HUMAN ANTIBODY LIBRARIES & ITERATIVE COLONY FILTER SCREENING

Monoclonal antibodies represent the fastest growing class of pharmaceutical biotechnology with cumulative yearly sales of > 30 Billion US Dollars. Advances in this pharmaceutical area, crucially rely on monoclonal antibodies of good quality which should be isolated rapidly and, whenever in vivo applications are planned, should not elicit an immunogenic response.

Recombinant antibody technology has revolutionized the way monoclonal antibodies are isolated both for research applications and for the development of pharmaceutical products. Recent developments have made it possible to designand construct large combinatorial libraries, which contain billions of different binding specificities.

For practical applications, such antibody libraries should be usable as “single-pot” libraries, from which many different binders towards a variety of target antigens can be isolated. Ideally, the resulting antibodies should display acceptable biophysical properties (e.g., stability, solubility, chromatographic properties) and should express well. At both academic and industrial level, many different strategies for library construction have been considered, ranging from the combinatorial assembly of antibody domains amplified from lymphocytes to the construction of synthetic libraries based on a large set of germline genes.

Philogen has been one of the most active companies in constructing original antibody libraries. Through its daughter company Philochem, Philogen owns four antibody libraries (ETH-2 GOLD, PHILO-1, PHILO-2, PHILOtop), designed to produce high-affinity antibodies both for pharmaceutical product development and for research applications. These libraries, which contain billions of different binding specificities, are designed in a modular fashion, in which single antibody “scaffolds” display aminoacid diversity at the level of combinatorially-mutated residues in CDR3 loops of heavy and light chains. Antibodies from single-scaffold libraries typically display similar favorable biophysical properties while the modular library design facilitates general Affinity Maturation strategies. Another notable asset, is that all antibodies isolated from our libraries, bind to Protein A even if expressed in scFv antibody fragment format.

Furthermore, while most of the other antibody companies isolate monoclonal antibodies from libraries using phage display technology, Philogen has developed and patented a new screening technique called Iterative Colony Filter Screening (ICFS) (EU patent n°: EP1339750; US patent n° 7,723, 269) which bypasses the use of phages. In most cases, minute amounts of pure protein antigen (typically, few milligrams) are sufficient for the selection and characterization of antibodies from the libraries.
Finally, our libraries contain antibody fragments in scFv format, which can easily undergo Antibody Reformatting and be produced as whole IgG, mini-antibody, Fab and other recombinant antibody formats.