# US 10,869,830 B2 · Rapid establishment and/or termination of substantial steady-state drug delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,830 B2 - Document ID: US10869830B2 - Status: Granted - Kind: B2 - Application number: 16/029,232 - Filed: 2018-07-06 - Published: 2019-04-11 - Granted: 2020-12-22 - Earliest claimed: 2009-09-28 - Assignees: Intarcia Therapeutics, Inc. - Applicants: Intarcia Therapeutics, Inc. - Inventors: Thomas R. Alessi; Kenneth Luskey - Web page: https://patentgrep.com/patent/US10869830B2 ## CPC - A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas} - A61F 5/0013: {Implantable devices or invasive measures} - A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)} - A61K 38/26: Glucagons - A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} - A61M 5/14276: {specially adapted for implantation} - A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system - A61P 1/08: for nausea, cinetosis or vertigo; Antiemetics - A61P 3/04: Anorexiants; Antiobesity agents - A61P 3/06: Antihyperlipidemics - A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48) - A61P 3/10: for hyperglycaemia, e.g. antidiabetics - A61P 5/48: of the pancreatic hormones - A61P 9/12: Antihypertensives - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61M 2005/14513: {with secondary fluid driving or regulating the infusion} - A61M 2205/04: implanted - 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) - 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) - 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) - 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)} - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention is directed to treatment methods for a disease or condition, in a subject in need of such treatment, that provide alternatives to treatment by injection that give, relative to treatment by injection, improved treatment outcomes, 100% treatment compliance, reduced side effects, and rapid establishment and/or termination of substantial steady-state drug delivery. The method typically includes providing continuous delivery of a drug from an implanted osmotic delivery device, wherein substantial steady-state delivery of the drug at therapeutic concentrations is typically achieved within about 7 days or less after implantation of the osmotic delivery device in the subject and the substantial steady-state delivery of the drug from the osmotic delivery device is continuous over a period of at least about 3 months. In one embodiment, the present invention is directed to treatment of type 2 diabetes mellitus using incretin mimetics. ## Claims ### Claim 1 Multiple osmotic delivery devices, comprising a first implantable osmotic delivery device comprising exenatide that provides continuous administration of 20 mcg/day exenatide, the first implantable osmotic delivery device being configured for administration during a first dosing period, and a second implantable osmotic delivery device comprising exenatide that provides continuous administration of 60 mcg/day exenatide, the second implantable osmotic delivery device being configured for administration during a second dosing period, wherein the multiple osmotic delivery devices are configured to provide a dose escalation of exenatide to a human subject upon implantation of the first osmotic delivery device in the human subject, removal of the first osmotic delivery device from the human subject, and implantation of the second osmotic delivery device in the human subject. ### Claim 2 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein each of the first and second implantable osmotic delivery devices comprises a suspension formulation of the exenatide. ### Claim 3 (depends on 2) The multiple osmotic delivery devices according to claim 2, wherein the suspension formulation comprises a particle formulation of the exenatide. ### Claim 4 (depends on 2) The multiple osmotic delivery devices according to claim 2, wherein the suspension formulation comprises a particle formulation of the exenatide and a vehicle formulation, wherein the vehicle formulation comprises a solvent and a polymer, wherein the solvent is selected from the group consisting of benzyl benzoate, lauryl lactate, and lauryl alcohol, and the polymer is polyvinylpyrrolidone. ### Claim 5 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein each of the first and second implantable osmotic delivery devices provides substantial steady-state delivery of the exenatide that is continuous for at least about three months to about one year. ### Claim 6 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein the first implantable osmotic delivery device provides continuous administration of 20 mcg/day of exenatide for about 3 months. ### Claim 7 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein the first implantable osmotic delivery device provides continuous administration of 20 mcg/day of exenatide for about 3 months, and the second implantable osmotic delivery device provides continuous administration of 60 mcg/day of exenatide for about 6 months. ### Claim 8 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein each of the first and second implantable osmotic delivery devices comprises a cylindrical reservoir that is capped at one end by a rate-controlled semi-permeable membrane and capped at the other end by a diffusion moderator. ### Claim 9 (depends on 8) The multiple osmotic delivery devices according to claim 8, wherein each osmotic delivery device comprises: an impermeable reservoir comprising interior and exterior surfaces and first and second open ends; a semi-permeable membrane in sealing relationship with the first open end of the reservoir; an osmotic engine within the reservoir and adjacent the semi-permeable membrane; a piston adjacent the osmotic engine, wherein the piston forms a movable seal with the interior surface of the reservoir, the piston divides the reservoir into a first chamber and a second chamber, the first chamber comprising the osmotic engine; a suspension formulation, wherein the second chamber comprises the suspension formulation; and a diffusion moderator inserted in the second open end of the reservoir, the diffusion moderator adjacent the suspension formulation. ### Claim 10 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for treating type 2 diabetes in the human subject. ### Claim 11 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing body weight in the human subject. ### Claim 12 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured to facilitate weight loss in the human subject. ### Claim 13 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for treating obesity in the human subject. ### Claim 14 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for suppressing appetite in the human subject. ### Claim 15 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing HbAlc plasma concentration in the human subject. ### Claim 16 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing LDL-C in the human subject. ### Claim 17 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing glucose levels in the human subject. ### Claim 18 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing fructosamine levels in the human subject. ### Claim 19 (depends on 1) The multiple osmotic delivery devices according to claim 1, configured for reducing systolic blood pressure in the human subject. ### Claim 20 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein each of the first and second implantable osmotic delivery devices is configured to provide substantial steady-state delivery of exenatide at a therapeutic concentration within about 5 days after each implantation of each osmotic delivery device. ### Claim 21 (depends on 1) The multiple osmotic delivery devices according to claim 1, wherein each of the first and second implantable osmotic delivery devices is further configured to provide substantial steady-state delivery of exenatide that is continuous for at least about 3 months.