METHODS AND COMPOSITIONS FOR CONTROLLING ANTIBODY AGGREGATION
Disclosed herein are methods of purifying monoclonal antibodies and related compositions.
1 . An antibody processing method, comprising filtering through a membrane filter a phosphate buffered antibody solution having a pH of 5.7 to 6.7 and comprising infliximab, thereby producing an antibody concentrate, wherein antibody aggregation in the phosphate buffered antibody solution is reduced relative to a control antibody solution comprising infliximab and having a pH of 7.2.
2 . The method of claim 1 , wherein the antibody solution has a pH of 6.0 to 6.5.
3 . The method of claim 2 , wherein the antibody solution has a pH of 6.5.
4 . The method of claim 2 , wherein the antibody solution has a pH of 6.4.
5 . The method of claim 2 , wherein the antibody solution has a pH of 6.3.
6 . The method of claim 2 , wherein the antibody solution has a pH of 6.2.
7 . The method of claim 2 , wherein the antibody solution has a pH of 6.1.
8 . The method of claim 2 , wherein the antibody solution has a pH of 6.0.
9 . The method of any one of claims 1 - 8 , wherein the antibody solution comprises sodium phosphate.
10 . The method of claim 9 , wherein the antibody solution comprises sodium phosphate at a concentration of 5 mM to 15 mM.
11 . The method of claim 10 , wherein the antibody solution comprises sodium phosphate at a concentration of 10 mM.
12 . The method of any one of claims 1 - 11 , wherein the antibody solution comprises sucrose.
13 . The method of claim 12 , wherein the antibody solution comprises sucrose at a concentration of 5% to 15% (w/v).
14 . The method of claim 13 , wherein the antibody solution comprises sucrose at a concentration of 10% (w/v).
15 . The method of any one of claims 1 - 14 , wherein the antibody solution comprises a surfactant.
16 . The method of claim 15 , wherein the antibody solution comprises surfactant at a concentration of 0.005% to 0.015% (w/v).
17 . The method of claim 16 , wherein the antibody solution comprises surfactant at a concentration of 0.01% (w/v).
18 . The method of any one of claims 15 - 17 , wherein the surfactant is polysorbate 80.
19 . The method of any one of claims 1 - 18 , wherein the antibody solution comprises infliximab at a concentration of 15 g/L to 100 g/L.
20 . The method of claim 19 , wherein the antibody solution comprises infliximab at a concentration of 20 g/L to 60 g/L.
21 . The method of any one of claims 1 - 20 , wherein the temperature of the antibody solution is 2° C. to 12° C.
22 . The method of claim 21 , wherein the temperature of the antibody solution is 4° C. to 6° C.
23 . The method of any one of claims 1 - 22 , wherein the membrane filter has a pore size of 0.1 to 0.001 micron.
24 . The method of any one of claims 1 - 23 , wherein the antibody solution is filtered through the membrane filter by tangential flow filtration.
25 . The method of any one of claims 1 - 24 further comprising collecting the antibody concentrate.
26 . A composition comprising an antibody solution comprising infliximab and having a pH of 5.7 to 6.7.
27 . The composition of claim 26 , wherein the antibody solution has a pH of 6.0 to 6.5.
28 . The composition of claim 27 , wherein the antibody solution has a pH of 6.5.
29 . The composition of claim 27 , wherein the antibody solution has a pH of 6.4.
30 . The composition of claim 27 , wherein the antibody solution has a pH of 6.3.
31 . The composition of claim 27 , wherein the antibody solution has a pH of 6.2.
32 . The composition of claim 27 , wherein the antibody solution has a pH of 6.1.
33 . The composition of claim 27 , wherein the antibody solution has a pH of 6.0.
34 . The composition of any one of claims 26 - 33 , wherein the antibody solution comprises sodium phosphate.
35 . The composition of claim 34 , wherein the antibody solution comprises sodium phosphate at a concentration of 5 mM to 15 mM.
36 . The composition of claim 35 , wherein the antibody solution comprises sodium phosphate at a concentration of 10 mM.
37 . The composition of any one of claims 26 - 36 , wherein the antibody solution comprises sucrose.
38 . The composition of claim 37 , wherein the antibody solution comprises sucrose at a concentration of 5% to 15% (w/v).
39 . The composition of claim 38 , wherein the antibody solution comprises sucrose at a concentration of 10% (w/v).
40 . The composition of any one of claims 26 - 39 , wherein the antibody solution comprises a surfactant.
41 . The composition of claim 40 , wherein the antibody solution comprises surfactant at a concentration of 0.005% to 0.015% (w/v).
42 . The composition of claim 41 , wherein the antibody solution comprises surfactant at a concentration of 0.01% (w/v).
43 . The composition of any one of claims 40 - 42 , wherein the surfactant is polysorbate 80.
44 . The composition of any one of claims 26 - 43 , wherein the antibody solution comprises the chimeric monoclonal antibody at a concentration of 15 g/L to 100 g/L.
45 . The composition of claim 44 , wherein the antibody solution comprises the chimeric monoclonal antibody at a concentration of 20 g/L to 60g/L.
46 . The composition of any one of claims 26 - 45 , wherein the infliximab is more stable when the composition is stored at temperatures of −70° C. to at least 40° C. relative to a control composition having a pH of 7.2.