# US 11,028,060 B2 · Crystalline forms of ozanimod and processes for preparation thereof

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- Number: US 11,028,060 B2
- Document ID: US11028060B2
- Status: Granted
- Kind: B2
- Application number: 16/326,353
- Filed: 2017-08-18
- Published: 2020-07-09
- Granted: 2021-06-08
- Earliest claimed: 2016-08-19
- Assignees: Receptos, Inc.
- Applicants: Receptos LLC
- Inventors: Minhua Chen; Yanfeng Zhang; Xiaoting Zhai; Kaiqiang Yan; Chaohui Yang; Xiaoyu Zhang
- Web page: https://patentgrep.com/patent/US11028060B2

## CPC

- A61K 31/4245: Oxadiazoles
- C07D 271/06: 1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 37/02: Immunomodulators
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## 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.

## Claims

### Claim 1

A crystalline form CS10 of ozanimod, wherein the X-ray powder diffraction pattern shows characteristic peaks at 2theta values of 5.7°±0.2°, 25.0°±0.2° and 26.6°±0.2° using CuKα radiation.

### Claim 2 (depends on 1)

The crystalline form CS10 of ozanimod according to claim 1, wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 13.4°±0.2°, 28.3°±0.2° and 16.2°±0.2° using CuKα radiation.

### Claim 3 (depends on 1)

The crystalline form CS10 of ozanimod according to claim 1, wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 8.6°±0.2°, 19.3°±0.2° and 14.6°±0.2° using CuKα radiation.

### Claim 4 (depends on 1)

A process for preparing crystalline form CS10 of ozanimod according to claim 1, wherein the process comprises:
suspending amorphous ozanimod into arenes or a mixture of acetone and water,
stirring at room temperature to obtain solid, and the obtained solid is form CS10 of ozanimod.

### Claim 5 (depends on 4)

The process for preparing crystalline form CS10 of ozanimod according to claim 4, wherein said arene is toluene; said volume ratio of acetone and water is 1:1.

### Claim 6 (depends on 4)

The process for preparing crystalline form CS10 of ozanimod according to claim 4, wherein the amorphous ozanimod was prepared by melting the ozanimod solid at 150° C., and then crash cooling at −20° C. to obtain amorphous ozanimod.

### Claim 7 (depends on 1)

A pharmaceutical composition, wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form CS10 of ozanimod according to claim 1, and pharmaceutically acceptable carriers, diluents or excipients.

### Claim 8 (depends on 2)

The crystalline form CS10 of ozanimod according to claim 2, wherein the X-ray powder diffraction pattern shows one or two or three characteristic peaks at 2theta values of 8.6°±0.2°, 19.3°±0.2° and 14.6°±0.2° using CuKα radiation.

### Claim 9 (depends on 4)

The process for preparing crystalline form CS10 of ozanimod according to claim 4, wherein said arene is toluene; said volume ratio of acetone and water is 1:10 to 10:1.

### Claim 10 (depends on 1)

A method for treating ulcerative colitis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 1.

### Claim 11 (depends on 1)

A method for treating multiple sclerosis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 1.

### Claim 12 (depends on 2)

A pharmaceutical composition, wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form CS10 of ozanimod according to claim 2, and pharmaceutically acceptable carriers, diluents or excipients.

### Claim 13 (depends on 2)

A method for treating ulcerative colitis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 2.

### Claim 14 (depends on 2)

A method for treating multiple sclerosis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 2.

### Claim 15 (depends on 8)

A pharmaceutical composition, wherein said pharmaceutical composition comprises a therapeutically effective amount of crystalline form CS10 of ozanimod according to claim 8, and pharmaceutically acceptable carriers, diluents or excipients.

### Claim 16 (depends on 8)

A method for treating ulcerative colitis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 8.

### Claim 17 (depends on 8)

A method for treating multiple sclerosis, comprising administering to a patient in need thereof a therapeutically effective amount of the crystalline form CS10 of ozanimod according to claim 8.