Stabilizing formulations
View Patent ↗Formulations are described that are suitable for storage of proteins, such as antibodies, over a relatively broad range of protein concentrations, pH, and buffer types. Also described are methods of storing a protein and methods of identifying a suitable formulation for storage of a specific protein. In general, a formulation contains low to no surfactant, no to relatively low salt concentrations, and requires a relatively low buffer concentration.
1. A formulation comprising
(a) an isolated polypeptide, wherein the polypeptide is an anti-CD22 antibody; and (b) an aqueous solution having pH 4.0 to pH 8.0, wherein the formulation does not contain a cryoprotectant or surfactant, provided that the anti-CD22 antibody is present at a concentration of about 10 to about 30 mg/mL, and the formulation comprises a buffer concentration of about 1 mM to about 100 mM.
2. The formulation of claim 1 , wherein the buffer is an acetate buffer, HEPES, succinate buffer, phosphate buffer, citrate buffer, or combinations thereof.
3. The formulation of claim 1 , wherein the anti-CD22 antibody has a pl of at least 6.0, 7.0, or 8.0.
4. The formulation of claim 1 , wherein the pH of the formulation is about pH 5.0 to about pH 6.0.
5. The formulation of claim 1 , wherein the pH of the formulation is about pH 5.0 to about pH 6.0 and the formulation is stored at about −80° C. to 0° C.
6. The formulation of claim 1 , wherein the aqueous solution is about 20mM succinate, pH 6.0.
7. The formulation of claim 1 , wherein the protein is an anti-Lewis Y antibody and the aqueous solution is about 10 mM Na citrate, pH 5.5 and about 75 mM NaCI.
8. The formulation of claim 1 , wherein the protein is an anti-5T4antibody and the aqueous solution is about 10 mM Na acetate, pH 5.5.
9. The formulation of claim 1 , wherein stability is determined by assaying at least one of (i) the percentage of high molecular weight species, (ii) the percentage of low molecular weight species, or (iii) the percentage of acidic species of the polypeptide compared to a control.
10. The formulation of claim 1 , wherein the anti-CD22 antibody is purified at least 95%.
11. The formulation of claim 1 , wherein the formulation is sterile.
12. A method of conjugating a polypeptide to a second agent, the method comprising.
(a) obtaining a polypeptide from the formulation of claim 1 , and
(b) conjugating the polypeptide to the second agent.
13. The method of claim 12 , wherein the polypeptide is an antibody.
14. The method of claim 12 , wherein the second agent is a toxin.
15. A conjugated polypeptide produced by the method of claim 12 .
16. The formulation of claim 1 , wherein the anti-CD22 antibody is stable at frozen stage for at least 3 weeks at about −80° C. to 0° C.
17. The formulation of claim 1 , wherein not more than 0.5% of the polypeptide is a high molecular weight species.