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    METHODS AND COMPOSITIONS USING FGF23 VARIANT POLYPEPTIDES
    2.
    发明申请
    METHODS AND COMPOSITIONS USING FGF23 VARIANT POLYPEPTIDES 审中-公开
    使用FGF23变体多糖的方法和组合物

    公开(公告)号：US20130122004A1

    公开(公告)日：2013-05-16

    申请号：US13743770

    申请日：2013-01-17

    Applicant: Novartis AG

    Inventor： David GLASS ,  Shou-Ih HU

    IPC: C07K14/50

    CPC classification number: C07K14/50 ,  A61K38/00 ,  A61K38/1825 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/30 ,  C07K2319/74 ,  C12N9/2402 ,  C12Y302/01031

    Abstract: The present disclosure is directed to methods, kits and compositions for preventing or treating age-related conditions or metabolic disorders. The fusion polypeptides of the disclosure include FGF23 or an active fragment thereof. In one embodiment, the fusion polypeptide comprises (a) a polypeptide comprising fibroblast growth factor 23 (FGF23), or a functionally active variant or derivative thereof, wherein FGF23 has a mutation at one or more of the positions Q156, C206 and C244; and (b) either a modified Fc fragment having decreased affinity for Fc-gamma-receptor and/or increased serum half-life, or a polypeptide comprising at least one extracellular subdomain of a Klotho protein, or a functionally active variant or derivative thereof; and, optionally (c) a linker. The Klotho fusion proteins are useful in the treatment and prevention of a variety of age-related conditions and metabolic disorders. In another embodiment, the fusion polypeptide comprises a FGF (such as FGF23), or a functionally active variant or derivative thereof and a modified Fc fragment, or a functionally active variant or derivative thereof. In various embodiments of the fusion polypeptides, FGF23 has mutations which decrease aggregation and protease-mediated cleavage.

    Abstract translation: 本公开涉及用于预防或治疗年龄相关病症或代谢紊乱的方法，试剂盒和组合物。 本公开的融合多肽包括FGF23或其活性片段。 在一个实施方案中，融合多肽包含（a）包含成纤维细胞生长因子23（FGF23）或其功能活性变体或衍生物的多肽，其中FGF23在一个或多个位置Q156，C206和C244处具有突变; 或（b）具有降低的对Fc-γ受体的亲和力和/或增加的血清半衰期的修饰的Fc片段或包含Klotho蛋白质的至少一个细胞外亚结构域的多肽或其功能活性变体或衍生物; 和（c）连接体。 Klotho融合蛋白可用于治疗和预防各种年龄相关病症和代谢紊乱。 在另一个实施方案中，融合多肽包含FGF（例如FGF23）或其功能活性变体或衍生物和修饰的Fc片段或其功能活性变体或衍生物。 在融合多肽的各种实施方案中，FGF23具有减少聚集和蛋白酶介导的切割的突变。

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