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Human antigen binding proteins that bind β-Klotho, FGF receptors and complexes thereof

机译:结合β-Klotho,FGF受体及其复合物的人抗原结合蛋白

摘要

The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, 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.
机译:本发明提供了涉及或衍生自抗原结合蛋白的,活化FGF21介导的信号传导的组合物和方法。在实施方案中,抗原结合蛋白特异性结合(i)β-Klotho; (ii)FGFR1c,FGFR2c,FGFR3c或FGFR4; (iii)包含β-Klotho和FGFR1c,FGFR2c,FGFR3c和FGFR4之一的复合物。在一些实施方案中,抗原结合蛋白诱导FGF21样信号传导。在一些实施方案中,抗原结合蛋白是完全人的,人源化的或嵌合的抗体,此类抗体的结合片段和衍生物以及与(i)β-Klotho特异性结合的多肽。 (ii)FGFR1c,FGFR2c,FGFR3c或FGFR4; (iii)包含β-Klotho和FGFR1c,FGFR2c,FGFR3c和FGFR4之一的复合物。其他实施方案提供了编码此类抗原结合蛋白及其片段和衍生物的核酸,以及多肽,包含此类多核苷酸的细胞,制备此类抗原结合蛋白及其片段和衍生物的方法,多肽以及使用此类抗原结合蛋白的方法,其片段和衍生物以及多肽,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的受试者的方法。

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