Claims for Patent: 9,795,605

Summary for Patent: 9,795,605

Title:	Inhibitors of Bruton\'s tyrosine kinase for the treatment of solid tumors
Abstract:	Described herein are irreversible Btk inhibitor compounds, and methods for using such irreversible inhibitors in the treatment of diseases and disorders characterized by the presence or development of solid tumors.
Inventor(s):	Buggy; Joseph J. (Mountain View, CA), Elias; Laurence (Berkeley, CA)
Assignee:	Pharmacyclics LLC (Sunnyvale, CA)
Application Number:	14/793,366
Patent Claims:	1. A method for treating HER2 amplified breast cancer in an individual in need thereof comprising administering to the individual in need thereof a composition comprising a therapeutically-effective amount of a compound of Formula (C1) having the structure: ##STR00116## or a pharmaceutically acceptable salt thereof, wherein: Y is selected from alkyl, heteroalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, and alkylheterocycloalkyl; R.sub.12 is H or lower alkyl; or Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring; G is ##STR00117## wherein R.sup.a is H, alkyl, or cycloalkyl; and either (i) R.sub.7 and R.sub.8 are H; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl); or (ii) R.sub.6 and R.sub.8 are H; and R.sub.7 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl); or (iii) R.sub.7 and R.sub.8 taken together form a bond; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 2. The method of claim 1, wherein: Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring. 3. The method of claim 2, wherein R.sub.6 and R.sub.8 are H; and R.sub.7 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 4. The method of claim 3, wherein: Y and R.sub.12 taken together form a 6-membered heterocyclic ring. 5. The method of claim 1, wherein the compound is selected from: ##STR00118## ##STR00119## ##STR00120## ##STR00121## ##STR00122## ##STR00123## ##STR00124## or a pharmaceutically acceptable salt thereof. 6. The method of claim 1, further comprising administering an additional therapeutic agent selected from: trastuzumab, paclitaxel, doxorubicin, cyclophosphamide, and cisplatin. 7. The method of claim 1, further comprising administering trastuzumab. 8. A method for treating HER2 amplified cancer in an individual in need thereof, wherein the HER2 amplified cancer is selected from pancreatic cancer and non-small-cell lung carcinoma, the method comprising administering to the individual in need thereof a composition comprising a therapeutically-effective amount of a compound of Formula (C1) having the structure: ##STR00125## or a pharmaceutically acceptable salt thereof, wherein: Y is selected from alkyl, heteroalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl, and alkylheterocycloalkyl; R.sub.12 is H or lower alkyl; or Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring; G is ##STR00126## wherein R.sup.a is H, alkyl, or cycloalkyl; and either (i) R.sub.7 and R.sub.8 are H; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl); or (ii) R.sub.6 and R.sub.8 are H; and R.sub.7 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl); or (iii) R.sub.7 and R.sub.8 taken together form a bond; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 9. The method of claim 8, wherein: Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring. 10. The method of claim 9, wherein R.sub.6 and R.sub.8 are H; and R.sub.7 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 11. The method of claim 9, wherein: Y and R.sub.12 taken together form a 6-membered heterocyclic ring; R.sub.6 and R.sub.8 are H; and R.sub.7 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 12. The method of claim 8, wherein the compound is ##STR00127## 13. The method of claim 8, further comprising administering an additional therapeutic agent selected from: trastuzumab, paclitaxel, doxorubicin, cyclophosphamide, and cisplatin. 14. The method of claim 8, further comprising administering trastuzumab. 15. The method of claim 2, wherein R.sub.7 and R.sub.8 taken together form a bond; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 16. The method of claim 9, wherein R.sub.7 and R.sub.8 taken together form a bond; and R.sub.6 is H, C.sub.1-C.sub.4alkyl, C.sub.1-C.sub.4heteroalkyl, C.sub.1-C.sub.8alkylaminoalkyl, C.sub.1-C.sub.8hydroxyalkylaminoalkyl, C.sub.1-C.sub.8alkoxyalkylaminoalkyl, C.sub.3-C.sub.6cycloalkyl, C.sub.1-C.sub.8alkylC.sub.3-C.sub.6cycloalkyl, aryl, C.sub.2-C.sub.8heterocycloalkyl, heteroaryl, C.sub.1-C.sub.4alkyl(aryl), C.sub.1-C.sub.4alkyl(heteroaryl), C.sub.1-C.sub.8alkylether, C.sub.1-C.sub.8alkylamide, or C.sub.1-C.sub.4alkyl(C.sub.2-C.sub.8heterocycloalkyl). 17. The method of claim 8, wherein the compound is selected from ##STR00128## ##STR00129## ##STR00130## ##STR00131## ##STR00132## ##STR00133## ##STR00134## or a pharmaceutically acceptable salt thereof. 18. The method of claim 1, wherein Y is alkyl; or Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring. 19. The method of claim 8, wherein Y is alkyl; or Y and R.sub.12 taken together form a 4-, 5-, or 6-membered heterocyclic ring. 20. The method of claim 18, wherein G is ##STR00135## wherein R.sup.a is H or alkyl. 21. The method of claim 19, wherein G is ##STR00136## wherein R.sup.a is H or alkyl. 22. The method of claim 12, further comprising administering an additional therapeutic agent comprising paclitaxel or gemcitabine, or a combination thereof.

Details for Patent 9,795,605

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2028-07-16
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2028-07-16
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2028-07-16