Affimed's has three distinct antibody libraries composed of around one billion different antibodies each:
- Naïve human antibodies
- Synthetic antibodies
- Semi-synthetic combining elements of both naïve and synthetic antibodies
Human antibodies for therapeutic use are usually sourced either through the immunization of transgenic mice harboring a substantial part of the human antibody gene repertoire or through the generation and screening of human antibody libraries. Affimed has generated its three libraries by the latter method, from a fully human source.
Affimed's naïve library is derived from human B-lymphocytes. The variety and complexity of this library is achieved by the random combination of all genes that code for the binding domain of the heavy chain of the antibody with those coding for the light chains. The result is a library composed of all possible natural variations of human antibodies.
The second library is a synthetic human antibody library, which has been generated through the introduction of randomized sequences in the antibody binding site. These antibodies, though based on human sources, extend the repertoire beyond what is found naturally.
Affimed's third and most recently completed library is a semi-synthetic antibody library that combines aspects of both the above mentioned naïve and synthetic antibody libraries. This library further extends the diversity of binding molecules found in the other two libraries.
As full length antibodies are hard to express in bacteria, each library is usually comprised of antibody fragments: single chain variable domains linked by peptides (scFv) or 'Fabs' representing both the variable and constant domains of one of the upper arms of the "Y" (see An Introduction To Antibodies).
In order to increase the likelihood of selecting an antibody with excellent binding properties from each library, the size of each was increased to comprise at least one billion different antibodies. The libraries can be screened using phage display to identify the best binders for a specific target. The result is a library resource of unmatched diversity, which allows Affimed to select antibodies for difficult targets that would be impossible using traditional antibody discovery tools.