Claims for Patent: 10,662,188

Summary for Patent: 10,662,188

Title:	Forms of methyl {4,6-diamino-2-[1 (2-fluorobenzyl)-1H-pyrazolo[3-4-b]pyridino-3-yl]pyrimidino-5-yl} methyl carbamate
Abstract:	This present invention relates to forms of methyl {4.6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3.4-b]pyridino-3-yl]pyrimi- dino-5-yl}methylcarbamate comprising its Modification I. Modification II. mono-DMSO solvate. sesqui-DMSO solvate and 1/4-ethyl acetate solvate.
Inventor(s):	Keil; Birgit (Duesseldorf, DE), Mais; Franz-Josef (Duesseldorf, DE), Joentgen; Winfried (Cologne, DE), Grunenberg; Alfons (Wuppertal, DE)
Assignee:	ADVERIO PHARMA GmbH (Schoenefeld, DE)
Application Number:	16/119,671
Patent Claims:	1. A pharmaceutical composition comprising a sesqui- DMSO solvate of a compound of formula (I) ##STR00007## wherein the sesqui-DMSO solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angel of 8.3, 13.7, 15.7, and further wherein the pharmaceutical composition contains more than 90 percent by weight of the sesqui-DMSO solvate of the compound of formula (I) related to the total amount of all forms of the compound of formula (I) present in the pharmaceutical composition. 2. The pharmaceutical composition of claim 1, wherein the sesqui-DMSO solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.3, 13.7, 15.7, 17.2, 24.9. 3. The pharmaceutical composition of claim 1, wherein the sesqui-DMSO solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.3, 13.7, 15.7, 17.2, 18.4, 19.6, 24.9. 4. The pharmaceutical composition of claim 1, wherein the sesqui-DMSO solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.3, 8.4, 13.7, 13.9, 15.7, 17.2, 18.4, 19.6, 21.4, 24.9. 5. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition contains more than 95 percent by weight of the compound of the formula (I) as the sesqui-DMSO solvate related to the total amount of all forms of the compound of formula (I) present in the pharmaceutical composition. 6. The pharmaceutical composition of claim 1 that is a solid or liquid preparation suitable for oral administration selected from the group consisting of a solid dispersion, capsule, pill, tablet, troche, lozenge, melt, powder, solution, suspension, and emulsion. 7. A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic, or fibrotic diseases comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 1 to a patient in need thereof. 8. A pharmaceutical composition comprising a .sup.1/.sub.4-ethyl acetate solvate of a compound of formula (I) ##STR00008## wherein the .sup.1/.sub.4-ethyl acetate solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.7, 17.8, 26.7, and further wherein the pharmaceutical composition contains more than 90 percent by weight of the .sup.1/.sub.4-ethyl acetate solvate of the compound of formula (I) related to the total amount of all forms of the compound of formula (I) present in the pharmaceutical composition. 9. The pharmaceutical composition of claim 8, wherein the .sup.1/.sub.4-ethyl acetate solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.7, 14.2, 17.8, 24.0, 26.7. 10. The pharmaceutical composition of claim 8, wherein the .sup.1/.sub.4-ethyl acetate solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.7, 14.2, 17.8, 19.3, 24.0, 25.1, 26.7. 11. The pharmaceutical composition of claim 8, wherein the .sup.1/.sub.4-ethyl acetate solvate of the compound of formula (I) is characterized by an X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 8.3, 8.7, 12.9, 14.2, 17.8, 19.3, 24.0, 25.1, 26.7. 12. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition contains more than 95 percent by weight of the compound of the formula (I) as the .sup.1/.sub.4-ethyl acetate solvate related to the total amount of all forms of the compound of formula (I) present in the pharmaceutical composition. 13. The pharmaceutical composition of claim 8 that is a solid or liquid preparation suitable for oral administration selected from the group consisting of a solid dispersion, capsule, pill, tablet, troche, lozenge, melt, powder, solution, suspension, and emulsion. 14. A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic, or fibrotic diseases comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 8 to a patient in need thereof. 15. A compound of the formula (I) ##STR00009## in the form of Modification I, as 1/4-ethyl acetate solvate, or a mixture thereof. 16. The compound of claim 15 characterized by one or more of the following: X-Ray powder diffractogram substantially as shown in FIGS. 1, 4; DSC- and TGA-Thermogram substantially as shown in FIGS. 2,5; IR-Spectrum (ATR) substantially a shown in FIGS. 3, 6. 17. The compound of claim 15 which is methyl {4,6 -diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrim idino-5-yl}methylcarbamate in the Modification I. 18. The compound of claim 17 characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1, and 17.8. 19. The compound of claim 15 which is the 1/4-ethyl acetate solvate of methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl- ]pyrimidino-5-yl}lmethylcarbamate. 20. The compound of claim 19 characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.7, 17.8, 26.7. 21. A pharmaceutical composition comprising only one of the forms selected from the group consisting of Modification I and 1/4- ethyl acetate solvate of a compound of the formula (I) ##STR00010## and a pharmaceutically acceptable carrier. 22. The pharmaceutical composition of claim 21 comprising only Modification I of the compound of the formula (I). 23. The pharmaceutical composition of claim 21 comprising only the 1/4-ethyl acetate solvate of the compound of the formula (I). 24. A pharmaceutical composition comprising the compound of claim 15 in the Modification I and as the mono-DMSO solvate and no other form of the compound of the formula (I). 25. A pharmaceutical composition comprising the compound of claim 15 in the Modification I and as the 1/4-ethyl acetate solvate and no other form of the compound of the formula (I). 26. A pharmaceutical composition of claim 21 further comprising one or more inert, nontoxic, pharmaceutically suitable excipients. 27. A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic, or fibrotic diseases comprising administering a therapeutically effective amount of the compound of claim 15 to a patient in need thereof. 28. A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic, or fibrotic diseases comprising administering a therapeutically effective amount of the compound of claim 17 to a patient in need thereof. 29. A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic, or fibrotic diseases comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 21 to a patient in need thereof. 30. A pharmaceutical composition comprising the compound of claim 15, in which more than 90 percent by weight relative to the total weight of all forms of the compound of formula (I) in the composition is the compound of formula (I) in the Modification I.