Composition Comprising Antibodies to LINGO or Fragments Thereof

Abstract

Endogenous LINGO-1 is a negative regulator for neuronal survival, axon regeneration, oligodendrocyte differentiation and myelination. Molecules that block endogenous LINGO-1 function, such anti-LINGO-1 antibodies can be used as therapeutics for the treatment of neuron and oligodendrocyte dysfunction. The present invention provides antibodies specific for LINGO-1, and methods of using such antibodies as antagonists of endogenous LINGO-1 function. The invention further provides specific hybridoma and phage library-derived monoclonal antibodies, nucleic acids encoding these antibodies, and vectors and host cells comprising these antibodies. The invention further provides methods of promoting oligodendrocyte survival and myelination in a vertebrate, comprising administering to a vertebrate in need of such treatment an effective amount of an anti-LINGO-1 antibody

1 - 62 . (canceled) 
     
     
         63 . An isolated polynucleotide comprising a nucleic acid encoding an immunoglobulin light chain variable region (VL), wherein the CDR1, CDR2, and CDR3 regions of said VL comprise the sequences of SEQ ID NOs: 10, 11 and 12, and wherein an antibody or antigen-binding fragment thereof comprising said VL specifically binds to LINGO-1. 
     
     
         64 - 222 . (canceled) 
     
     
         222 . The polynucleotide of  claim 63 , wherein the VL comprises the sequence of SEQ ID NO:9. 
     
     
         223 . A vector comprising the polynucleotide of  claim 63 . 
     
     
         224 . A vector comprising the polynucleotide of  claim 222 . 
     
     
         225 . The polynucleotide of  claim 63 , wherein the nucleic acid encoding the VL is a cDNA. 
     
     
         226 . The polynucleotide of  claim 222 , wherein the nucleic acid encoding the VL is a cDNA. 
     
     
         227 . A host cell comprising the polynucleotide of  claim 63 , wherein the host cell further comprises a nucleic acid encoding an immunoglobulin heavy chain variable region (VH), wherein the CDR1, CDR2, and CDR3 regions of said VH comprise the sequences of SEQ ID NOs: 2, 3 and 4. 
     
     
         228 . A host cell comprising the polynucleotide of  claim 222 . 
     
     
         229 . A host cell comprising the vector of  claim 223 , wherein the host cell further comprises a nucleic acid encoding a VH, wherein the CDR1, CDR2, and CDR3 regions of said VH comprise the sequences of SEQ ID NOs: 2, 3 and 4. 
     
     
         230 . The host cell of  claim 229 , wherein the nucleic acid encoding the VH is present in the same vector as the nucleic acid encoding the VL. 
     
     
         231 . The host cell of  claim 229 , wherein the nucleic acid encoding the VH is present in separate vector than the nucleic acid encoding the VL. 
     
     
         232 . A host cell comprising the vector of  claim 224 . 
     
     
         233 . The host cell of  claim 232 , wherein the host cell further comprises a nucleic acid encoding a VIA comprising the sequence of SEQ ID NO:1. 
     
     
         234 . The host cell of  claim 233 , wherein the nucleic acid encoding the VH is present in the same vector as the nucleic acid encoding the VL. 
     
     
         235 . The host cell of  claim 233 , wherein the nucleic acid encoding the VH is present in separate vector than the nucleic acid encoding the VL. 
     
     
         236 . A method of producing an anti-LINGO-1 antibody or an antigen-binding fragment thereof, comprising culturing the host cell of  claim 227 , and recovering said antibody or antigen-binding fragment. 
     
     
         237 . A method of producing an anti-LINGO-1 antibody or an antigen-binding fragment thereof, comprising culturing the host cell of  claim 229 , and recovering said antibody or antigen-binding fragment. 
     
     
         238 . A method of producing an anti-LINGO-1 antibody or an antigen-binding fragment thereof, comprising culturing the host cell of  claim 233 , and recovering said antibody or antigen-binding fragment. 
     
     
         239 . The polynucleotide of  claim 63 , wherein the antibody or antigen-binding fragment that specifically binds to LINGO-1 is a recombinant antibody. 
     
     
         240 . The polynucleotide of  claim 222 , wherein the antibody or antigen-binding fragment that specifically binds to LINGO-1 is a recombinant antibody.