Low acidic species compositions and methods for producing and using the same

摘要

The instant invention relates to low acidic species (AR) 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 low AR 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 an immunoglobulin comprising the 6 CDR domains of adalimumab, the method comprising:
culturing a mammalian cell producing an immunoglobulin comprising the 6 CDR domains of adalimumab in a cell culture media comprising 2 g/L to 11 g/L of each of one or more basic amino acids selected from the group consisting of arginine, lysine, ornithine and histidine, and combinations thereof, to produce a composition comprising an immunoglobulin comprising the 6 CDR domains of adalimumab, wherein the composition comprises less than 20% total acidic species of the immunoglobulin, and wherein the acidic species of the immunoglobulin correspond to the peaks that elute earlier than the main peak in a WCX-10 HPLC chromatogram of the immunoglobulin, and wherein the WCX-10 HPLC chromatogram is generated using a first mobile phase of 10 mM Sodium Phosphate dibasic (pH 7.5) and a second mobile phase of 10 mM Sodium Phosphate dibasic, 500 mM Sodium Chloride (pH 5.5), and wherein the WCX-10 HPLC chromatogram is generated using detection at 280 nm.