PURIFIED ANTIBODY COMPOSITION
The invention provides a method for producing a host cell protein-(HCP) reduced antibody preparation from a mixture comprising an antibody and at least one HCP, comprising an ion exchange separation step wherein the mixture is subjected to a first ion exchange material, such that the HCP-reduced antibody preparation is obtained.
1 . A liquid pharmaceutical composition comprising:
a) adalimumab;
b) a polyol selected from the group consisting of sucrose, trehalose, and sorbitol;
c) a surfactant; and
d) a buffer system having a pH of 4 to 8,
wherein the adalimumab is expressed in a Chinese Hamster Ovary (CHO) cell expression system; and the composition is characterized in that when the composition is assayed in a cathepsin L kinetic assay, a level of cathepsin L activity less than 1.3 RFU/s/mg of adalimumab is observed, wherein the cathepsin L kinetic assay comprises:
i.) diluting the composition in a polystyrene container in a solution containing 25 mM NaOAc, 5 mM DTT and 1 mM EDTA at pH 5.5,
ii.) adding dextran sulfate to a concentration of 0.035 μg/mL and incubating at 37° C. for six hours,
iii.) adding Z-leucine-arginine covalently bound at its C-terminus to a fluorescent 7-amino-4-methyl coumarin (Z-leucine-arginine-AMC), wherein the diluting, adding, and incubating steps are sufficient to permit the measurement of cathepsin L hydrolysis of the Z-leucine-arginine-AMC within a linear range, and
iv.) measuring Z-leucine-arginine-AMC hydrolysis in the linear range in RFU/s/mg of adalimumab.
2 . The liquid composition of claim 1 , wherein the composition is packaged in a pre-filled syringe.
3 . The liquid composition of claim 2 , wherein the composition comprises 50 mg/ml of adalimumab.
4 . The liquid composition of claim 3 , wherein the composition is suitable for subcutaneous injection.
5 . The liquid composition of claim 4 , wherein the pH is from 4.8 to 5.5.
6 . The liquid composition of claim 5 , wherein the surfactant is polysorbate 20 or polysorbate 80.
7 . The liquid composition of claim 6 , wherein the polysorbate 80 concentration is between 0.1 and 10 mg/ml.
8 . The liquid composition of claim 6 , wherein the polyol is sorbitol.
9 . The liquid composition of claim 6 , wherein the polyol is sucrose.
10 . The liquid composition of claim 6 , wherein the buffer system comprises histidine, acetate, succinate, phosphate or gluconate.
11 . A liquid pharmaceutical composition comprising:
a) adalimumab;
b) a polyol,
c) polysorbate 20, and
d) a buffer system having a pH of 4 to 8,
wherein the adalimumab is expressed in a Chinese Hamster Ovary (CHO) cell expression system; and the composition is characterized in that when the composition is assayed in a cathepsin L kinetic assay, a level of cathepsin L activity less than 1.3 RFU/s/mg of adalimumab is observed, wherein the cathepsin L kinetic assay comprises:
i.) diluting the composition in a polystyrene container in a solution containing 25 mM NaOAc, 5 mM DTT and 1 mM EDTA at pH 5.5,
ii.) adding dextran sulfate to a concentration of 0.035 μg/mL and incubating at 37° C. for six hours,
iii.) adding Z-leucine-arginine covalently bound at its C-terminus to a fluorescent 7-amino-4-methyl coumarin (Z-leucine-arginine-AMC), wherein the diluting, adding, and incubating steps are sufficient to permit the measurement of cathepsin L hydrolysis of the Z-leucine-arginine-AMC within a linear range, and
iv.) measuring Z-leucine-arginine-AMC hydrolysis in the linear range in RFU/s/mg of adalimumab.
12 . The liquid composition of claim 11 , wherein the composition is packaged in a pre-filled syringe.
13 . The liquid composition of claim 12 , wherein the composition comprises 50 mg/ml of adalimumab.
14 . The liquid composition of claim 13 , wherein the composition is suitable for subcutaneous injection.
15 . The liquid composition of claim 14 , wherein polyol is selected from the group consisting of mannitol, sucrose, trehalose, and sorbitol.
16 . The liquid composition of claim 14 , wherein the polyol is sorbitol.
17 . The liquid composition of claim 14 , wherein the polyol is sucrose or mannitol.
18 . The liquid composition of claim 14 , wherein the polysorbate 20 concentration is between 0.1 and 10 mg/ml.
19 . The liquid composition of claim 15 , wherein the buffer system comprises histidine, acetate, succinate, phosphate, or gluconate.
20 . A liquid pharmaceutical composition comprising:
a) adalimumab
b) a polyol,
c) a polysorbate, and
d) a buffer system having a pH of 4 to 8, comprising histidine, succinate, acetate, or gluconate,
wherein the adalimumab is expressed in a Chinese Hamster Ovary (CHO) cell expression system; and the composition is characterized in that when the composition is assayed in a cathepsin L kinetic assay, a level of cathepsin L activity less than 1.3 RFU/s/mg of adalimumab is observed, wherein the cathepsin L kinetic assay comprises:
i.) diluting the composition in a polystyrene container in a solution containing 25 mM NaOAc, 5 mM DTT and 1 mM EDTA at pH 5.5,
ii.) adding dextran sulfate to a concentration of 0.035 μg/mL and incubating at 37° C. for six hours,
iii.) adding Z-leucine-arginine covalently bound at its C-terminus to a fluorescent 7-amino-4-methyl coumarin (Z-leucine-arginine-AMC), wherein the diluting, adding, and incubating steps are sufficient to permit the measurement of cathepsin L hydrolysis of the Z-leucine-arginine-AMC within a linear range, and
iv.) measuring Z-leucine-arginine-AMC hydrolysis in the linear range in RFU/s/mg of adalimumab.
21 . The liquid composition of claim 20 , wherein the composition is packaged in a pre-filled syringe.
22 . The liquid composition of claim 21 , wherein the composition comprises 50 mg/ml of adalimumab.
23 . The liquid composition of claim 22 , wherein the composition is suitable for subcutaneous injection.
24 . The liquid composition of claim 23 , wherein the pH is from 4.8 to 5.5.
25 . The liquid composition of claim 24 , wherein polyol is selected from the group consisting of mannitol, sucrose, trehalose, and sorbitol.
26 . The liquid composition of claim 25 , wherein the polyol is sorbitol.
27 . The liquid composition of claim 25 , wherein the polyol is sucrose or mannitol.
28 . The liquid composition of claim 25 , wherein the polysorbate 20 concentration is between 0.1 and 10 mg/ml.
29 . The liquid composition of claim 25 , wherein the buffer system comprises succinate.
30 . The liquid composition of claim 25 , wherein the buffer system comprises histidine.