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    METHOD FOR MAKING HETEROMULTIMERIC POLYPEPTIDES
    4.
    发明申请
    METHOD FOR MAKING HETEROMULTIMERIC POLYPEPTIDES 失效
    制备异构多糖的方法

    公开(公告)号：US20100254986A1

    公开(公告)日：2010-10-07

    申请号：US12700618

    申请日：2010-02-04

    申请人： PAUL J. CARTER ,  LEONARD G. PRESTA ,  JOHN B. RIDGWAY

    发明人： PAUL J. CARTER ,  LEONARD G. PRESTA ,  JOHN B. RIDGWAY

    IPC分类号： A61K39/395 ,  C12P21/06 ,  C07K16/00 ,  C12N5/10

    CPC分类号： C07K16/468 ,  A61K38/00 ,  C07K14/70514 ,  C07K16/2809 ,  C07K16/46 ,  C07K19/00 ,  C07K2317/526 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention relates to a method of preparing heteromultimeric polypeptides such as bispecific antibodies, bispecific immunoadhesins and antibody-immunoadhesin chimeras. The invention also relates to the heteromultimers prepared using the method. Generally, the method involves introducing a protuberance at the interface of a first polypeptide and a corresponding cavity in the interface of a second polypeptide, such that the protuberance can be positioned in the cavity so as to promote heteromultimer formation and hinder homomultimer formation. “Protuberances” are constructed by replacing small amino acid side chains from the interface of the first polypeptide with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). The protuberance and cavity can be made by synthetic means such as altering the nucleic acid encoding the polypeptides or by peptide synthesis.

    摘要翻译： 本发明涉及制备异源多聚体多肽如双特异性抗体，双特异性免疫粘附素和抗体免疫粘附素嵌合体的方法。 本发明还涉及使用该方法制备的异源多聚体。 通常，该方法包括在第二多肽的界面中的第一多肽和相应空腔的界面处引入突起，使得突起可以位于空腔中，以促进异源多聚体形成并阻止同源多聚体形成。 通过用较大侧链（例如酪氨酸或色氨酸）从第一多肽的界面替代小的氨基酸侧链构建“突起”。 通过用较小的（例如丙氨酸或苏氨酸）代替大的氨基酸侧链，在第二多肽的界面中产生与突起相同或相似大小的补偿性“空腔”。 突起和空腔可以通过合成方式制备，例如改变编码多肽的核酸或通过肽合成。