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 from a new generation of human monoclonal antibody library 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 selection and expression of the whole fully human antibody molecule.
FULLY HUMAN MONOCLONAL ANTIBODY DISCOVERY.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). In addition, a proofreading process has enriched the library with open reading frame (ORF) antibody sequences and improved the library quality selecting soluble antibodies. This new generation of library of 3.4 billion clones is the higher quality library on the market with 94 % of clones encoding full-length and functional antibodies. The high rate of functional antibodies allow a rapid and successful screening in order to provide an even wider range of promising antibody drug candidates per target.
These new libraries are proposed to customers as a service/contracted work. This service/contracted work includes selecting fully human antibody candidates and their optimisation by directed molecular evolution (MutaGenâ„¢). The high potent products will be expressed in the format of a whole human antibody molecule ready to enter into clinical development.
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. Furthermore, an antibody can be identified by the DNA sequence thus strengthening its patent rights.
ANTIBODY GENETIC ENGINEERING. Optimization of immunological properties of the antibodies from our library or of mouse, rat or humanized antibodies. The isolated VH and VL fragments could be engineered to form a recombinant antibody. The antibody can be further engineered in a multitude of ways to produce antibody variants with lower immunogenicity, higher affinity 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 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.
Humanization, genetic engineering and evaluation of immunogenicity risk. To render mouse monoclonal antibodies suitable for human therapy, there is a requirement for antibody engineering. The antibody humanization is performed in collaboration with a Scottish partner, Accuro Biologics, holding extensive experience in this area. This partnership brings together MilleGen’s DME platform MutaGen™ and Accuro Biologics know-how and expertise in antibody humanization and T cell epitope identification. The collaboration has led to the generation of a new and innovative platform , MilleMAb, directed towards the development of therapeutic antibody candidates with superior and significantly enhanced properties.
