HARDING FIONA A.,AKAMATSU YOSHIKO,DUBRIDGE ROBERT B.,POWERS DAVID B.
申请号：
CO11179622
公开号：
CO6480962A2
申请日:
2011.12.28
申请国别(地区):
CO
年份:
2012
代理人:
摘要：
This Disclosure relates to variants of the anti VEGF monoclonal antibody bevacizumab with reduced immunogenicity and / or Enhanced Affinity towards VEGF compared with bevacizumab and ranibizumab.Bevacizumab has three CDRs of the heavy chain, called here (in order from the carboxy terminal amino) - CDR CdR H1, H2 and H3 cor - and three CDRs of the light chain, called here (in order from the carboxy terminal amino) - CDR - L1, L2 and L3 Cor cor -.The sequences of the CDRs of bevacizumab are shown in Figures 1A and 1B, and their numbering is presented in Table 1 (for the CDRs of the heavy chain) and Table 2 (for the CDRs of the light chain). Ranibizumab, a monoclonal antibody, was generated by the Affinity maturation of bevacizumab.Ranibizumab has sequences Cor cor - L1, L2, L3 and Cor cor - H2 identical to bevacizumab, but varies in its sequences of cor Cor H1 and H3 of bevacizumab. The sequences of the heavy and light chains of ranibizumab are shown in Figure 1C, and the CDRs are shown in Figure 1D.The Antibodies of the Disclosure generally have at least one amino acid Substitution in at least one of heavy chain CDR compared with bevacizumab and ranibizumab.La presente divulgación se refiere a variantes del anticuerpo anti-VEGF bevacizumab con inmunogenicidad reducida y/o afinidad mejorada hacia VEGF, en comparación con bevacizumab o ranibizumab. Bevacizumab tiene tres CDRs de la cadena pesada, denominadas aquí (en orden desde el terminal amino al carboxi) CDR-H1, CDR-H2 y CDR-H3, y tres CDRs de la cadena liviana, denominadas aquí (en orden desde el terminal amino al carboxi) CDR-L1, CDR-L2 y CDR-L3. Las secuencias de las CDRs de bevacizumab se muestran en las Figuras 1A y 1B, y su numeración se presenta en la Tabla 1 (para las CDRs de la cadena pesada) y la Tabla 2 (para las CDRs de la cadena liviana). Un anticuerpo relacionado, ranibizumab, fue generado por maduración de la afinidad de bevacizumab. Ranibizumab tiene las secuencias de CDR-L1, CDR-L2, CDR-L3 y CDR-H
