Claims for Patent: 8,241,632

Summary for Patent: 8,241,632

Title:	Stable polypeptide formulations
Abstract:	The invention provides a formulation including a buffer having a pH less than 6.0, a divalent cation between about 5-200 mM, an excipient comprising a sugar or polyol and an effective amount of a therapeutic polypeptide. Also provided is a method of stabilizing a polypeptide. The method includes contacting a therapeutic polypeptide with a concentration of divalent cation between about 5-150 150 mM in a buffer having a pH less than 6.0 and an excipient comprising a sugar or polyol.
Inventor(s):	Rehder; Douglas (Seattle, WA), Bondarenko; Pavel (Thousand Oaks, CA), Chelius; Dirk (Geretsried, DE), McAuley; Arnold (Moorpark, CA), Matsumura; Masazumi (Thousand Oaks, CA)
Assignee:	Amgen Inc. (Thousand Oaks, CA)
Application Number:	12/718,898
Patent Claims:	1. A formulation comprising a buffer having a pH from about 4.8 to about 5.2, a divalent cation, an excipient comprising a sugar or polyol and an effective amount of a therapeutic antibody having specific binding activity to human epidermal growth factor receptor (EGFR), wherein said therapeutic antibody is panitumumab or cetuximab and said antibody retains at least about 80% stability for up to two months in solution, and wherein said divalent cation is at least one of CaCl.sub.2, ZnCl.sub.2, MnCl.sub.2 or MgCl.sub.2, wherein said divalent cation concentration is selected from about 25 mM, about 50 mM, about 75 mM, about 100 mM, or about 125 mM, and wherein said buffer is at least one of acetic acid, glutamic acid, or succinic acid, or a salt thereof, and wherein said buffer is present in a concentration of about 1 mM to about 50 mM. 2. The formulation of claim 1, wherein said divalent cation is CaCl.sub.2. 3. The formulation of claim 2, wherein said CaCl.sub.2 concentration is 75 mM. 4. The formulation of claim 1, wherein said sugar or polyol is selected from glycerol, sucrose, trehalose or sorbitol. 5. The formulation of claim 4, further comprising about 1-20% of glycerol, sucrose, trehalose or sorbitol. 6. The formulation of claim 4, further comprising about 1-3% glycerol. 7. The formulation of claim 1, further comprising a surfactant. 8. The formulation of claim 7, wherein said surfactant comprises a polysorbate. 9. The formulation of claim 7, wherein said surfactant is present at a concentration of about 0.001-0.10% (w/v). 10. The formulation of claim 1, further comprising a second excipient. 11. The formulation of claim 10, wherein said second excipient is selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, anti-oxidant, metal ion, chelating agent and preservative. 12. The formulation of claim 1, wherein said therapeutic antibody comprises an Asp or Asn residue susceptible to isomerization to isoaspartic acid. 13. The formulation of claim 1, wherein said therapeutic antibody is present at a concentration of between about 10-200 mg/ml. 14. A method of stabilizing a polypeptide, comprising contacting panitumumab or cetuximab with a concentration of divalent cation in a buffer having a pH from about 4.8 to about 5.2 and an excipient comprising a sugar or polyol, wherein said therapeutic antibody retains at least about 80% stability for up to two months in solution, wherein said divalent cation is at least one of CaCl.sub.2, ZnCl.sub.2, MnCl.sub.2 or MgCl.sub.2, and wherein said divalent cation concentration is selected from about 25 mM, about 50 mM, about 75 mM, about 100 mM, or about 125 mM, and wherein said buffer is at least one of acetic acid, glutamic acid, or succinic acid, or a salt thereof, and wherein said buffer is present in a concentration of about 1 mM to about 50 mM. 15. The method of claim 14, wherein said divalent cation is CaCl.sub.2. 16. The method of claim 15, wherein said CaCl.sub.2 concentration is 75 mM. 17. The method of claim 14, wherein said sugar or polyol is selected from glycerol, sucrose, trehalose or sorbitol. 18. The method of claim 17, wherein said glycerol, sucrose, trehalose or sorbitol comprises a concentration of about 1-20%. 19. The method of claim 17, wherein said glycerol comprises a concentration of between about 1-3%. 20. The method of claim 14, further comprising a surfactant. 21. The method of claim 20, wherein said surfactant comprises a polysorbate. 22. The method of claim 20, wherein said surfactant comprises a concentration of about 0.001-0.10% (w/v). 23. The method of claim 14, further comprising a second excipient. 24. The method of claim 23, wherein said second excipient is selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, anti-oxidant, metal ion, chelating agent and preservative. 25. The method of claim 14, wherein said therapeutic antibody having specific binding activity to human EGFR comprises an Asp or Asn residue susceptible to isomerization to isoaspartic acid.

Details for Patent 8,241,632

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2026-10-20
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2026-10-20
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2026-10-20