Claims for Patent: 10,385,008

Summary for Patent: 10,385,008

Title:	Polymorphic forms of RAD1901-2HCL
Abstract:	Various polymorphic forms of RAD1901-2HCl, including three crystalline and amorphous forms, are prepared and characterized. Uses of the various polymorphic forms of RAD1901-2HCl for cancer treatment are also disclosed.
Inventor(s):	Michael Paul CRUSKIE, JR., Joshua Kyle BOLGER, Jonathan Blake MCKENZIE, Pratik SHETH, Richard Edwards, Alex Eberlin, Michael MARKEY
Assignee:	Radius Pharmaceuticals Inc
Application Number:	US15/863,850
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,385,008
Patent Claims:	1. A solid form of RAD1901-2HCl, having an X-ray powder diffraction pattern comprising a peak, in terms of 2-theta, at 7.1 degrees 2θ±0.2 degree 2θ at about relative humidity 0%. 2. The solid form of claim 1, having an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at 7.1 degrees 2θ±0.2 degree 2θ and 14.3 degrees 2θ±0.2 degree 2θ at about relative humidity 0%. 3. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least one peak, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ and 18.3 degrees 2θ±0.2 degree 2θ at about relative humidity 0%. 4. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least two peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ and 12.0 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 5. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least three peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ and 18.9 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 6. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least four peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ and 11.0 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 7. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least four peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ, 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 8. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least six peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ, 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 9. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least seven peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ, 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 10. The solid form of claim 1, having an X-ray powder diffraction pattern further comprising at least eight peaks, in terms of 2-theta, selected from the group consisting of 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ, 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 11. The solid form of claim 1, having an X-ray powder diffraction pattern comprising the peaks, in terms of 2-theta, of 7.1 degrees 2θ±0.2 degree 2θ, 14.3 degrees 2θ±0.2 degree 2θ, 18.3 degrees 2θ±0.2 degree 2θ, 13.8 degrees 2θ±0.2 degree 2θ, 12.0 degrees 2θ±0.2 degree 2θ, 25.1 degrees 2θ±0.2 degree 2θ, 18.9 degrees 2θ±0.2 degree 2θ, 27.2 degrees 2θ±0.2 degree 2θ, 11.0 degrees 2θ±0.2 degree 2θ and 16.2 degrees 2θ±0.2 degree 2θ, at about relative humidity 0%. 12. The solid form of claim 1, having an X-ray powder diffraction pattern as shown in FIG. 4G at about relative humidity 0%. 13. A solid form of RAD1901-2HCl, having a differential scanning calorimetry (DSC) thermogram comprising a melting onset at 218.2° C. and an endothermic peak at 232.1° C. 14. The solid form of claim 13, having a differential scanning calorimetry (DSC) thermogram as shown in the bottom figure of FIG. 8. 15. A solid form of RAD1901-2HCl, having a thermogravimetric analysis (TGA) as shown in the top graph of FIG. 8. 16. A pharmaceutical composition comprising the solid form of claim 1 and one or more pharmaceutically acceptable excipients. 17. A process for preparing the solid form of claim 1 comprising precipitating from a solution comprising RAD1901-2HCl and a solvent, or slurrying RAD1901-2HCl in a solvent, wherein the solvent comprises an organic solvent excluding methanol, and the content of water is at or below 5% v/v. 18. The process according to claim 17 wherein the organic solvent is selected from the group consisting of n-heptane, propyl acetate, ethyl acetate, isopropyl acetate, methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), 1-propanol, ethanol, t-butyl methyl ether (TBME), 1,4-dioxane, toluene, 1,2-dimethoxyethane, tetrahydrofuran, dichloromethane, acetonitrile, nitromethane, and mixtures thereof.