Claims for Patent: 11,087,354

Summary for Patent: 11,087,354

Title:	Combination therapies
Abstract:	The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention relates to therapies for the treatment of pathological conditions, such as cancer.
Inventor(s):	Bray; Gordon (San Francisco, CA), Chan; Iris (San Francisco, CA)
Assignee:	Genentech, Inc. (North San Franscisco, CA)
Application Number:	13/967,782
Patent Claims:	1. A method for treating BRAF.sup.V600 mutation-positive unresectable or metastatic melanoma in a patient, the method comprising administering to the patient (i) a first composition comprising [3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl][3-hydroxy-3-[(2S)-2- -piperidinyl]-1-azetidinyl]methanone, or a pharmaceutically acceptable salt thereof, at a dose of 60 mg, on days 1-21 of a 28 day cycle; and (ii) a second composition comprising propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically acceptable salt thereof, at a dose of 960 mg twice daily, on days 1-28 of the 28 day cycle. 2. The method of claim 1, wherein the first composition is administered sequentially with the second composition. 3. The method of claim 1, wherein the first composition is administered concurrently with the second composition. 4. The method of claim 1, wherein the first and second compositions are co-formulated. 5. The method of claim 1, wherein propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, is substantially in amorphous form. 6. The method of claim 1, wherein propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, is in amorphous form. 7. The method of claim 5 or 6, wherein propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, is contained in a solid molecular complex formed with hydroxypropyl methyl cellulose acetate succinate such that it is immobilized in its amorphous form. 8. The method of claim 7, wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -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. 9. The method of claim 7, wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of from about 2:8 to about 4:6, respectively. 10. The method of claim 7, wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -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, respectively. 11. The method of claim 7, wherein the amounts of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate in said complex are in a ratio of 3:7, respectively. 12. The method of claim 1, wherein the second composition comprises a blend wherein about 97% by weight of the blend is the solid molecular complex according to claim 7 and about 3% by weight of the blend is silicon dioxide. 13. The method of claim 1, wherein the second composition comprises a suspension of the solid molecular complex according to claim 7 in a pharmaceutically acceptable carrier. 14. The method of claim 1, wherein the second composition comprises a tablet comprising a solid molecular complex of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically-acceptable salt thereof, and hydroxypropyl methyl cellulose acetate succinate. 15. The method of claim 1, wherein the first composition comprises one or more of lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. 16. The method of claim 1, wherein [3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl][3-hydroxy-3-[(2S)-2- -piperidinyl]-1-azetidinyl]methanone is provided as a tablet comprising lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. 17. The method of claim 16, wherein the tablet comprises a tablet coating comprising polyvinyl alcohol-part hydrolyzed, titanium dioxide, polyethylene glycol 3350, and talc. 18. The method of claim 16 or 17, wherein [3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl][3-hydroxy-3-[(2S)-2- -piperidinyl]-1-azetidinyl]methanone is provided as a 20 mg tablet, as a 40 mg tablet, or as a 60 mg tablet. 19. The method of claim 1, wherein a second 960 mg dose of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically acceptable salt thereof is administered about 12 hours after a first 960 mg dose of propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically acceptable salt thereof. 20. The method of claim 1, wherein propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro- -phenyl}-amide, or a pharmaceutically acceptable salt thereof, and [3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl][3-hydroxy-3-[(2S)-2- -piperidinyl]-1-azetidinyl]methanone, or a pharmaceutically acceptable salt thereof, are each administered orally, with or without food. 21. The method of claim 1, wherein the unresectable or metastatic melanoma is BRAF.sup.V600E mutation-positive melanoma. 22. The method of claim 1, wherein the unresectable or metastatic melanoma is metastatic melanoma. 23. The method of claim 1, wherein BRAF.sup.V600 mutation is determined using a method comprising (a) performing PCR or sequencing on nucleic acid extracted from a sample of the patient's melanoma; and (b) determining expression of BRAF.sup.V600 in the sample. 24. The method of claim 23, wherein the melanoma sample is formalin-fixed paraffin-embedded. 25. The method of claim 1, further comprising treatment with an additional therapeutic agent. 26. The method of claim 1, wherein the patient's unresectable or metastatic melanoma was previously untreated.