Claims for Patent: 11,458,119

Summary for Patent: 11,458,119

Title:	Amorphous and a crystalline form of genz 112638 hemitartrate as inhibitor of glucosylceramide synthase
Abstract:	The hemitartrate salt of a compound represented by the following structural formula: (Formula I Hemitartrate), which may be used in pharmaceutical applications, are disclosed. Particular single crystalline forms of the Formula (I) Hemitartrate are characterized by a variety of properties and physical measurements. As well, methods of producing crystalline Formula (I) Hemitartrate, and using it to inhibit glucosylceramide synthase or lowering glycosphingolipid concentrations in subjects to treat a number of diseases, are also discussed. Pharmaceutical compositions are also described.
Inventor(s):	Hanlan Liu, Chris Willis, Renu Bhardwaj, Jianmei Kochling, Craig Siegel
Assignee:	Genzyme Corp
Application Number:	US13/511,768
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,458,119
Patent Claims:	1. A hemitartrate salt of a compound represented by the following structural formula: wherein the salt is in a crystalline form, the crystalline form characterized by at least two major X-ray powder diffraction peaks at 2θ angles selected from the group consisting of 5.1°, 6.6°, 10.7°, 11.0°, 15.9°, and 21.7°, wherein the specified 2θ angle means the specified value ±0.2°, and the X-ray powder diffraction diagram is obtained by using Cu K α radiation. 2. The hemitartrate salt of claim 1, wherein the hemitartrate salt is L-hemitartrate. 3. The hemitartrate salt of claim 1, wherein the crystalline form is characterized by major X-ray powder diffraction peaks at 2θ angles of 5.1°, 6.6°, 10.7°, 11.0°, 15.9°, and 21.7°, wherein the specified 2θ angle means the specified value±0.2°. 4. The hemitartrate salt of claim 1, wherein the crystalline form is characterized by X-ray powder diffraction peaks at 2 θ angles of 5.1°, 6.6°, 10.7°, 11.0°, 13.3°, 15.1°, 15.9°, 16.5°, 17.6°, 18.6°, 18.7°, 19.0°, 20.2°, 21.7°, and 23.5°, wherein the specified 2θ angle means the specified value±0.2°. 5. A pharmaceutical composition comprising the hemitartrate salt of claim 1, and a pharmaceutically acceptable carrier or diluent. 6. A pharmaceutical composition comprising: the hemitartrate salt of claim 1; at least one water-soluble filler; at least one water-insoluble filler; at least one binder; and at least one lubricant. 7. The pharmaceutical composition of claim 6, wherein the at least one water-soluble filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, mannitol, sodium chloride, powdered sugar, sorbitol, sucrose, inositol and pregelatinized starch; the at least one water-insoluble filler is selected from the group consisting of microcrystalline cellulose, calcium phosphate and starch; the at least one binder is selected from the group consisting of pre-gelatinized starch, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, gelatin, natural gums, starch paste, sucrose, corn syrup, polyethylene glycols and sodium alginate; and the at least one lubricant is selected from the group consisting of hydrogenated vegetable oil, calcium stearate, and glyceryl behenate. 8. The pharmaceutical composition of claim 7, wherein the composition comprises 14 wt % to 18 wt % of the at least one water-insoluble filler on a dry solids basis. 9. The pharmaceutical composition of claim 7, wherein the composition comprises 35 wt % to 40 wt % of the hemitartrate salt; 26 wt % to 50 wt % of lactose monohydrate; 8 wt % to 32 wt % of microcrystalline cellulose; 2 wt % to 6 wt % of hydroxypropyl methylcellulose; and 0.1 wt % to 2 wt % of glyceryl behenate, all on a dry solids basis. 10. A pharmaceutical composition comprising: the hemitartrate salt of claim 2; at least one water-soluble filler; at least one water-insoluble filler; at least one binder; and at least one lubricant. 11. The pharmaceutical composition of claim 10, wherein the at least one water-soluble filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, mannitol, sodium chloride, powdered sugar, sorbitol, sucrose, inositol and pregelatinized starch; the at least one water-insoluble filler is selected from the group consisting of microcrystalline cellulose, calcium phosphate and starch; the at least one binder is selected from the group consisting of pre-gelatinized starch, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, gelatin, natural gums, starch paste, sucrose, corn syrup, polyethylene glycols and sodium alginate; and the at least one lubricant is selected from the group consisting of hydrogenated vegetable oil, calcium stearate, and glyceryl behenate. 12. The pharmaceutical composition of claim 10, wherein the composition comprises 14 wt % to 18 wt % of the at least one water-insoluble filler on a dry solids basis. 