# US 2021/0275524 A1 · Method of treating cancer associated with a ras mutation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2021/0275524 A1 - Document ID: US20210275524A1 - Status: Published application - Kind: A1 - Application number: 17/328,091 - Filed: 2021-05-24 - Published: 2021-09-09 - Earliest claimed: 2015-03-06 - Assignees: BeyondSpring Pharmaceuticals, Inc. - Applicants: BeyondSpring Pharmaceuticals, Inc. - Inventors: Lan Huang - Web page: https://patentgrep.com/patent/US20210275524A1 ## CPC - A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - 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 Disclosed herein are methods of treating a cancer characterized by expressing a mutant form of a RAS protein. Some embodiments relate to treatment of cancer by administering Plinabulin to a subject in need thereof. ## Claims ### Claim 1 A method of treating a cancer characterized by expressing a mutant form of a RAS protein, comprising administering Plinabulin to a subject in need thereof, wherein: the mutant form of the RAS protein is a mutant form of a NRAS protein, a mutant form of an HRAS protein, or a mutant form of a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12D, G12F, G12L, G12N, G13C, G13R, G13S, G13A, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, Q61H, K117N, A146P, A146T, A146V, and D153V. ### Claim 2 (depends on 1) The method of claim 1, wherein the cancer is selected from colorectal cancer, pancreatic cancer, renal caner, lung cancer, liver cancer, breast cancer, prostate cancer, gastrointestinal cancer, peritoneal cancer, melanoma, endometrial cancer, ovarian cancer, cervical cancer, uterine carcinoma, bladder cancer, glioblastoma, brain metastases, salivary gland carcinoma, thyroid cancer, brain cancer, lymphoma, myeloma, and head and neck cancer. ### Claim 3 (depends on 1) The method of claim 1, wherein the cancer is selected from squamous cell cancer, small-cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung, squamous carcinoma of the lung, hepatocellular carcinoma, colon cancer, endometrial carcinoma, and hepatocellular carcinoma. ### Claim 4 (depends on 1) The method of claim 1, comprising co-administering Plinabulin with an additional therapeutic agent selected from temozolomide, bevicizumab, everolimus, carmustine, lomustine, procarbazine, vincristine, irinotecan, cisplatin, carboplatin, methatrexate, etoposide, vinblasatine, bleomycin, actinomycin, cyclophosphamide, or ifosfamide. ### Claim 5 (depends on 1) The method of claim 1, wherein the Plinabulin is administered at a dose from about 5 mg/m2 to 150 mg/m2. ### Claim 6 (depends on 1) The method of claim 1, wherein the Plinabulin is administered orally, sublingually, buccally, subcutaneously, intravenously, intranasally, topically, transdermally, intradermally, intraperitoneally, intramuscularly, intrapulmonarilly, vaginally, rectally, or intraocularly. ### Claim 7 (depends on 1) The method of claim 1, wherein the Plinabulin is administered in combination with radiation. ### Claim 8 (depends on 1) The method of claim 1, wherein the Plinabulin is administered once a week. ### Claim 9 (depends on 1) The method of claim 1, wherein the Plinabulin is administered once on each of day 1 and day 8 of a three-week (21 day) treatment cycle. ### Claim 10 A method of inhibiting proliferation of a cell having a RAS mutation, comprising contacting the cell with Plinabulin, wherein: the mutant form of the RAS protein is a mutant form of a NRAS protein, a mutant form of an HRAS protein, or a mutant form of a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12D, G12F, G12L, G12N, G13C, G13R, G13S, G13A, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, Q61H, K117N, A146P, A146T, A146V, and D153V. ### Claim 11 (depends on 10) The method of claim 10, wherein the contacting comprises administering Plinabulin to a subject having the cell. ### Claim 12 (depends on 10) The method of claim 10, wherein the mutant form of the RAS protein is a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12F, G12L, G12N, G12A, G12D, G13C, G13S, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, and Q61H. ### Claim 13 (depends on 10) The method of claim 10, wherein the Plinabulin is administered at a dose from about 5 mg/m2 to 150 mg/m2. ### Claim 14 A method of inducing apoptosis in a cell having a RAS mutation, comprising contacting the cell with Plinabulin, wherein: the mutant form of the RAS protein is a mutant form of a NRAS protein, a mutant form of an HRAS protein, or a mutant form of a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12D, G12F, G12L, G12N, G13C, G13R, G13S, G13A, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, Q61H, K117N, A146P, A146T, A146V, and D153V. ### Claim 15 (depends on 14) The method of claim 14, wherein the mutant form of the RAS protein is a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12F, G12L, G12N, G12A, G12D, G13C, G13S, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, and Q61H. ### Claim 16 (depends on 14) The method of claim 14, wherein the Plinabulin is administered at a dose from about 5 mg/m2 to 150 mg/m2. ### Claim 17 A method of inhibiting progression of a cancer characterized by expressing a mutant form of a RAS protein in a subject, comprising administering Plinabulin to a subject in need thereof, wherein the mutant form of the RAS protein is a mutant form of a NRAS protein, a mutant form of an HRAS protein, or a mutant form of a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12D, G12F, G12L, G12N, G13C, G13R, G13S, G13A, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, Q61H, K117N, A146P, A146T, A146V, and D153V. ### Claim 18 (depends on 17) The method of claim 17, wherein the mutant form of the RAS protein is a KRAS protein that comprises one or more amino acid substitutions selected from the group consisting of G12C, G12R, G12F, G12L, G12N, G12A, G12D, G13C, G13S, G13V, G13P, S17G, P34S, A59E, A59G, A59T, Q61K, Q61R, and Q61H. ### Claim 19 (depends on 17) The method of claim 17, wherein the Plinabulin is administered at a dose from about 5 mg/m2 to 150 mg/m2. ### Claim 20 (depends on 17) The method of claim 17, wherein the Plinabulin is administered once on each of day 1 and day 8 of a three-week (21 day) treatment cycle.