Claims for Patent: 9,114,179

Summary for Patent: 9,114,179

Title:	Immunoconjugate formulations
Abstract:	The present invention provides an immunoconjugate formulation that is substantially free of particles, the immunoconjugate formulation comprising: an immunoconjugate and one or more excipients selected from the group consisting of: sucrose, polysorbate 20, polysorbate 80, cyclodextrin, dextrose, glycerol, polyethylene glycol, mannitol, sodium chloride, and an amino acid, wherein the formulation is a buffered aqueous solution having a pH of 4.5 to 7.6. The present invention also provides an immunoconjugate formulation that is substantially free of aggregates, the immunoconjugate formulation comprising: an immunoconjugate and one or more excipients selected from the group consisting of histidine, sucrose, glycine and sodium chloride, wherein the formulation is a buffered aqueous solution having a pH of 4.5 to 7.6. The present invention further provides an immunoconjugate formulation that is substantially free of both particles and aggregates.
Inventor(s):	Zhang; Wei (Philadelphia, PA), Fleming; Michael S. (Londonderry, NH), Amphlett; Godfrey (Cambridge, MA), Chih; Hung-wei (Burlingame, CA), Bartlett; Elizabeth (Cambridge, MA)
Assignee:	ImmunoGen, Inc. (Waltham, MA)
Application Number:	11/498,139
Patent Claims:	1. An immunoconjugate liquid formulation comprising: (i) an immunoconjugate, which is an antibody comprising one or more covalently linked hydrophobic cytotoxic drugs, (ii) 5-20 mM histidine, (iii) 100-300 mM glycine, (iv) 0.1-12% sucrose, and (v) 0.5-2% beta-cyclodextrin, wherein the pH of the formulation is 4.5 to 7.6. 2. The formulation of claim 1, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml. 3. The formulation of claim 1, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml, said histidine is present in an amount of 10-15 mM, said glycine is present in an amount of 130-250 mM, said sucrose is present in an amount of 5-10%, and said beta-cyclodextrin is present in an amount of 0.5-1%. 4. The formulation of claim 3, wherein the formulation further comprises polysorbate 80 or polysorbate 20 in an amount of 0.005-0.2%. 5. The formulation of claim 4, wherein: said sucrose is present in an amount of 5%, said histidine is present in an amount of 10 mM, and said glycine is present in an amount of 130 mM. 6. The formulation of claim 1, wherein the pH is from 5-7. 7. The formulation of claim 1, wherein the pH is from 5-6. 8. The formulation of claim 1, wherein said antibody is a humanized antibody selected from the group consisting of huMy 9-6, huN901, huC242, huB4, DS6, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab. 9. The formulation of claim 1, wherein said antibody is huC242. 10. The formulation of claim 1, wherein said antibody is huN901. 11. The formulation of claim 1, wherein the cytotoxic drug is selected from the group consisting of a maytansinoid, a taxane, and a CC-1065. 12. The formulation of claim 10, wherein the cytotoxic drug is a maytansinoid. 13. The formulation of claim 11, wherein the cytotoxic drug is a maytansinoid. 14. The formulation of claim 11, wherein the cytotoxic drug is N.sup.2'-deacetyl-N.sup.2'-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N.sup.2'-deacetyl-N.sup.2'-(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4). 15. The formulation of claim 5, wherein: said immunoconjugate is a humanized N901-DM1 immunoconjugate and is present in an amount of 0.5-10 mg/ml. 16. The formulation of claim 5, wherein: said cytotoxic drug is N.sup.2'-deacetyl-N.sup.2'-(4-methyl-4-mercapto -1-oxopentyl) -maytansine(DM4) and said immunoconjugate is present in an amount of 0.5-10 mg/ml. 17. The formulation of claim 5, wherein: said immunoconjugate is a humanized C242-DM4 immunoconjugate and is present in an amount of 0.5-10 mg/ml. 18. An immunoconjugate liquid formulation comprising: (i) an immunoconjugate, which is an antibody comprising one or more covalently linked hydrophobic cytotoxic drugs, (ii) 100-300 mM glycine, (iii) 0.1-12% sucrose, and (iv) 0.5-2% beta-cyclodextrin, wherein the formulation is a buffered aqueous solution having a pH of 4.5 to 7.6. 19. The formulation of claim 18, wherein the formulation further comprises polysorbate 20 or polysorbate 80 in an amount of 0.005-1%. 20. The formulation of claim 18, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml. 21. The formulation of claim 18, wherein the pH is from 5-7. 22. The formulation of claim 18, wherein the pH is from 5-6. 23. The formulation of claim 18, wherein said antibody is a humanized antibody selected from the group consisting of huMy9-6, huN901, huC242, huB4, DS6, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab. 24. The formulation of claims 23, wherein said antibody is huN901 or huC242. 