Crystalline prostacyclin (IP) receptor agonist and uses thereof
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Publication Number
US-12098116-B2
Publication Date
2024-09-24
Expiration Date
Abstract
Described herein are crystalline forms of a prostacyclin (IP) receptor agonist compound, as well as pharmaceutical compositions thereof, and methods of use thereof in the treatment of diseases or conditions that would benefit from treatment with a prostacyclin (IP) receptor agonist compound.
Core Innovation
The disclosure relates to solid-state forms of the prostacyclin (IP) receptor agonist ralinepag, including crystalline forms and an amorphous form. The crystalline forms are characterized as specific solid forms defined by XRPD patterns and by corroborating thermal and physical characterization including TGA/DTA thermograms and DSC/DVS water uptake, together with unit-cell parameters.
Crystalline forms are described with specific XRPD peak positions measured using Cu Kα radiation and corresponding TGA/DTA thermogram features. Amorphous ralinepag is disclosed and is associated with phase conversion behavior to a crystalline form upon drying, while crystalline forms are disclosed with water uptake behavior and potential solvate/hydrate states.
The disclosure further includes pharmaceutical compositions comprising these ralinepag solid forms, with solid dosage forms suitable for oral, intranasal, and inhalation administration, including tablet/pill/capsule formats. Inhalation suitability is described with dry powder inhaler (DPI) and metered dose inhaler (MDI) contexts, and therapeutic methods are described for treating pulmonary arterial hypertension (PAH) by administering the crystalline form of ralinepag to subjects, including subjects having WHO/NYHA functional class II–IV.
Claims Coverage
The independent claims cover three crystalline forms of ralinepag, each defined by specific XRPD peak sets measured using Cu Kα radiation together with thermal characterization features. The claim set also includes therapeutic and formulation contexts tied to the claimed solid forms.
Crystalline form defined by XRPD peaks and specific TGA/DTA events
A crystalline form of ralinepag characterized by an XRPD pattern with peaks at 4.1±0.2°2-Theta, 15.5±0.2°2-Theta, and 16.9±0.2°2-Theta as measured using Cu Kα radiation, together with a TGA/DTA thermogram showing weak endothermic and exothermic events from 81 to 89° C. and a broad endothermic event having an onset at about 124.7° C.
Crystalline form defined by XRPD peaks with TGA mass loss and sharp DTA onset
A crystalline form of ralinepag characterized by an XRPD pattern with peaks at 3.6±0.2°2-Theta, 18.7±0.2°2-Theta, and 22.2±0.2°2-Theta as measured using Cu Kα radiation, together with a TGA trace showing mass loss of about 17.8% from the onset of heating up to approximately 238° C. and a DTA thermogram showing a sharp endothermic event having an onset at about 74.6° C.
Crystalline form defined by XRPD peaks with DTA broad and sharp endothermic onsets
A crystalline form of ralinepag characterized by an XRPD pattern with peaks at 15.0±0.2°2-Theta, 16.7±0.2°2-Theta, and 18.0±0.2°2-Theta as measured using Cu Kα radiation, together with a DTA thermogram showing a broad endothermic event having an onset at about 29.0° C., a sharp endothermic event having an onset at about 127.8° C., or both.
The independent claims define crystalline forms of ralinepag by specific XRPD peak positions measured using Cu Kα radiation and corresponding thermal characterization features. The claim set further ties the solid forms to PAH treatment and solid pharmaceutical composition and administration contexts.
Stated Advantages
Documented Applications
Treating pulmonary arterial hypertension (PAH) by administering the crystalline form of ralinepag to a subject with WHO/NYHA functional class II to IV symptoms.
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