Many monoclonal antibodies are discovered from non-human species. Of the 107 antibody-based therapeutics approved for use in the USA and/or Europe, approximately 15% are murine and 12% are chimeric. Because non-humanized antibodies and chimeras (human Fc backbone) are often highly immunogenic, the advent of human-antibody producing transgenic animals and humanization techniques can lower the risk of patient immunogenicity. Over 70% of the approved antibody therapeutics are fully human or humanized.
Curia has developed an efficient platform for complementarity-determining regions (CDR) grafting, which involves transferring the antibody (CDRs) into a proper human antibody framework while retaining its original affinity and specificity. Using Curia’s T20 Score Analyzer tool, users are able to calculate a monoclonal antibody humanness score to distinguish between human and non-human antibodies. If you are seeking both humanization and affinity maturation, the our HuMAT™ platform leverages our capabilities in CDR grafting and display discovery to offer a one-step antibody humanization and affinity maturation with time and cost savings, all while delivering consistent high-quality antibody leads.
Humanization workflow at Curia
|Sequence Analysis||Generate Humanized Variants||Variant Analysis|
|– Antibody sequence analysis and homology modeling of mAb 3D structure
– Identification of key positions supporting CDR loop and VH-VL interface
|– Design humanized variants (3VH, 3VL)
– Assess the humanness of the variants using the T20 Score Analyzer
– Construct and express nine humanized antibodies and chimeric version
|– Assess expression levels and measure antigen binding by direct ELISA
– Measure affinity by Octet, or competitive binding and compare to chimeric
Humanization and HuMAT™ projects are customizable and the number of molecules can be increased.