# US 11,439,592 B2 · Ocular implant containing a tyrosine kinase inhibitor > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,592 B2 - Document ID: US11439592B2 - Status: Granted - Kind: B2 - Application number: 17/210,696 - Filed: 2021-03-24 - Published: 2021-10-07 - Granted: 2022-09-13 - Earliest claimed: 2020-03-25 - Assignees: Ocular Therapeutix, Inc. - Applicants: Ocular Therapeutix, Inc. - Inventors: Charles D. Blizzard; Arthur Driscoll; Rami El-Hayek; Michael Goldstein; Joseph Iacona; Peter Jarrett; Timothy S. Jarrett; Erica Kahn; Zachary Lattrell - Web page: https://patentgrep.com/patent/US11439592B2 ## CPC - A61K 9/0051: {Ocular inserts or implants} - A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} - A61K 31/4427: containing further heterocyclic ring systems - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers - A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) - A61P 27/02: Ophthalmic agents - A61F 9/0017: {implantable in, or in contact with, the eye, e.g. ocular inserts} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract The invention relates to a sustained release biodegradable ocular implant containing a tyrosine kinase inhibitor dispersed in a hydrogel for the treatment of a retinal disease for an extended period of time. ## Claims ### Claim 1 A sustained release biodegradable ocular implant comprising a hydrogel and a dose of axitinib from about 150 μg to about 1200 μg, wherein the axitinib is dispersed within the hydrogel, and wherein the implant in its dry state prior to implantation is cylindrical; has a length of about 6 mm to about 17 mm and a diameter of 0.2 mm to 0.5 mm; and has a total implant weight of about 0.2 mg to about 1.5 mg. ### Claim 2 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant comprises axitinib in an amount of about 480 μg to about 750 μg. ### Claim 3 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant comprises axitinib in an amount of about 160 μg to about 250 μg. ### Claim 4 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant in its dry state has a total weight of about 0.4 mg to about 1.2 mg. ### Claim 5 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is cylindrical and in its hydrated state (after 24 hours in phosphate-buffered saline at a pH of 7.2 at 37° C.) has a length of about 6 mm to about 9 mm and a diameter of equal to or less than about 0.8 mm. ### Claim 6 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is cylindrical and has a ratio of the diameter in the hydrated state to the diameter in the dry state of less than about 5. ### Claim 7 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is cylindrical and has a ratio of the length in the dry state to the length in the hydrated state of greater than about 0.7. ### Claim 8 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant provides for the release of axitinib at an average rate of about 0.25 μg to about 2.5 μg per day in phosphate-buffered saline at a pH of 7.2 and 37° C. for a period of 30 days under non-sink simulated physiological conditions. ### Claim 9 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is an intravitreal implant. ### Claim 10 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant provides for the release of axitinib for a period from about 3 months to about 38 months after administration. ### Claim 11 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant provides for the release of axitinib for a period of about 6 to about 9 months after administration. ### Claim 12 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the hydrogel comprises polyethylene glycol (PEG) units. ### Claim 13 (depends on 12) The sustained release biodegradable ocular implant of claim 12, wherein the hydrogel comprises PEG units that have a number average molecular weight of about 20,000 Daltons. ### Claim 14 (depends on 12) The sustained release biodegradable ocular implant of claim 12, wherein the hydrogel comprises crosslinked PEG units and the crosslinks between the PEG units include a group represented by the following formula wherein m is an integer from 0 to 10. ### Claim 15 (depends on 14) The sustained release biodegradable ocular implant of claim 14, wherein m is 6. ### Claim 16 (depends on 14) The sustained release biodegradable ocular implant of claim 14, wherein the PEG units comprise 4-arm and/or 8-arm PEG units. ### Claim 17 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the axitinib is in the form of particles having a d90 particle size of less than about 30 μm as determined by laser diffraction. ### Claim 18 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is free or substantially free of antimicrobial preservatives. ### Claim 19 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant in its dry state contains from about 200 μg to about 900 μg axitinib per mm3. ### Claim 20 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant in its dry state contains from about 60% to about 75% by weight axitinib and from about 21% to about 31% by weight PEG units (dry composition). ### Claim 21 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant in its dry state contains from about 45% to about 55% by weight axitinib and from about 37% to about 47% by weight PEG units (dry composition). ### Claim 22 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is an intravitreal implant and comprises from about 540 μg to about 660 μg axitinib, is cylindrical and has in its dry state a length about 6 mm to about 9 mm and a diameter of about 0.3 mm to about 0.4 mm, and in its hydrated state (after 24 hours in phosphate-buffered saline at a pH of 7.2 at 37° C.) has a length of from about 6 mm to about 10.5 mm and a diameter of from about 0.6 mm to about 0.8 mm, and wherein the hydrogel comprises crosslinked 4a20k and 8a20k PEG units, wherein the crosslinks between the PEG units include a group represented by the following formula wherein m is 6. ### Claim 23 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is an intravitreal implant and comprises from about 180 μg to about 220 μg axitinib, is cylindrical and has in its dry state a length of about 6 mm to about 9 mm and a diameter of about 0.2 mm to about 0.3 mm, and in its hydrated state (after 24 hours in phosphate-buffered saline at a pH of 7.2, at 37° C.) has a length of from about 6.5 mm to about 8 mm and a diameter of from about 0.7 mm to about 0.8 mm, and wherein the hydrogel comprises crosslinked 4a20k and 8a20k PEG units, wherein the crosslinks between the PEG units include a group represented by the following formula wherein m is 6. ### Claim 24 (depends on 1) The sustained release biodegradable ocular implant of claim 1, wherein the implant is loaded in a needle for injection. ### Claim 25 (depends on 24) The sustained release biodegradable ocular implant of claim 24, wherein the lumen of the needle is occluded by a material that is solid at room temperature and molten at body temperature. ### Claim 26 A sustained release biodegradable ocular implant comprising a hydrogel and a dose of axitinib from about 150 μg to about 1200 μg, wherein the axitinib is dispersed within the hydrogel, and wherein the implant in its dry state prior to implantation is cylindrical; has a length of about 6 mm to about 17 mm and a diameter of 0.2 mm to 0.5 mm; has a total weight of about 0.2 mg to about 1.5 mg; provides for the release of axitinib at an average rate of about 0.1 μg to about 3 μg per day in phosphate-buffered saline at a pH of 7.2 and 37° C. under non-sink simulated physiological conditions; and in its dry state contains from about 200 μg to about 900 μg axitinib per mm3. ### Claim 27 (depends on 26) The sustained release biodegradable ocular implant of claim 26, that provides for the release of axitinib at an average rate of about 0.1 μg to about 3 μg per day in phosphate-buffered saline at a pH of 7.2 and 37° C. for a period of 30 days under non-sink simulated physiological conditions.