13. The pharmaceutical composition of claim 10, wherein the composition comprises 35 wt % to 40 wt % of the hemitartrate salt; 26 wt % to 50 wt % of lactose monohydrate; 8 wt % to 32 wt % of microcrystalline cellulose; 2 wt % to 6 wt % of hydroxypropyl methylcellulose; and 0.1 wt % to 2 wt % of glyceryl behenate, all on a dry solids basis. 14. A pharmaceutical composition comprising: the hemitartrate salt of claim 3; at least one water-soluble filler; at least one water-insoluble filler; at least one binder; and at least one lubricant. 15. The pharmaceutical composition of claim 14, wherein the at least one water-soluble filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, mannitol, sodium chloride, powdered sugar, sorbitol, sucrose, inositol and pregelatinized starch; the at least one water-insoluble filler is selected from the group consisting of microcrystalline cellulose, calcium phosphate and starch; the at least one binder is selected from the group consisting of pre-gelatinized starch, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, gelatin, natural gums, starch paste, sucrose, corn syrup, polyethylene glycols and sodium alginate; and the at least one lubricant is selected from the group consisting of hydrogenated vegetable oil, calcium stearate, and glyceryl behenate. 16. The pharmaceutical composition of claim 14, wherein the composition comprises 14 wt % to 18 wt % of the at least one water-insoluble filler on a dry solids basis. 17. The pharmaceutical composition of claim 14, wherein the composition comprises 35 wt % to 40 wt % of the hemitartrate salt; 26 wt % to 50 wt % of lactose monohydrate; 8 wt % to 32 wt % of microcrystalline cellulose; 2 wt % to 6 wt % of hydroxypropyl methylcellulose; and 0.1 wt % to 2 wt % of glyceryl behenate, all on a dry solids basis. 18. A pharmaceutical composition comprising: the hemitartrate salt of claim 4; at least one water-soluble filler; at least one water-insoluble filler; at least one binder; and at least one lubricant. 19. The pharmaceutical composition of claim 18, wherein the at least one water-soluble filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, mannitol, sodium chloride, powdered sugar, sorbitol, sucrose, inositol and pregelatinized starch; the at least one water-insoluble filler is selected from the group consisting of microcrystalline cellulose, calcium phosphate and starch; the at least one binder is selected from the group consisting of pre-gelatinized starch, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, gelatin, natural gums, starch paste, sucrose, corn syrup, polyethylene glycols and sodium alginate; and the at least one lubricant is selected from the group consisting of hydrogenated vegetable oil, calcium stearate, and glyceryl behenate. 20. The pharmaceutical composition of claim 18, wherein the composition comprises 14 wt % to 18 w t% of the at least one water-insoluble filler on a dry solids basis. 21. The pharmaceutical composition of claim 18, wherein the composition comprises 35 wt % to 40 wt % of the hemitartrate salt; 26 wt % to 50 wt % of lactose monohydrate; 8 wt % to 32 wt % of microcrystalline cellulose; 2 wt % to 6 wt % of hydroxypropyl methylcellulose; and 0.1 wt % to 2 wt % of glyceryl behenate, all on a dry solids basis. 22. A pharmaceutical composition comprising: the hemitartrate salt of claim 5; at least one water-soluble filler; at least one water-insoluble filler; at least one binder; and at least one lubricant. 23. The pharmaceutical composition of claim 22, wherein the at least one water-soluble filler is selected from the group consisting of anhydrous lactose, lactose monohydrate, mannitol, sodium chloride, powdered sugar, sorbitol, sucrose, inositol and pregelatinized starch; the at least one water-insoluble filler is selected from the group consisting of microcrystalline cellulose, calcium phosphate and starch; the at least one binder is selected from the group consisting of pre-gelatinized starch, sodium carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, copolyvidone, gelatin, natural gums, starch paste, sucrose, corn syrup, polyethylene glycols and sodium alginate; and the at least one lubricant is selected from the group consisting of hydrogenated vegetable oil, calcium stearate, and glyceryl behenate. 24. The pharmaceutical composition of claim 22, wherein the composition comprises 14 wt % to 18 wt % of the at least one water-insoluble filler on a dry solids basis. 25. The pharmaceutical composition of claim 22, wherein the composition comprises 35 wt % to 40 wt % of the hemitartrate salt; 26 wt % to 50 wt % of lactose monohydrate; 8 wt % to 32 wt% of microcrystalline cellulose; 2 wt % to 6 wt % of hydroxypropyl methylcellulose; and 0.1 wt % to 2 wt % of glyceryl behenate, all on a dry solids basis.