# US 8,788,037 B2 · Device, method, and system for neural modulation as vaccine adjuvant in a vertebrate subject > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 8,788,037 B2 - Document ID: US8788037B2 - Status: Granted - Kind: B2 - Application number: 13/673,517 - Filed: 2012-11-09 - Published: 2013-03-28 - Granted: 2014-07-22 - Earliest claimed: 2009-12-22 - Assignees: The Invention Science Fund I, LLC - Applicants: Searete LLC - Inventors: Gregory J. Della Rocca; Joshua L. Dowling; Eleanor V. Goodall; Roderick A. Hyde; Jordin T. Kare; Muriel Y. Ishikawa; Eric C. Leuthardt; Stephen L. Malaska; Nathan P. Myhrvold; Paul Santiago; Todd J. Stewart; Elizabeth A. Sweeney; Clarence T. Tegreene; Lowell L. Wood, Jr.; Victoria Y. H. Wood - Web page: https://patentgrep.com/patent/US8788037B2 ## CPC - A61M 37/00: Other apparatus for introducing media into the body (for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30); Percutany, i.e. introducing medicines into the body by diffusion through the skin (salt baths A61H33/04) - A61F 7/00: Heating or cooling appliances for medical or therapeutic treatment of the human body (hyperthermia using electric or magnetic fields or ultrasound A61N) - A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants - A61M 37/0092: {using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis} - A61N 1/303: {Constructional details (electrodes for external use A61N1/0428)} - A61N 1/306: {Arrangements where at least part of the apparatus is introduced into the body} - A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)} - A61N 1/36121: {Production of neurotransmitters; Modulation of genes expression} - A61N 2/00: Magnetotherapy - A61N 2/002: {in combination with another treatment} - A61N 2/006: {for magnetic stimulation of nerve tissue} - A61P 37/00: Drugs for immunological or allergic disorders - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61N 2/02: using magnetic fields produced by coils, including single turn loops or electromagnets (A61N2/12 takes precedence) - A61N 5/0622: {Optical stimulation for exciting neural tissue} - 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)} - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method for enhancing an immune response in a vertebrate subject is described. The method includes providing at least one energy stimulus configured to modulate one or more nervous system components of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are provided in a combination and in a temporal sequence sufficient to enhance an immune response in the vertebrate subject. ## Claims ### Claim 1 A method for eliciting an enhanced immune response to a neoplasm in a vertebrate subject comprising: providing at least one energy stimulus from one or more transducers, wherein the at least one energy stimulus is configured to modulate one or more nervous system components in a tissue of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are configured to provide in a combination and in a temporal sequence sufficient to enhance an immune response to the one or more immunogen in the vertebrate subject. ### Claim 2 (depends on 1) The method of claim 1, wherein the at least one energy stimulus includes one or more of electrical energy, magnetic energy, electromagnetic energy, ultrasonic energy, acoustic energy, mechanical energy, or thermal energy. ### Claim 3 (depends on 2) The method of claim 2, wherein the at least one energy stimulus includes at least one energy characteristic having one or more of waveform, frequency, amplitude, or duration. ### Claim 4 (depends on 3) The method of claim 3, wherein an application pattern of the at least one energy stimulus includes one or more of a cyclical pattern, an intermittent pattern, a repetitive pattern, a random pattern, or a non-random pattern. ### Claim 5 (depends on 1) The method of claim 1, wherein the neoplasm includes a neoplasm in one or more of a lymphoid tissue, a myeloid tissue, a hematopoietic tissue, a nervous tissue, an epithelial tissue, an endothelial tissue, or a muscle tissue. ### Claim 6 (depends on 1) The method of claim 1, wherein the one or more immunogen includes one or more of a polypeptide, a lipid, a carbohydrate, a lipopolysaccharide, a nucleic acid, a peptide mimetic, a viral antigen, a bacterial antigen, a carcinoembryonic antigen, a mucin, a glycosphingolipid, a genetically engineered antigen, an antigen designed in silico, or a synthetic antigen. ### Claim 7 (depends on 1) The method of claim 1, wherein the at least one energy stimulus and immunogen are provided simultaneously. ### Claim 8 (depends on 1) The method of claim 1, wherein the at least one energy stimulus is provided prior to administering the immunogen. ### Claim 9 (depends on 1) The method of claim 1, wherein the immunogen is provided prior to providing the at least one energy stimulus. ### Claim 10 (depends on 1) The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided at one administration site. ### Claim 11 (depends on 1) The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided at different administration sites. ### Claim 12 (depends on 1) The method of claim 1, wherein the at least one energy stimulus and the immunogen are provided as a booster immunization. ### Claim 13 (depends on 1) The method of claim 1, comprising directing the at least one energy stimulus from an energy generator through the one or more transducers to a tissue. ### Claim 14 (depends on 1) The method of claim 1, comprising providing the at least one energy stimulus to a tissue near an immunogen administration site. ### Claim 15 (depends on 1) The method of claim 1, wherein providing the at least one energy stimulus includes stimulating the one or more nervous system components in the vertebrate subject. ### Claim 16 (depends on 1) The method of claim 1, wherein providing the at least one energy stimulus includes inhibiting the one or more nervous system components in the vertebrate subject. ### Claim 17 (depends on 1) The method of claim 1, wherein providing the at least one energy stimulus includes modulating release of a neurotransmitter. ### Claim 18 (depends on 17) The method of claim 17, wherein the neurotransmitter modulates one or more nerve impulses in the vertebrate subject. ### Claim 19 (depends on 17) The method