Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12208166-B2
Publication Date
2025-01-28
Expiration Date
Abstract
Lyophilized formulations of tegavivint, methods of making such formulations, and methods of treatment of cancer by administering the formulations.
Core Innovation
The invention relates to stable lyophilized tegavivint formulations presented as a nanosuspension of tegavivint particles or a pharmaceutically acceptable salt. The formulation includes poloxamer and one or more stabilizers selected from sucrose, trehalose, and sorbitol, and it is characterized by nanoscale particle sizing measured by laser diffraction, with D50 less than or equal to 500 nm and D90 less than or equal to 1.0 micron.
A process aspect uses either Form I or Form IV polymorph of tegavivint as a starting material and mills the starting material with the poloxamer at a temperature of between about 40°C and about 60°C. The document describes good cake integrity and a readily resuspendable lyophilized product, with no significant crystal growth, and indicates that polymorph conversion can be supported by PSD, microscopy, and DSC, including an observed conversion from Form IV to Form I during milling.
The invention also addresses chemical and physical stability of the lyophilized product over storage, including assay and impurities stability and PSD overlap after storage at different temperatures. Documented characterization includes nanoscale particle size behavior and thermal and crystal behavior assessed by DSC, together with optical microscopy. In addition, the document describes therapeutic methods using administration of the formulation or a reconstituted formulation derived from the lyophilized product for cancer, tumor metastasis, and fibrotic disease.
Claims Coverage
The independent claim defines a nanosuspension pharmaceutical formulation with specific nanoscale particle-size targets and formulation components. It also requires a process constraint based on using tegavivint Form I or Form IV polymorph as starting material and milling at a temperature between about 40°C and about 60°C, with dependent claims further refining the poloxamer identity and concentration, polymorph choice, milling modality, and therapeutic use.
Nanosuspension with specified particle size by laser diffraction
A pharmaceutical formulation comprising particles of tegavivint or a pharmaceutically acceptable salt thereof, wherein the particles have a median particle diameter D50 of less than or equal to 500 nm and wherein 90% of particles have a diameter D90 of less than or equal to 1.0 micron when measured using laser diffraction.
Poloxamer with sucrose, trehalose, or sorbitol stabilizers
The formulation comprises a poloxamer and one or more stabilizers selected from the group consisting of sucrose, trehalose, and sorbitol.
Starting from tegavivint Form I or Form IV and milling at 40°C to 60°C
The formulation is a nanosuspension prepared by a process comprising using either Form I or Form IV polymorph of tegavivint as a starting material and milling the starting material with the poloxamer at a temperature of between about 40°C and about 60°C.
Poloxamer 188 as the poloxamer
The pharmaceutical formulation comprises poloxamer 188.
Poloxamer concentration constraint
The pharmaceutical formulation has a poloxamer concentration of about 6 mg/ml.
Using Form I polymorph as the starting material
The formulation is defined such that its starting material is the Form I polymorph of tegavivint.
Allowed milling modalities
The milling is performed by ball milling or high energy agitator milling.
Method of treating cancer or tumor metastasis by administration
A method of treating cancer or a tumor metastasis in a mammal by administering an effective amount of a pharmaceutical formulation according to claim 1.
Overall, claim coverage centers on a tegavivint nanosuspension formulation meeting laser-diffraction particle-size limits, containing poloxamer plus sucrose, trehalose, or sorbitol stabilizers, and prepared by milling Form I or Form IV polymorph with poloxamer at about 40°C to about 60°C. Dependent features narrow the poloxamer identity and concentration, restrict the starting polymorph choice, specify milling modality, and include administration for cancer or tumor metastasis in mammals.
Stated Advantages
Good cake integrity.
Readily resuspendable lyophilized product.
No significant crystal growth.
Chemical stability maintained with assay and impurities stability.
PSD overlap observed after storage at 5°C versus 25°C up to at least 3 months.
Documented Applications
Therapeutic method using administration of the formulation or a reconstituted formulation derived from the lyophilized product for cancer and tumor metastasis in mammals.
Therapeutic method using administration of the formulation for fibrotic disease.
Interested in licensing this patent?