Antibody Affinity Maturation    



AFFINITY MATURATION OF RECOMBINANT ANTIBODIES BY DIRECTED MOLECULAR EVOLUTION TECHNOLOGY.

 Antibodies often need to be optimized in order to be used as a candidate product for diagnostics or therapeutics.

The antibody can be further engineered in a multitude of ways to produce antibody variants with lower immunogenicity, higher affinity and/or enhanced stability. Variable domains are engineered through MilleGen’s directed molecular evolution platform. 

The MutaGen™ system (patent WO 02387566) is a molecular evolution process that allows somatic hypermutation phenomenon mimicking, which is responsible for in vivo maturation of antibodies. The variable regions are cloned in an expression vector adapted for the mutagenesis step and screening. One cycle of MutaGen™  generates a library with a very high level of mutants and one or two cycles of MutaGen™  is often enough to obtain several optimised antibodies. The best binders characterised (ELISA, SPR) are compared to the parental monoclonal antibody.  Invented and patented (WO 02/387566) by MilleGen, MutaGen™, associated to a HTS platform (MutaScreen) and a computer modelling platform (MilleGate), is currently the only available molecular evolution technology on the market able to create the largest libraries, controllable diversity and in the shortest delays.


Through MutaGen™ technology, MilleGen proposes:

• Antibody engineering
  Antibody discovery (from our human libraries), antibody improvement for human, humanized and rodent antibodies, including humanization and immunogenicity profiling.
• Pharmaceutical proteins (new therapeutic targets) developed with pharmaceuticals and biotechnology partners, 

MutaGen™

MilleGen uses its proprietary MutaGen™ molecular evolution technology to generate large libraries of randomly mutated genes with a control of genetic diversity (patent WO 02387566; Mondon et al, Biotechnology J. 2007, 2:76-82; Emond et al,  Protein Eng. Des. Sel. 2008, 21:267-274). Based on an in vitro replication with « mutases », MutaGen™ technology provides a powerful and simple approach to carrying out in vitro protein optimisation.

MutaScreen

Millegen's expertise in screening processes and a robotic platform allows a fast high throughput screening of the mutants generated by the Mutagen™ system. The platform is adaptable according to the properties (affinity, activity, stability and/or specificity) to improve.

MilleGate

MilleGate combines our molecular evolution methods and bioinformatic tools and Databases to deliver additional values to the MutaGen™ technology strategies in the field of Antibody discovery.