# US 11,026,842 B2 · Method of providing agents to the cochlea > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,026,842 B2 - Document ID: US11026842B2 - Status: Granted - Kind: B2 - Application number: 15/387,344 - Filed: 2016-12-21 - Published: 2017-06-22 - Granted: 2021-06-08 - Earliest claimed: 2009-07-15 - Assignees: NewSouth Innovations Pty Limited - Applicants: NewSouth Innovations Pty Limited - Inventors: Gary David Housley - Web page: https://patentgrep.com/patent/US11026842B2 ## CPC - A61F 11/00: Methods or devices for treatment of the ears or hearing sense (implantable prostheses that substitute or replace internal ear parts, e.g. ear-drums, A61F2/18; methods or devices to cause a change in the state of auditory consciousness A61M21/00; electrotherapy applying electrical stimulation of the auditory system, or circuits therefor A61N1/36; radiotherapy using optical stimulation of the auditory system A61N5/06; electro-acoustic hearing aids H04R25/00); Non-electric hearing aids; Methods or devices for enabling ear patients to achieve auditory perception through physiological senses other than hearing sense; Protective devices for the ears, carried on the body or in the hand (headwear, e.g. caps or helmets, with means for protecting the ears A42B1/0188, A42B3/16) - A61K 41/0047: {Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent} - A61K 48/0075: {characterised by an aspect of the delivery route, e.g. oral, subcutaneous} - A61N 1/0412: {Specially adapted for transcutaneous electroporation, e.g. including drug reservoirs} - A61N 1/0541: {Cochlear electrodes} - A61N 1/327: {for enhancing the absorption properties of tissue, e.g. by electroporation} - A61M 2037/0007: {having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents} - A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - 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) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} ## Abstract Provided is a method of transfecting cells of the cochlea with an agent by electroporation, and in certain embodiments using a cochlear implant to provide at least one electroporation electrode. ## Claims ### Claim 1 A cochlear implant, comprising: auditory nerve stimulator circuitry to generate an auditory nerve stimulator electrical pulse profile; a linear array of electrodes configured as a series of independently addressable nodes along a length of the cochlear implant which lies within the cochlea, each of the series of independently addressable nodes coupled to the auditory nerve stimulator circuitry for providing the auditory nerve stimulator electrical pulse profile to the cochlea; and electroporation-driving circuitry, separate from the auditory nerve stimulator circuitry, coupled to a plurality of the independently addressable nodes of the linear array of electrodes of the cochlear implant for electroporation using one or more electrodes as anodes and one or more other electrodes interspersed along the linear electrode array as cathodes for electroporation current delivery such that the cochlear implant can generate an electroporation mode electrical pulse profile delivering high field strength current, and provide the electroporation electrical pulse profiles to the cochlea via the plurality of addressable nodes to transfect cells along the length of the linear array. ### Claim 2 (depends on 1) The cochlear implant of claim 1, wherein the implant comprises a lumen or channel for delivery of an agent to the cochlea. ### Claim 3 (depends on 2) The cochlear implant of claim 2, wherein the agent comprises a nucleic acid module encoding a neurotropic factor for spiral ganglion cells. ### Claim 4 (depends on 3) The cochlear implant of claim 3, wherein the neurotropic factor is selected from any one of Neurotrophin-3, Neurotrophin-3 precursor molecule, Neurotrophin 4/5, Nerve growth factor, Brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and Activity dependent neurotrophic factor. ### Claim 5 (depends on 1) The cochlear implant of claim 1, wherein groups of nodes of said cochlear implant are driven together to act as one electrode for electroporation. ### Claim 6 (depends on 1) The cochlear implant of claim 1, wherein said electroporation mode electrical pulse profile is provided with a voltage of from 10 to 100 volts. ### Claim 7 (depends on 1) The cochlear implant of claim 1, wherein polarity of individual nodes is altered over time during electroporation. ### Claim 8 (depends on 1) The cochlear implant of claim 1, wherein the electroporation-driving circuitry is configured to deliver a square wave or ramped electroporation stimulus of from 100 μs to 500 ms duration, optionally 30 ms duration. ### Claim 9 (depends on 1) The cochlear implant of claim 1, wherein the electroporation-driving circuitry is configured to deliver said electroporation stimulus in from 25 to 200 pulses, optionally, 50 to 100 pulses, with intervals between pulses of 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 seconds. ### Claim 10 An electroporation apparatus for transfecting cells of the cochlea with an agent, the apparatus comprising: an electroporation electrode array shaped to model a cochlear implant prosthesis configured for temporary insertion into the cochlear for performing electroporation and subsequently removed, the electroporation electrode array being electrically conductive at its surface along one or more portions of the entire length of the electrode, and electrically non-conductive at its surface along other portions of its length to provide a linear array of two or more contiguous electrodes, without tissue in between, to be driven as anodes and cathodes for electroporation; and external electroporation-driving circuitry connected to the electrodes of the electroporation electrode array and configured to provide electroporation electrical pulse profiles having a square wave or ramped electroporation stimulus with pulse width from 100 μs to 500 ms and a voltage of at least 10 volts via the electroporation electrode array, to drive the electrodes in the linear array as anodes and cathodes to generate an electric field adjacent the array to transfect cells in tissue adjacent the linear array. ### Claim 11 (depends on 10) The electroporation apparatus as claimed in claim 10, wherein the non-conductive portions are insulated at the surface of the electrode with a coating. ### Claim 12 (depends on 10) The electroporation apparatus as claimed in claim 10 wherein the electrode comprises a lumen or channel for delivery of an agent to the cochlea. ### Claim 13 (depends on 12) The electroporation apparatus as claimed in claim 12, wherein the agent comprises a nucleic acid module encoding a neurotropic factor for spiral ganglion cells. ### Claim 14 (depends on 13) The electroporation apparatus as claimed in claim 13, wherein the neurotropic factor is selected from any one of Neurotrophin-3, Neurotrophin-3 precursor molecule, Neurotrophin 4/5, Nerve growth factor, Brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and Activity dependent neurotrophic factor. ### Claim 15 (depends on 10) The electroporation apparatus of claim 10, wherein the electroporation electrode array comprises a lumen or channel for delivery of an agent.