Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof
申请人:Diversa Corporation
公开号:US20030219752A1
公开(公告)日:2003-11-27
The invention is directed to methods for generating sets, or libraries, of nucleic acids encoding antigen-binding sites, such as antibodies, antibody domains or other fragments, including single and double stranded antibodies, major histocompatibility complex (MHC) molecules, T cell receptors (TCRs), and the like. This invention provides methods for generating variant antigen binding sites, e.g., antibodies and specific domains or fragments of antibodies (e.g., Fab or Fc domains), by altering template nucleic acids including by saturation mutagenesis, synthetic ligation reassembly, or a combination thereof. In one aspect, invention provides methods for generating all human or humanized antibodies and evolving them to achieve optimized properties related to stability, duration, expression, production, enzymatic activity, affinity, avidity, localization, and other immunological properties. Polypeptides generated by these methods can be analyzed using a novel capillary array platform, which provides unprecedented ultra-high throughput screening.
本发明涉及生成编码抗原结合位点(如抗体、抗体结构域或其他片段,包括单链和双链抗体、主要组织相容性复合体(MHC)分子、T细胞受体(TCR)等)的核酸集或核酸库的方法。本发明提供了通过改变模板核酸(包括饱和诱变、合成连接重组或它们的组合)来产生变体抗原结合位点的方法,例如抗体和抗体的特定结构域或片段(如 Fab 或 Fc 结构域)。在一个方面,本发明提供了生成全人源或人源化抗体的方法,并使其进化以获得与稳定性、持续时间、表达、生产、酶活性、亲和力、亲和性、定位和其他免疫学特性相关的优化特性。通过这些方法生成的多肽可使用新型毛细管阵列平台进行分析,该平台可提供前所未有的超高通量筛选。