# US 10,864,203 B2 · Combination of a PD-1 antagonist and a RAF inhibitor for treating cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,864,203 B2 - Document ID: US10864203B2 - Status: Granted - Kind: B2 - Application number: 16/315,539 - Filed: 2017-06-14 - Published: 2020-03-05 - Granted: 2020-12-15 - Earliest claimed: 2016-07-05 - Assignees: BeiGene, Ltd. - Applicants: BeiGene, Ltd. - Inventors: Jing Song; Lai Wang; Kang Li; Tong Zhang; Lusong Luo; Min Wei; Zhiyu Tang; Guoliang Zhang; Changyou Zhou - Web page: https://patentgrep.com/patent/US10864203B2 ## CPC - A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine - A61K 39/39541: {against normal tissues, cells} - A61P 35/00: Antineoplastic agents - C07K 16/2818: {against CD28 or CD152} - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - 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 - 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) ## Abstract Disclosed herein is a pharmaceutical combination for use in the prevention, delay of progression or treatment of cancer, wherein the pharmaceutical combination exhibits a synergistic efficacy. The pharmaceutical combination comprises a humanized antagonist monoclonal antibody against PD- and a RAF inhibitor. Also disclosed herein is a combination for use in the prevention, delay of progression or treatment of cancer in a subject, comprising administering to the subject a therapeutically effective amount of a humanized antagonist monoclonal antibody against PD-1 and a therapeutically effective amount of a RAF inhibitor. ## Claims ### Claim 1 A method for the treatment of lung cancer or colorectal cancer in a subject, comprising administering to the subject in need thereof a therapeutically effective amount of a PD-1 antagonist in combination with a therapeutically effective amount of a RAF inhibitor, wherein the PD-1 antagonist is an antibody or an antigen binding fragment thereof, which specifically binds to human PD-1 and which comprises a heavy chain variable region (Vh) and a light chain variable region (Vk), wherein the Vh comprises complimentary determining region (CDR) 1, CDR2, and CDR3 comprising SEQ ID NOs: 31, 32, and 33, respectively; and the Vk comprises CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 34, 35, and 36, respectively; and wherein the RAF inhibitor is a compound of Formula (II), or a pharmaceutically acceptable salt thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein the (Vh) of the antibody comprises SEQ ID NO: 24 and the (Vk) of the antibody comprises SEQ ID NO: 26. ### Claim 3 (depends on 1) The method of claim 1, wherein the antibody contains a IgG4 heavy chain effector or constant domain comprising any of SEQ ID NOs: 83-88. ### Claim 4 (depends on 1) The method according to claim 1, wherein the PD-1 antagonist is an antibody which comprises an IgG4 heavy chain effector or constant domain comprising SEQ ID NO: 88, wherein the heavy chain variable region (Vh) and the light chain variable region (Vk) comprises SEQ ID NO: 24 and SEQ ID NO: 26, respectively. ### Claim 5 (depends on 1) The method of claim 1, wherein the RAF inhibitor is a compound of Formula (III), wherein n is a number from about 0.5 to about 1.5. ### Claim 6 (depends on 1) The method of claim 1, wherein the RAF inhibitor is a compound of Formula (IIIa), ### Claim 7 (depends on 1) The method of claim 1, wherein the PD-1 antagonist and the RAF inhibitor are administered simultaneously, sequentially or separately. ### Claim 8 (depends on 1) The method of claim 1, wherein the RAF inhibitor is administrated orally at a dose of 5-80 mg QD. ### Claim 9 (depends on 1) The method of claim 1, wherein the PD-1 antagonist is administered parenterally at a dose of 0.5-10 mg/kg QW, or Q2W, or Q3W, or Q4W. ### Claim 10 (depends on 1) The method of claim 1, wherein the PD-1 antagonist is an antibody which comprises a heavy chain variable region (Vh) and a light chain variable region (Vk), and a IgG4 heavy chain effector or constant domain comprising SEQ ID NO: 88, wherein the heavy chain variable region (Vh) and the light chain variable region (Vk) comprise SEQ ID NO: 24 and SEQ ID NO: 26, respectively; and the RAF inhibitor is the compound of Formula (IIIa) ### Claim 11 (depends on 10) The method of claim 10, wherein the PD-1 antagonist is administrated at a dose of 0.5-10 mg/kg QW or Q2W or Q3W, and the compound of Formula (IIIa) as the RAF inhibitor is administrated at a dose of 5-80 mg QD. ### Claim 12 (depends on 10) The method of claim 10, wherein the PD-1 antagonist is administrated at a dose of 0.5-10 mg/kg QW or Q2W or Q3W, and the compound of Formula (IIIa) as the RAF inhibitor is administrated at a dose of 10-30 mg QD. ### Claim 13 A pharmaceutical combination for use in the treatment of lung cancer or colorectal cancer, comprising a PD-1 antagonist and a RAF inhibitor, wherein the PD-1 antagonist is an antibody or a fragment antigen binding thereof, which specifically binds to human PD-1, comprising a heavy chain variable region (Vh) and a light chain variable region (Vk) that contain complement determinant regions (CDRs) listed as follows: CDR-H1, CDR-H2 and CDR-H3 (SEQ ID NOs: 31, 32, 33, respectively); and CDR-L1, CDR-L2 and CDR-L3 (SEQ ID NOs: 34, 35, 36, respectively); and wherein the RAF inhibitor is a compound of Formula (H), or a pharmaceutically acceptable salt thereof.