Antibody conjugation and formulation

Abstract

In an era where ultra-high antibody concentrations, high viscosities, low volumes, auto-injectors and long storage requirements are already complex problems with the current unconjugated monoclonal antibodies on the market, the formulation demands for antibody-drug conjugates (ADCs) are significant. Antibodies have historically been administered at relatively low concentrations through intravenous (IV) infusion due to their large size and the inability to formulate for oral delivery. Due to the high demands associated with IV infusion and the development of novel antibody targets and unique antibody conjugates, more accessible routes of administration such as intramuscular and subcutaneous are being explored. This review will summarize various site-specific and non-site-specific antibody conjugation techniques in the context of ADCs and the demands of formulation for high concentration clinical implementation.

Keywords: antibody-drug conjugates; conjugation; formulation; high concentration; site-specific.

Figure 1

Formulation difficulty increases comparing monoclonal antibodies to polyclonal antibodies and ADCs utilizing non-site-specific and site-specific conjugation strategies.

Figure 2

(1) Natural amino acids, (2) N-terminus heavy and light chain, (3) Interchain disulfide bonds, (4) Carbohydrate moiety, (5) NBS photoaffinity labeling, (6) Non-natural amino acids, (7) Engineered cysteines, (8) Protein-protein interactions, (9) Engineered tags, (10) Catalytic activity.