Engineered rabbit antibody variable domains and uses thereof

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/00 (2006.01)

Patent

CA 2685213

The present invention relates to methods for screening and producing polypeptides that immunospecifically bind to an antigen, which : polypeptides comprise binding domains that are derived from rabbit immunoglobulin. Using rabbit antibody heavy-chain or light-chain scaffolds, the methods of the invention allow identification of novel CDR loops and framework regions that confer enhanced stability and/or affinity to isolated immunoglobulin variable domains, in particular, relative to those derived from rodent antibodies. The enhanced stability and/or affinity of the variable domains of the invention permit their use in the production research tools or therapeutic immunospecific polypeptides, including single domain immunospecific polypeptides, i.e., comprising one of a VH or VL domain.

La présente invention concerne des procédés de criblage et de production de polypeptides qui se lient de manière immunospécifique à un antigène, lesdits polypeptides comprenant des domaines de liaison provenant de l'immunoglobuline de lapin. Grâce à l'utilisation des structures de chaîne lourde ou légère d'anticorps de lapin, les procédés de l'invention permettent d'identifier de nouvelles boucles CDR et de nouvelles régions cadre qui confèrent une stabilité et/ou une affinité accrues aux domaines variables d'immunoglobuline isolés, notamment, par rapport à ceux provenant d'anticorps de rongeurs. La stabilité et/ou l'affinité accrues des domaines variables de l'invention permettent d'utiliser ces derniers dans des outils de recherche de production ou des polypeptides immunospécifiques aux fins thérapeutiques, y compris des polypeptides immunospécifiques à domaine unique, à savoir, qui renferment un domaine VH ou VL.

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