Antibody engineering & humanisation

Extensive expertise in antibody engineering

GTP has managed hundreds of antibody engineering and production projects. Our services cover the production of classical monoclonal antibodies as well as the expression and purification of modified antibodies such as antibody fusion proteins, bispecific antibodies, and antibody fragments (ScFv, VHH, Fab, minibodies…). Our antibody engineering expertise includes:

• Hybridoma sequencing
• Isotype, subtype and/or species switching
• Reformatting
• Humanisation
• Bispecific antibodies design (knobs-into-holes)

Humanisation by CDR grafting

Antibody humanisation is crucial in the development of your therapeutic antibody. If addressed in a proper way, it will increase the chances of success of your antibody development programme, by obtaining a safe and effective antibody with improved developability.

The most common antibody humanisation method is CDR grafting, the transplantation of CDRs from the original antibody into a human framework. However, this process is not as simple as transplanting murine CDRs directly onto the most homologous human backbone (see our blog article “Everything you always wanted to know about Antibody Humanisation”). Indeed, some parental residues which are critical in maintaining the function of the antibody need to be conserved.

A successful humanisation process therefore requires a strong experience in identifying the CDRs boundaries and in selecting a human framework as well as residues to substitute from the parental mAb into the human framework regions (back mutations).

Comprehensive humanization services

GTP proposes a CDR grafting antibody humanisation offer in partnership with experts with over 25 years' experience and a successful track record in antibody engineering and development.

Our offer is based on a two-round improved humanisation process involving a combination of CDR grafting, in silico molecular modelling and framework sequences optimisation.

Through this humanisation process, we deliver an antibody sequence compliant with the WHO guidelines for humanised antibodies, but also aim to provide an antibody with improved manufacturability and affinity.

Our humanisation service includes the following activities:

• Production and characterisation of the chimeric antibody
• Antibody humanisation:

               -Selection of the most adapted framework sequences,

               -Identification of critical parental antibody residues

• Antibody structure modeling
• Sequence optimisation for improved manufacturability
• Expression and characterisation of humanised variants for selection of a lead sequence