Crystalline forms and salt forms of a kinase inhibitor
Inventors
DeMorin, Frenel • Shah, Khalid • Shakya, Sagar • Wong, Peter • JOHNSON, COURTNEY S. • Bevill, Melanie Janelle • PARENT, Stephan D.
Assignees
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Publication Number
US-12017995-B2
Publication Date
2024-06-25
Expiration Date
Abstract
The present invention relates to crystalline forms of the free base of the c-Met inhibitor, Compound 1. The invention also relates to crystalline forms of salts of Compound 1. The invention also relates to pharmaceutical compositions comprising the solid polymorphs of the free base and salts of Compound 1. The invention further relates to methods of treating a disease, disorder, or syndrome mediated at least in part by modulating in vivo activity of a protein kinase.
Core Innovation
The invention relates to crystalline and salt forms of Compound 1, including the free base and multiple solid-state polymorphic forms, as well as crystalline acid/addition salt forms including hydrochloride, fumarate, hemifumarate, and phosphate form A. The disclosure characterizes these forms using XRPD peak lists, DSC thermograms, TGA thermograms, DVS, and related solid-state characterization features.
The crystalline hemifumarate salt of Compound 1 is specifically described as having a defined structure and is identified as Hemifumarate Form B. The document also provides characterization criteria for this form, including XRPD peaks, DSC thermal behavior, and TGA/DVS moisture behavior, and it identifies additional crystalline HCl forms labeled A-D and other crystalline forms by 2θ ranges, 1H NMR similarity, stability, and unit-cell indexing or isostructural notes.
The document states that the crystalline forms and salts can be used in pharmaceutical compositions with a pharmaceutically acceptable excipient. It further frames these forms for protein kinase inhibition, including Axl/Mer/c-Met/KDR, for cancer treatment, and also refers to pharmaceutical administration and formulation concepts, combination therapy with immunotherapeutic agents, imaging, TAM kinase assays, and pack and kit concepts.
Claims Coverage
The provided claim coverage centers on one inventive feature: a crystalline hemifumarate salt of Compound 1 having a specified structure. A related inventive feature adds a pharmaceutical composition comprising that crystalline hemifumarate salt with a pharmaceutically acceptable excipient.
Crystalline hemifumarate salt of Compound 1
A crystalline hemifumarate salt of Compound 1 having the structure specified in the claim.
Pharmaceutical composition including crystalline hemifumarate salt
A pharmaceutical composition comprising the crystalline hemifumarate salt of Compound 1 together with a pharmaceutically acceptable excipient.
Across the provided claim set, coverage is focused on a crystalline hemifumarate salt of Compound 1 and pharmaceutical compositions that include that crystalline hemifumarate salt with a pharmaceutically acceptable excipient.
Stated Advantages
Improved stability.
Improved solubility.
Improved bioavailability.
Documented Applications
Pharmaceutical compositions for protein kinase inhibition (Axl/Mer/c-Met/KDR) for cancer treatment.
Therapeutic use of the described c-Met inhibitor crystalline forms and pharmaceutical compositions for treating kinase-mediated diseases.
Cancer combination therapy by co-administration with immunotherapeutic agents, especially immune checkpoint inhibitors, with therapeutic benefit assessed using response criteria such as irRC.
Imaging use via labeled or isotopically labeled crystalline forms and associated radioconjugate or radiolabeled compound mentions.
Assay use via TAM kinase assays involving labeled or isotopically labeled crystalline forms.
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