# US 9,751,889 B2 · Crystalline form I of ibrutinib > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,751,889 B2 - Document ID: US9751889B2 - Status: Granted - Kind: B2 - Application number: 15/100,247 - Filed: 2014-11-26 - Published: 2017-01-05 - Granted: 2017-09-05 - Earliest claimed: 2013-11-27 - Assignees: Crystal Pharmatech Co., Ltd.; Suzhou Pengxu Pharmatech Co., Ltd. - Applicants: Crystal Pharmatech Inc.; Suzhou Pengxu Pharmatech Co., Ltd. - Inventors: Minhua Chen; Yanfeng Zhang; Chaohui Yang; Xiaoyu Zhang; Peng Wang; Pixu Li; Fei Lu; Heng Ge - Web page: https://patentgrep.com/patent/US9751889B2 ## CPC - C07D 487/04: Ortho-condensed systems - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61P 35/00: Antineoplastic agents - A61P 35/02: specific for leukemia - C07B 2200/13: Crystalline forms, e.g. polymorphs - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - 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 - C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F) ## Abstract Crystalline Form I of ibrutinib, processes for its preparation, pharmaceutical compositions comprising the new Form, and use of Form I of ibrutinib for treating or delaying diseases or disorders related to activity of Bruton's tyrosine kinase (BTK) proteins are disclosed. The novel Form was characterized by X-ray powder diffraction, differential scanning calorimetry, and other techniques. It can be readily prepared and is suitable for use in the preparation of solid dosage forms. ## Claims ### Claim 1 A crystalline form of ibrutinib, designated as Form I, having an X-ray powder diffraction pattern comprising the following 2θ values measured using CuKα radiation: 5.2°±0.2°, 17.6°±0.2°, and 22.1°±0.2°. ### Claim 2 (depends on 1) The crystalline form of claim 1, wherein the X-ray powder diffraction pattern further comprises the following 2θ values measured using CuKα radiation: 19.3°±0.2°, 20.8°±0.2°, and 22.4°±0.2°. ### Claim 3 (depends on 1) The crystalline form of claim 1, wherein the X-ray powder diffraction pattern further comprises the following 2θ values measured using CuKα radiation: 16.2°±0.2°, 18.1°±0.2°, 18.9°±0.2°, and 23.0°±0.2°. ### Claim 4 (depends on 1) The crystalline form of claim 1, having an X-ray powder diffraction pattern substantially as depicted in FIG. 1. ### Claim 5 (depends on 1) The crystalline form of claim 1, having a differential scanning calorimetric thermogram substantially as depicted in FIG. 2. ### Claim 6 (depends on 1) The crystalline form of claim 1, having a thermal gravimetric analysis thermogram substantially as depicted in FIG. 3. ### Claim 7 A process for the preparation of ibrutinib Form I, comprising: dissolving ibrutinib in a solvent system selected from the group consisting of alcohol having three or more carbon atoms, ether, ketone, a mixture of alcohol with alkane, a mixture of ether and alkane, and a mixture of ketone with alkane to form a solution; and crystallizing said Form I by cooling the solution under ambient conditions or in a controlled manner. ### Claim 8 (depends on 7) The process according to claim 7, wherein said solvent system is a mixture of an alcohol or ketone and an alkane. ### Claim 9 (depends on 8) The process according to claim 8, wherein said alcohol is a lower alcohol, and said alkane is a C4-C10 alkane. ### Claim 10 (depends on 8) The process according to claim 8, wherein the solvent system is a mixture of 2-propanol and n-heptane. ### Claim 11 (depends on 8) The process according to claim 8, wherein said ketone is a C3-C6 ketone, and said alkane is a C4-C10 alkane. ### Claim 12 (depends on 8) The process according to claim 8, wherein the solvent system is a mixture of acetone and n-heptane. ### Claim 13 A pharmaceutical composition comprising crystalline Form I of ibrutinib and a pharmaceutically acceptable carrier, wherein said crystalline Form I has an X-ray powder diffraction pattern comprising the following 2θ values measured using CuKα radiation: 5.2°±0.2°, 17.6°±0.2°, and 22.1°±0.2°. ### Claim 14 (depends on 13) The pharmaceutical composition of claim 13, wherein the X-ray powder diffraction pattern of said crystalline Form I further comprises the following 2θ values measured using CuKα radiation: 19.3°±0.2°, 20.8°±0.2°, and 22.4°±0.2°. ### Claim 15 (depends on 13) The pharmaceutical composition of claim 13, wherein the X-ray powder diffraction pattern further comprises the following 2θ values measured using CuKα radiation: 16.2°±0.2°, 18.1°±0.2°, 18.9°±0.2°, and 23.0°±0.2°. ### Claim 16 (depends on 13) The pharmaceutical composition of claim 13, wherein said crystalline Form I has a melting point at about 135.1° C. as measured by differential scanning calorimetry (DSC). ### Claim 17 (depends on 13) The pharmaceutical composition of claim 13, wherein the X-ray powder diffraction pattern of said crystalline Form I has an X-ray powder diffraction pattern substantially as depicted in FIG. 1. ### Claim 18 A method of treating or delaying the progression or onset of a disease or disorder in connection with activity of a Bruton's tyrosine kinase (BTK), comprising administering to a subject in need thereof a pharmaceutical composition comprising crystalline Form I of ibrutinib. ### Claim 19 (depends on 18) The method of claim 18, wherein said disease or disorder is a B cell malignancy selected from the group consisting of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), diffuse large B Cell lymphoma (DLBCL), and multiple myeloma.