# US 10,369,217 B2 · Antigen-loaded chitosan nanoparticles for immunotherapy > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,369,217 B2 - Document ID: US10369217B2 - Status: Granted - Kind: B2 - Application number: 15/316,709 - Filed: 2015-05-12 - Published: 2017-05-25 - Granted: 2019-08-06 - Earliest claimed: 2014-06-06 - Assignees: Merck Patent GmbH - Applicants: Merck Patent GmbH - Inventors: Andrea Hanefeld; Markus Weigandt; Michael Wolf; Percy Knolle; Matthias Schroeder; Regina Scherliess; Peter Walden; Andrea Diedrich; Hartwig Steckel; Renato Brito Baleeiro - Web page: https://patentgrep.com/patent/US10369217B2 ## CPC - A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants - A61K 9/1623: {Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules} - A61K 9/1682: {Processes} - A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin} - A61P 35/00: Antineoplastic agents - A61P 37/04: Immunostimulants - A61K 2039/541: {Mucosal route} - A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers} - A61K 2039/55583: {Polysaccharides} - A61K 2039/6087: {Polysaccharides; Lipopolysaccharides [LPS]} - 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 ## Abstract The present invention is directed to nanoparticles comprising chitosan and an antigen, whereby the chitosan has a degree of deacetylation of about 90% and a molecular weight from 5 kDa to 80 kDa, to microparticles containing such nanoparticles as well as to a process for preparation of such particles. The particles are usable for vaccination. ## Claims ### Claim 1 A nanoparticle comprising chitosan and an antigen, wherein the chitosan has a degree of deacetylation of about 90% and a molecular weight from 5 kDa to 80 kDa. ### Claim 2 (depends on 1) The nanoparticle according to claim 1, wherein the chitosan has a molecular weight from 10 kDa to 70 kDa. ### Claim 3 (depends on 1) The nanoparticle according to claim 1, wherein the nanoparticle has a mean size from 100 nm to 500 nm. ### Claim 4 (depends on 1) The nanoparticle according to claim 1, further comprising a counterion. ### Claim 5 (depends on 4) The nanoparticle according to claim 4, wherein the counterion is carboxymethylcellulose, pentasodium tripolyphosphate, sodium cholate, heparin, low MW hyaluronic acid, alginate, pectin, carrageenan or poly(acrylic acid). ### Claim 6 (depends on 1) The nanoparticle according to claim 1, wherein the antigen is a peptide, a protein or a nucleic acid. ### Claim 7 (depends on 1) The nanoparticle according to claim 1, further comprising an adjuvant. ### Claim 8 (depends on 1) A vaccine comprising the nanoparticle according to claim 1. ### Claim 9 (depends on 1) A method of treatment comprising administering the nanoparticle according to claim 1 by therapeutic vaccination. ### Claim 10 (depends on 9) The method according to claim 9 wherein the nanoparticle is administrated by mucosal administration or by parenteral injection. ### Claim 11 (depends on 10) The method according to claim 10, wherein the mucosal administration is pulmonal or nasal administration. ### Claim 12 (depends on 1) A process for the preparation of the nanoparticle according to claim 1, wherein the nanoparticle is prepared by ionic gelation. ### Claim 13 (depends on 12) The process according to claim 12 comprising; (a) preparing an aqueous solution comprising chitosan and an antigen; (b) preparing an aqueous solution comprising a counterion; (c) mixing the aqueous solution prepared in step (a) and the aqueous solution prepared by step (b); (d) stirring the mixture obtained in step (c) to produce an aqueous dispersion containing chitosan nanoparticles; (e) collecting the nanoparticles obtained in step (d). ### Claim 14 (depends on 13) The process according to claim 13, wherein step (c) is performed by addition of the aqueous solution prepared in step (b) to the aqueous solution prepared by step (a). ### Claim 15 (depends on 1) A microparticle comprising the nanoparticle according to claim 1 and a matrix agent. ### Claim 16 (depends on 15) The microparticle according to claim 15, wherein the matrix agent is a monosaccharide, a disaccharide, a sugar alcohol or a polysaccharide. ### Claim 17 (depends on 16) The microparticle according to claim 16, wherein the matrix agent monosaccharide is glucose, the matrix agent disaccharide is trehalose, sucrose or lactose, the matrix agent sugar alcohol is mannitol or sorbitol, and the matrix agent polysaccharide is starch or dextrane. ### Claim 18 (depends on 15) The microparticle according to claim 15, wherein the microparticle has a mass median aerodynamic diameter from 0.5 μm to 5 μm. ### Claim 19 (depends on 15) A vaccine comprising the microparticle according to claim 15. ### Claim 20 (depends on 15) A method of treatment comprising administering a microparticle according to claim 15 for therapeutic vaccination. ### Claim 21 (depends on 20) The method according to claim 20, wherein the microparticle is administrated by mucosal administration. ### Claim 22 (depends on 21) The method according to claim 21, wherein the mucosal administration is pulmonal or nasal administration. ### Claim 23 (depends on 1) A process for the preparation of a microparticle comprising spray drying a liquid containing the nanoparticle according to claim 1 and a matrix agent. ### Claim 24 (depends on 23) The process according to claim 23, comprising: (a) preparing an aqueous dispersion comprising the nanoparticle and the matrix agent being dissolved therein; (b) spray-drying the aqueous dispersion prepared in step (a) to produce nanoparticle-containing microparticle; (c) collecting the microparticle obtained in step (b). ### Claim 25 (depends on 3) The nanoparticle according to claim 3, wherein the nanoparticle has a mean size from 200 nm to 400 nm. ### Claim 26 (depends on 25) The nanoparticle according to claim 25, wherein the nanoparticle has a mean size from 200 nm to 300 nm. ### Claim 27 (depends on 18) The microparticle according to claim 18, wherein the microparticle has a mass median aerodynamic diameter from 2 μm to 5 μm. ### Claim 28 (depends on 2) The nanoparticle according to claim 2, wherein the chitosan has a molecular weight from 25 kDa to 50 kDa.