GFRalpha3 and its uses

Abstract

The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, vectors and host cells expressing, and immunoadhesions and antibodies to mammalian GFRα3, a novel α-subunit receptor of the GDNF (i.e. GFR) receptor family. It further relates to an assay for measuring activation of an α-subunit receptor by detecting tyrosine kinase receptor activation (i.e., autophosphorylation) or other activities related to ligand-induced α-subunit receptor homo-dimerization or homo-oligomerization.

1 - 22 . (canceled)  
     
     
         23 . An antibody which specifically binds to GFRα3 polypeptide comprising amino acids 84 to 329 of SEQ ID NO: 17.  
     
     
         24 . The antibody of  claim 23  that is an agonist antibody.  
     
     
         25 . The use of the antibody of  claim 23  to treat a neuronal disorder involving the peripheral nervous system.  
     
     
         25 - 66 . (canceled)  
     
     
         67 . The antibody of  claim 23  that specifically binds to GFRα3 polypeptide that is a monoclonal antibody.  
     
     
         68 . The use of  claim 25 , wherein the neuronal disorder involving the peripheral nervous system that is treated is selected from the group of disorders consisting of peripheral neuropathies, neuropathic pain, non-neuropathic chronic pain, dysfunctions of the autonomic nervous system, post-herpetic neuralbia, shingles, asthma, irritable bowel, inflammatory bowel, constipation, cystitis, headache, migraine, arthritis, spinal cord injury, chronic back pain, hypertension, mucositis, dry mouth, dry eyes, fibromyalgia, and wound healing.  
     
     
         69 . The use of  claim 68 , wherein the neuronal disorder that is treated is a peripheral neuropathy.  
     
     
         70 . The use of  claim 69 , wherein the peripheral neuropathy to be treated is a peripheral neuropathy selected from the group of peripheral neuropathies consisting of a peripheral neuropathy associated with diabetes, a peripheral neuropathy associated with human immunodeficiency virus (HIV), and a peripheral neuropathy associated with chemotherapeutic agent treatments.  
     
     
         71 . The use of  claim 68 , wherein the neuronal disorder that is treated is a dysfunction of the autonomic nervous system.  
     
     
         72 . The use of  claim 70 , wherein the neuronal disorder involving the peripheral nervous system to be treated is a dysfunction of the autonomic nervous system selected from the group of consisting of a dysfunction of the autonomic nervous system selected from the group consisting of disturbances of blood pressure, disturbances of cardiac rhythm, disturbances of gastrointestinal function, impotence, and urinary incontinence.  
     
     
         73 . The use of  claim 68 , wherein the neuronal disorder involving the peripheral nervous system is non-neuropathic chronic pain.  
     
     
         74 . The use of  claim 73 , wherein the non-neuropathic chronic pain is associated with an inflammatory state.  
     
     
         75 . The antibody of  claim 23  which specifically binds to GFRα3 polypeptide comprising amino acids 27 to 369 of SEQ ID NO: 17.  
     
     
         76 . The antibody of  claim 75  that is a monoclonal antibody.  
     
     
         77 . The use of the antibody of  claim 75  to treat a neuronal disorder involving the peripheral nervous system.  
     
     
         78 . The use of  claim 77 , wherein the neuronal disorder involving the peripheral nervous system that is treated is selected from the group of disorders consisting of peripheral neuropathies, neuropathic pain, non-neuropathic chronic pain, dysfunctions of the autonomic nervous system, post-herpetic neuralbia, shingles, asthma, irritable bowel, inflammatory bowel, constipation, cystitis, headache, migraine, arthritis, spinal cord injury, chronic back pain, hypertension, mucositis, dry mouth, dry eyes, fibromyalgia, and wound healing.