CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
Inventors
Siddiqui-Jain, Adam • Flynn, Paul • Masumoto, Shuji • Tanaka, Hiroaki • Kurebayashi, Hirotaka • HASHIZUKA, Takahiko • Arikawa, Yuka
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11530231-B2
Publication Date
2022-12-20
Expiration Date
Abstract
A crystalline form and/or polymorph of a compound having the following structure (I), including tautomeric and zwitterionic forms thereof, are provided: Methods associated with preparation and use of the polymorphs, and pharmaceutical compositions comprising the same are also provided. Also provided are methods for preparing a compound having formula (I), or a salt, tautomer or zwitterionic form thereof.
Core Innovation
The disclosure characterizes crystalline Form B of a compound having structure (I) and a zwitterionic form thereof by x-ray powder diffraction (XRPD), including specified 2-theta peak angles and D spacings. A monoclinic crystal form is identified by space group P2_1 together with lattice parameters and unit-cell volume, supporting identification of the polymorph as Form B.
The disclosure further describes pharmaceutical compositions containing crystalline Form B with pharmaceutically acceptable carrier or excipient, including filler, disintegrant, lubricant, fluidizer, glidant, and lubricant. Physicochemical stability targets, purity after storage, DSC endotherm peak ranges, and formulation stability and excipient compatibility are described for the Form B polymorph.
The document also describes preparation concepts for obtaining Form B, including conversion of an amorphous form to Form B using maleic acid and low-water solvent conditions, and salt-screening results indicating that maleic acid and other agents form polymorph Form B rather than salts or co-crystals. The disclosure further presents use of crystalline Form B or its zwitterionic form in pharmaceutical compositions and for treating cancer.
Claims Coverage
The independent claims cover three aspects: two pharmaceutical compositions and one method of treating cancer in a mammal. In each claim, crystalline Form B or a zwitterionic form of the compound having structure (I) is defined by an XRPD pattern comprising at least three peaks at specified 2-theta angles, with composition claims differing by excipient scope and the method claim adding a daily amount range.
Crystalline form B pharmaceutical composition with XRPD-defined peaks
A pharmaceutical composition comprising crystalline Form B of a compound having structure (I) or a zwitterionic form thereof and a pharmaceutically acceptable carrier or excipient, wherein the carrier or excipient is a filler, disintegrant, lubricant or fluidizer, and wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising at least three peaks at 2-theta angles selected from 4.8±0.2°, 10.8±0.2°, 13.7±0.2°, 14.9±0.2°, 20.0±0.2° and 24.6±0.2°.
Crystalline form B composition with glidant and lubricant and XRPD-defined peaks
A pharmaceutical composition comprising crystalline Form B of a compound having structure (I) or a zwitterionic form thereof, a pharmaceutically acceptable carrier or excipient, a glidant, and a lubricant, wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising at least three peaks at 2-theta angles selected from 4.8±0.2°, 10.8±0.2°, 13.7±0.2°, 14.9±0.2°, 20.0±0.2° and 24.6±0.2°.
Cancer treatment with XRPD-defined crystalline Form B dose
A method for treating cancer in a mammal in need thereof, comprising administering crystalline Form B of a compound having structure (I) or a zwitterionic form thereof in an amount from about 1 mg to about 30 mg per day, wherein crystalline Form B is characterized by an x-ray powder diffraction pattern comprising at least three peaks at 2-theta angles selected from 4.8±0.2°, 10.8±0.2°, 13.7±0.2°, 14.9±0.2°, 20.0±0.2° and 24.6±0.2°.
Across the independent claims, crystalline Form B or a zwitterionic form is the defining element, with Form B identity established by an XRPD pattern containing at least three specified peaks at defined 2-theta angles. The composition claims differ in excipient scope, and the method claim applies Form B administration to cancer treatment at a specified daily amount range in a mammal.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer in a mammal.
Pharmaceutical compositions comprising crystalline Form B or a zwitterionic form thereof.
Interested in licensing this patent?