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Humanized Antibody Germinalization Service

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Humanized Antibody Germinalization ServiceFig. 1 The structure of humanized recombinant Fab (left) and superposition in tube representation of two Fabs (right). (Robert et al. 2010)

Creative Biolabs has established the GHA® platform to germinalize humanized antibodies. Antibody humanization followed by germinalization produces human antibodies with excellent germinality index (GI). Human antibodies optimized from this platform are almost equivalent to mature human antibodies in sequence and have minimal immunogenicity, while retaining parental affinity and specificity.

Many antibody therapeutics are developed based on the humanization of antibodies raised in various species, therefore a humanized antibody usually remains a few non-human residues, especially in CDR regions which are essential for antigen recognition. However, the majority of the non-human residues in both CDR (and FR) regions are still immunogenic in humans. Also, engineered human antibodies with over 10% non-germline mutations often carry potential risks in generating more side effects; our state-of-the-art humanized antibody sequence germinalization strategies propose utmost amino acid substitutions to reduce immunogenicity yet with the affinity remained. Using in silico germinalization analyses, potential substitution residues on VL and VH (FR and CDR) will be identified and subsequently a mutant library with extensive germinalization will be constructed, combined with our unparalleled expertise in phage display library screening, the best lead candidates will be selected, purified and thoroughly characterized.

Humanized Antibody Germinalization Service

Antibodies derived from monkeys and other NHP (non-human primates) are of the most similarity in sequence to human antibodies. As a result, humanized NHP antibodies are the easiest ones to be further germinalized to have the highest germinality index (GI). For this reason, monoclonal antibodies raised in NHP (non-human primates) potentially have the lowest risk when developed into therapeutics for human use. We have strong expertise in monoclonal NHP (non-human Primates) antibody production, and we are particularly experienced in performing in-depth humanization for monoclonal antibodies raised in NHP (non-human primates). Germinalization of humanized NHP antibodies can deliver human antibodies with about 95% homology to the human germinal antibody sequences. 

Reference
Robert, R., Streltsov, V. A., Newman, J., Pearce, L. A., Wark, K. L. and Dolezal, O. (2010) 'Germline humanization of a murine Aβ antibody and crystal structure of the humanized recombinant Fab fragment', Protein Science, 19(2), 299-308.




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