Anti-fgfr2 antibodies

Abstract

Monoclonal antibodies that bind and inhibit biological activities of human FGFR2 are disclosed. The antibodies can be used to treat cell proliferative diseases and disorders, including certain forms of cancer, associated with activation or overexpression of FGFR2.

1 - 2 . (canceled) 
     
     
         3 . An isolated nucleic acid comprising a nucleotide sequence encoding an immunoglobulin heavy chain variable region comprising a CDR H1  comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 5 and SEQ ID NO: 47, a CDR H2  comprising the amino acid sequence of SEQ ID NO: 38, and a CDR H3  comprising the amino acid sequence of SEQ ID NO: 11. 
     
     
         4 . An isolated nucleic acid comprising a nucleotide sequence encoding an immunoglobulin light chain variable region comprising a CDR L1  comprising the amino acid sequence of SEQ ID NO: 41, a CDR L2  comprising the amino acid sequence of SEQ ID NO: 42, and a CDR L3  comprising the amino acid sequence of SEQ ID NO: 14. 
     
     
         5 . An expression vector containing the nucleic acid of  claim 3 . 
     
     
         6 . An expression vector containing the nucleic acid of  claim 4 . 
     
     
         7 . The expression vector of  claim 6 , further comprising the nucleic acid of  claim 3 . 
     
     
         8 . A host cell comprising the expression vector of  claim 5 . 
     
     
         9 . A host cell comprising the expression vector of  claim 6 . 
     
     
         10 . A host cell comprising the expression vector of  claim 7 . 
     
     
         11 . The host cell of  claim 9 , further comprising the expression vector of  claim 5 . 
     
     
         12 . A method of producing a polypeptide comprising an immunoglobulin heavy chain variable region or an immunoglobulin light chain variable region, the method comprising:
 (a) growing the host cell of  claim 8  or  9  under conditions so that the host cell expresses the polypeptide comprising the immunoglobulin heavy chain variable region or the immunoglobulin light chain variable region; and   (b) purifying the polypeptide comprising the immunoglobulin heavy chain variable region or the immunoglobulin light chain variable region.   
     
     
         13 . A method of producing an antibody that binds human FGFR2 or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 10  or  11  under conditions so that the host cell expresses a polypeptide comprising the immunoglobulin heavy chain variable region and 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.   
     
     
         14 . (canceled) 
     
     
         15 . The isolated nucleic acid of  claim 3 , wherein the nucleotide sequence encodes an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 37. 
     
     
         16 . The isolated nucleic acid of  claim 4 , wherein the nucleotide sequence encodes an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 46. 
     
     
         17 . An expression vector containing the nucleic acid of  claim 15 . 
     
     
         18 . An expression vector containing the nucleic acid of  claim 16 . 
     
     
         19 . The expression vector of  claim 18 , further comprising the nucleic acid of  claim 15 . 
     
     
         20 . A host cell comprising the expression vector of  claim 17 . 
     
     
         21 . A host cell comprising the expression vector of  claim 18 . 
     
     
         22 . A host cell comprising the expression vector of  claim 19 . 
     
     
         23 . The host cell of  claim 21 , further comprising the expression vector of  claim 17 . 
     
     
         24 . A method of producing a polypeptide comprising an immunoglobulin heavy chain variable region or an immunoglobulin light chain variable region, the method comprising:
 (a) growing the host cell of  claim 20  or  21  under conditions so that the host cell expresses the polypeptide comprising the immunoglobulin heavy chain variable region of the immunoglobulin light chain variable region; and   (b) purifying the polypeptide comprising the immunoglobulin heavy chain variable region or the immunoglobulin light chain variable region.   
     
     
         25 . A method of producing an antibody that binds human FGFR2 or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 22  or  23  under conditions so that the host cell expresses a polypeptide comprising the immunoglobulin heavy chain variable region and 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.   
     
     
         26 . (canceled) 
     
     
         27 . The isolated nucleic acid of  claim 3 , wherein the nucleotide sequence encodes an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 56. 
     
     
         28 . The isolated nucleic acid of  claim 4 , wherein the nucleotide sequence encodes an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 62. 
     
     
         29 . An expression vector containing the nucleic acid of  claim 27 . 
     
     
         30 . An expression vector containing the nucleic acid of  claim 28 . 
     
     
         31 . The expression vector of  claim 30 , further comprising the nucleic acid of  claim 27 . 
     
     
         32 . A host cell comprising the expression vector of  claim 29 . 
     
     
         33 . A host cell comprising the expression vector of  claim 30 . 
     
     
         34 . A host cell comprising the expression vector of  claim 31 . 
     
     
         35 . The host cell of  claim 33 , further comprising the expression vector of  claim 29 . 
     
     
         36 . A method of producing a polypeptide comprising an immunoglobulin heavy chain, the method comprising:
 (a) growing the host cell of  claim 32  or  33  under conditions so that the host cell expresses the polypeptide comprising the immunoglobulin heavy chain or the immunoglobulin light chain; and   (b) purifying the polypeptide comprising the immunoglobulin heavy chain or the immunoglobulin light chain.   
     
     
         37 . A method of producing an antibody that binds human FGFR2 or an antigen binding fragment of the antibody, the method comprising:
 (a) growing the host cell of  claim 34  of  35  under conditions so that the host cell expresses a polypeptide comprising the immunoglobulin heavy chain and 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.   
     
     
         38 - 43 . (canceled) 
     
     
         44 . The isolated nucleic acid of  claim 3 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1  comprising the amino acid sequence of SEQ ID NO: 5, a CDR H2  comprising the amino acid sequence of SEQ ID NO: 38, and a CDR H3  comprising the amino acid sequence of SEQ ID NO: 11. 
     
     
         45 . The isolated nucleic acid of  claim 3 , wherein the immunoglobulin heavy chain variable region comprises a CDR H1  comprising the amino acid sequence of SEQ ID NO: 47, a CDR H2  comprising the amino acid sequence of SEQ ID NO: 38, and a CDR H3  comprising the amino acid sequence of SEQ ID NO: 11.