Claims for Patent: 8,709,419

Summary for Patent: 8,709,419

Title:	Combination therapy
Abstract:	The present invention relates to a combination therapy of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically acceptable salt thereof, and an EGFR inhibitor for treating a patient suffering from a proliferative disorder, in particular a solid tumor, for example, colorectal cancer, melanoma, and thyroid cancer.
Inventor(s):	Dhingra; Kapil (Sparta, NJ), Higgins; Brian (Fresh Meadows, NY), Kolinsky; Kenneth (Bloomingdale, NJ), Lee; Richard J. (Montclair, NJ), Lestini; Brian (Union City, NJ), Packman; Kathryn (Bloomfield, NJ), Su; Fei (Paramus, NJ)
Assignee:	Hoffmann-La Roche, Inc. (Nutley, NJ)
Application Number:	13/206,557
Patent Claims:	1. A method of treating a patient suffering from a proliferative disorder, comprising administering to the patient: (A) a first component which comprises, as an active agent, propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof; and (B) a second component which comprises, as an active agent, an EGFR inhibitor; the amount of said active agents being such that the combination thereof is therapeutically-effective in the treatment of said proliferative disorder, wherein the proliferative disorder is a tumor comprising b-Raf having the V600E mutation. 2. A method according to claim 1 wherein said proliferative disorder is selected from the group consisting of colorectal cancer, melanoma, and thyroid cancer. 3. A method according to claim 1 wherein said proliferative disorder is colorectal cancer. 4. A method according to claim 1 or claim 3 wherein said propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amid, or a pharmaceutically-acceptable salt thereof, is administered in an amount of from about 200 mg/day to about 3000 mg/day. 5. A method according to claim 1 or claim 3 wherein said propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof, is administered in an amount of from about 1700 mg/day to about 2100 mg/day. 6. A method according to claim 1 or claim 3 wherein said EGFR inhibitor is erlotinib, or a pharmaceutically acceptable salt thereof. 7. A method according to claim 6 wherein said erlotinib, or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 20 mg/day to about 500 mg/day. 8. A method according to claim 6 wherein said erlotinib, or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 100 mg/day to about 200 mg/day. 9. A method according to claim 1 or claim 3 wherein said EGFR inhibitor is cetuximab. 10. A method according to claim 9 wherein said cetuximab is administered in an amount of from about 50 mg/m.sup.2/week to about 700 mg/m.sup.2/week. 11. A method according to claim 9 wherein said cetuximab is administered in an amount of from about 200 mg/m.sup.2/week to about 500 mg/m.sup.2/week. 12. A method according to claim 1 or claim 3 wherein said method further comprises the administration of a third component which comprises, as an active agent, a topoisomerase inhibitor. 13. A method according to claim 12 wherein said topoisomerase inhibitor is irinotecan, or a pharmaceutically acceptable salt thereof. 14. A method according to claim 13 wherein said irinotecan, or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 1 mg/m.sup.2/week to about 250 mg/m.sup.2/week. 15. A method according to claim 13 wherein said irinotecan, or a pharmaceutically acceptable salt thereof, is administered in an amount of from about 50 mg/m.sup.2/week to about 200 mg/m.sup.2/week. 16. A method according to claim 1 or claim 3 wherein said propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof, is contained in a solid molecular complex with hydroxypropyl methyl cellulose acetate succinate such that it is immobilized in its amorphous form. 17. A method according to claim 16 wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of from about 1:9 to about 5:5, respectively. 18. A method according to claim 16 wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of about 3:7. 19. A method according to claim 16 wherein said first component comprises a blend wherein about 97% by weight of the blend is said complex and about 3% by weight of the blend is silicon dioxide. 20. A kit comprising: (A) a first component which comprises, as an active agent, propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof; and (B) a second component which comprises, as an active agent, an EGFR inhibitor. 21. A kit according to claim 20 further comprising a third component which comprises, as an active agent, a topoisomerase inhibitor. 22. A composition comprising: (A) a first component which comprises, as an active agent, propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluor- o-phenyl}-amide, or a pharmaceutically-acceptable salt thereof; and (B) a second component which comprises, as an active agent, an EGFR inhibitor.

Details for Patent 8,709,419

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2030-08-17
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2030-08-17