Recombinant antibodies    

Antibody discovery platform

MilleGen has developed and patented (5 patents) new and innovative technologies involved in each phase of the recombinant antibodies discovery process.

MilleGen's technology platform allows generation and high-affinity improvement of recombinant antibody candidates. Our team provides a whole range of skills from the cloning steps of antibody recombinant fragments to the expression of the whole fully human antibody molecule.

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Fully human monoclonal antibody. Using MutaGen™, its own  patented technology, MilleGen has genetically engineered human recombinant antibody libraries with high complexity (Mondon et al, Biotechnology J. 2007, 2:76-82. PMID: 17225253 and patent WO2007137616). These new libraries are proposed to customers as a service/contracted work. This service/contracted work includes selecting (display and intra-cellular screening technologies) fully human antibody candidates and their optimisation by directed molecular evolution (MutaGen™). The high potent products will be expressed in the format of a whole human antibody molecule (patent WO2007135515) ready to enter into clinical development.

Directed molecular evolution of the antibodies. Variable domains could be 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 MutaGen™ technology allows to generate random mutations on the variable region (VH and VL) and select an antibody with a higher affinity. With this technique, antibody affinity maturation can be obtained without any structural interaction information of the antigen-antibody complex.

Antibody cloning and sequencing. MilleGen proposes to clone and sequence the variable genes of the heavy (VH) and light (VL) chains of rodent (mouse and rat) monoclonal immunoglobulin starting from hybridoma cell lines. The sequencing of the VH and VL retains and immortalizes the mAb which can be crucial for the rescue of unstable hybridoma cell lines.

Antibody engineering. The isolated VH and VL fragments could be engineered to form a recombinant antibody. The test of the binding properties of the recombinant antibody fragment provides a tool to validate the VH and VL sequences. The antibody domains can be further engineered in a multitude of ways to produce antibody variants with lower immunogenicity, higher affinity or enhanced stability. 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 two cycles of MutaGen™  is often enough to obtain several optimised antibodies.