Granted Patent B2

US 9,296,753 · App. 13/908,949 · Granted Mar 29, 2016

Abstract

Claims (47)

1. A crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has (a) an X-Ray powder diffraction (XRPD) pattern as shown in FIG. 1 and optionally at least one of the following properties:

(a) an X-Ray powder diffraction (XRPD) pattern as shown in FIG. 1 ;

(b) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.7±0.1° 2-Theta, 13.6±0.1° 2-Theta, 16.1±0.1° 2-Theta, 18.9±0.1° 2-Theta, 21.3±0.1° 2-Theta, and 21.6±0.1° 2-Theta;

(c) the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week;

(d) the same X-ray powder diffraction (XRPD) pattern post storage at 25° C. and 97% RH for at least a week;

(e) Infrared (IR) spectrum as the one set forth in FIG. 2 ;

(f) Infrared (IR) spectrum weak peaks at about 1584 cm −1 , about 1240 cm −1 , about 1147 cm −1 , about 1134 cm −1 , about 1099 cm −1 , and about 1067 cm −1 ;

(g) a DSC thermogram as the one set forth in FIG. 3 ;

(h) a thermo-gravimetric analysis (TGA) thermogram as the one set forth in FIG. 4 ;

(i) a DSC thermogram with an endotherm having an onset at about 154° C. and a peak at about 157° C. and an exotherm at about 159° C.;

(j) non-hygroscopicity;

(k) an observed aqueous solubility of about 0.013 mg/mL at about pH 8;

or

(l) combinations thereof.

2. The crystalline form of claim 1 , wherein the crystalline form has the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week.

3. The crystalline form of claim 1 , wherein the crystalline form has the same X-ray powder diffraction (XRPD) pattern post storage at 25° C. and 97% RH for at least a week.

4. The crystalline form of claim 1 , wherein the crystalline form has an Infrared (IR) spectrum as the one set forth in FIG. 2 .

5. The crystalline form of claim 1 , wherein the crystalline form has an Infrared (IR) spectrum weak peaks at about 1584 cm −1 , about 1240 cm −1 , about 1147 cm −1 , about 1134 cm −1 , about 1099 cm −1 , and about 1067 cm −1 .

6. The crystalline form of claim 1 , wherein the crystalline form has a melting temperature of about 155-156° C.

7. The crystalline form of claim 1 , wherein the crystalline form has a DSC thermogram as the one set forth in FIG. 3 .

8. The crystalline form of claim 1 , wherein the crystalline form has a thermo-gravimetric analysis (TGA) thermogram as the one set forth in FIG. 4 .

9. The crystalline form of claim 1 , wherein the crystalline form has a DSC thermogram with an endotherm having an onset at about 154° C. and a peak at about 157° C. and an exotherm at about 159° C.

10. The crystalline form of claim 1 , wherein the crystalline form is non-hygroscopic.

11. The crystalline form of claim 1 , wherein the crystalline form has an observed aqueous solubility of about 0.013 mg/mL at about pH 8.

12. The crystalline form of claim 1 , wherein the crystalline form that is characterized as having properties (a), (b), (c), (d), (e), (f), (g), (h), (i), (j), and (k).

13. The crystalline form of claim 1 , wherein the crystalline form was obtained from ethyl acetate, isopropyl acetate, tetrahydrofuran, methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), nitromethane, methanol, ethanol, acetonitrile, dioxane, methyl tert-butyl ether (MTBE), anisole, acetone, heptanes, a methanol/water or an acetone/heptane mixture.

14. The crystalline form of claim 1 , wherein the crystalline form is unsolvated.

15. The crystalline form of claim 1 , wherein the crystalline form is anhydrous.

16. A pharmaceutical formulation for oral administration comprising:

(a) 140 mgs of crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an X-Ray powder diffraction (XRPD) pattern as shown in FIG. 1 ;

(b) 45.9 wt % of microcrystalline cellulose;

(c) 7.0 wt % of croscarmellose sodium;

(d) 4.2 wt % of sodium lauryl sulfate; and

(e) 0.5 wt % of magnesium stearate.

17. A crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.7±0.1 ° 2-Theta, 13.6±0.1° 2-Theta, 16.1±0.1° 2-Theta, 18.9±0.1 ° 2-Theta, 21.3±0.1° 2-Theta, and 21.6±0.1° 2-Theta; and at least one of the following properties:

(i) an X-Ray powder diffraction (XRPD) pattern as shown in FIG. 1 ;

(ii) the same X-ray powder diffraction (XRPD) pattern post storage at 40° C. and 75% RH for at least a week;

(iii) the same X-ray powder diffraction (XRPD) pattern post storage at 25° C. and 97% RH for at least a week;

(iv) Infrared (IR) spectrum as the one set forth in FIG. 2 ;

(v) Infrared (IR) spectrum weak peaks at about 1584 cm −1 , about 1240 cm −1 , about 1147 cm −1 , about 1134 cm −1 , about 1099 cm −1 , and about 1067 cm −1 ;

(vi) a DSC thermogram as the one set forth in FIG. 3 ;

(vii) a thermo-gravimetric analysis (TGA) thermogram as the one set forth in FIG. 4 ;

(viii) a DSC thermogram with an endotherm having an onset at about 154° C. and a peak at about 157° C. and an exotherm at about 159° C.;

(ix) non-hygroscopicity;

(x) an observed aqueous solubility of about 0.013 mg/mL at about pH 8; or

(xi) combinations thereof.

18. A pharmaceutical formulation for oral administration comprising: (a) 140 mgs of crystalline Form A of 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one that has an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 5.7±0.1° 2-Theta, 13.6±0.1° 2-Theta, 16.1±0.1° 2-Theta, 18.9±0.1° 2-Theta, 21.3±0.1° 2-Theta, and 21.6±0.1° 2-Theta; (b) 45.9 wt % of microcrystalline cellulose; (c) 7.0 wt % of croscarmellose sodium; (d) 4.2 wt % of sodium lauryl sulfate; and (e) 0.5 wt % of magnesium stearate.

Assignments (8)