NOGO Receptor Antagonists

Abstract

Disclosed are immunogenic Nogo receptor-1 polypeptides, Nogo receptor-1 antibodies, antigen-binding fragments thereof, soluble Nogo receptors and fusion proteins thereof and nucleic acids encoding the same. Also disclosed are Nogo receptor antagonist polynucleotides. Also disclosed are compositions comprising, and methods for making and using, such Nogo receptor antibodies, antigen-binding fragments thereof, soluble Nogo receptors and fusion proteins thereof, nucleic acids encoding the same and antagonist polynucleotides.

1 - 127 . (canceled) 
     
     
         128 . An isolated polypeptide comprising:
 (a) an amino acid sequence identical to a reference amino acid sequence except that at least one cysteine residue of said reference amino acid sequence is substituted with a different amino acid, wherein said reference amino acid sequence is selected from the group consisting of:
 (i) amino acids a to 445 of SEQ ID NO:49, 
 (iii) amino acids 27 to b of SEQ ID NO:49, and 
 (iii) amino acids a to b of SEQ ID NO:49, 
   wherein a is any integer from 25 to 35, and b is any integer from 300 to 450; and   (b) a heterologous polypeptide;   wherein said polypeptide inhibits nogo-receptor-mediated neurite outgrowth inhibition   wherein the one or more cysteine residues to be substituted are selected from: the cysteine residue corresponding to the cysteine residue found at amino acid 266 of SEQ ID NO:49 (C266); the cysteine residue corresponding to the cysteine residue found at amino acid 309 of SEQ ID NO:49 (C309); or the cysteine residue corresponding to the cysteine residue found at amino acid 335 of SEQ ID NO:49 (C335); or combinations thereof.   
     
     
         129 . The polypeptide of  claim 128 , wherein C266 and C309 of said reference amino acid sequence are substituted with different amino acids. 
     
     
         130 . The polypeptide of  claim 128 , wherein C309 and C335 of said reference amino acid sequence are substituted with different amino acids. 
     
     
         131 . The polypeptide of  claim 128 , wherein said different amino acid is alanine. 
     
     
         132 . The polypeptide of  claim 128 , wherein said heterologous polypeptide is selected from the group consisting of:
 (a) serum albumin,   (b) an Fc region,   (c) a signal peptide,   (d) a polypeptide tag, and   (e) a combination of two or more of said heterologous polypeptides.   
     
     
         133 . The polypeptide of  claim 132 , wherein said heterologous polypeptide is an Fc region. 
     
     
         134 . The polypeptide of  claim 133 , wherein said Fc region is selected from the group consisting of: an IgA Fc region; an IgD Fc region; an IgG Fc region, an IgE Fc region; and an IgM Fc region. 
     
     
         135 . The polypeptide of  claim 134 , wherein said Fc region is an IgG Fc region. 
     
     
         136 . The polypeptide of  claim 133 , wherein said polypeptide tag is selected from the group consisting of: FLAG tag; Strep tag; poly-histidine tag; VSV-G tag; influenza virus hemagglutinin (HA) tag; and c-Myc tag. 
     
     
         137 . The polypeptide of  claim 128 , wherein said polypeptide is attached to one or more polyalkylene glycol moieties. 
     
     
         138 . The polypeptide of  claim 137 , wherein said one or more polyalkylene glycol moieties is a polyethylene glycol (PEG) moiety. 
     
     
         139 . The polypeptide of  claim 138 , wherein said polypeptide is attached to 1 to 5 PEG moieties.