Hepatocyte growth factor (hgf) binding proteins

Abstract

The present invention provides a family of binding proteins that bind and neutralize the activity of hepatocyte growth factor (HGF), in particular human HGF. The binding proteins can be used as diagnostic and/or therapeutic agents. With regard to their therapeutic activity, the binding proteins can be used to treat certain HGF responsive disorders, for example, certain HGF responsive tumors.

1 - 100 . (canceled) 
     
     
         101 . An isolated nucleic acid comprising a nucleotide sequence encoding an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 169, and encoding an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 179, wherein the immunoglobulin heavy chain variable region and the immunoglobulin light chain variable region together bind human hepatocyte growth factor (HGF). 
     
     
         102 . The isolated nucleic acid of  claim 101 , wherein the nucleotide sequence encodes an immunoglobulin heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 171. 
     
     
         103 . The isolated nucleic acid of  claim 101 , wherein the nucleotide sequence encodes an immunoglobulin heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 210. 
     
     
         104 . The isolated nucleic acid of  claim 101 , wherein the nucleotide sequence encodes an immunoglobulin light chain sequence comprising the amino acid sequence of SEQ ID NO: 181. 
     
     
         105 . An expression vector comprising the nucleic acid of  claim 101 . 
     
     
         106 . A host cell comprising the expression vector of  claim 105 . 
     
     
         107 . A host cell comprising:
 a first expression vector comprising a nucleic acid sequence encoding an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 169; and   a second expression vector comprising a nucleic acid sequence encoding an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 179;   wherein the immunoglobulin light chain variable region and the immunoglobulin heavy chain variable region together bind human hepatocyte growth factor (HGF).   
     
     
         108 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 107  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain variable region and a polypeptide comprising the immunoglobulin light chain variable region, thereby producing the antibody or antigen binding fragment of the antibody; and   (b) purifying the antibody or the antigen binding fragment of the antibody.   
     
     
         109 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 106  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain variable region and a polypeptide comprising the immunoglobulin light chain variable region, thereby producing the antibody or the antigen-binding fragment of the antibody; and   (b) purifying the antibody or the antigen-binding fragment of the antibody.   
     
     
         110 . An isolated nucleic acid comprising a nucleotide sequence encoding an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 171, and encoding an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 181, wherein the immunoglobulin heavy chain and the immunoglobulin light chain together bind human hepatocyte growth factor (HGF). 
     
     
         111 . An expression vector comprising the nucleic acid of  claim 110 . 
     
     
         112 . A host cell comprising the expression vector of  claim 111 . 
     
     
         113 . A host cell comprising:
 a first expression vector comprising a nucleic acid sequence encoding an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 171; and   a second expression vector comprising a nucleic acid sequence encoding an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 181;   wherein the immunoglobulin light chain and the immunoglobulin heavy chain together bind human hepatocyte growth factor (HGF).   
     
     
         114 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 113  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain and a polypeptide comprising the immunoglobulin light chain, thereby producing the antibody or antigen binding fragment of the antibody; and   (b) purifying the antibody or the antigen binding fragment of the antibody.   
     
     
         115 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 112  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain and a polypeptide comprising the immunoglobulin light chain, thereby producing the antibody or the antigen-binding fragment of the antibody; and   (b) purifying the antibody or the antigen-binding fragment of the antibody.   
     
     
         116 . An isolated nucleic acid comprising a nucleotide sequence encoding an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 210, and encoding an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 181, wherein the immunoglobulin light chain and the immunoglobulin heavy chain together bind human hepatocyte growth factor (HGF). 
     
     
         117 . An expression vector comprising the nucleic acid of  claim 116 . 
     
     
         118 . A host cell comprising the expression vector of  claim 117 . 
     
     
         119 . A host cell comprising:
 a first expression vector comprising a nucleic acid sequence encoding an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 210; and   a second expression vector comprising a nucleic acid sequence encoding an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 181;   wherein the immunoglobulin light chain and the immunoglobulin heavy chain together bind human hepatocyte growth factor (HGF).   
     
     
         120 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 119  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain and a polypeptide comprising the immunoglobulin light chain, thereby producing the antibody or antigen binding fragment of the antibody; and   (b) purifying the antibody or the antigen binding fragment of the antibody.   
     
     
         121 . A method of producing a monoclonal antibody that binds human hepatocyte growth factor (HGF) or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 118  under conditions that permit the expression of a polypeptide comprising the immunoglobulin heavy chain and a polypeptide comprising the immunoglobulin light chain, thereby producing the antibody or the antigen-binding fragment of the antibody; and   (b) purifying the antibody or the antigen-binding fragment of the antibody.