Claims for Patent: 9,969,740

Summary for Patent: 9,969,740

Title:	Forms of a PI3K delta selective inhibitor for use in pharmaceutical formulations
Abstract:	The present invention relates to solid state forms of a p-toluenesulfonic acid salt (PTSA) of the selective PI3K delta inhibitor (S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrim- idin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one (TGR-1202). The present invention also relates to methods of preparing the same, pharmaceutical compositions containing them, and methods of treating a PI3K kinase mediated disease or disorder, such as cancer, by administering the same.
Inventor(s):	Vakkalanka; Swaroop K. (La Chaux-de-Fonds, CH)
Assignee:	RHIZEN PHARMACEUTICALS SA (La Chaux-de-Fonds, CH)
Application Number:	15/313,454
Patent Claims:	1. A p-toluenesulfonic acid salt of the compound ##STR00004## wherein the salt has a d(0.9) of from about 5 to about 50 .mu.m. 2. The salt of claim 1, wherein the salt has a d(0.9) of from about 5 to about 25 .mu.M. 3. The salt of claim 1, wherein the salt has a d(0.9) of from about 5 to about 15 .mu.m. 4. The salt of claim 1, wherein the salt has a d(0.5) of from about 1 to about 10 .mu.m. 5. The salt of claim 1, wherein the salt has a d(0.5) of from about 2 to about 5 .mu.m. 6. The salt of claim 1, wherein the salt has a d(0.1) of from about 0.5 to about 1.5 .mu.m. 7. The salt of claim 1, wherein the salt has a d(0.1) of from about 0.5 to about 1.0 .mu.m. 8. The salt of claim 1, wherein the salt exhibits a XRPD pattern having one or more peaks selected from 5.0, 10.1, 22.1, and 24.5.+-.0.2.degree.2.THETA.. 9. The salt of claim 1, wherein the salt exhibits a differential scanning calorimeter (DSC) pattern with a characteristic endothermic peak at about 146 .degree. C. 10. The salt of claim 1, wherein the ratio of p-toluenesulfonic acid to the compound ##STR00005## is about 1:1. 11. A pharmaceutical composition comprising a salt of claim 1 and a pharmaceutically acceptable excipient. 12. A method of inhibiting a catalytic activity of a PI3 .delta.kinase present in a cell, comprising contacting the cell with an effective amount of a salt of claim 1. 13. The method of claim 12, wherein the inhibition takes place in a subject suffering from a disease or disorder which is cancer, bone disorder, inflammatory disease, immune disease, nervous system disease, metabolic disease, respiratory disease, thrombosis, or cardiac disease. 14. A method of preparing a crystalline p-toluenesulfonic acid salt of the compound ##STR00006## comprising the step of removing the solvent from a mixture of a p-toluenesulfonic acid salt of the compound ##STR00007## and an ether solvent, wherein the mixture is a suspension of crystalline p-toluenesulfonic acid salt of the compound ##STR00008## in an ether solvent. 15. A method of preparing a crystalline p-toluenesulfonic acid salt of the compound ##STR00009## comprising the step of removing the solvent from a mixture of a p-toluenesulfonic acid salt of the compound ##STR00010## and an ether solvent, wherein the method comprises stirring the mixture prior to removing the solvent. 16. The method of claim 15, wherein the stirring is performed for at least 3 hours. 17. The method of claim 14, wherein the solvent is removed by drying. 18. The salt of claim 2, wherein the salt has a d(0.5) of from about 1 to about 10 .mu.m. 19. The salt of claim 2, wherein the salt has a d(0.5) of from about 2 to about 5 .mu.m. 20. The salt of claim 3, wherein the salt has a d(0.5) of from about 1 to about 10 .mu.m. 21. The salt of claim 3, wherein the salt has a d(0.5) of from about 2 to about 5 .mu.m. 22. The salt of claim 2, wherein the salt has a d(0.1) of from about 0.5 to about 1.5 .mu.m. 23. The salt of claim 2, wherein the salt has a d(0.1) of from about 0.5 to about 1.0 .mu.m. 24. The salt of claim 18, wherein the salt has a d(0.1) of from about 0.5 to about 1.5 .mu.m. 25. The salt of claim 18, wherein the salt has a d(0.1) of from about 0.5 to about 1.0 .mu.m. 26. The salt of claim 8, wherein the salt exhibits a XRPD pattern having two or more peaks selected from 5.0, 10.1, 22.1, and 24.5.+-.0.2.degree.2.THETA.. 27. The salt of claim 8, wherein the salt exhibits a XRPD pattern having three or more peaks selected from 5.0, 10.1, 22.1, and 24.5.+-.0.2.degree.2.THETA.. 28. The salt of claim 8, wherein the salt exhibits a XRPD pattern having peaks at 5.0, 10.1, 22.1, and 24.5.+-.0.2.degree.2.THETA.. 29. The pharmaceutical composition of claim 1, wherein (i) the salt exhibits a XRPD pattern having one or more peaks selected from 5.0, 10.1, 22.1, and 24.5.+-.0.2.degree.2.THETA., and (ii) the composition contains less than 5% of other solid state forms of the p-toluenesulfonic acid salt of the compound ##STR00011## based on the total amount of the p-toluenesulfonic acid salt present in the composition.