Antibodies that specifically bind to Reg IV

Abstract

The present invention relates to antibodies and related molecules that specifically bind to Reg IV. Such antibodies have uses, for example, in the prevention and treatment of gastrointestinal tract cancers, inflammatory bowel disorders, and diabetes. The invention also relates to nucleic acid molecules encoding anti-Reg IV antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or ameliorating a disease or disorder, especially gastrointestinal tract cancers, inflammatory bowel disorders, and diabetes, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that specifically bind to Reg IV.

1 . An isolated antibody that specifically binds Reg IV comprising: 
 (a) an amino acid sequence that is at least 80% identical to a VH domain of any one of the scFvs of SEQ ID NOS: 1-67;    (b) an amino acid sequence that is at least 80% identical to a VL domain of any one of the scFvs of SEQ ID NOS: 1-67; or    (c) both (a) and (b).    
     
     
         2 . The antibody of  claim 1  comprising: 
 (a) the amino acid sequence of a VH domain of any one of the scFvs of SEQ ID NOS: 1-67;    (b) the amino acid sequence of a VL domain of any one of the scFvs of SEQ ID NOS: 1-67; or    (c) both (a) and (b).    
     
     
         3 . The antibody of  claim 2  comprising the amino acid sequence of a VH domain of any one of the scFvs of SEQ ID NOS: 1-67 and the amino acid sequence of a VL domain of any one of the scFVs of SEQ ID NOS: 1-67.  
     
     
         4 . The antibody of  claim 3  wherein the VH domain and the VL domain are from the same scFv.  
     
     
         5 . The isolated antibody or fragment thereof of  claim 1  that specifically binds Reg IV purified from a cell culture, wherein Reg IV is encoded by a polynucleotide encoding amino acids 1 to 158 of SEQ ID NO:172 operably associated with a regulatory sequence that controls expression of said polynucleotide.  
     
     
         6 . The antibody of  claim 1  wherein the antibody is selected from the group consisting of: 
 (a) a whole immunoglobulin molecule;    (b) an scFv;    (c) a monoclonal antibody;    (d) a human antibody;    (e) a chimeric antibody;    (f) a Fab fragment;    (g) an F(ab′)2;    (h) an Fv; and    (i) a disulfide linked Fv.    
     
     
         7 . The antibody of  claim 1  which also comprises a heavy chain immunoglobulin constant domain selected from the group consisting of: 
 (a) a human IgM constant domain;    (b) a human IgG1 constant domain;    (c) a human IgG2 constant domain;    (d) a human IgG3 constant domain;    (e) a human IgG4 constant domain; and    (f) a human IgA constant domain.    
     
     
         8 . The antibody of  claim 1  which also comprises a light chain immunoglobulin constant domain selected from the group consisting of: 
 (a) a human Ig kappa constant domain; and    (b) a human Ig lambda constant domain.    
     
     
         9 . The antibody of  claim 1  wherein the antibody has a dissociation constant (K D ) less than or equal to 10 −9 M.  
     
     
         10 . The antibody of  claim 1  wherein the antibody is conjugated to a detectable label.  
     
     
         11 . The antibody or portion thereof of  claim 1  wherein said antibody specifically binds to Reg IV in a Western blot or ELISA.  
     
     
         12 . The antibody of  claim 1  wherein the antibody inhibits proliferation of Reg IV receptor expressing cells.  
     
     
         13 . The antibody of  claim 1  wherein the antibody downregulates Reg IV expression.  
     
     
         14 . The antibody of  claim 1  wherein the antibody inhibits Reg IV binding to a Reg IV receptor.  
     
     
         15 . The antibody of  claim 1  wherein the antibody stimulates proliferation of cells expressing a Reg IV receptor.  
     
     
         16 . The antibody of  claim 1  wherein the antibody upregulates Reg IV expression.  
     
     
         17 . An antibody that competitively inhibts the binding of an antibody of  claim 3  to a Reg IV polypeptide.  
     
     
         18 . An isolated antibody that specifically binds Reg IV comprising a first amino acid sequence at least 95% identical to a second amino acid sequence selected from the group consisting of: 
 (a) the amino acid sequence of either VHCDR1, VHCDR2, or VHCDR3 of any one of the scFvs of SEQ ID NOS:1-67.    (b) the amino acid sequence of either VLCDR1, VLCDR2, or VLCDR3 of any one of the scFvs of SEQ ID NOS:1-67.    
     
     
         19 . The antibody of  claim 18 , wherein the second amino acid sequence consists of the amino acid sequence of a VHCDR3 of any one of the scFvs of SEQ ID NOS: 1-67.  
     
     
         20 . The isolated antibody or fragment thereof of  claim 18  that specifically binds Reg IV purified from a cell culture, wherein Reg IV is encoded by a polynucleotide encoding amino acids 1 to 158 of SEQ ID NO:172 operably associated with a regulatory sequence that controls expression of said polynucleotide.