# US 2023/0057071 A1 · Combination of anti tim-3 antibody mbg453 and anti tgf-beta antibody nis793, with or without decitabine or the anti pd-1 antibody spartalizumab, for treating myelofibrosis and myelodysplastic syndrome > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0057071 A1 - Document ID: US20230057071A1 - Status: Published application - Kind: A1 - Application number: 17/786,717 - Filed: 2020-12-03 - Published: 2023-02-23 - Earliest claimed: 2019-12-20 - Assignees: Novartis AG - Applicants: Novartis AG - Inventors: K. Gary J. VANASSE; Haiying SUN; Mirek DOSTALEK; Mikael RINNE; Anshu MARATHE; Luigi MANENTI; Claire FABRE; Fariba KHANSHAN - Web page: https://patentgrep.com/patent/US20230057071A1 ## CPC - C07K 16/22: against growth factors {; against growth regulators} - A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C07K 16/245: {IL-1} - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/2818: {against CD28 or CD152} - A61K 2039/505: {comprising antibodies} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - A61K 2039/54: {characterised by the route of administration} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/31: multispecific - C07K 2317/565: Complementarity determining region [CDR] - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - 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 Combination therapies comprising TIM-3 inhibitors and TGF-β inhibitors are disclosed. The combinations can be used to treat or prevent cancerous conditions and disorders, including myelofibrosis or myelodysplastic syndrome. ## Claims ### Claim 1 A combination comprising a TIM-3 inhibitor and a TGF-β inhibitor for use in treating a myelofibrosis in a subject. ### Claim 2 A combination comprising a TIM-3 inhibitor and a TGF-β inhibitor for use in treating a myelodysplastic syndrome in a subject. ### Claim 3 A method of treating a myelodysplastic syndrome (MDS) in a subject, comprising administering to the subject a combination of a TIM-3 inhibitor and a TGF-β inhibitor. ### Claim 4 A method of treating a myelofibrosis in a subject, comprising administering to the subject a combination of a TIM-3 inhibitor and a TGF-β inhibitor. ### Claim 5 (depends on 1, 2, 3, 4) The combination for use of claim 1 or 2, or the method of claim 3 or 4, wherein the TIM-3 inhibitor comprises an anti-TIM-3 antibody molecule. ### Claim 6 (depends on 1, 2, 3, 4, 5) The combination for use of claim 1, 2, or 5, or the method of claim 3-5, wherein the TIM-3 inhibitor comprises MBG453, TSR-022, LY3321367, Sym023, BGB-A425, INCAGN-2390, MBS-986258, RO-7121661, BC-3402, SHR-1702, or LY-3415244. ### Claim 7 (depends on 1, 2, 3, 4, 5, 6) The combination for use of any one of claims 1, 2 or 5-6, or the method of any one of claims 3-6, wherein the TIM-3 inhibitor comprises MBG453. ### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7) The combination for use of any one of claims 1, 2 or 5-7, or the method of any one of claims 3-7, wherein the TIM-3 inhibitor is administered at a dose of about 700 mg to about 900 mg. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The combination for use of any one of claims 1, 2 or 5-8, or the method of any one of claims 3-8, wherein the TIM-3 inhibitor is administered at a dose of about 800 mg. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The combination for use of any one of claims 1, 2 or 5-9, or the method of any one of claims 3-9, wherein the TIM-3 inhibitor is administered once every four weeks. ### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The combination for use of any one of claims 1, 2 or 5-9, or the method of any one of claims 3-9, wherein the TIM-3 inhibitor is administered once every eight weeks. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7) The combination for use of any one of claims 1, 2 or 5-7, or the method of any one of claims 3-7, wherein the TIM-3 inhibitor is administered at a dose of about 500 mg to about 700 mg. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7) The combination for use of any one of claims 1, 2, 5-7, or 12, or the method of any one of claims 3-7, or 12, wherein the TIM-3 inhibitor is administered at a dose of about 600 mg. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7) The combination for use of any one of claims 1, 2 or 5-7, or the method of any one of claims 3-7, wherein the TIM-3 inhibitor is administered at a dose of about 300 mg to about 500 mg. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7) The combination for use of any one of claims 1, 2, 5-7, or 14, or the method of any one of claims 3-7, or 14, wherein the TIM-3 inhibitor is administered at a dose of about 400 mg. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15) The combination for use of any one of claims 1, 2, 5-9 or 12-15, or the method of any one of claims 3-9 or 12-15, wherein the TIM-3 inhibitor is administered once every three weeks. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14, 15) The combination for use of any one of claims 1, 2, 5-9 or 12-15, or the method of any one of claims 3-9 or 12-15, wherein the TIM-3 inhibitor is administered once every six weeks. ### Claim 18 (depends on 12, 13, 14, 15) The combination for use of any one of claims 12-15, or the method of any one of claims 12-15, wherein the TIM-3 inhibitor is administered once every four weeks. ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The combination for use of any one of claims 1, 2 or 5-18, or the method of any one of claims 3-18, wherein the TIM-3 inhibitor is administered intravenously. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The combination for use of any one of claims 1, 2 or 5-19, or the method of any one of claims 3-19, wherein the TIM-3 inhibitor is administered over a period of about 20 to about 40 minutes. ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The combination for use of any one of claims 1, 2 or 5-20, or the method of any one of claims 3-20, wherein the TIM-3 inhibitor is administered over a period of about 30 minutes. ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21) The combination for use of any one of claims 1, 2 or 5-21, or the method of any one of claims 3-21, wherein the TGF-β inhibitor is an anti-TGF-β antibody molecule. ### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The combination for use of any one of claims 1, 2 or 5-22, or the method of any one of claims 3-22, wherein the TGF-β inhibitor comprises NIS793, fresolimumab, PF-06952229, or AVID200. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The combination for use of any one of claims 1, 2 or 5-23, or the method of any one of claims 3-23, wherein the TGF-β inhibitor comprises NIS793. ### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The combination for use of any one of claims 1, 2 or 5-24, or the method of any one of claims 3-24, wherein the TGF-β inhibitor is administered at a dose of about 1300 mg to about 1500 mg. ### Claim 26 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25) The combination for use of any one of claims 1, 2, or 5-25, or the method of any one of claims 3-25, wherein the TGF-β inhibitor is administered at a dose of about 1400 mg. ### Claim 27 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26) The combination for use of any one of claims 1, 2, or 5-26, or the method of any one of claims 3-26, wherein the TGF-β inhibitor is administered once every two weeks. ### Claim 28 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The combination for use of any one of claims 1, 2, or 5-24, or the method of any one of claims 3-24, wherein the TGF-β inhibitor is administered at a dose of about 2000 mg to about 2200 mg. ### Claim 29 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The combination for use of any one of claims 1, 2, 5-24, or 28, or the method of any one of claims 3-24, or 28, wherein the TGF-β inhibitor is administered at a dose of about 2100 mg. ### Claim 30 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The combination for use of any one of claims 1, 2, or 5-24, or the method of any one of claims 3-24, wherein the TGF-β inhibitor is administered at a dose of about 600 mg to about 800 mg. ### Claim 31 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The combination for use of any one of claims 1, 2, 5-24, or 30, or the method of any one of claims 3-24, or 30, wherein the TGF-β inhibitor is administered at a dose of about 700 mg. ### Claim 32 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 28, 29, 30, 31) The combination for use of any one of claims 1, 2, 5-26, or 28-31 or the method of any one of claims 3-26 or 28-31, wherein the TGF-β inhibitor is administered once every three weeks. ### Claim 33 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 28, 29) The combination for use of any one of claims 1, 2, 5-26, or 28-29, or the method of any one of claims 3-26 or 28-29, wherein the TGF-β inhibitor is administered once every six weeks. ### Claim 34 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33) The combination for use of any one of claims 1, 2, or 5-33, or the method of any one of claims 3-33, wherein the TGF-β inhibitor is administered over a period of about 20 to about 40 minutes. ### Claim 35 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34) The combination for use of any one of claims 1, 2, or 5-34, or the method of any one of claims 3-34, wherein the TGF-β inhibitor is administered over a period of about 30 minutes. ### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35) The combination for use of any one of claims 1, 2, or 5-35, or the method of any one of claims 3-35, wherein the TGF-β inhibitor is administered on the same day as the TIM-3 inhibitor. ### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36) The combination for use of any one of claims 1, 2, or 5-36, or the method of any one of claims 3-36, wherein the TGF-β inhibitor is administered after administration of the TIM-3 inhibitor is completed. ### Claim 38 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37) The