Crystalline forms of ozanimod and processes for preparation thereof

Inventors

Chen, Minhua • Zhang, Yanfeng • ZHAI, Xiaoting • YAN, Kaiqiang • YANG, Chaohui • Zhang, Xiaoyu

Assignees

Receptos LLC

Abstract

The present disclosure relates to novel crystalline forms of ozanimod and preparation method thereof. The provided crystalline forms of ozanimod comprise crystalline form CS9, crystalline form CS10 and crystalline form CS11, and can be used for treating autoimmune diseases, particularly used for preparing drugs for treating multiple sclerosis and ulcerative colitis. The crystalline forms of the present disclosure have one or more advantages in solubility, stability, hygroscopicity and processability and provide new and better choices for the preparation of ozanimod drug product, and are very valuable for drug development.

Core Innovation

The patent discloses crystalline form CS11 of ozanimod defined by an X-ray powder diffraction pattern with characteristic peaks at specific 2theta values, including peaks at 5.7°±0.2°, 24.6°±0.2°, and 0.3°±0.2°. The diffraction fingerprint is used to distinguish the crystalline form by its characteristic peak positions.

The document further describes additional crystalline forms of ozanimod, including CS9 (hydrate) and CS10 (anhydrate), with corresponding preparation routes from amorphous ozanimod using particular solvent systems. The characterization includes XRPD, DVS for hygroscopicity, water solubility measurements, and particle size distribution and morphology assessment using PSD and PLM.

The patent states that these crystalline forms, including CS11, are suitable for pharmaceutical use and are associated with improved performance characteristics relevant to drug development. The described assessment includes stability under defined temperature and humidity conditions, and the document connects the crystalline-form properties to water solubility, hygroscopicity behavior, and particulate characteristics that support processing and industrial manufacture.

Claims Coverage

The independent claim set centers on crystalline form CS11 of ozanimod defined by an XRPD-based diffraction fingerprint. The claims further include pharmaceutical composition embodiments, selective modulation of sphingosine-1-phosphate receptor, and process embodiments for preparing crystalline form CS11 from amorphous ozanimod using specified solvent systems and solvent volume ratios.

Claim coverage centers on crystalline form CS11 of ozanimod defined by a characteristic XRPD peak set, with further refinement to peak-count and additional peak positions. The claims also cover pharmaceutical compositions, selective S1PR modulation, and preparation embodiments using specified solvent systems and volume-ratio constraints.

Stated Advantages

Documented Applications