Monoclonal Antibodies

During the last decade monoclonal antibodies have increasingly been used as therapeutic compounds. Antibodies are instrumental in the body's natural defence against diseases and as such have several characteristics which make them ideal to use as drugs. The molecules bind tightly and very specifically to their antigens, are very stable and have a natural tendency to interact with the immune system. There is a lot of variation between antibodies, making it critical to find the development candidates which have optimal binding characteristics. Furthermore, it is important that the therapeutic antibodies should be as human-like as possible, to avoid patients having a negative/allergic reaction against the treatment.

In the industry, there are two principal ways to find the optimal antibody. One is to inoculate the target compound into an animal.  To ensure the antibodies produced are as human-like as possible the animal can be genetically modified, or alternatively, the antibody created can be genetically engineered to add human sequences. The other way is to create a library of antibody-genes, which can be expressed and screened to identify molecules which bind to the target. The antibodies in such libraries should be designed to be as human-like as possible or, even better, be fully human. Several characteristics influence the quality of the library and thus the probability of finding the optimal antibody drug i.e. library size, its functionality and the inherent diversity of the antibodies.

BioInvent has created a highly functional and diverse library called n-CoDeR^®, which contains 2 x 10¹⁰ fully-human antibody genes. This proprietary antibody library is the cornerstone of BioInvent's antibody discovery platform, and is used in order to rapidly find therapeutic antibody candidates with desired properties.

What is an Antibody?

Monoclonal antibodies are composed of two identical heavy chain molecules and two light chains. The ability to bind to different antigens comes from the variable regions of the light and heavy chains (VL and VH), as the antigen binding site is formed at the interface of these two domains.

Each variable region contains three Complementarity Determining Regions (CDRs), which are the most variable sections. These are the regions of the antibody that bind directly to the antigen. The diversity of the variable regions comes initially from the recombination of numerous genetic segments.

Antibodies with higher specificity and affinity for particular targets are created in the body following antibody-antigen binding, as this triggers somatic mutation and mutants that are better at binding the antigen can be selected.