combination for use of any one of claim 1 or 5-37, or the method of any one of claims 4-37, wherein the combination further comprises a PD-1 inhibitor. ### Claim 39 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38) The combination for use of any one of claim 1 or 5-38, or the method of any one of claims 4-38, wherein the PD-1 inhibitor comprises spartalizumab, nivolumab, pembrolizumab, pidilizumab, MEDI0680, REGN2810, TSR-042, PF-06801591, BGB-A317, BGB-108, INCSHR1210, or AMP-224. ### Claim 40 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31) The combination for use of any one of claim 1 or 5-31, or the method of any one of claims 4-31, wherein the PD-1 inhibitor comprises spartalizumab. ### Claim 41 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40) The combination for use of any one of claim 1 or 5-40, or the method of any one of claims 4-40, wherein the PD-1 inhibitor is administered at a dose of about 300 mg to about 500 mg. ### Claim 42 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41) The combination for use of any one of claim 1 or 5-41, or the method of any one of claims 4-41, wherein the PD-1 inhibitor is administered at a dose of about 400 mg. ### Claim 43 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42) The combination for use of any one of claim 1 or 5-42, or the method of any one of claims 4-42, wherein the PD-1 inhibitor is administered once every four weeks. ### Claim 44 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40) The combination for use of any one of claim 1 or 5-20, or the method of any one of claims 4-40, wherein the PD-1 inhibitor is administered at a dose of about 200 mg to about 400 mg. ### Claim 45 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The combination for use of any one of claims 1, 5-20, or 44, or the method of any one of claims 4-20, or 44 wherein the PD-1 inhibitor is administered at a dose of about 300 mg. ### Claim 46 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45) The combination for use of any one of claim 1 or 5-45, or the method of any one of claims 4-45, wherein the PD-1 inhibitor is administered once every three weeks. ### Claim 47 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46) The combination for use of any one of claim 1 or 5-46, or the method of any one of claims 4-46, wherein the PD-1 inhibitor is administered intravenously. ### Claim 48 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47) The combination for use of any one of claim 1 or 5-47, or the method of any one of claims 4-47, wherein the PD-1 inhibitor is administered over a period of about 20 to about 40 minutes. ### Claim 49 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48) The combination for use of any one of claim 1 or 5-48, or the method of any one of claims 4-48, wherein the PD-1 inhibitor is administered over a period of about 30 minutes. ### Claim 50 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37) The combination for use of any one of claims 1, 2, or 5-37, or the method of any one of claims 3-37, wherein the combination further comprises an IL-1β inhibitor. ### Claim 51 (depends on 50) The combination for use of claim 50, or the method of claim 50, wherein the IL-1β inhibitor comprises canakinumab, gevokizumab, Anakinra, diacerein, Rilonacept, IL-1 Affibody (SOBI 006, Z-FC (Swedish Orphan Biovitrum/Affibody)) and Lutikizumab (ABT-981) (Abbott), CDP-484 (Celltech), or LY-2189102 (Lilly). ### Claim 52 (depends on 50, 51) The combination for use of claim 50 or 51, or the method of claim 50 or 51, wherein the IL-1β inhibitor comprises canakinumab. ### Claim 53 (depends on 50, 51, 52) The combination for use of any one of claims 50 to 52, or the method of any one of claims 50-52, wherein IL-1β inhibitor is dosed at 200 mg every 3 weeks. ### Claim 54 (depends on 50, 51, 52) The combination for use of any one of claims 50 to 52, or the method of any one of claims 50-52, wherein the IL-1β inhibitor is dosed at 250 mg every 4 weeks. ### Claim 55 (depends on 50, 51, 52) The combination for use of any one of claims 50 to 52, or the method of any one of claims 50-52, wherein the IL-1β inhibitor is dosed at 250 mg every 8 weeks. ### Claim 56 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55) The combination for use of any one of claim 1 or 5-55, or the method of any one of claims 4-46, wherein the combination further comprises a hypomethylating agent. ### Claim 57 (depends on 56) The combination for use of claim 56, or the method of claim 56, wherein the hypomethylating agent comprises azacitidine, decitabine, CC-486 or ASTX727. ### Claim 58 (depends on 56, 57) The combination for use of claim 56 or 57, or the method of claim 56 or 57, wherein the hypomethylating agent comprises decitabine. ### Claim 59 (depends on 56, 57, 58) The combination for use of any one of claims 56-58, or the method of any one of claims 56-58, wherein the hypomethylating agent is administered at a dose of about 2 mg/m2 to about 25 mg/m2. ### Claim 60 (depends on 56, 57, 58, 59) The combination for use of any one of claims 56-59, or the method of any one of claims 56-59, wherein the hypomethylating agent is administered at a dose of about 2.5 mg/m2, about 5 mg/m2, about 10 mg/m2, or about 20 mg/m2. ### Claim 61 (depends on 56, 57, 58, 59, 60) The combination for use of any one of claims 56-60, or the method of any one of claims 56-60, wherein the hypomethylating agent is administered once a day. ### Claim 62 (depends on 56, 57, 58, 59, 60, 61) The combination for use of any one of claims 56-61, or the method of any one of claims 56-61, wherein the hypomethylating agent is administered for 5 consecutive days. ### Claim 63 (depends on 56, 57, 58, 59, 60, 61, 62) The combination for use of any one of claims 56-62, or the method of any one of claims 56-62, wherein the hypomethylating agent is administered on days 1, 2, 3, 4, and 5 of a 42-day cycle. ### Claim 64 (depends on 56, 57, 58, 59, 60, 61, 62, 63) The combination for use of any one of claims 56-63, or the method of any one of claims 56-63, wherein the hypomethylating agent is administered over a period of about 0.5 hour to about 1.5 hour. ### Claim 65 (depends on 56, 57, 58, 59, 60, 61, 62, 63) The combination for use of any one of claims 56-63, or the method of any one of claims 56-63, wherein the hypomethylating agent is administered over a period of about 1 hour. ### Claim 66 (depends on 56, 57, 58, 59) The combination for use of any one of claims 56-59, or the method of any one of claims 56-58, wherein the hypomethylating agent is administered at a dose of about 2 mg/m2 to about 20 mg/m2. ### Claim 67 (depends on 56, 57, 58, 59, 66) The combination for use of any one of claims 56-59 or 66, or the method of any one of claims 56-59 or 66, wherein the hypomethylating agent is administered at a dose of about 2.5 mg/m2, about 5 mg/m2, about 7.5 mg/m2, about 15 mg/m2, or about 20 mg/m2. ### Claim 68 (depends on 56, 57, 58, 59, 60, 66, 67) The combination for use of any one of claims 56-60 or 66-67, or the method of any one of claims 56-60 or 66-67, wherein the hypomethylating agent is administered once daily. ### Claim 69 (depends on 56, 57, 58, 59, 60, 61, 66, 67, 68) The combination for use of any one of claims 56-61 or 66-68, or the method of any one of claims 56-61 or 66-68, wherein the hypomethylating agent is administered for 3 consecutive days. ### Claim 70 (depends on 56, 57, 58, 59, 60, 61, 66, 67, 68, 69) The combination for use of any one of claims 56-61 or 66-69, or the method of any one of claims 56-61 or 66-69, wherein the hypomethylating agent is administered on days 1, 2, and 3 of a 42 days cycle. ### Claim 71 (depends on 56, 57, 58, 59, 60, 61, 66, 67, 68, 69) The combination for use of any one of claims 56-61 or 66-69, or the method of any one of claims 56-61 or 66-69, wherein the hypomethylating agent is administered on days 1, 2, and 3 of a 28 days cycle. ### Claim 72 (depends on 56, 57, 58, 59, 60, 61, 66, 67, 68, 69, 70, 71) The combination for use of any one of claims 56-61 or 66-71, or the method of any one of claims 56-61 or 66-71, wherein the hypomethylating agent is administered over a period of about 0.5 hour to about 1.5 hour. ### Claim 73 (depends on 56, 57, 58, 59, 60, 61, 66, 67, 68, 69, 70, 71, 72) The combination for use of any one of claims 56-61 or 66-72, or the method of any one of claims 56-61 or 66-72, wherein the hypomethylating agent is administered over a period of about 1 hour. ### Claim 74 (depends on 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73) The combination for use of any one of claims 56-73, or the method of any one of claims 56-73, wherein the hypomethylating agent is administered subcutaneously, orally or intravenously. ### Claim 75 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74) The combination for use of any one of claim 1 or 5-74, or the method of any one of claims 4-74, wherein the myelofibrosis is a primary myelofibrosis (PMF), post-ET (PET-MF) myelofibrosis, or post-PV myelofibrosis (PPV-MF). ### Claim 76 (depends on 1, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75) The combination for use of any one of claim 1 or 5-75, or the method of any one of claims 4-75, wherein the myelofibrosis is a primary myelofibrosis (PMF). ### Claim 77 (depends on 2, 3, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37) The combination for use of any one of claims 2, 5-37, or 50-55, or the method of any one of claims 3, 5-37, or 50-55, wherein the myelodysplastic syndrome is a lower risk myelodysplastic syndrome (MDS), e.g., a very low risk MDS, a low risk MDS, or an intermediate risk MDS, or a higher risk myelodysplastic syndrome, e.g., a high risk MDS or a very high risk MDS. ### Claim 78 (depends on 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 50, 51, 52, 53, 54, 55, 77) The combination for use of any one of claims 2, 5-37, 50-55, or 77, or the method of any one of claims 3-37, 50-55 or 77, wherein the myelodysplastic syndrome is a lower risk