Anti-CTLA-4 antibody compositions
The present invention provides for novel compositions of anti-CTLA-4 antibodies comprising a chelating agent. Also provided are method of treating diseases and conditions with novel compositions of CTLA-4 antibodies, including various neoplasia conditions.
1. A composition comprising:
a chelating agent at a concentration of about 0.01 mM to about 5.0 mM;
histidine at a concentration of about 1 mM to about 100 mM;
a surfactant at a concentration of about 0.01 mg/ml to about 10 mg/ml;
trehalose at a concentration of about 100 mM to about 300 mM; and
an antibody at a concentration of about 1 mg/ml to about 200 mg/ml, wherein said antibody binds to human CTLA-4 and comprises the heavy chain CDR1, CDR2, and CDR3 amino acid sequences in SEQ ID NO: 2 and the light chain CDR1, CDR2, and CDR3 amino acid sequences in SEQ ID NO: 4.
2. The composition according to claim 1 , wherein the antibody is a human IgG antibody.
3. The composition according to claim 1 , wherein the antibody comprises a heavy chain amino acid sequence as shown in SEQ ID NO: 2 and a light chain amino acid sequence as shown in SEQ ID NO: 4.
4. The composition according to claim 1 , wherein the chelating agent is EDTA, DTPA, or DFM.
5. The composition according to claim 4 , wherein the chelating agent is EDTA.
6. The composition according to claim 1 , wherein the surfactant is polysorbate 80.
7. The composition according to claim 1 , wherein the chelating agent is EDTA and the surfactant is polysorbate 80.
8. The composition according to claim 1 , wherein the composition is a liquid composition and has a pH of 5.0-6.5.
9. The composition according to claim 8 , wherein the chelating agent is EDTA.
10. The composition according to claim 1 , wherein:
the antibody is at a concentration of about 1 mg/ml to about 100 mg/ml;
the chelating agent is at a concentration of about 0.01 mM to about 1.0 mM; and
the composition is a liquid composition with a pH of 5.0-6.5.
11. The composition according to claim 1 , wherein the composition comprises:
the antibody at a concentration of about 1 mg/ml to about 100 mg/ml;
EDTA at a concentration of about 0.01 mM to about 1.0 mM;
histidine at a concentration of about 1 mM to about 50 mM;
polysorbate 80 at a concentration of about 0.01 mg/ml to about 5 mg/ml; and
trehalose at a concentration of about 100 mM to about 300 mM,
wherein the composition is a liquid composition with a pH of 5.0-6.5.
12. The composition according to claim 1 , wherein the composition comprises:
about 20 mg/mL antibody;
about 0.27 mM EDTA;
about 20 mM histidine;
about 0.2 mg/mL polysorbate 80; and
about 222 mM trehalose.
13. The composition according to claim 1 , wherein the composition comprises:
about 20 mg/mL antibody;
about 0.1 mg/mL EDTA;
about 20 mM histidine;
about 0.2 mg/mL polysorbate 80; and
about 84 mg/mL trehalose,
wherein the composition is a liquid composition with a pH of 5.5.
14. The composition according to claim 1 , wherein after storage for a period of about 24 weeks at a temperature of about 40° C., an aggregate chromatogram peak area for the composition is at least 2% less than an aggregate chromatogram peak area for an otherwise identical composition that lacks the chelating agent and that is stored under identical conditions.
15. A process for preparing the composition according to claim 1 , comprising combining the antibody, the chelating agent, the surfactant, trehalose, and histidine.
16. A method for inhibiting binding between CTLA-4 and B7-1, B7-2 or both in a subject, comprising administering to the subject the composition according to claim 1 .
17. The composition according to claim 1 , 12 , or 13 , wherein the antibody comprises the heavy chain variable domain amino acid sequence in SEQ ID NO: 2 and the light chain variable domain amino acid sequence in SEQ ID NO: 4.
18. The method according to claim 16 , wherein the subject suffers from a neoplasia condition.
19. The composition according to claim 12 or 13 , wherein the antibody is ticilimumab.
20. The method according to claim 18 , wherein the neoplasia condition is melanoma.