Bristol-Myers Squibb Compnay

Zhijun Tan

Zhengjian Li

Xuankuo Xu

Yueming Qian

Chao Huang

Zhiqiang Chen

Ameya Umesh Borwankar

Joon Chong Yee

Cheng Du

The invention is a method of preventing the generation of pink color during antibody manufacturing by either preventing the reduction of antibodies during manufacturing and harvest or inhibiting the conversion of cyanocobalamin (CN-Cbl) to hydroxocobalamin (HO-Cbl) during manufacturing and harvest. Replacement of white light in the cell culture media preparation and storage areas with red light inhibits the conversion of CN-Cbl to HO-Cbl. Addition of peroxides to the clarified bulk at harvest inhibits reduction of the antibody disulfide bonds.

Method of controlling the pink color generated during antibody manufacturing

In certain embodiments, the disclosure provides an IgG4 antibody comprising a heavy chain and a light chain, wherein the heavy chain comprises: (a) a modified IgG4 CH1 region having a substitution of the lysine residue at position 196; or (b) a modified IgG4 hinge region having a substitution of the serine residue at position 217, the glycine residue at position 220, the proline residue at position 224 or the proline residue at position 225. Preferably, the IgG4 antibody further comprises a substitution of the serine residue at position 228 in the heavy chain hinge region.

Therapeutic immunoglobulin G4 for improved bioanalytical and bioprocessing properties

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Acton, MA, United States of America

Zhijun Tan