| 摘要 |
Disclosed is a pharmaceutical composition comprising an isolated human anti-TNFalpha antibody, or an antigen-binding portion thereof, and a pharmaceutically acceptable carrier, wherein the anti-TNFalpha antibody, or antigen-binding portion thereof, comprises a light chain variable region comprising a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 3 or an amino acid sequence differing from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8, a light chain CDR 2 comprising the amino acid sequence of SEQ ID NO: 5, and a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 7; and a heavy chain variable region comprising a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 4 or an amino acid sequence differing from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 8, wherein the composition is characterised in that when the composition is assayed in a cathepsin L kinetic assay, a level of cathepsin L activity less than 1.84 RFU/s/mg of antibody is observed, and 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 degrees Celsius 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 antibody, wherein the sequences are as defined in the complete specification. |
