# US 10,308,630 B2 · Crystalline forms of an androgen receptor modulator

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- Number: US 10,308,630 B2
- Document ID: US10308630B2
- Status: Granted
- Kind: B2
- Application number: 15/975,449
- Filed: 2018-05-09
- Published: 2018-09-13
- Granted: 2019-06-04
- Earliest claimed: 2012-06-07
- Assignees: Sloan-Kettering Institute for Cancer Research; Aragon Pharmaceuticals, Inc.
- Applicants: Aragon Pharmaceuticals, Inc.; Sloan-Kettering Institute For Cancer Research
- Inventors: Anna Dilhas; Mark R. Herbert; Ouathek Ouerfelli; Nicholas D. Smith
- Web page: https://patentgrep.com/patent/US10308630B2

## CPC

- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/28: Antiandrogens
- A61P 13/08: of the prostate
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Described herein are amorphous and crystalline forms of the androgen receptor modulator 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide. Also described are pharmaceutical compositions suitable for administration to a mammal that include the androgen receptor modulator, and methods of using the androgen receptor modulator, alone and in combination with other compounds, for treating diseases or conditions that are associated with androgen receptor activity.

## Claims

### Claim 1

A crystalline Form I of 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide that exhibits an an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 7.7±0.1° 2-Theta, 10.4±0.1° 2-Theta, 11.6±0.1° 2-Theta, 17.0±0.1° 2-Theta, 20.0±0.1° 2-Theta, and 20.6±0.1° 2-Theta.

### Claim 2 (depends on 1)

The crystalline Form I of claim 1 that is further characterized as exhibiting an X-Ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 9.

### Claim 3 (depends on 1)

A pharmaceutical composition comprising 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide and at least one additional ingredient selected from pharmaceutically acceptable carriers, diluents and excipients, in which the 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide in the composition comprises the crystalline Form I according to claim 1.

### Claim 4 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pharmaceutical composition is in a form formulated for oral administration to a mammal.

### Claim 5 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pharmaceutical composition is in an oral solid dosage form.

### Claim 6 (depends on 3)

The pharmaceutical composition according to claim 3, wherein the pharmaceutical composition comprises about 0.5 mg to about 1000 mg of the crystalline form of 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide.

### Claim 7 (depends on 1)

A method of treating prostate cancer in a mammal comprising administering the crystalline Form I of 4-[7-(6-cyano-5-trifluoromethylpyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]oct-5-yl]-2-fluoro-N-methylbenzamide according to claim 1 to a mammal in need of such treatment.

### Claim 8 (depends on 3)

A method of treating prostate cancer in a mammal comprising administering the pharmaceutical composition according to claim 3 to a mammal in need of such treatment.

### Claim 9 (depends on 7)

The method of claim 7, wherein the prostate cancer is hormone sensitive prostate cancer or hormone refractory prostate cancer.