Antibodies are proteins produced by the body in response to invading pathogens and infectious agents. They serve to neutralize and inactivate these foreign intruders due to their capacity to bind with very high affinity to their target (referred to as the ‘antigen'). In other words, antibodies make large molecular complexes with the antigen and renders them more easily identified and hence more effectively removed from the body.  NovImmune exploits this characteristic by using monoclonal antibodies to seek out and neutralize proteins that are aberrantly orchestrating the chronic inflammation associated with autoimmune diseases and respiratory disorders.
Over the last three decades, the evolution of molecular biology has arrived at a point that facilitates the re-engineering of the native structure of antibodies.  As such, monoclonal antibodies are a relatively new yet important emerging therapeutic class for the pharmaceutical industry.

Structure of Antibodies

Antibodies belong to a class of proteins called immunoglobulins. They consist of 4 protein chains (two light (L) chains and two heavy (H) chains) linked by disulphide bonds. Antibodies have two structurally and functionally distinct domains: the variable region responsible for the binding of the antigen, and the constant domain which mediates different physiological effects including opsonization, cell lysis, and degranulation of mast cells, basophils and eosinophils.

Within the variable domains, three complementarity determining regions (CDR) on both the H and L chains contain the most hypervariability. The CDRs confer the specificity and most of the affinity of the antibody for its target antigen. The constant region of the H and L chains can be of several distinct classes, also referred to as isotypes. The L chain can be either kappa or lambda, while the H chain can be of five different classes IgM, IgD, IgG, IgA and IgE.    

Generation of Antibodies

As the protocol was first established with mice, monoclonal antibodies were initially structurally mouse (murine) proteins. The first waves of therapeutic monoclonal antibodies were thus murine antibodies directed towards human protein targets. When injected into patients, this strategy gave rise to immune rejection via a human anti-mouse antibody (HAMA) response eventually neutralizing the efficacy of therapeutic antibodies, and posing significant safety issues.

Because of the generation of HAMA and the related unwanted side effects, the variable domains of mouse antibodies were subsequently linked to a human H and L constant region (= chimeric), or, alternatively, the sequences of the murine CDRs grafted onto a human constant "backbone" (= humanized). While these strategies generated antibodies containing less murine derived sequences, both still generated unwanted anti-mouse antibody responses (HAMA), often with neutralizing effect on the antibody.

New technologies have evolved permitting the creation of fully human antibodies still endowed with the exquisite specificity for a given therapeutic target (e.g. transgenic mice and phage display).

Various Types of Therapeutic Antibodies