Nucleotide and protein sequences of Nogo genes and methods based thereon

Abstract

The present invention relates to the gene, $i(Nogo), its encoded protein products, as well as derivatives and analogs thereof. Production of Nogo proteins, derivatives, and antibodies is also provided. The invention further relates to therapeutic compositions and methods of diagnosis and therapy.

1 . A binding molecule, which immunospecifically binds to a fragment of a protein, wherein said protein has an amino acid sequence of at least 90% identity to the amino acid sequence of SEQ ID NO:29, wherein said fragment consists of at least 10 amino acids of an amino acid sequence selected from the group consisting of: SEQ ID NO:45, amino acids 183-989 of SEQ ID NO:29, amino acids residues 132-939 of SEQ ID NO:29, or amino acids 206-501 of SEQ ID NO:29, wherein said fragment inhibits spreading of PC12 cells. 
     
     
         2 . The binding molecule of  claim 1 , wherein said fragment consists of at least 17 amino acids of an amino acid sequence selected from the group consisting of: SEQ ID NO:45, amino acid residues 183-989 of SEQ ID NO:29, amino acids residues 132-939 of SEQ ID NO:29, or amino acids 206-501 of SEQ ID NO:29. 
     
     
         3 . The binding molecule of  claim 2 , wherein said fragment consists of has an amino acid sequence selected from the group consisting of: SEQ ID NO:45, amino acids 183-989 of SEQ ID NO:29, amino acid residues 183-731 of SEQ ID NO:29, amino acids residues 132-939 of SEQ ID NO:29, or amino acids 206-501 of SEQ ID NO:29. 
     
     
         4 . The binding molecule of any one of  claims 1 - 3 , wherein said fragment is a synthetic peptide. 
     
     
         5 . The binding molecule of any one of  claims 1 - 3 , which is a monoclonal antibody. 
     
     
         6 . The binding molecule of any one of  claims 1 - 3 , which is a polyclonal antibody. 
     
     
         7 . The binding molecule of  claim 5 , wherein said antibody is selected from the group consisting of: a human antibody, a chimeric antibody, a single chain antibody, a Fab-fragment, a Fab′ fragment, an Fv-fragment, or an F(ab′) 2  fragment of an antibody. 
     
     
         8 . The binding molecule of  claim 6 , wherein said antibody is a human antibody. 
     
     
         9 . A composition comprising a binding molecule of any one of  claims 1 - 3 , and a carrier. 
     
     
         10 . A pharmaceutical composition comprising a binding molecule of any one of  claims 1 - 3 , and a pharmaceutically acceptable carrier. 
     
     
         11 . A method for treating damage to the central nervous system comprising administering to a subject in need thereof, a therapeutically effective amount of the binding molecule of any one of  claims 1 - 3 . 
     
     
         12 . A method for promoting plasticity of the central nervous system comprising administering to a subject in need thereof, a therapeutically effective amount of the binding molecule of any one of  claims 1 - 3 . 
     
     
         13 . A method for inducing regeneration of sprouting neurons comprising administering to a subject in need thereof, a therapeutically effective amount of the binding molecule of any one of  claims 1 - 3 . 
     
     
         14 . The method of  claim 11 , wherein said subject is human. 
     
     
         15 . The method of  claim 12 , wherein said subject is human. 
     
     
         16 . The method of  claim 13 , wherein said subject is human.