Claims for Patent: 7,705,132

Summary for Patent: 7,705,132

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:	11/973,051
Patent Claims:	1. A formulation comprising a buffer having a pH from about 4.0 to less than 6.0, a divalent cation between about 5-150 mM, 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 retains at least about 80% stability for up to two months in solution, and wherein the divalent cation is at least one of CaCl.sub.2, ZnCl.sub.2, MnCl.sub.2 or MgCl.sub.2. 2. The formulation of claim 1, wherein said divalent cation concentration is selected from about 25 mM, 50 mM, 75 mM, 100 mM or 125 mM. 3. The formulation of claim 1, wherein the divalent cation is CaCl.sub.2 and is present at a concentration of 75 mM. 4. The formulation of claim 1, wherein said pH is between 4.8-5.2. 5. The formulation of claim 1, wherein said buffer is selected from acetic acid, glutamic acid or succinic acid, or a salt thereof. 6. The formulation of claim 1, wherein said buffer comprises a concentration of about 1-50 mM. 7. The formulation of claim 1, wherein said sugar or polyol is selected from glycerol, sucrose, trehalose or sorbitol. 8. The formulation of claim 7, further comprising about 1-20% glycerol, sucrose, trehalose or sorbitol. 9. The formulation of claim 7, further comprising about 1-3% glycerol. 10. The formulation of claim 1, further comprising a surfactant. 11. The formulation of claim 10, wherein said surfactant comprises a polysorbate. 12. The formulation of claim 10, wherein said surfactant is present at a concentration of about 0.001-0.10% (w/v). 13. The formulation of claim 1, further comprising a second excipient. 14. The formulation of claim 13, 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. 15. The formulation of claim 1, wherein said therapeutic antibody having specific binding activity to human EGFR comprises an Asp or Asn residue susceptible to isomerization to isoaspartic acid. 16. The formulation of claim 1, wherein said therapeutic antibody having specific binding activity to human EGFR is a human antibody, a humanized antibody, a chimeric antibody, or a functional fragment thereof. 17. The formulation of claim 16, wherein said human antibody is panitumumab. 18. The formulation of claim 16, wherein said chimeric antibody is Erbitux.RTM. (cetuximab). 19. The formulation of claim 16, wherein said human antibody is selected from IMC-11F8 or HUMAX-EGFR. 20. The formulation of claim 16, wherein said humanized antibody is selected from matuzumab (EMD-7200) or nimotuzumab (TheraCIM hR3). 21. The formulation of claim 16, wherein said functional fragment thereof comprises a Fd, Fv, Fab, F(ab'), F(ab).sub.2, F(ab').sub.2, single chain Fv (scFv) or chimeric antibody. 22. The formulation of claim 1, wherein said therapeutic antibody is present at a concentration selected from between about 10-200 mg/ml.

Details for Patent 7,705,132

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