Stable polypeptide formulations
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.
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 2 , ZnCl 2 , MnCl 2 or MgCl 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 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® (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) 2 , F(ab′) 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.