Therapeutic anti-tirc7 antibodies for use in immune related and other diseases

Abstract

Provided are specific antibodies against T-cell immune response cDNA7 (TIRC7) costimulatory molecule, which are capable of inhibiting proliferation of peripheral blood mononuclear cells (PBMCs). In particular, high affinity monoclonal and chimeric anti-TIRC7 antibodies are described. Compositions comprising such antibodies and their use for the treatment of immune diseases are provided.

1 . A monoclonal antibody or antigen binding molecule which is capable of binding to an antigen comprising or consisting of the amino acid sequence of any one of SEQ ID NOs: 9 to 11.  
     
     
         2 . The antibody or antigen binding molecule of  claim 1 , comprising in its variable region at least one complementarity determining region (CDR) of the V H  and/or V L  of the variable region comprising 
 (a) the amino acid sequence depicted in  FIG. 4  (V H ) (SEQ ID NO: 2) and  FIG. 5  (V L ) (SEQ ID NO: 4); or    (b) the amino acid sequence depicted in  FIG. 6  (V H ) (SEQ ID NO: 6) and  FIG. 7  (V L ) (SEQ ID NO: 8).    
     
     
         3 . The antibody of  claim 1 , wherein said antibody is a chimeric or humanized antibody.  
     
     
         4 . The antibody of  claim 1  comprising the amino acid sequence of the V H  and/or V L  region as depicted in any one of FIGS.  4  to  7 .  
     
     
         5 . An antigen or an epitope thereof which is recognized by the antibody of  claim 1 .  
     
     
         6 . A polynucleotide encoding at least a variable region of an immunoglobulin chain of the antibody of  claim 1 .  
     
     
         7 . A vector comprising the polynucleotide of  claim 6 , optionally in combination with a polynucleotide of  claim 6  that encodes the variable region of the other immunoglobulin chain of said antibody.  
     
     
         8 . A host cell comprising a polynucleotide of  claim 6 .  
     
     
         9 . A method for preparing an antibody or a functional fragment or immunoglobulin chain(s) thereof comprising 
 (a) culturing the cell of  claim 8;  and    (b) isolating said antibody or functional fragment or immunoglobulin chain(s) thereof from the culture.    
     
     
         10 . An antibody, an immunoglobulin chain thereof or an antigen binding fragment thereof encoded by a polynucleotide of  claim 6 .  
     
     
         11 . A composition comprising the antibody of  claim 1 .  
     
     
         12 . The composition of  claim 11  which is a pharmaceutical composition and further comprises a pharmaceutically acceptable carrier.  
     
     
         13 . The pharmaceutical composition of  claim 12  further comprising an immunosuppressive agent.  
     
     
         14 . A diagnostic composition comprising the antibody of  claim 8   claim 1;  and optionally appropriate reagents conventionally used in immuno or nucleic acid based diagnostic methods.  
     
     
         15 . Use of the antibody of  claim 1  for the preparation of a pharmaceutical composition for inhibition of an immune response.  
     
     
         16 . The use of  claim 15 , wherein said pharmaceutical composition is administered intravenious, intramuscular, subcutaneous, intraperitoneal, or as an aerosol.  
     
     
         17 . A method of modulating the immune response in a subject in need thereof, comprising administering the antibody of  claim 1 .  
     
     
         18 . Use of a ligand binding molecule comprising at least one CDR of an antibody of  claim 1  for diagnosing and/or treatment of a disorder related to the aberrant expression or malfunction of T-cell immune response cDNA 7 (TIRC7).  
     
     
         19 . The use of  claim 18 , wherein said ligand binding molecule is an antibody or an immunoglobulin chain thereof.  
     
     
         20 . An oligonucleotide consisting essentially of the nucleotide sequence of any one of SEQ ID NOs: 12 to 40.  
     
     
         21 . Use of an oligonucleotide comprising a nucleotide sequence of any one of SEQ ID NOs: 12 to 40 for the cloning of an anti-TIRC7 antibody or TIRC7 binding molecule.  
     
     
         22 . A host cell comprising a vector of  claim 7 .  
     
     
         23 . An antibody, an immunoglobulin chain thereof or an antigen binding fragment thereof obtainable by the method of  claim 9.