Antibody formulations and uses thereof
The present application relates to formulations of anti-CD105 antibodies, antigen-binding fragments thereof, and uses thereof. Another aspect relates to pre-filled syringes of the formulations of anti-CD105 antibodies or antigen-binding fragments thereof. Another aspect relates to the use of the formulations to reduce one or more signs or symptoms of an angiogenesis-related disorder such as cancers and ophthalmologic diseases.
1. A formulation that comprises from about 1 mg/ml to about 150 mg/ml of an anti-CD105 antibody, or an antigen-binding fragment thereof; from about 10 mM to about 20 mM of a buffering agent; from about 120 mM to about 240 mM of a polyol; and a pH of about 4.0; wherein the buffering agent comprises acetate.
2. The formulation of claim 1 , wherein the average isoelectric point (pI) of the anti-CD105 antibody, or the antigen-binding fragment thereof, is from about 8.7 to about 9.2 after storage at 2 to 8° C. for at least 12 months, as measured by capillary electrophoresis-isoelectric focusing.
3. The formulation of claim 1 , wherein the anti-CD105 antibody comprises a light chain variable region (V L ) having the amino acid sequence set forth as SEQ ID NO: 1; a light chain constant region having the amino acid sequence set forth as SEQ ID NO: 2; a heavy chain variable region (V H ) having the amino acid sequence set forth as SEQ ID NO: 3; and a constant region having the amino acid sequence set forth as SEQ ID NO: 4.
4. The formulation of claim 1 , wherein the anti-CD105 antibody, or the antigen-binding fragment thereof, comprises a V L CDR1 having the amino acid sequence set forth as SEQ ID NO: 5; a V L CDR2 having the amino acid sequence set forth as SEQ ID NO: 6; a V L CDR3 having the amino acid sequence set forth as SEQ ID NO: 7; a V H CDR1 having the amino acid sequence set forth as SEQ ID NO: 8; a V H CDR2 having the amino acid sequence set forth as SEQ ID NO: 9; and a V H CDR3 having the amino acid sequence set forth as SEQ ID NO: 10.
5. The formulation of claim 1 , that comprises about 25 mg/ml, about 50 mg/ml, or about 100 mg/ml of the anti-CD105 antibody or the antigen-binding fragment thereof.
6. The formulation of claim 1 , that comprises about 10 mM or about 20 mM acetate.
7. The formulation of claim 1 , wherein the formulation is formulated for intravitreal or intravenous administration.
8. The formulation of claim 1 , that further comprises an acceptable carrier or excipient.
9. The formulation of claim 1 , which is isotonic or hypertonic.
10. The formulation of claim 1 , wherein the formulation is made isotonic with a salt.
11. The formulation of claim 1 , wherein the polyol comprises a sugar.
12. The formulation of claim 11 , wherein the sugar comprises a non-reducing sugar.
13. The formulation of claim 12 , wherein the non-reducing sugar comprises trehalose or sucrose.
14. The formulation of claim 11 , wherein the sugar comprises sorbitol.
15. The formulation of claim 1 , that further comprises a surfactant.
16. A pre-filled syringe suitable for intravenous or intravitreal administration that comprises the formulation of claim 1 .
17. The formulation of claim 1 , wherein the pH of the formulation is 4.0±0.1.
18. The formulation of claim 1 , wherein the anti-CD105 antibody, or antigen binding fragment thereof, comprises a light chain variable region (V L ) having the amino acid sequence set forth as SEQ ID NO: 1; and a heavy chain variable region (V H ) having the amino acid sequence set forth as SEQ ID NO: 3.
19. The formulation of claim 1 , wherein the pH of the formulation is from 3.8 to 4.2.
20. The formulation of claim 1 , wherein the pH of the formulation is 3.8, 3.9, 4.0, 4.1, or 4.2.
21. A formulation that comprises from about 25 mg/ml to about 150 mg/ml of an anti-CD105 antibody, or antigen-binding fragment thereof; from about 10 mM to about 20 mM of a buffering agent; from about 10 mM to about 20 mM of a buffering agent; from about 120 mM to about 240 mM of a polyol; and a pH of 4.0±0.2; wherein the buffering agent comprises acetate and the polyol comprises trehalose or sorbitol.
22. The formulation of claim 21 , wherein the pH of the formulation is from 3.9 to 4.1.
23. The formulation of claim 21 , wherein the pH of the formulation is 4.0.
24. The formulation of claim 21 , wherein the formulation is formulated for intravitreal administration.
25. The formulation of claim 21 , wherein the formulation is formulated for intravenous administration.
26. A prefilled syringe that comprises the formulation of claim 21 .
27. The formulation of claim 15 , wherein the surfactant comprises polysorbate 20 or polysorbate 80.
28. The formulation of claim 15 , wherein the surfactant is present in the formulation in an amount of about 0.1% or about 0.005%.
29. The formulation of claim 21 , wherein the formulation further comprises a surfactant.
30. The formulation of claim 29 , wherein the surfactant comprises polysorbate 20 or polysorbate 80.
31. The formulation of claim 30 , wherein the surfactant is present in the formulation in an amount of about 0.1% or about 0.005%.
32. The formulation of claim 21 , that further comprises an acceptable carrier or excipient.
33. The formulation of claim 1 , that comprises about 10 mM or about 20 mM of the buffering agent.
34. The formulation of claim 21 , that comprises about 10 mM or about 20 mM of the buffering agent.
35. The formulation of claim 1 , that comprises about 120 mM or about 240 mM of the polyol.
36. The formulation of claim 21 , that comprises about 120 mM or about 240 mM of the polyol.