Amgen Inc.

Susie Miki Harris

Ian Nevin Foltz

Jeonghoon Sun

Mark Leo Michaels

Seog Joon Han

Ji Lu

Yang Li

Chadwick Terence King

Randal Robert Ketchem

Shaw-Fen Sylvia Hu

Mei-Mei Tsai

Irwin Chen

Daniel Lu

Roger Fachini

Shilpa Sambashivan

Dora Toledo Warshaviak

Ian Driver

Marc W Retter

Ian Foltz

The present invention relates to antigen binding proteins, such as monoclonal antibodies, that specifically bind to and activate human triggering receptor expressed on myeloid cells-2 (TREM2) and pharmaceutical compositions comprising such antigen binding proteins. The agonist antigen binding proteins (e.g. antibodies) of the invention are capable of activating TREM2/DAP12 signaling in myeloid cells in the absence of Fc-mediated cross-linking of the antigen binding proteins. Methods of treating or preventing conditions associated with TREM2 loss of function, such as Alzheimer's disease and multiple sclerosis, using the antigen binding proteins are also described.

Anti-human TREM2 antibodies and uses thereof

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

Newbury Park, CA, United States of America

Susie Miki Harris