Human FGF receptor and β-Klotho binding proteins
    1.
    发明授权
    Human FGF receptor and β-Klotho binding proteins 有权
    人FGF受体和β-Klotho结合蛋白

    公开(公告)号:US09517264B2

    公开(公告)日:2016-12-13

    申请号:US13641041

    申请日:2011-04-13

    摘要: The present invention provides compositions and methods relating to or derived from antigen binding proteins and antigen binding protein-FGF21 fusions that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins and antigen binding protein-FGF21 fusions induce FGF21-like signaling. In some embodiments, an antigen binding protein or antigen binding protein-FGF21 fusion antigen binding component is a fully human, humanized, or chimeric antibody, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to β-Klotho, or β-Klotho and one or more of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins and antigen binding protein-FGF21 fusions, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins and antigen binding protein-FGF21 fusions, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

    摘要翻译: 本发明提供与抗原结合蛋白和特异性结合β-Klotho或β-Klotho以及FGFR1c,FGFR2c,FGFR3c和FGFR4中的一种或多种的抗原结合蛋白和抗原结合蛋白-FGF21融合相关或衍生的组合物和方法。 在一些实施方案中,抗原结合蛋白和抗原结合蛋白FGF21融合物诱导FGF21样信号传导。 在一些实施方案中,抗原结合蛋白或抗原结合蛋白FGF21融合抗原结合组分是完全人,人源化或嵌合抗体,所述抗体的结合片段和衍生物,以及特异性结合β-Klotho或β- Klotho和FGFR1c,FGFR2c,FGFR3c和FGFR4中的一种或多种。 其他实施方案提供编码这种抗原结合蛋白和抗原结合蛋白-FGF21融合体的核酸,及其片段和衍生物,以及多肽,包含这种多核苷酸的细胞,制备这种抗原结合蛋白的方法和抗原结合蛋白-FGF21融合物, 其衍生物和多肽,以及使用这种抗原结合蛋白和抗原结合蛋白-FGF21融合体,其片段和衍生物和多肽的方法,包括治疗或诊断患有2型糖尿病,肥胖症,NASH,代谢综合征和 相关疾病或病症。

    FGF21 mutants multimers and uses thereof
    6.
    发明授权
    FGF21 mutants multimers and uses thereof 有权
    FGF21突变体多聚体及其用途

    公开(公告)号:US08618053B2

    公开(公告)日:2013-12-31

    申请号:US13463731

    申请日:2012-05-03

    CPC分类号: C07K14/50 A61K38/00

    摘要: The invention provides a multimer comprising at least a first and a second chain, the first chain comprising the polypeptide of SEQ ID NO:4, wherein the leucine at position 98 is substituted with an arginine; the proline at position 171 is substituted with glycine; and the alanine at position 180 is substituted with glutamic acid; a linker sequence comprising SEQ ID NO:31; and an Fe domain comprising SEQ NO:11; and a second chain comprising the polypeptide of SEQ ID NO:4, wherein the leucine at position 98 is substituted with an arginine; the proline at position 171 is substituted with glycine; and the alanine at position 180 is substituted with glutamic acid; a linker sequence comprising SEQ ID NO:31; and an Fe domain comprising SEQ ID NO:11, nucleic acids encoding the multimer, pharmaceutical compositions comprising the multimer and methods for treating metabolic disorders using such nucleic acids, multimers or pharmaceutical compositions.

    摘要翻译: 本发明提供包含至少第一和第二链的多聚体,所述第一链包含SEQ ID NO:4的多肽,其中98位的亮氨酸被精氨酸取代; 位置171的脯氨酸被甘氨酸取代; 位置180处的丙氨酸被谷氨酸取代; 包含SEQ ID NO:31的接头序列; 和包含SEQ ID NO:11的Fe结构域; 和包含SEQ ID NO:4的多肽的第二链,其中98位的亮氨酸被精氨酸取代; 位置171的脯氨酸被甘氨酸取代; 位置180处的丙氨酸被谷氨酸取代; 包含SEQ ID NO:31的接头序列; 和包含SEQ ID NO:11的Fe结构域,编码多聚体的核酸,包含多聚体的药物组合物和使用这种核酸,多聚体或药物组合物治疗代谢紊乱的方法。