MODULATED LYSINE VARIANT SPECIES COMPOSITIONS AND METHODS FOR PRODUCING AND USING THE SAME

摘要

The instant invention relates to modulated lysine variant species compositions comprising a protein, e.g., an antibody, or antigen-binding portion thereof, and methods, e.g., cell culture and/or protein purification methods, for producing such modulated lysine variant species compositions. Methods for using such compositions to treat a disorder, e.g., a disorder in which TNFα is detrimental, are also provided.

主权项

1. A method for producing a composition comprising a human anti-TNFα antibody, comprising
culturing a cell producing the antibody in a cell culture media comprising an amount of one or more basic amino acids sufficient to produce a composition comprising the antibody in which less than 65% of the lysine variant species of the antibody have zero C-terminal lysines (Lys 0), wherein the lysine variant species include the main peak and peaks that elute at a relative residence time later than the main peak, as detected using weak cation-exchange chromatography, and wherein the antibody comprises a light chain variable region (LCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:7, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3; and a heavy chain variable region (HCVR) having a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:6, and a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4.