Claims for Patent: 9,833,428

Summary for Patent: 9,833,428

Title:	Therapeutic compositions
Abstract:	Ingenol angelate is a potent anticancer agent, and can be stabilized by dissolving it in an aprotic solvent in the presence of an acidic buffer.
Inventor(s):	Brown; Marc Barry (Watford, GB), Crothers; Michael (Hillsborough, GB), Nazir; Tahir (Isleworth, GB)
Assignee:	LEO Laboratories Limited (Dublin, IE)
Application Number:	14/269,055
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,833,428
Patent Claims:	1. A formulation of ingenol angelate, wherein the ingenol angelate has been dissolved in a pharmaceutically acceptable solvent, said formulation further comprising a pharmaceutically acceptable acidifying agent which provides the formulation with a pH of no greater than 4.5, wherein at least about 95% of the ingenol angelate is ingenol-3-angelate (isoform `b`), the formulation is a topical formulation, the solvent is benzyl alcohol, and the acidifying agent is an acid buffer. 2. A formulation according to claim 1, wherein the acid buffer is selected from the group consisting of a citrate buffer, a phosphate buffer, an acetate buffer, and a citrate-phosphate buffer. 3. A formulation according to claim 2, wherein the acid buffer is a citrate buffer. 4. The formulation of claim 1, wherein the formulation comprises ingenol-3-angelate (isoform `b`) in an amount from 0.001% by weight to 0.15% by weight. 5. The formulation of claim 1, wherein the formulation comprises ingenol-3-angelate (isoform `b`) in an amount from 0.01% by weight to 0.1% by weight. 6. The formulation of claim 1, wherein the formulation comprises from 0.5% by weight to 10% by weight acid buffer. 7. The formulation of claim 1, wherein the formulation comprises 0.9% by weight benzyl alcohol. 8. The formulation of claim 1, further comprising a penetration enhancer. 9. The formulation of claim 8, wherein the penetration enhancer is selected from the group consisting of isopropyl alcohol, a sulphoxide, an azone, a pyrrolidone, and an alkanol. 10. The formulation of claim 9, wherein the penetration enhancer is isopropyl alcohol. 11. The formulation of claim 10, wherein the formulation comprises 30% by weight isopropyl alcohol. 12. The formulation of claim 1, further comprising a gelling agent. 13. The formulation of claim 12, wherein the gelling agent is selected from the group consisting of a hydroxyalkyl cellulose polymer, carboxymethyl cellulose, methylhydroxyethyl cellulose, methyl cellulose, a carbomer, and a carrageenan. 14. The formulation of claim 13, wherein the gelling agent is hydroxyethylcellulose. 15. The formulation of claim 14, wherein the formulation comprises 1.5% by weight hydroxyethylcellulose. 16. The formulation of claim 12, wherein the formulation comprises from 1% by weight to 5% by weight gelling agent. 17. The formulation of claim 1, wherein the formulation has a pH of less than 4. 18. The formulation of claim 1, wherein the formulation has a pH of no less than 2.5. 19. The formulation of claim 1, wherein ingenol-3-angelate (isoform `b`) is the only active ingredient. 20. The formulation of claim 1, wherein the formulation is selected from the group consisting of a gel, a cream, an ointment, a paint, and a lotion. 21. The formulation of claim 1, wherein the formulation is sterilized. 22. The formulation of claim 1, wherein the formulation is suitable for storage at 2-8.degree. C. 23. The formulation of claim 1, wherein the formulation is suitable for storage at 2-8.degree. C. for at least one year. 24. A formulation, comprising: ingenol angelate, at least about 95% of the ingenol angelate being ingenol-3-angelate (isoform `b`); an acidifying agent; and a pharmaceutically acceptable solvent; wherein the formulation is a topical, gel formulation and comprises ingenol-3-angelate (isoform `b`) in an amount from 0.001% by weight to 0.15% by weight. 25. The formulation of claim 24, wherein the acidifying agent is an acid buffer. 26. The formulation of claim 25, wherein the acid buffer is selected from the group consisting of a citrate buffer, a phosphate buffer, an acetate buffer, and a citrate-phosphate buffer. 27. The formulation of claim 25, wherein the acid buffer is a citrate buffer. 28. The formulation of claim 24, wherein the pharmaceutically acceptable solvent is benzyl alcohol. 29. The formulation of claim 24, wherein the formulation is suitable for storage at 2-8.degree. C. 30. The formulation of claim 24, wherein the formulation is suitable for storage at 2-8.degree. C. for at least one year. 31. The formulation of claim 24, wherein at least about 99% of the ingenol angelate is ingenol-3-angelate (isoform `b`).