25. The formulation of claim 18, wherein the cytotoxic drug is selected from the group consisting of a maytansinoid, a taxane, and a CC-1065. 26. The formulation of claim 18, wherein: said immunoconjugate is a humanized N901-DM1 immunoconjugate and is present in an amount of 0.5-10 mg/ml. 27. An immunoconjugate liquid formulation comprising: (i) an immunoconjugate, which is an antibody comprising one or more covalently linked hydrophobic cytotoxic drugs, (ii) 100-300 mM glycine, (iii) 2-8% glycerol, (iv) 0.5-2% beta-cyclodextrin, and (v) 0.005-1.0% polysorbate 20 or polysorbate 80, wherein the formulation is a buffered aqueous solution having a pH of 4.5-7.6. 28. The formulation of claim 27, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml, said glycine is present in an amount of 130-250 mM, said glycerol is present in an amount of 2-5%, said beta-cyclodextrin is present in an amount of 0.5-1%, and said is polysorbate 80 or polysorbate 20 is present in an amount of 0.005-0.2%. 29. The formulation of claim 27, wherein the pH is from 5-7. 30. The formulation of claim 27, wherein the pH is from 5-6. 31. The formulation of claim 27, wherein said antibody is a humanized antibody selected from the group consisting of huMy9-6, huN901, huC242, huB4, DS6, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab. 32. The formulation of claim 27, wherein the cytotoxic drug is selected from the group consisting of a maytansinoid, a taxane, and a CC-1065. 33. The formulation of claim 27, wherein said cytotoxic drug is N.sup.2'-deacetyl-N.sup.2'-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N.sup.2'-deacetyl-N.sup.2'-(4-methyl-4 -merecapto-1 -oxopentyl)-maytansine (DM4). 34. An immunoconjugate liquid formulation comprising: (i) an immunoconjugate, which is an antibody comprising one or more covalently linked hydrophobic cytotoxic drugs, (ii) 2-8% mannitol, (iii) 0.1-12% sucrose, (iv) 0.5-2% beta-cyclodextrin, and (v) 0.005-1.0% polysorbate 20 or polysorbate 80, wherein the formulation is a buffered aqueous solution having a pH of 4.5-7.6. 35. The formulation of claim 34, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml, said mannitol is present in and amount of 3-5%, said sucrose is present in an amount of 5-10%, and said is polysorbate 80 or polysorbate 20 is present in an amount of 0.005-0.2%. 36. The formulation of claim 34, wherein the pH is from 5-7. 37. The formulation of claim 34, wherein the pH is from 5-6. 38. The formulation of claim 34, wherein said antibody is a humanized antibody selected from the group consisting of huMy9-6, huN901, huC242, huB4, DS6, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab. 39. The formulation of claim 34, wherein the cytotoxic drug is selected from the group consisting of a maytansinoid, a taxane, and a CC-1065. 40. The formulation of claim 18, wherein the buffered aqueous solution contains one or more of histidine, succinate, citrate, phosphate, and acetate. 41. The formulation of claim 40, wherein the buffered aqueous solution contains succinate. 42. The formulation of claim 40, wherein the buffered aqueous solution contains citrate. 43. The formulation of claim 18, wherein said immunoconjugate is present in an amount of 0.5-20 mg/ml, said glycine is present in an amount of 130-250 mM, said sucrose is present in an amount of 5-10%, and said beta-cyclodextrin is present in an amount of 0.5-1%. 44. The formulation of claim 43, wherein the formulation further comprises polysorbate 80 or polysorbate 20 in an amount of 0.005-0.2%. 45. The formulation of claim 18, wherein said cytotoxic drug is N.sup.2'-deacetyl-N.sup.2'-(3-mercapto-1-oxopropyl)-maytansine (DM1) or N.sup.2'-deacetyl-N.sup.2'-(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4). 46. The formulation of claim 27, wherein the buffered aqueous solution contains one or more of histidine, succinate, citrate, phosphate, and acetate. 47. The formulation of claim 46, wherein the buffered aqueous solution contains succinate. 48. The formulation of claim 27, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml. 49. The formulation of claim 34, wherein the buffered aqueous solution contains one or more of histidine, succinate, citrate, phosphate, and acetate. 50. The formulation of claim 49, wherein the buffered aqueous solution contains succinate. 51. The formulation of claim 34, wherein: said immunoconjugate is present in an amount of 0.5-20 mg/ml. 52. The formulation of claim 34, wherein said cytotoxic drug is N.sup.2'-deacetyl-N.sup.2'-(3-mercapto -1 -oxopropyl)-maytansine (DM1) or N.sup.2'-deacetyl-N.sup.2'-(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4).

Details for Patent 9,114,179

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2025-08-03
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2025-08-03
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2025-08-03