At Absolute Antibody, our investors and scientific advisors have a long history in humanization dating back to the first humanized antibody Campath-1H in 1988. We deliver a panel of humanized variants from your clone, and guarantee to produce a variant with comparable activity to the parent. Our process also identifies variants with preferential manufacturing criteria (e.g. high expression, low aggregation). Get in touch for a quote.
100% success rate
No success, no fee
Scale up to grams of antibody
Scale out to 10s of variants
Delivery in as little as 8 weeks
- Sequencing if necessary (hybridoma sequencing or de novo protein sequencing)
- Modelling of the parent VH and VL domains
- Alignment with a panel of preferred human germline sequences
- Analysis of sequence liabilities and selection of de-risked frameworks
- Structure guided CDR grafting onto preferred germline backbones
- A minimum of 12 different humanized sequences generated
- Synthesis, cloning and small scale production of all humanized variants, original parent and chimeric controls
- Early stage manufacturability assessment: measurement of titre and aggregate content
- 8 weeks from receipt of sequence
- Humanization report detailing humanization strategy, sequences and antibody production analytics (measurement of titre and aggregate content)
- Small scale production (~1mg) of all humanized variants, original parent and chimeric controls
Contact us to discuss your project today.
Antibody humanization background information
The strive to reduce the immunogenicity of antibodies in the 1980s first led to the engineering of chimeric antibodies (1,2), consisting of human constant domains with the original non-human variable domains. Shortly after, this was followed by humanization (3) where complementarity determining regions (CDRs) from the original antibody were grafted on to a human variable domain framework. Crystal structures subsequently showed that selection of the appropriate human framework supports the CDRs in the correct orientation and minimizes affinity losses (4). Although the process of humanization, also referred to as antibody reshaping or germlining, has developed since this early work the concept remains much the same – namely to make the antibody more human-like and less immunogenic. It is now routine for all therapeutic antibodies originally derived from non-human sources (e.g. hybridomas) to undergo humanization as part of the antibody development pipeline. For more information on the background to humanization please refer to the Absolute Antibody resource section on humanization.
- Boulianne, G.L., Hozumi, N., and Shulman, M.J. (1984). Production of functional chimaeric mouse/human antibody. Nature 312, 643–646.
- Morrison, S.L., Johnson, M.J., Herzenberg, L.A., and Oi, V.T. (1984). Chimeric human antibody molecules: mouse antigen-binding domains with human constant region domains. Proc. Natl. Acad. Sci. U.S.A. 81, 6851–6855.
- Jones, P.T., Dear, P.H., Foote, J., Neuberger, M.S., and Winter, G. (1986). Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321, 522–525.
- Cheetham, G.M., Hale, G., Waldmann, H., and Bloomer, A.C. (1998). Crystal structures of a rat anti-CD52 (CAMPATH-1) therapeutic antibody Fab fragment and its humanized counterpart. J. Mol. Biol. 284, 85–99.