A Purification Strategy Utilizing Hydrophobic Interaction Chromatography to Obtain Homogeneous Species from a Site-Specific Antibody Drug Conjugate Produced by AJICAP™ First Generation

Yutaka Matsuda; Monica Leung; Tatsuya Okuzumi; Brian Mendelsohn

doi:10.3390/antib9020016

A Purification Strategy Utilizing Hydrophobic Interaction Chromatography to Obtain Homogeneous Species from a Site-Specific Antibody Drug Conjugate Produced by AJICAP™ First Generation

Antibodies (Basel). 2020 May 18;9(2):16. doi: 10.3390/antib9020016.

Authors

Yutaka Matsuda¹, Monica Leung¹, Tatsuya Okuzumi², Brian Mendelsohn¹

Affiliations

¹ Ajinomoto Bio-Pharma Services, 11040 Roselle Street, San Diego, CA 92121, USA.
² Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 2108681, Japan.

Abstract

In recent years, site-specific antibody drug conjugates (ADC)s have been in great demand because they have an expanded therapeutic index compared with conventional ADCs. AJICAP™ technology is a chemical conjugation platform to obtain site-specific ADCs through the use of a class of Fc-affinity compounds. Promising results from early technology development studies led to further investigation of AJICAP™ ADC materials to obtain site-specific and homogeneous drug antibody ratio (DAR) ADCs. Here we report site-specific conjugation followed by a preparative hydrophobic interaction chromatography (HIC) purification strategy to obtain purified "DAR = 1.0" and "DAR = 2.0" AJICAP™ ADC materials. Optimization of the mobile phase conditions and resin achieved a high recovery rate. In vitro biological assay demonstrated the target selective activity for purified homogeneous DAR ADCs. These results indicate the ability of a HIC purification strategy to provide "DAR = 1.0" and "DAR = 2.0" AJICAP™ ADCs with considerable potency and target selectivity.

Keywords: AJICAP™; antibody drug conjugate; hydrophobic interaction chromatography (HIC) purification; site-specific conjugation.