Claims for Patent: 9,457,093

Summary for Patent: 9,457,093

Title:	Solid dispersions of a ERB2 (HER2) inhibitor
Abstract:	A solid dispersion of N4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)-N6-(4,4-dim- ethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and processes for preparing the solid dispersion are provided herein. Also, a pharmaceutical composition comprising a solid dispersion of N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and uses thereof are provided herein. ##STR00001##
Inventor(s):	Fry; David Shank (Boulder, CO), Lindemann; Christopher M. (Boulder, CO), Preigh; Michael (Boulder, CO), Bloom; Corey Jay (Boulder, CO), Craig; Christopher Donovan (Boulder, CO), Dubose; Devon Brevard (Boulder, CO), Gautschi; Jeff (Boulder, CO), Smithey; Dan (Boulder, CO)
Assignee:	Array BioPharma Inc. (Boulder, CO)
Application Number:	14/351,840
Patent Claims:	1. A solid dispersion comprising amorphous N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and a dispersion polymer, wherein the dispersion polymer is PVP-VA. 2. The solid dispersion of claim 1, wherein the N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is present in an amount of from about 0.1% to about 50% by weight relative to the dispersion polymer. 3. The solid dispersion of claim 1, wherein the N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is present in an amount of from about 5% to about 35% by weight relative to the dispersion polymer. 4. The solid dispersion of claim 1, wherein the N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is present in an amount of from about 25% to about 35% by weight relative to the dispersion polymer. 5. The solid dispersion of claim 1, wherein at least 80% of the N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is in amorphous form. 6. The solid dispersion of claim 1, wherein at least 95% of the N4-(4-([1,2,4]triazolo[1,5-.alpha.]pyridin-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine is in amorphous form. 7. A pharmaceutical composition comprising a solid dispersion according to claim 1 and one or more pharmaceutically acceptable excipients. 8. The pharmaceutical composition of claim 7, wherein the composition is a tablet. 9. A pharmaceutical composition comprising: (a) about 1 to about 70 weight % of the solid dispersion of claim 1; (b) about 0.1 to 20 weight % of a disintegrant; (c) about 0.1 to 25 weight % of an osmogen; (d) about 0.1 to 10 weight % of a glidant; (e) about 0.1 to 10 weight % of a lubricant; and (f) about 0.1 to 25 weight % of a binder. 10. A pharmaceutical composition comprising: (a) about 1 to about 70 weight % of the solid dispersion of claim 1; (b) about 0.1 to 20 weight % of a disintegrant; (c) about 0.1 to 25 weight % of an osmogen; (d) about 0.1 to 10 weight % of a glidant; (e) about 0.1 to 10 weight % of a lubricant; and (f) about 0.1 to 25 weight % of a filler. 11. The pharmaceutical composition of claim 9, wherein the binder is about 10 to 25 weight %. 12. The pharmaceutical composition of claim 9, wherein the disintegrant is about 5 to 15 weight %. 13. The pharmaceutical composition of claim 10, wherein the filler is about 10 to 25 weight %. 14. The pharmaceutical composition of claim 9, wherein the disintegrant is about 1 to 10 weight %. 15. The pharmaceutical composition of claim 9, wherein the osmogen is about 15 to 25 weight %. 16. The pharmaceutical composition of claim 9, wherein the glidant is about 0.1 to 3 weight %. 17. The pharmaceutical composition of claim 9, wherein the lubricant is about 0.1 to 3 weight %. 18. A pharmaceutical composition comprising: (a) solid dispersion of claim 1; and (b) sodium bicarbonate. 19. A pharmaceutical composition comprising: (a) about 1 to about 70 weight % of the solid dispersion of claim 1; and (b) about 0.1 to about 30 weight % sodium bicarbonate. 20. The pharmaceutical composition of claim 9, wherein the solid dispersion is about 25 to about 60 weight %. 21. The pharmaceutical composition of claim 9, wherein the solid dispersion is about 40 to about 60 weight %. 22. The pharmaceutical composition of claim 9, wherein the composition is a tablet. 23. A method for the treatment of ErbB2 positive breast cancer comprising administering to a patient in need thereof a therapeutically effective amount of the solid dispersion of claim 1. 24. A process of preparing the solid dispersion of claim 1 comprising the steps of: (a) dissolving N4-(4-(1,2,4]triazolo[1,5-.alpha.]pyridine-7-yloxy)-3-methylphenyl)-N6-(4- ,4-dimethyl-4,5-dihydrooxazol-2-yl)quinazoline-4,6-diamine and the dispersion polymer in a suitable solvent to form a feed solution; and (b) evaporating the solvent by spray drying the feed solution to form the solid dispersion.