Crystalline forms of N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine salts and uses thereof

Patent metadata

Field	Value
Publication number	US-10053452-B2
Application number	US-201415101373-A
Country	US
Kind code	B2
Filing date	Nov 25, 2014
Priority date	Dec 3, 2013
Publication date	Aug 21, 2018
Grant date	Aug 21, 2018

Abstract

The present invention relates to crystalline forms and co-crystal forms of pharmaceutically acceptable salts of the compound, N-(4-((3-(2-amino-4-pyrimidinyl)-2-pyridinyl)oxy)phenyl)-4-(4-methyl-2-thienyl)-1-phthalazinamine (AMG 900, and pharmaceutical compositions comprising said crystalline and co-crystal forms thereof. The invention further provides uses of the crystalline forms and compositions, to treat cancer, including various types of solid tumors and hematologic cancer including myeloma and leukemia.

First claim

What is claimed is:

1. A crystalline form A of a mesylate salt of AMG 900 having the formula

characterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 9.89+/−0.16°, 12.96+/−0.10°, 16.52+/−0.10°, 17.84+/−0.16°, 20.05+/−0.10° and 21.55+/−0.19°.

2. A crystalline form A of a mesylate salt of the AMG 900 according to claim 1 , characterized as providing an X-ray powder diffraction pattern substantially as shown in FIG. 1 .

3. A crystalline form of a bismesylate salt of AMG 900 having the formula

said form selected from Form A (dihydrate), Form B (dihydrate), Form C (monohydrate) or Form D (monohydrate).

4. A crystalline form A of a bismesylate dihydrate salt of AMG 900 according to claim 3 , characterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 5.60+/−0.10°, 8.07+/−0.10°, 11.17+/−0.13°, 16.76+/−0.13° and 17.52+/−0.13°.

5. A crystalline Form B of the bismesylate dihydrate salt of AMG 900 according to claim 3 , characterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 7.44+/−0.13°, 9.28+/−0.13°, 12.66+/−0.10°, 16.90+/−0.13° and 24.93+/−0.19°, and wherein the strongest peak in the X-ray diffraction diagram is observed at an angle of refraction 2theta of 24.93+/−0.19°.

6. A crystalline Form B of a bismesylate salt of the AMG 900 according to claim 5 , characterized as providing an X-ray powder diffraction pattern substantially as shown in FIG. 3 .

7. A crystalline form C of a bismesylate monohydrate salt of AMG 900 according to claim 3 characterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 8.29+/−0.10°, 8.55+/−0.10°, 12.96+/−0.10° and 16.51+/−0.23°.

8. A crystalline form D of a bismesylate monohydrate salt of AMG 900 according to claim 3 characterized by an X-ray powder diffraction (XRPD) diagram comprising peaks at the following angles of refraction 2theta: 6.88+/−0.16°, 8.89+/−0.13°, 9.59+/−0.13°, 13.46+/−0.13° and 13.80+/−0.13°.

9. A pharmaceutical composition comprising a therapeutically effective dosage amount of a crystalline form of AMG 900 according to claim 1 and a pharmaceutically acceptable excipient, carrier or diluent.

10. A pharmaceutical composition comprising a therapeutically effective dosage amount of a crystalline form of AMG 900 according to claim 4 and a pharmaceutically acceptable excipient, carrier or diluent.

11. A pharmaceutical composition comprising a therapeutically effective dosage amount of a crystalline form of AMG 900 according to claim 5 and a pharmaceutically acceptable excipient, carrier or diluent.

12. A pharmaceutical composition comprising a therapeutically effective dosage amount of a crystalline form of AMG 900 according to claim 7 and a pharmaceutically acceptable excipient, carrier or diluent.

13. A pharmaceutical composition comprising a therapeutically effective dosage amount of a crystalline form of AMG 900 according to claim 8 and a pharmaceutically acceptable excipient, carrier or diluent.

Assignees

• Amgen Inc

Inventors

• Chaves Mary
• Bio Matthew
• Peterson Matthew

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P15/14

  for lactation disorders, e.g. galactorrhoea · CPC title

• A61P15/08

  for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis · CPC title

• A61P13/08

  of the prostate · CPC title