Antibody formulations
View Patent ↗Formulations of anti-VLA-1 antibodies are described.
1. An aqueous pharmaceutical composition comprising an anti-Very Late Antigen-1(VLA-1) antibody at a concentration of about 100 mg/ml to about 225 mg/ml and at least one buffer,
wherein said anti-VLA-1 antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5,
wherein said at least one buffer is selected from one or more of at least one histidine buffer, at least, one acetate buffer, at least one succinate buffer, at least one citrate buffer, at least one glutamate buffer, and at least one phosphate buffer;
wherein said aqueous pharmaceutical composition further comprises at least one additional excipient at a concentration of about 100 mM to about 300 mM, wherein said at least one additional excipient is selected from one or more of sorbitol, sodium chloride, sucrose, trehalose, and mannitol; and
wherein the aqueous pharmaceutical composition is stable after storage at 2° C. to 8° C. for at least 3 years, as indicated by the presence of less than 10% total aggregation as assessed by size exclusion chromatography.
2. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one histidine buffer.
3. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one acetate buffer.
4. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one succinate buffer.
5. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one citrate buffer.
6. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one glutamate buffer.
7. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one buffer comprises at least one phosphate buffer.
8. The aqueous pharmaceutical composition according to claim 1 , wherein said aqueous pharmaceutical composition comprises an anti-VLA-1 antibody at a concentration of at least about 150 mg/ml.
9. The aqueous pharmaceutical composition according to claim 2 , wherein said at least one histidine buffer is present at a concentration of about 10 mM to about 50 mM.
10. The aqueous pharmaceutical composition according to claim 2 , wherein said at least one histidine buffer is present at a concentration of about 20 mM to about 40 mM.
11. The aqueous pharmaceutical composition according to claim 1 , wherein said at least one additional excipient is sorbitol.
12. The aqueous pharmaceutical composition accord claim 1 , wherein said aqueous pharmaceutical composition further comprises at least one surfactant at a concentration of about 0.001% to about 0.5%.
13. The aqueous pharmaceutical composition according to claim 12 , wherein said at least one surfactant is at least one polysorbate.
14. The aqueous pharmaceutical composition according to claim 13 , wherein said at least one polysorbate is polysorbate 80 or polysorbate 20.
15. The aqueous pharmaceutical composition according to claim 1 , wherein said aqueous pharmaceutical composition further comprises at least one excipient and at least one surfactant.
16. The aqueous pharmaceutical composition according to claim 2 , wherein said aqueous pharmaceutical composition further comprises sorbitol and polysorbate 20.
17. The aqueous pharmaceutical composition according to claim 3 , wherein said aqueous pharmaceutical composition further comprises sorbitol and polysorbate 80.
18. The aqueous pharmaceutical composition according to claim 1 , said aqueous pharmaceutical composition has a pH of about 4.5 to about 7.
19. The aqueous pharmaceutical composition according to claim 1 , wherein said aqueous pharmaceutical composition has a viscosity of less than about 21 cP.
20. The aqueous pharmaceutical composition according to claim 1 , wherein said aqueous pharmaceutical composition has an osmolality of about 80 mOsm/kg to about 500 mOsm/kg.
21. The aqueous pharmaceutical composition according to claim 1 , wherein said anti-VLA-1 antibody comprises a light chain and a heavy chain, wherein the amino acid sequence of the light chain is the same as or differs by no more than 10 amino acids from the sequence of SEQ NO:1 and wherein the amino acid sequence of the heavy chain is the same as or differs by no more than 10 amino acids from the sequence of SEQ ID NO:2.
22. The aqueous pharmaceutical composition according to claim 1 , wherein said anti-VLA-1 antibody comprises a light chain and a heavy chain, wherein the amino acid sequence of the light chain is that of SEQ ID NO:1 and the amino acid sequence of the heavy chain is that of SEQ ID NO:2.
23. A unit dose of an aqueous pharmaceutical composition according to claim 1 , wherein administration of the unit dose to a subject will deliver about 0.03 mg of the anti-VIA-1 antibody per kg body weight of said subject to about 10 mg of the anti-VLA-1 antibody per kg body weight of said subject.
24. The aqueous pharmaceutical composition according to claim 1 , wherein said aqueous pharmaceutical composition is suitable for subcutaneous administration to a subject in need thereof.
25. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition is stable after storage at 2° C. to 8° C. for at least 3 years as indicated by <15% impurities as assessed by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS).
26. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition is stable after storage at 2° C. to 8° C. for at least 3 years as indicated by less than 5% total aggregation as assessed by size exclusion chromatography.
27. The aqueous pharmaceutical composition of claim 1 , wherein the aqueous pharmaceutical composition is stable after storage at 2° C. to 8° C. for at least 48 months.