# US 10,869,916 B2 · Therapeutic immune modulation by stem cell secreted exosomes > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,869,916 B2 - Document ID: US10869916B2 - Status: Granted - Kind: B2 - Application number: 16/016,234 - Filed: 2018-06-22 - Published: 2018-12-27 - Granted: 2020-12-22 - Earliest claimed: 2012-01-31 - Assignees: XON Cells, Inc. - Applicants: XON Cells, Inc. - Inventors: Thomas Ichim; Vladimir Bogin - Web page: https://patentgrep.com/patent/US10869916B2 ## CPC - A61K 39/0008: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance} - A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00) - A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells - A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy - 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) ## Abstract Disclosed are methods, compositions of matter, and protocols useful for the induction of a therapeutic immune modulatory response through administration of exosomes derived from a stem cell source. In one embodiment, said stem cell source is endometrial regenerative cells. Specifically, in one embodiment stem cell derived exosomes are used as a method of treating an autoimmune condition such as rheumatoid arthritis, multiple sclerosis, or systemic lupus erythromatosis. ## Claims ### Claim 1 A method of treating a patient comprising the steps of: a) extracting endometrial regenerative cells (ERCs); b) culturing said ERCs for a sufficient time period, under conditions permissible for exosome production; c) collecting exosomes produced by said ERCs; d) concentrating said collected exosomes; and e) administering said concentrated exosomes and said ERCs to said patient, wherein said patient has an autoimmune condition selected from the group consisting of: diabetes; multiple sclerosis; rheumatoid arthritis; Hashimoto's thyroiditis; graft rejection; graft versus host disease; and systemic lupus erythromatosis. ### Claim 2 (depends on 1) The method of claim 1, wherein said ERCs are induced to increase exosome production. ### Claim 3 (depends on 2) The method of claim 2, wherein said induction of exosome production from said ERCs is achieved by treatment of said ERCs with cytokines. ### Claim 4 (depends on 1) The method of claim 1, wherein said exosomes are concentrated by ultracentrifugation; column chromatography; size exclusion; or filtration through a device containing an affinity matrix selective towards exosomes. ### Claim 5 (depends on 1) The method of claim 1, wherein said exosomes are transfected with a genetic material, and wherein said genetic material is delivered into an immune cell. ### Claim 6 (depends on 1) The method of claim 1, wherein said exosomes are produced from ERCs transferred with a genetic material, and wherein said genetic material is delivered into an immune cell. ### Claim 7 A method of treating a patient comprising the steps of: a) extracting endometrial regenerative cells (ERCs); b) culturing said ERCs for a sufficient time period, under conditions permissible for exosome production; c) collecting exosomes generated by said ERC population; d) concentrating said collected exosomes to at least 1 μg/mL; and e) administering 1-2 μg of said concentrated exosomes and at least 100,000 of said ERCs to said patient, wherein said patient has an autoimmune condition selected from the group consisting of: diabetes; multiple sclerosis; rheumatoid arthritis; Hashimoto's thyroiditis; graft rejection; graft versus host disease; and systemic lupus erythromatosis. ### Claim 8 (depends on 7) The method of claim 7, further comprising incorporating one or more autoantigens into said concentrated exosomes. ### Claim 9 (depends on 7) The method of claim 7, further comprising transfecting said ERCs with one or more autoantigen genes, wherein the one or more autoantigens are representative of said autoimmune condition. ### Claim 10 A method of treating a patient having an autoimmune condition comprising the steps of: a) obtaining endometrial regenerative cells (ERCs); b) introducing into said ERCs an antigen, wherein said antigen is present in one or more exosomes produced by said ERCs; c) purifying and concentrating said exosomes to at least 1 μg/mL; d) administering an amount of said concentrated exosomes and an amount of said ERCs into the patient to suppress a biological pathway associated with an immune pathway associated with the autoimmune condition, wherein said autoimmune condition is selected from the group consisting of: diabetes; multiple sclerosis; rheumatoid arthritis; Hashimoto's thyroiditis; graft rejection; graft versus host disease; and systemic lupus erythromatosis. ### Claim 11 (depends on 10) The method of claim 10, wherein said ERCs are cultured in a DMEM F12 medium comprising approximately 10% fetal calf serum for a period of 1-100 hours to produce said exosomes. ### Claim 12 (depends on 10) The method of claim 10, wherein said exosomes are concentrated by ultracentrifugation; column chromatography; size exclusion; or filtration through a device containing an affinity matrix selective towards exosomes. ### Claim 13 (depends on 10) The method of claim 10, wherein said antigen is incorporated into said exosome-producing ERCs by transfection with a gene encoding said antigen; transfection with an antigenic protein; or transfection with an antigenic peptide. ### Claim 14 (depends on 10) The method of claim 10, wherein said antigen is loaded into said exosomes. ### Claim 15 (depends on 14) The method of claim 14, wherein said loading is by a chemical means.