# US 10,865,378 B2 · Thin film cell encapsulation devices > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,865,378 B2 - Document ID: US10865378B2 - Status: Granted - Kind: B2 - Application number: 16/111,773 - Filed: 2018-08-24 - Published: 2019-03-28 - Granted: 2020-12-15 - Earliest claimed: 2015-03-23 - Assignees: The Regents of the University of California - Applicants: The Regents of the University of California - Inventors: Tejal A. Desai; Crystal Nyitray; Ryan Chang - Web page: https://patentgrep.com/patent/US10865378B2 ## CPC - C12N 5/0012: {Cell encapsulation} - A61F 2/022: {Artificial gland structures using bioreactors (hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36)} - 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 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) - C08G 63/08: Lactones or lactides - C12N 5/0676: {Pancreatic cells} - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - 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) - C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS ## Abstract Thin film devices, e.g., multilayer thin film devices, that encapsulate cells for transplantation into a subject are provided. Also provided are methods of using and methods of preparing the subject devices. The thin film devices include a first porous polymer layer and a second porous polymer layer that define a lumen therebetween and encapsulate a population of cells within the lumen. The thin film devices can promote vascularization into the lumen of the device via the pores in the first polymer layer and/or second polymer layer; limit foreign body response to the device; limit ingress of cells, immunoglobulins, and cytokines into the lumen via the first and the second polymer layers; and release from the first polymer layer and/or the second polymer layer molecules secreted by the population of cells. ## Claims ### Claim 1 A method of treating a subject in need of a therapeutic molecule, said method comprising: (a) introducing into said subject a device comprising: (i) a lumen containing a plurality of cells capable of secreting the therapeutic molecule; and (ii) a layer comprising a biocompatible polymer surrounding said lumen and comprising a plurality of pores sized such that said therapeutic molecule can diffuse from said device, wherein said plurality of pores are nanopores; and (b) secreting, from said plurality of cells, said therapeutic molecule at a therapeutically effective amount for at least 30 days, wherein said plurality of cells are selected from the group consisting of: allogeneic cells and xenogeneic cells, and wherein said subject has not received immunosuppression therapy. ### Claim 2 (depends on 1) The method of claim 1, wherein said layer of biocompatible polymer comprises a first layer of biocompatible polymer and a second layer of biocompatible polymer, wherein said lumen is disposed between said first layer of biocompatible polymer and said second layer of biocompatible polymer. ### Claim 3 (depends on 1) The method of claim 1, wherein said biocompatible polymer is selected from the group consisting of: methacrylate polymer, polyethyleneimine, polyethyleneimine-dextran sulfate, poly(vinylsiloxane) ecopolymerepolyethyleneimine, phosphorylcholine, poly(ethyl methacrylate), polyurethane, poly(ethylene glycol), poly(lactic-glycolic acid), hydroxyapatite, poly(lactic acid), polyhydroxyvalerte and copolymers thereof, polyhydroxybutyrate and copolymers thereof, polycaprolactone, polydiaxanone, polyanhydride, polycyanocrylate, poly(amino acids), poly(orthoesters), polyesters, collagen, gelatin, cellulose polymer, chitosans, alginates, and any combination thereof. ### Claim 4 (depends on 3) The method of claim 3, wherein said biocompatible polymer comprises polycaprolactone. ### Claim 5 (depends on 1) The method of claim 1, wherein said therapeutic molecule has a molecular weight of less than 10 kDa. ### Claim 6 (depends on 1) The method of claim 1, wherein said therapeutic molecule has a hydrodynamic radius of less than 2 nm. ### Claim 7 (depends on 1) The method of claim 1, wherein said plurality of pores are sized such that a concentration of cytokines that is capable of accessing said lumen is below a level required for an immune response against said plurality of cells. ### Claim 8 (depends on 7) The method of claim 7, wherein said cytokines have a molecular weight of greater than 15 kDa. ### Claim 9 (depends on 7) The method of claim 7, wherein said cytokines have a hydrodynamic radius of greater than 2 nm. ### Claim 10 (depends on 7) The method of claim 7, wherein said cytokines are selected from the group consisting of: interferons, interleukins, and tumor necrosis factors. ### Claim 11 (depends on 1) The method of claim 1, wherein said nanopores have an average diameter from 5 nm to 500 nm. ### Claim 12 (depends on 1) The method of claim 1, wherein said nanopores have an average diameter from 10 nm to about 300 nm. ### Claim 13 (depends on 1) The method of claim 1, wherein said first layer of biocompatible polymer and said second layer of biocompatible polymer each have a thickness of less than 15 μm. ### Claim 14 (depends on 1) The method of claim 1, wherein said device has a thickness of less than 30 μm. ### Claim 15 (depends on 1) The method of claim 1, wherein said introducing comprises transplanting said device subcutaneously into said subject. ### Claim 16 (depends on 1) The method of claim 1, wherein said subject has or is predisposed to developing Type I diabetes. ### Claim 17 (depends on 16) The method of claim 16, wherein said plurality of cells comprise insulin-secreting cells. ### Claim 18 (depends on 17) The method of claim 17, wherein said therapeutic molecule is insulin. ### Claim 19 (depends on 17) The method of claim 17, wherein said insulin-secreting cells have a glucose stimulation index (GSI) that is not statistically significantly changed over a period of at least 30 days after introducing said device into said subject. ### Claim 20 (depends on 1) The method of claim 1, wherein said device is substantially planar.