Formulations comprising heterocyclic protein kinase inhibitors
Inventors
Warner, Steven L. • Siddiqui-Jain, Adam • Flynn, Paul
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11471456-B2
Publication Date
2022-10-18
Expiration Date
Abstract
Provided is a composition comprising a polyglycolized glyceride and a compound having the following structure (I): or a pharmaceutically acceptable salt thereof. Also provided are crystalline forms of the compound of structure (I), or a pharmaceutically acceptable salt thereof. Methods of making the same, and methods for using the same in the treatment of cancer, autoimmune, inflammatory and other Pim kinase-associated diseases, disorders or conditions are also disclosed.
Core Innovation
The invention relates to a crystalline form of the hydrochloric acid salt of a compound having structure (I). The crystalline form is characterized by an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at 21.5.2b0, 19.9.2b0, and 17.8.2b0. This crystalline form corresponds to a defined solid-state material for the hydrochloric acid salt of structure (I).
The invention further concerns pharmaceutical compositions and unit dose forms that include the crystalline form together with a pharmaceutically acceptable carrier. The compositions additionally include a polyglycolized glyceride together with a compound of structure (I), or a pharmaceutically acceptable salt thereof. In certain embodiments, the polyglycolized glyceride is characterized by melting point and hydrophile/lipophile balance (HLB) ranges.
The compositions are described in the context of therapeutic use for Pim-kinase mediated diseases. Exemplified disease areas include cancer and autoimmune/inflammatory disorders, including myelofibrosis, with mention of use after ruxolitinib or fedratinib. Crystalline-form and formulation characterization are referenced using XRPD, DSC, TGA, and polarized light microscopy.
Claims Coverage
The independent claims identified in the provided claim set cover four inventive features: a specific crystalline hydrochloric acid salt form defined by X-ray powder diffraction peaks, compositions including that crystalline form with a pharmaceutically acceptable carrier, compositions combining a polyglycolized glyceride with the compound of structure (I) or its pharmaceutically acceptable salt, and a unit dose form with defined component amounts.
Crystalline hydrochloride salt characterized by specified XRPD peaks
A crystalline form of the hydrochloric acid salt of a compound having structure (I), characterized by an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at 21.5.2b0, 19.9.2b0, and 17.8.2b0.
Composition comprising the crystalline form and a pharmaceutically acceptable carrier
A composition comprising the crystalline form and a pharmaceutically acceptable carrier.
Composition of polyglycolized glyceride with structure (I) compound or salt
A composition comprising a polyglycolized glyceride and a compound having structure (I), or a pharmaceutically acceptable salt thereof.
Unit dose form with defined polyglycolized glyceride and structure (I) amounts
A unit dose form comprising a composition, the composition comprising a polyglycolized glyceride in an amount of about 560 mg to about 600 mg and a compound having structure (I), or a pharmaceutically acceptable salt thereof, in an amount of about 115 mg to about 125 mg, as determined using the molecular weight of the compound of structure (I) as a free base.
Overall, the claims define a crystalline hydrochloric acid salt form of structure (I) by specified XRPD peak positions, compositions that include this crystalline form with pharmaceutically acceptable carriers, and formulations that combine the structure (I) compound with polyglycolized glycerides, including a unit-dose embodiment with specified quantitative amounts.
Stated Advantages
Improved exposure versus other excipients is described in the provided summary content.
Documented Applications
Pharmaceutical compositions and unit dose forms comprising the structure (I) compound in combination with polyglycolized glycerides are documented in the provided summary content, including a capsule unit dose form.
Therapeutic use for Pim-kinase mediated diseases including cancer, autoimmune/inflammatory disorders, and myelofibrosis, with mention of use after ruxolitinib or fedratinib.
A Phase 1 clinical trial protocol is described for an oral hydrochloride Form 1 salt in myelofibrosis patients.
Rats pharmacokinetic studies are described for oral formulations, including improved oral bioavailability with the disclosed formulation vehicles, notably GELUCIREae 44/14.
Interested in licensing this patent?