Progress towards recombinant anti-infective antibodies

Abstract

The global market for monoclonal antibody therapeutics reached a total of $11.2 billion in 2004, with an impressive 42% growth rate over the previous five years and is expected to reach approximately $34 billion by 2010. Coupled with this growth are stream-lined product development, production scale-up and regulatory approval processes for the highly conserved antibody structure. While only one of the 21 current FDA-approved antibodies, and one of the 38 products in advanced clinical trials target infectious diseases, there is increasing academic, government and commercial interest in this area. Synagis, an antibody neutralizing respiratory syncitial virus (RSV), garnered impressive sales of $1.1 billion in 2006 in spite of its high cost and undocumented effects on viral titres in human patients. The success of anti-RSV passive immunization has motivated the continued development of anti-infectives to treat a number of other infectious diseases, including those mediated by viruses, toxins and bacterial/ fungal cells. Concurrently, advances in antibody technology suggest that cocktails of several monoclonal antibodies with unique epitope specificity or single monoclonal antibodies with broad serotype specificity may be the most successful format. Recent patents and patent applications in these areas will be discussed as predictors of future anti-infective therapeutics.

Figure 1

A, Anti-Infective Mechanism of Antibodies for Inhibition of Toxin B by blocking access to Target Cell and facilitate toxin removal; B, Inhibition of Bacterial/Fungal Bodies by blocking cellular binding and removal through natural killer cells or phagocytes; C, Inhibition of Virals (adapted from Marasco, 2007) - i. mAb bound to co-receptor or combination prevents target cell interaction; ii. mAb bound to EnV prevents blocks target cell interaction; iii. mAb bound to Env binds but prevents endosome formation; iv. mAb bound to EnV prevents release from endosome; v. mAb bound to EnV prevents release of replicated viral RNA from the target cell; D, Viral Escape from antibodies via i) EnV mutation; ii) EnV conformational change.

Figure 2

Toxin neutralizing antibodies: A. monoclonal antibody consisting of a single antibody binding a single unique epitope on the toxin, B. bi-specific antibody in which each arm is able to bind a different epitope on the toxin, C. oligoclonal antibodies consiting of a mixture of two or more monoclonal antibodies that each bind a single unique epitope on the toxin, D. polyclonal antibodies consisting of a mixture of several monoclonal antibodies that either bind or don’t bind to the toxin.