Amgen Inc.

Seog Joon Han

Jeonghoon Sun

Mark Leo Michaels

Susie Miki Harris

Ji Lu

Yang Li

Ian Nevin Foltz

Chadwick Terence King

Randal Robert Ketchem

Shaw-Fen Sylvia Hu

Mei-Mei Tsai

Marc W Retter

Roger Fachini

Susie M Harris

Described herein are variant Fc-fragments that contain an insertion within or adjacent to a loop that bind to the neonatal Fc receptor (FcRn) with higher affinity and/or higher binding activity at pH 5-6 and approximately the same or lower affinity at a physiologic pH as compared to a control Fc-fragment, that is, little or no binding activity at a physiologic pH. Also described are variant Fc-polypeptides that comprise these variant Fc-fragments. Further described are methods of making and identifying such Fc-fragments and methods for making and using such Fc-polypeptides.

Variant Fc-polypeptides with enhanced binding to the neonatal Fc receptor

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 &#x3b2;-Klotho, or &#x3b2;-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 &#x3b2;-Klotho, or &#x3b2;-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.

Human FGF receptor and &#x3b2;-Klotho binding proteins

Growing community of inventors

Simi Valley, CA, United States of America

Seog Joon Han