Claims for Patent: 8,278,292

Summary for Patent: 8,278,292

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), Crowthers; Michael Edward Donald (Hillsborough, GB), Nazir; Tahir (Isleworth, GB)
Assignee:	LEO Laboroatories Limited (Dublin, IE)
Application Number:	12/097,258
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,278,292
Patent Claims:	1. A pharmaceutical formulation of ingenol-3-angelate (isoform `b`), said pharmaceutical formulation comprising ingenol-3-angelate (isoform `b`) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform `b`) after twelve months of storage at a temperature within the range of about 2.degree. C. to about 8.degree. C. 2. The pharmaceutical formulation of claim 1, wherein said solvent is selected from the group consisting of polyethylene glycol, methyl ethyl ketone, ethyl acetate, diethyl ether, benzyl alcohol, and mixtures thereof. 3. The pharmaceutical formulation of claim 1, wherein said solvent consists essentially of benzyl alcohol. 4. The pharmaceutical formulation of claim 1, wherein said acidifying agent is an acid buffer. 5. The pharmaceutical formulation of claim 4, wherein said acid buffer is a citrate or phosphate buffer. 6. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation comprises: a) isopropyl alcohol; b) hydroxyethylcellulose; c) benzyl alcohol; and d) citrate buffer. 7. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform `b`) after twelve months of storage at a temperature within the range of about 2.degree. C. to about 8.degree. C. 8. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation retains at least 99.0% of said ingenol-3-angelate (isoform `b`) after twelve months of storage at a temperature within the range of about 2.degree. C. to about 8.degree. C. 9. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform `b`) after three months of storage at a temperature within the range of about 2.degree. C. to about 8.degree. C. 10. The pharmaceutical formulation of claim 1, wherein said pharmaceutical formulation retains at least 99.0% of said ingenol-3-angelate (isoform `b`) after three months of storage at a temperature within the range of about 2.degree. C. to about 8.degree. C. 11. A pharmaceutical formulation of ingenol-3-angelate (isoform `b`), said pharmaceutical formulation comprising ingenol-3-angelate (isoform `b`) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform `b`) after two weeks of storage at about 25.degree. C. 12. The pharmaceutical formulation of claim 11, wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform `b`) after two weeks of storage at about 25.degree. C. 13. The pharmaceutical formulation of claim 11, wherein said pharmaceutical formulation retains at least 98.5% of said ingenol-3-angelate (isoform `b`) after two weeks of storage at about 25.degree. C. 14. A pharmaceutical formulation of ingenol-3-angelate (isoform `b`), said pharmaceutical formulation comprising ingenol-3-angelate (isoform `b`) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform `b`) after four weeks of storage at about 40.degree. C. 15. A pharmaceutical formulation of ingenol-3-angelate (isoform `b`), said pharmaceutical formulation comprising ingenol-3-angelate (isoform `b`) and a pharmaceutically acceptable solvent, said pharmaceutical formulation further comprising a pharmaceutically acceptable acidifying agent, wherein said pharmaceutical formulation retains at least about 95% of said ingenol-3-angelate (isoform `b`) after two weeks of storage at about 40.degree. C. 16. The pharmaceutical formulation of claim 15, wherein said pharmaceutical formulation retains at least 97.5% of said ingenol-3-angelate (isoform `b`) after two weeks of storage at about 40.degree. C. 17. The pharmaceutical formulation of any one of claims 1, 11, 14, or 15, wherein said pharmaceutical formulation is a gel. 18. The pharmaceutical formulation of any one of claims 1, 11, 14, or 15, wherein said acidifying agent is an organic acid.