Uses of GDNF and GDNF receptor
AssigneeGenentech, Inc.
InventorsRobert Klein, Mark Moore, Arnon Rosenthal, Anne Ryan
Life of this patent
Estimating the term…
Abstract
GDNFRα, GDNFRα extracellular domain (ECD), GDNFRα variants, chimeric GDNFRα (e.g., GDNFRα immunoadhesin), and antibodies which bind thereto (including agonist and neutralizing antibodies) are disclosed. Various uses for these molecules are described, including methods to modulate cell activity and survival by response to GDNFRα-ligands, for example GDNF, by providing GDNFRα to the cell. Also provided are methods for using GDNFRα, GDNF, or agonists thereof, separately or in complex, to treat kidney diseases.
Claims12
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a Glial-Derived Neurotrophic Factor Receptor α (GDNFRα) polypeptide selected from the group of polypeptides consisting of:
- an isolated GDNFRα polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2;
- an isolated GDNFRα polypeptide comprising an amino acid sequence having at least 99% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2;
- and
- an isolated GDNFRα polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2, and comprising the GDNFRα extracellular domain sequence as set out between amino acids Asp25 and Gly427 of SEQ ID NO:
- 2;
- wherein said polypeptide is capable of binding Glial-Derived Neurotrophic Factor (GDNF) and activating Ret tyrosine kinase.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a chimeric polypeptide selected from the group of chimeric polypeptides consisting of:
- a chimeric polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2, fused, at its C-terminus to the N-terminus of an immunoglobulin heavy chain constant domain sequence;
- a chimeric polypeptide comprising an amino acid sequence having at least 99% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2, fused, at its C-terminus to the N-terminus of an immunoglobulin heavy chain constant domain sequence;
- and
- a chimeric polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence as set out between amino acids Asp25 and Ser468 of SEQ ID NO:
- 2, and comprising the GDNFRα extracellular domain sequence as set out between amino acids Asp25 and Gly427 of SEQ ID NO:
- 2, fused, at its C-terminus to the N-terminus of an immunoglobulin heavy chain constant domain sequence;
- wherein said chimeric polypeptide is capable of binding GDNF and activating Ret tyrosine kinase.
Dependencies are inferred from the claim text.