Modulated lysine variant species compositions and methods for producing and using the same
AssigneeAbbVie Inc.
InventorsKartik Subramanian, Mayda Perez Thiele, Xiaobei Zeng, Chee Furng Wong, Zehra Kaymakcalan, Ying Jing, Christopher M. Chumsae
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Abstract
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.
Claims30
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.
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 lysine 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 human anti-TNFα 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.
Dependencies are inferred from the claim text.