comprising a multi-channel with the multiple electrical leads, optionally configured as an implantable multi electrode array (MEA) and are imprinted on a carrier and coated with said insulator forming a passivation layer. ### Claim 9 (depends on 8) The multi-channel electrode according to claim 8, comprising 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 electrical leads, optionally configured as an implantable MEA, having a long shaft. ### Claim 10 (depends on 5) The multi-channel electrode according to claim 5, configured as an implantable MEA and comprising: (i) 10 electrical leads arranged on a penetrating tip, wherein said electrical leads are made of a conductive ceramic material, imprinted on silicon nitride as a carrier and coated with silicon nitride as an insulator forming a passivation layer; or (ii) 14 electrical leads arranged on a penetrating tip, wherein said electrical leads are made of a noble metal, imprinted on and coated with a polyimide. ### Claim 11 (depends on 10) The multi-channel electrode according to claim 10, wherein said conductive ceramic material is titanium-nitride. ### Claim 12 (depends on 1) The electrode according to claim 1, wherein said electrode is a single-shank electrode, or a member of a vector electrode or a three-dimensional electrode. ### Claim 13 (depends on 1) The electrode according to claim 1, wherein each one of said electrical leads is made of titanium-nitride; said insulator is silicon nitride; said lower adhesive layer comprises 3-aminopropyltrimethoxysilane; said upper adhesive layer comprises glutaraldehyde; and said carrier, when present, is made of silicon nitride. ### Claim 14 (depends on 1) The electrode according to claim 1, comprising a single channel with the sole electrical lead. ### Claim 15 (depends on 1) A method for central nervous system (CNS) recording and/or CNS stimulation in an individual suffering from a CNS dysfunction, disease or disorder, or CNS injury, said method comprising the steps of: implanting into the CNS of said individual at least one electrode each independently according to claim 1; and recording and/or stimulating said CNS with said at least one electrode. ### Claim 16 (depends on 15) The method of claim 15, wherein the at least one electrode is implanted in deep brain structures, further comprising receiving signals from the at least one electrode for deep brain recording, transmitting signals to the at least one electrode for deep brain stimulation, or both receiving signals from and transmitting signals to the at least one electrode for both deep brain recording and deep brain stimulation. ### Claim 17 (depends on 16) The method of claim 16, wherein the signals are received and/or transmitted in a manner configured for (i) treatment of a brain dysfunction, a brain disease or disorder, or a brain injury; (ii) electrotherapy; or (iii) establishing a brain computer interface, or a brain machine interface. ### Claim 18 (depends on 17) The method of claim 17, wherein (a) the individual is in need of treatment of said brain dysfunction, wherein said brain dysfunction is associated with an autoimmune disease, head trauma or neuronal trauma, or said brain dysfunction causes chronic pain or phantom limb pain; or (b) the individual is in need of treatment of said brain disease or disorder, wherein said brain disease or disorder is Parkinson's disease, epilepsy, dystonia, essential tremor, Tourette syndrome, a mental disorder, or an anxiety disorder; or said brain disease or disorder is associated with brain degradation or age-related brain degeneration. ### Claim 19 (depends on 15) The method of claim 15, wherein in said at least one electrode said insulator is silicon nitride; said lower adhesive layer comprises 3-aminopropyltrimethoxysilane; said upper adhesive layer comprises glutaraldehyde; or said electrical lead each is made of titanium-nitride. ### Claim 20 (depends on 15) The method of claim 15, wherein in said at least one electrode each one of said electrical leads is made of titanium-nitride; said insulator is silicon nitride; said lower adhesive layer comprises 3-aminopropyltrimethoxysilane; said upper adhesive layer comprises glutaraldehyde; and said carrier, when present, is made of silicon nitride. ### Claim 21 (depends on 15) The method of claim 15, wherein said at least one electrode is a single-channel electrode comprising a sole electrical lead. ### Claim 22 (depends on 15) The method of claim 15, wherein said at least one electrode is a multi-channel electrode comprising multiple electrical leads, optionally configured as an implantable multi electrode array (MEA) wherein said electrical leads are imprinted on a carrier and coated with said insulator forming a passivation layer.