Antibodies specific to cadherin-17

Abstract

The present disclosure provides antibodies, including isolated monoclonal antibodies, which specifically bind to Cadherin-17 with high affinity. Nucleic acid molecules encoding Cadherin-17 antibodies, expression vectors, host cells and methods for expressing the Cadherin-17 antibodies are also provided. Bispecific molecules and pharmaceutical compositions comprising the Cadherin-17 antibodies are also provided. Methods for detecting Cadherin-17, as well as methods for treating various cancers, including colorectal cancer, are disclosed.

What is claimed is: 
     
         1 . An isolated anti-Cadherin-17 antibody comprising a heavy chain variable region CDR1 comprising SEQ ID NO: 1, a heavy chain variable region CDR2 comprising SEQ ID NO: 5, a heavy chain variable region CDR3 comprising SEQ ID NO: 14, a light chain variable region CDR1 comprising SEQ ID NO: 22, a light chain variable region CDR2 comprising SEQ ID NO: 28, and a light chain variable region CDR3 comprising SEQ ID NO: 32. 
     
     
         2 . An isolated anti-Cadherin-17 antibody comprising heavy and light chain variable regions, wherein the heavy chain variable region comprises the mature portion of SEQ ID NO:35. 
     
     
         3 . An isolated anti-Cadherin-17 antibody comprising heavy and light chain variable regions, wherein the light chain variable region comprises the mature portion of SEQ ID NO:47. 
     
     
         4 . An isolated anti-Cadherin-17 antibody comprising a heavy chain variable region comprising the mature portion of SEQ ID NO:35, or an amino acid sequence at least 95% identical thereto, and a light chain variable region comprising the mature portion of SEQ ID NO:47, or an amino acid sequence at least 95% identical thereto. 
     
     
         5 . The isolated anti-Cadherin-17 antibody of  claim 4 , wherein the antibody comprises a heavy chain variable region comprising the mature portion of SEQ ID NO:35 and a light chain variable region comprising the mature portion of SEQ ID NO:47. 
     
     
         6 . An isolated antibody which binds an epitope on human Cadherin-17 recognized by an antibody comprising a heavy chain variable region comprising SEQ ID NO:35 and a light chain variable region comprising SEQ ID NO:47. 
     
     
         7 . The antibody of  claim 1 , wherein the antibody is a full-length antibody of an IgG1, IgG2, IgG3, or IgG4 isotype. 
     
     
         8 . The antibody of  claim 1 , wherein the antibody is selected from the group consisting of: a whole antibody, a monoclonal antibody, an antibody fragment, a humanized antibody, a single chain antibody, a defucosylated antibody, an antibody mimetic and a bispecific antibody. 
     
     
         9 . An immunoconjugate comprising the antibody of  claim 1  conjugated to a therapeutic agent. 
     
     
         10 . The immunoconjugate of  claim 9 , wherein the therapeutic agent is a cytotoxin. 
     
     
         11 . A composition comprising the antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . An isolated nucleic acid molecule encoding the heavy or light chain of the antibody of  claim 1 . 
     
     
         13 . An isolated nucleic acid comprising a nucleotide sequence encoding an antibody variable region, wherein the nucleotide sequences comprises SEQ ID NO:59 or SEQ ID NO:71. 
     
     
         14 . An expression vector comprising the nucleic acid molecule of  claim 12 . 
     
     
         15 . A host cell comprising the expression vector of  claim 14 . 
     
     
         16 . A method for preparing an anti-Cadherin-17 antibody, said method comprising the steps of:
 obtaining a host cell that contains one or more nucleic acid molecules encoding the antibody of  claim 1 ;   growing the host cell in a host cell culture; providing host cell culture conditions wherein the one or more nucleic acid molecules are expressed; and   recovering the antibody from the host cell or from the host cell culture.   
     
     
         17 . A method for treating cancer associated with target cancer cells expressing Cadherin-17, said method comprising the step of administering to a subject the immunoconjugate of  claim 9 , in an amount effective to treat the cancer. 
     
     
         18 . The method of  claim 17 , wherein said cancer is a human cancer. 
     
     
         19 . The method of  claim 18 , wherein said human cancer is colorectal cancer. 
     
     
         20 . The method of  claim 18 , wherein said human cancer is gastric cancer or pancreatic cancer. 
     
     
         21 . An isolated anti-Cadherin-17 antibody comprising:
 (a) a heavy chain variable region CDR1 comprising SEQ ID NO: 2, a heavy chain variable region CDR2 comprising SEQ ID NO: 6, a heavy chain variable region CDR3 comprising SEQ ID NO: 15, a light chain variable region CDR1 comprising SEQ ID NO: 23, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (b) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 7, a heavy chain variable region CDR3 comprising SEQ ID NO: 16, a light chain variable region CDR1 comprising SEQ ID NO: 23, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (c) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 7, a heavy chain variable region CDR3 comprising SEQ ID NO: 18, a light chain variable region CDR1 comprising SEQ ID NO: 25, a light chain variable region CDR2 comprising SEQ ID NO: 31, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (d) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 9, a heavy chain variable region CDR3 comprising SEQ ID NO: 19, a light chain variable region CDR1 comprising SEQ ID NO: 26, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (e) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 7, a heavy chain variable region CDR3 comprising SEQ ID NO: 16, a light chain variable region CDR1 comprising SEQ ID NO: 25, a light chain variable region CDR2 comprising SEQ ID NO: 31, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (f) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 7, a heavy chain variable region CDR3 comprising SEQ ID NO: 16, a light chain variable region CDR1 comprising SEQ ID NO: 25, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (g) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 10, a heavy chain variable region CDR3 comprising SEQ ID NO: 20, a light chain variable region CDR1 comprising SEQ ID NO: 27, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (h) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 11, a heavy chain variable region CDR3 comprising SEQ ID NO: 21, a light chain variable region CDR1 comprising SEQ ID NO: 25, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO: 33;   (i) a heavy chain variable region CDR1 comprising SEQ ID NO: 3, a heavy chain variable region CDR2 comprising SEQ ID NO: 12, a heavy chain variable region CDR3 comprising SEQ ID NO: 18, a light chain variable region CDR1 comprising SEQ ID NO: 25, a light chain variable region CDR2 comprising SEQ ID NO: 31, and a light chain variable region CDR3 comprising SEQ ID NO: 33; or   (j) a heavy chain variable region CDR1 comprising SEQ ID NO: 2, a heavy chain variable region CDR2 comprising SEQ ID NO: 13, a heavy chain variable region CDR3 comprising SEQ ID NO: 15, a light chain variable region CDR1 comprising SEQ ID NO: 23, a light chain variable region CDR2 comprising SEQ ID NO: 29, and a light chain variable region CDR3 comprising SEQ ID NO:33.