myelodysplastic syndrome (MDS), e.g., a very low risk MDS, a low risk MDS, or an intermediate risk MDS. ### Claim 79 A combination comprising MBG453 and NIS793 for use in treating a myelofibrosis in a subject, optionally wherein the combination further comprising decitabine; optionally wherein the combination further comprises PDR001, and optionally wherein MGB453 is administered at a dose of 600 mg once every three weeks, NIS793 is administered at a dose of 2100 mg once every three weeks, PDR001 is administered at a dose of 300 mg once every three weeks, and decitabine is administered at a dose of about 5 mg/m2 to about 20 mg/m2 on days 1, 2, and 3 of a 42 day cycle. ### Claim 80 A method of treating myelofibrosis in a subject, comprising administering to the subject a combination of MBG453 and NIS793, optionally wherein the combination further comprises decitabine, optionally wherein the combination further comprises PDR001, and optionally wherein MGB453 is administered at a dose of 600 mg once every three weeks, NIS793 is administered at a dose of 2100 mg once every three weeks, PDR001 is administered at a dose of 300 mg once every three weeks, and decitabine is administered at a dose of about 5 mg/m2 to about 20 mg/m2 on days 1, 2, and 3 of a 42 day cycle. ### Claim 81 A method of treating myelofibrosis in a subject, comprising administering to the subject a combination of a MBG453 and NIS793, optionally wherein the combination further comprises decitabine, optionally wherein the combination further comprises canakinumab; and optionally wherein MGB453 is administered at a dose of 600 mg once every three weeks, NIS793 is administered at a dose of 2100 mg once every three weeks, canakinumab is administered at a dose of 200 mg every three weeks, and decitabine is administered at a dose of about 5 mg/m2 to about 20 mg/m2 on days 1, 2, and 3 of a 42 day cycle. ### Claim 82 A method of treating a myelofibrosis in a subject, comprising administering to the subject a combination of a MBG453 and NIS793, optionally wherein the combination further comprises decitabine, optionally wherein the combination further comprises canakinumab; and optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, NIS793 is administered at a dose of 1400 mg once every two weeks, canakinumab is administered at a dose of 250 mg once every four weeks, and decitabine is administered at a dose of about 5 mg/m2 to about 20 mg/m2 on days 1, 2, and 3 of a 42 day cycle. ### Claim 83 A combination comprising MBG453 and NIS793 for use in treating a myelodysplastic syndrome (MDS) in a subject, optionally wherein MGB453 is administered at a dose of 600 mg once every three weeks, and NIS793 is administered at a dose of 2100 mg once every three weeks. ### Claim 84 A combination comprising MBG453 and NIS793 for use in treating a myelodysplastic syndrome (MDS) in a subject, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, and NIS793 is administered at a dose of 2100 mg once every three weeks. ### Claim 85 A method of treating myelodysplastic syndrome (MDS) in a subject, comprising administering to the subject a combination of MBG453 and NIS793, optionally wherein MGB453 is administered at a dose of 600 mg once every three weeks, and NIS793 is administered at a dose of 2100 mg once every three weeks. ### Claim 86 A method of treating myelodysplastic syndrome (MDS) in a subject, comprising administering to the subject a combination of MBG453 and NIS793, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, and NIS793 is administered at a dose of 2100 mg once every three weeks. ### Claim 87 A combination comprising MBG453, NIS793, and canakinumab, for use in treating a myelodysplastic syndrome (MDS) in a subject, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, NIS793 is administered at a dose of 2100 mg once every three weeks, and canakinumab is administered at a dose of 250 mg once every four weeks. ### Claim 88 A method of treating myelodysplastic syndrome (MDS) in a subject, comprising administering to the subject a combination of MBG453, NIS793, canakinumab, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, NIS793 is administered at a dose of 2100 mg once every three weeks, and canakinumab is administered at a dose of 250 mg once every four weeks. ### Claim 89 A combination comprising MBG453, NIS793, and canakinumab, for use in treating a myelodysplastic syndrome (MDS) in a subject, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, NIS793 is administered at a dose of 1400 mg once every three weeks, and canakinumab is administered at a dose of 250 mg once every four weeks. ### Claim 90 A method of treating myelodysplastic syndrome (MDS) in a subject, comprising administering to the subject a combination of MBG453, NIS793, canakinumab, optionally wherein MGB453 is administered at a dose of 800 mg once every four weeks, NIS793 is administered at a dose of 1400 mg once every three weeks, and canakinumab is administered at a dose of 250 mg once every four weeks.