of claim 17, wherein modulating release includes stimulating release of the neurotransmitter. ### Claim 20 (depends on 17) The method of claim 17, wherein modulating release includes inhibiting release of the neurotransmitter. ### Claim 21 (depends on 17) The method of claim 17, wherein the neurotransmitter modulates a function of one or more cells of the vertebrate subject. ### Claim 22 (depends on 21) The method of claim 21, wherein the one or more cells include nerve cells. ### Claim 23 (depends on 21) The method of claim 21, wherein the one or more cells include the same cells that released the neurotransmitter. ### Claim 24 (depends on 21) The method of claim 21, wherein the one or more cells include a non-nervous system cell type. ### Claim 25 (depends on 17) The method of claim 17, wherein the neurotransmitter includes a glucocorticoid, norepinephrine, noradrenalin, neuropeptide Y, substance P, CGRP, NGF or VIP. ### Claim 26 (depends on 1) The method of claim 1, wherein the at least one energy stimulus is provided to the vertebrate subject in the vicinity of an immunogen administration site. ### Claim 27 (depends on 1) The method of claim 1, wherein the at least one energy stimulus is provided to a tissue of the vertebrate subject in the vicinity of a lymph node, wherein the lymph node is located within a region of an immunogen administration site of the vertebrate subject. ### Claim 28 (depends on 1) The method of claim 1, wherein providing the at least one energy stimulus is configured to elicit a systemic neurogenic response in the vertebrate subject. ### Claim 29 (depends on 1) The method of claim 1, wherein providing the at least one energy stimulus is configured to elicit a local neurogenic response in the vertebrate subject. ### Claim 30 (depends on 1) The method of claim 1, wherein the at least one energy stimulus is provided to a tissue of the vertebrate subject and configured to enhance a response involving a lymphoid organ, thymus, spleen, bone marrow, peritoneum, mucosal tissue, or a portion of a digestive tract. ### Claim 31 (depends on 4) The method of claim 4, wherein providing the application pattern includes applying the pattern at one or more sites. ### Claim 32 (depends on 1) The method of claim 1, comprising providing one or more compounds to the vertebrate subject including an adjuvant, a hapten, an immunomodulatory compound, a cytokine, a chemokine, a growth factor, or a cell-signaling compound. ### Claim 33 A system comprising: an apparatus comprising an energy generator configured to provide at least one energy stimulus to one or more nervous system components at a first location on a vertebrate subject, and a device configured to deliver one or more immunogen at a second location on the vertebrate subject. ### Claim 34 A method for vaccinating a vertebrate subject against a disease comprising: providing at least one energy stimulus from one or more transducers, wherein the at least one energy stimulus is configured to modulate one or more nervous system components in a tissue of the vertebrate subject, and administering one or more immunogen to the vertebrate subject, wherein the at least one energy stimulus and the one or more immunogen are configured to provide in a combination and in a temporal sequence sufficient to accelerate, prolong, facilitate, or alter in form or type the immune response to the one or more immunogen in the vertebrate subject. ### Claim 35 (depends on 34) The method of claim 34, wherein the at least one energy stimulus includes one or more of electrical energy, magnetic energy, electromagnetic energy, ultrasonic energy, acoustic energy, mechanical energy, or thermal energy. ### Claim 36 (depends on 34) The method of claim 34, wherein the one or more immunogen includes one or more of a bacterial antigen, a viral antigen, a fungal antigen, or a parasital antigen. ### Claim 37 (depends on 34) The method of claim 34, wherein the one or more immunogen includes a tumor antigen. ### Claim 38 (depends on 34) The method of claim 34, wherein the one or more immunogens are self-administered prior to providing the at least one energy stimulus. ### Claim 39 (depends on 34) The method of claim 34, wherein the one or more immunogens are self-administered after providing the at least one energy stimulus. ### Claim 40 (depends on 34) The method of claim 34, comprising directing the at least one energy stimulus from an energy generator through the one or more transducers. ### Claim 41 (depends on 34) The method of claim 34, comprising providing the at least one energy stimulus to a tissue near an immunogen administration site. ### Claim 42 (depends on 34) The method of claim 34, wherein providing the at least one energy stimulus includes stimulating the one or more nervous system components in the vertebrate subject. ### Claim 43 (depends on 34) The method of claim 34, wherein providing the at least one energy stimulus includes inhibiting the one or more nervous system components in the vertebrate subject. ### Claim 44 (depends on 34) The method of claim 34, wherein providing the at least one energy stimulus includes modulating release of a neurotransmitter. ### Claim 45 (depends on 34) The method of claim 34, comprising providing the at least one energy stimulus and immunogen simultaneously. ### Claim 46 (depends on 34) The method of claim 34, comprising providing the at least one energy stimulus is prior to administering the immunogen. ### Claim 47 (depends on 34) The method of claim 34, comprising providing the immunogen prior to providing the at least one energy stimulus. ### Claim 48 (depends on 34) The method of claim 34, comprising providing the at least one energy stimulus and the immunogen at one administration site. ### Claim 49 (depends on 34) The method of claim 34, comprising providing the at least one energy stimulus and the immunogen at different administration sites. ### Claim 50 A system for enhancing an immune response in a vertebrate subject comprising: circuitry for an energy generator providing at least one energy stimulus configured to modulate one or more nervous system components at a first location on a vertebrate subject, and circuitry for an apparatus configured to deliver one or more immunogen at a second location on the vertebrate subject.