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IMMUNOGLOBULIN CONSTANT REGION DOMAINS WITH ENHANCED STABILITY
专利权人:
发明人:
申请号:
EP07755812.0
公开号:
EP2027154B1
申请日:
2007.04.20
申请国别(地区):
EP
年份:
2012
代理人:
摘要:
The invention provides an isolated polypeptide including an immunoglobulin CH3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution and exhibiting enhanced stability, including an enhanced folding rate, compared to an unsubstituted CH3 domain, wherein the at least one Pro to GIy substitution comprises CH3 residue Pro38 or a CH3 domain equivalent thereof. Multimeric complexes of an immunoglobulin CH3 region domain polypeptide, or functional fragment thereof, having at least one Pro to GIy substitution with a second immunoglobulin CH3 region domain polypeptide also are provided by the invention. The multimeric complexes can include antibodies, antibody functional fragments such as Fd, Fv, Fab, F(ab), F(ab)2, F(ab)2, single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies or minibody and other binding polypeptides having an immunoglobulin CH3 region domain polypeptide such as a peptibody or an Fc fusion polypeptide. An isolated population of polypeptides including a plurality of immunoglobulin CH3 region domain polypeptides, or functional fragments thereof, is further provided. Each CH3 region domain polypeptide within the populations includes at least one Pro to GIy substitution and exhibits enhanced stability, including an enhanced folding rate, compared to an unsubstituted CH3 domain, wherein the at least one Pro to GIy substitution comprises CH3 residue Pro38 or a CH3 domain equivalent thereof. The invention further provides a method of producing a multimeric binding polypeptide and a method of treating a pathological condition characterized by aberrant cell growth.La présente invention concerne un polypeptide isolé comprenant un polypeptide de domaine de région CH3 dimmunoglobuline, ou un fragment fonctionnel de celui-ci, comprenant au moins une substitution de Pro par Gly et ayant une stabilité améliorée, y compris un taux de repliement amélioré en comparaison avec un domaine CH3 non substi
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