( 2 (51) International Patent Classification: [US/US]; 1150 South Olive Street, Suite 2300, Los Ange¬ A61N 1/18 (2006.01) A47K 13/00 (2006.01) les, California 90015 (US). A61N 1/36 (2006.01) (72) Inventors: GAD, Parag; c/o The Regents of the Univer¬ (21) International Application Number: sity of California, 1111 Franklin Street, 12th Floor, Oak¬ PCT/US2020/033830 land, California 94607-5200 (US). EDGERTON, Victor Reggie; c/o The Regents of the University of Califor¬ (22) International Filing Date: nia, 1111 Franklin Street, 12th Floor, Oakaldn, Califor¬ 20 May 2020 (20.05.2020) nia 94607-5200 (US). TACCOLA, Giuliano; c/o SCUO¬ (25) Filing Language: English LA INTERN AZIONALE SUPERIORE DI STUDI AVAN- ZATI - SISSA, via Bonomea no. 265, 34136 Trieste (IT). (26) Publication Language: English KREYDIN, Evgenily I.; c/o UNIVERSITY OF SOUTH¬ (30) Priority Data: ERN CALIFORNIA, 1150 South Olive Street, Suite 2300, 62/85 1,572 22 May 2019 (22.05.2019) US Los Angeles, California 90015 (US). 62/876,583 19 July 2019 (19.07.2019) US (74) Agent: HUNTER, Tom et al.; WEAVER AUSTIN VIL- (71) Applicants: THE REGENTS OF THE UNIVERSITY LENEUVE & SAMPSON LLP, P.O. Box 70250, Oakland, OF CALIFORNIA [US/US]; 1111 Franklin Street, 12th California 94612-0250 (US). Floor, Oakland, California 94607-5200 (US). SCUOLA (81) Designated States (unless otherwise indicated, for every INTERNAZIONALE SUPERIORE DI STUDI AVAN- kind of national protection av ailable) . AE, AG, AL, AM, [IT/IT]; via Bonomea o. 265, 34136 Trieste ZATI - SISSA AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (IT) UNIVERSITY OF SOUTHERN CALIFORNIA (54) Title: TRANSCUTANEOUS ELECTRICAL SPINAL CORD NEUROMODULATOR AND USES THEREOF (57) Abstract: In various embodiments electrical stimulators are provided for transcutaneous and/or epidural stimulation. In certain embodiments the stimulator provides one or more channels configured to provide one or more of the following stimulation patterns: i) monophasic electrical stimulation with a DC offset; ii) monophasic electrical stimulation with charge balance; iii) delayed biphasic electrical stimulation with a DC offset; iv) delayed biphasic electrical stimulation with charge balance ;v) amplitude modulated dynamic stimulation; and/or vi) frequency modulated dynamic stimulation. [Continued on nextpage] CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, WS, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) TRANSCUTANEOUS ELECTRICAL SPINAL CORD NEUROMODULATOR AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims benefit of and priority to USSN 62/876,583, filed on July 19, 2019, and to USSN 62/851,572, filed on May 22, 2019, both of which are incorporated herein by reference in their entirety for all purposes. STATEMENT OF GOVERNMENTAL SUPPORT [0002] This invention was made with government support under Grant Number EB007165, awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND [0003] Serious spinal cord injuries (SCI) affect approximately 1.3 million people in the United States, and roughly 12-15,000 new injuries occur each year. Of these injuries, approximately 50% are complete spinal cord injuries in which there is essentially total loss of sensory and/or motor function and autonomic function below the level of the spinal lesion. Additionally, numerous neurodegenerative conditions (e.g., stroke, Parkinson's disease, Huntington's disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), dystonia, cerebral palsy, and the like) and other traumas (e.g., hemispherictomy, dorsal and/or ventral root rhizotomy or avulsion, and the like) can result in partial or total loss of sensory and/or motor function and autonomic function. Further, Overactive Bladder (OAB) leading to urgency, increased frequency and urinary incontinence and is one of the most prevalent conditions in the US and affects approximately 37M Americans. This condition, although not life-threatening, is a huge burden and takes a significant toll on the quality of life for anyone living with this condition and negatively affects people both physically, psychologically, economically and may lead people to alter their lives. [0004] Neuronal networks formed by the interneurons of the spinal cord that are located in the brainstem, cervical, thoracic, and