METHODS FOR DIVERSIFYING ANTIBODIES, ANTIBODIES DERIVED THEREFROM AND USES THEREOF
    9.
    发明申请
    METHODS FOR DIVERSIFYING ANTIBODIES, ANTIBODIES DERIVED THEREFROM AND USES THEREOF 审中-公开
    用于分化抗体的方法,其衍生的抗体及其用途

    公开(公告)号:US20140121123A1

    公开(公告)日:2014-05-01

    申请号:US13882285

    申请日:2011-10-24

    IPC分类号: C12N15/10

    摘要: The invention provides methods of introducing diversity into antibody molecules comprising introducing or substituting at least one amino acid sequence in the CDR of the target antibody together with at least one amino acid in the FW region spanning the 3 amino acid adjoining the CRD on each side. The resulting diverse antibodies with variant CDRs and FW region sequences comprising diverse amino acid sequences are also described. These polypeptides regions, herein referred to as 3+CDR3+, that form the gist of the invention contribution described herein provide a flexible and simple source of sequence diversity that can be used as a source for expressing and identifying diverse antibodies or antigen binding polypeptides. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided. A method of producing diverse antibodies comprising amino acid substitutions in one of the CDR region and the FW region comprising 3 contiguous FW sequence amino acids adjacent to each CDR on either side is described herein. The substitutions are relative to database or germline sequences. Not all substitution are preserved in conservative regions.

    摘要翻译: 本发明提供了将多样性引入抗体分子的方法,包括在靶抗体的CDR中引入或取代至少一个氨基酸序列以及跨越与CRD相邻的3个氨基酸的FW区域中的至少一个氨基酸。 还描述了所得到的具有包含不同氨基酸序列的变体CDR和FW区序列的多种抗体。 形成本文所述发明要点的这些多肽区域(本文称为3 + CDR3 +)提供了可用作表达和鉴定多种抗体或抗原结合多肽的来源的灵活和简单的序列多样性来源。 还提供了包含多个这些多肽的文库。 此外,提供了用于产生和使用这些多肽和文库的方法和组合物。 本文描述了在包含与任一侧上的每个CDR相邻的3个连续的FW序列氨基酸的CDR区域和FW区域之一中产生包含氨基酸取代的多种抗体的方法。 替代是相对于数据库或种系序列。 并非所有替代都保留在保守区域。