# US 9,517,243 B2 · Beta-mannosylceramide and stimulation of NKT cell anti-tumor immunity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,517,243 B2 - Document ID: US9517243B2 - Status: Granted - Kind: B2 - Application number: 14/879,476 - Filed: 2015-10-09 - Published: 2016-04-14 - Granted: 2016-12-13 - Earliest claimed: 2010-03-12 - Assignees: The United States of America, as represented by the Secretary, Department of Health and Human Services; The University of Birmingham Edgbaston - Applicants: The United States of America, as represented by the Secretary, Department of Health and Humam Services; The University of Birmingham, of Edgbaston - Inventors: Jay A. Berzofsky; Jessica J. O'Konek; Masaki Terabe; Petr A. Illarionov; Gurdyal S. Besra - Web page: https://patentgrep.com/patent/US9517243B2 ## CPC - A61K 31/7032: attached to a polyol, i.e. compounds having two or more free or esterified hydroxy groups, including the hydroxy group involved in the glycosidic linkage, e.g. monoglucosyldiacylglycerides, lactobionic acid, gangliosides - A61K 31/7004: Monosaccharides having only carbon, hydrogen and oxygen atoms - A61K 38/2013: {IL-2} - A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells - A61K 40/42: Cancer antigens - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - A61P 37/04: Immunostimulants - C07H 15/04: attached to an oxygen atom of the saccharide radical - C07H 15/06: being a hydroxyalkyl group esterified by a fatty acid - A61K 2039/585: {wherein the target is cancer} - 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 - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) ## Abstract β-mannosylceramides or salts or solvates thereof in a pharmaceutically acceptable carrier, for use as a Type I NKT cell agonist in conjunction with a therapeutically effective amount of α-galactosylceramide or a salt or a solvate thereof, and/or at least one or more T-cell co-stimulatory molecules, disclosed. Compositions comprising β-mannosylceramide, as well as methods of treatment of tumors are also provided. ## Claims ### Claim 1 A composition comprising a β-mannosylceramide (β-ManCer) or salt or solvate thereof in a pharmaceutically acceptable carrier, wherein the β-ManCer consists of a β-mannosyl moiety linked to a ceramide moiety, the ceramide moiety consisting of: a) a sphingosine moiety linked to b) a fatty acid moiety comprising a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 8 to about 49 carbon atoms, wherein the composition further comprises a therapeutically effective amount of one or more chemotherapeutic agents. ### Claim 2 (depends on 1) The composition of claim 1, wherein the fatty acid moiety comprises a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 8 to about 15 carbon atoms. ### Claim 3 (depends on 1) The composition of claim 1, wherein the fatty acid moiety comprises a linear or branched, saturated or unsaturated, aliphatic hydrocarbon group having from about 18 to about 30 carbon atoms. ### Claim 4 (depends on 1) The composition of claim 1, wherein the composition further comprises a therapeutically effective amount of IL-2. ### Claim 5 (depends on 1) The composition of claim 1, wherein the composition further comprises a therapeutically effective amount of an α-glycosylceramide or a salt or solvate thereof. ### Claim 6 (depends on 1) The composition of claim 1, wherein the composition further comprises GM-CSF, and/or other cytokines that induce cellular immunity. ### Claim 7 (depends on 6) The composition claim 6, wherein the cytokines that induce cellular immunity include IL-12 and/or IL-15. ### Claim 8 (depends on 1) The composition of claim 1, wherein the composition further comprises one or more T-cell co-stimulatory molecules, wherein the one or more co-stimulatory molecules are selected from the group consisting of B7-1, B7-2, B7-3, B7-H, ICAM1, ICAM2, ICAM3, LFA1, LFA2, LFA3, CD40L, OX40L and 4-1BBL. ### Claim 9 (depends on 1) The composition of claim 1, wherein the composition further comprises one or more Toll-like Receptor (TLR) ligands. ### Claim 10 (depends on 9) The composition of claim 9, wherein the one or more TLR ligands are selected from the group consisting of ligands for TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9. ### Claim 11 (depends on 1) The composition of claim 1, wherein the composition further comprises a vaccine. ### Claim 12 (depends on 11) The composition of claim 11, wherein the vaccine is selected from the group consisting of TARP 29-37-9V peptide, and Sargramostin (GM-CSF) emulsified in Montanide ISA 51 VG. ### Claim 13 (depends on 1) The composition of claim 1, wherein the composition further comprises an antibody. ### Claim 14 (depends on 13) The composition of claim 13, wherein the antibody is selected from the group consisting of antibodies against CTLA-4 or PD-1 or TGF-beta. ### Claim 15 (depends on 1) A method of inducing an immune response, treating cancer, or inhibiting growth of a tumor in a subject, the method comprising administering to the subject the composition of claim 1 in an amount effective to induce an immune response, treat cancer, or inhibit growth of a tumor, wherein the cancer is selected from the group consisting of liver cancer, brain cancer, neck cancer, skin cancer, lung cancer, kidney cancer, stomach cancer, colon cancer, prostate cancer, breast cancer, ovarian cancer, melanoma and lymphoid cancer and the tumor is selected from the group consisting of a lung tumor, a breast tumor, a colon tumor, a liver tumor, a brain tumor, a neck tumor, a prostate tumor, an ovarian tumor, a skin tumor, a melanoma tumor and a lymphoid tumor in the subject. ### Claim 16 (depends on 1) A method of making the composition according to claim 1, the method comprising: reacting 2-amino-1-O-β-mannopyranosyl-D-ribo-1,3,4-octadecanetriol with an electrophile to form β-ManCer; and combining the β-ManCer with a pharmaceutically acceptable carrier and the one or more chemotherapy agents.