lumbar enlargements, such as the spinal networks (SNs), can play an important role in the control of posture, locomotion, movements of the upper limbs, trunk, breathing, speech, coughing, eating, vision and cardiovascular, bladder and/or bowel and sexual function. Most researchers believe that essentially all mammals, including humans, have spinal networks in the various regions of the spinal cord. Normally, the activity of spinal cord networks is regulated supraspinally and by peripheral sensory input. In the case of disorders of the connections between the brain and spinal cord, e.g., as a result of traumatic spinal cord lesions or various neurodegenerative conditions, motor tasks can be enabled by electrical stimulation of the lumbosacral and cervical segments as well as the brainstem. Such stimulation has been provided using epidural stimulation or transcutaneous electrical stimulation (see, e.g., PCT/US2014/057886, PCT/US2014/029340, PCT/US2016/045898, PCT/US20 15/047268, PCT/US2015/046378, PCT/US2016/049129, and the like). [0005] However, the use of systems to provide transcutaneous electrical stimulation has been hampered by the necessity to deliver relatively high voltage stimulation at the skin surface often resulting in discomfort and/or irritation and reduced subject compliance. SUMMARY [0006] In various embodiments electrical stimulators are provided for transcutaneous and/or epidural stimulation. In certain embodiments the stimulator provides one or more channels configured to provide one or more of the following stimulation patterns: i) monophasic electrical stimulation with a DC offset; ii) monophasic electrical stimulation with charge balance; iii) delayed biphasic electrical stimulation with a DC offset; iv) delayed biphasic electrical stimulation with charge balance; v) amplitude modulated dynamic stimulation; and/or vi) frequency modulated dynamic stimulation. [0007] Various embodiments contemplated herein may include, but need not be limited to, one or more of the following: [0008] Embodiment 1: A transcutaneous or epidural electrical spinal cord stimulator, said stimulator comprising one or more channels configured to provide one or more of the following stimulation patterns: [0009] i) monophasic electrical stimulation with a DC offset; [0010] ii) monophasic electrical stimulation with charge balance; [0011] iii) delayed biphasic electrical stimulation with a DC offset; [0012] iv) delayed biphasic electrical stimulation with charge balance; [0013] v) amplitude modulated dynamic stimulation; and/or [0014] vi) frequency modulated dynamic stimulation. [0015] Embodiment 2 : The electrical stimulator of embodiment 1, wherein said stimulator comprises two or more independently configurable channels each capable of independently providing one or more of said stimulation patterns. [0016] Embodiment 3: The electrical stimulator of embodiment 1, wherein said stimulator comprises four or more independently configurable channels each capable of independently providing one or more of said stimulation patterns. [0017] Embodiment 4 : The electrical stimulator of embodiments 2-3, wherein said two or more or said four or more channels provide said stimulation patterns with respect to a common neutral line. [0018] Embodiment 5: The electrical stimulator of embodiments 2-3, wherein each of said two or more or each of said four or more channels provide said stimulation patterns with respect to neutral line for that channel. [0019] Embodiment 6: The electrical stimulator according to any one of embodiments 1-5, wherein the monophasic or biphasic electrical stimulation comprises bursts of carrier high frequency pulses where the frequency end amplitude of said bursts provides a stimulation signal frequency and amplitude, and the frequency of said high frequency carrier pulses comprising said bursts is a pain suppression carrier frequency. [0020] Embodiment 7 : The electrical stimulator of embodiment 6, where the high frequency carrier comprises a pulse frequency sufficient to reduce or block pain or discomfor produced by the stimulation signal. [0021] Embodiment 8: The electrical stimulator of embodiment 6, wherein said frequency provides pain relief to pelvic
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