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    Variants of vascular endothelial cell growth factors having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids
    129.
    发明申请
    Variants of vascular endothelial cell growth factors having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids 审中-公开
    具有拮抗性质的血管内皮细胞生长因子的变体，编码它们的核酸和包含这些核酸的宿主细胞

    公开(公告)号：US20040152636A1

    公开(公告)日：2004-08-05

    申请号：US10793094

    申请日：2004-03-03

    Applicant: Genentech, Inc.

    Inventor： Bruce A. Keyt ,  Francis Hung Nguyen ,  Napoleone Ferrara

    IPC: A61K038/18 ,  C07K014/475

    CPC classification number: A61K38/1866 ,  C07K14/52

    Abstract: The present invention involves the preparation of vascular endothelial growth factor (VEGF) antagonist molecules comprising variant VEGF polypeptides which are capable of binding to and occupying cell surface VEGF receptors without inducing a VEGF response, thereby antagonizing the biological activity of the native VEGF protein. Specifically, the variant VEGF polypeptides of the present invention comprise modifications of at least one cysteine residue in the native VEGF sequence, thereby inhibiting the ability of the variant polypeptide to dimerize through the formation of disulfide bonds. The present invention is further directed to methods for preparing such variant VEGF antagonists and to methods, compositions and assays utilizing such variants for producing pharmaceutically active materials having therapeutic and pharmacologic properties that differ from the native VEGF protein.

    Abstract translation: 本发明涉及制备包含变体VEGF多肽的血管内皮生长因子（VEGF）拮抗剂分子，其能够结合并占据细胞表面VEGF受体而不诱导VEGF应答，从而拮抗天然VEGF蛋白的生物学活性。 具体地，本发明的变体VEGF多肽包含天然VEGF序列中至少一个半胱氨酸残基的修饰，从而通过形成二硫键来抑制变体多肽二聚的能力。 本发明还涉及制备这种变体VEGF拮抗剂的方法以及利用这些变体产生具有不同于天然VEGF蛋白的治疗和药理学性质的药物活性物质的方法，组合物和测定法。

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