Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies

Abstract

Isolated peptides from the protein EMMPRIN (CD147/Basigin) and antibodies directed against antigenic determinants within the peptides. Pharmaceutical compositions including the peptides and antibodies and methods of their production and use in vaccination, immunotherapy and diagnosis of proliferative, hyperpermeability, inflammatory, and angiogenesis-related diseases and disorders.

1 .- 23 . (canceled) 
     
     
         24 . An antibody or an antibody fragment thereof comprising at least an antigen-binding portion, wherein said antibody or said antibody fragment thereof recognizes an epitope of the protein EMMPRIN within a sequence set forth in Formula I: 
       
         
           
                 
                 
               
                     
                   X 5 GHRWX 1 X 2 GGX 3 VLX 4  (Formula I), 
                 
             
                
               
            
           
         
         wherein X 1  is selected from Met and Leu, X 2  is selected from Arg and Lys, X 3  is selected from Lys and Val, X 4  is Cys, Lys or represents the peptide's C-terminal selected from carboxy acid, amide or alcohol group, and X 5  is Cys, Lys or represents the peptide's N-terminal. 
       
     
     
         25 . The antibody or antibody fragment of  claim 24 , wherein the epitope comprises at least six contiguous amino acids from the sequence set forth in Formula I. 
     
     
         26 . The antibody or antibody fragment of  claim 24 , wherein the epitope consists of 7-15 amino acids. 
     
     
         27 . The antibody or an antibody fragment of  claim 24 , wherein said antibody or said antibody fragment thereof recognizes antigenic determinant within a sequence selected from the group consisting of: 
       
         
           
                 
               
                   (SEQ ID NO.: 12) 
                 
                 
                 
               
                     
                   GHRWX 1 X 2 GGX 3 VLC; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 13) 
                 
                 
                 
               
                     
                   GHRWX 1 X 2 GGX 3 VLX 4 ; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 14) 
                 
                 
                 
               
                     
                   GHRWMRGGKVLX 4 ; 
                 
                     
                   and 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 15) 
                 
                 
                 
               
                     
                   GHRWLKGGVVLX 4   
                 
                     
                     
                 
                 
               
                   (SEQ ID NO: 42) 
                 
                 
                 
               
                     
                   X 5 GHRWX 1 X 2 GGX 3 VLX 4 ; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 43) 
                 
                 
                 
               
                     
                   X 5 GHRWX 1 X 2 GGX 3 VL; 
                 
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
           
         
         and wherein X 1  is selected from Met and Leu, X 2  is selected from Arg and Lys, X 3  is selected from Lys and Val and X 5  and X 4  are each independently Cys or Lys. 
       
     
     
         28 . The antibody or antibody fragment of  claim 24 , wherein said antibody or said antibody fragment thereof recognizes an antigenic determinant within a sequence selected from the group consisting of: 
       
         
           
                 
               
                   (SEQ ID NO.: 1) 
                 
                 
                 
               
                     
                   G-H-R-W-M-R-G-G-K-V-L-C; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 2) 
                 
                 
                 
               
                     
                   G-H-R-W-L-K-G-G-V-V-L-C. 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 3) 
                 
                 
                 
               
                     
                   G-H-R-W-X 1 -X 2 ; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 4) 
                 
                 
                 
               
                     
                   H-R-W-X 1 -X 2 -G; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 5) 
                 
                 
                 
               
                     
                   R-W-X 1 -X 2 -G-G; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 6) 
                 
                 
                 
               
                     
                   W-X 1 -X 2 -G-G-X 3 ; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 7) 
                 
                 
                 
               
                     
                   X 1 -X 2 -G-G-X 3 -V; 
                 
                     
                   and 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 8) 
                 
                 
                 
               
                     
                   X 2 -G-G-X 3 -V-L; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 9) 
                 
                 
                 
               
                     
                   G-H-R-W-X 1 -X 2 -G-G-X 3 -V-L; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 10) 
                 
                 
                 
               
                     
                   G-H-R-W-M-R-G-G-K-V-L; 
                 
                     
                     
                 
                 
               
                   (SEQ ID NO.: 11) 
                 
                 
                 
               
                     
                   G-H-R-W-L-K-G-G-V-V-L; 
                 
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
                
               
            
             
                
               
            
             
                
               
            
           
         
         wherein X 1  is selected from Met and Leu, X 2  is selected from Arg and Lys, and X 3  is selected from Lys and Val. 
       
     
     
         29 . A polynucleotide sequence encoding an antibody or antibody fragment according to  claim 24 . 
     
     
         30 . A pharmaceutical composition comprising at least one antibody or antibody fragment according to  claim 24 , and an excipient or diluent. 
     
     
         31 . A method of preventing, attenuating or treating a disease or disorder associated with expression of EMMPRIN, the method comprising administering to a subject in need thereof a pharmaceutical composition according to  claim 30 . 
     
     
         32 . The method of  claim 31 , wherein the disease or disorder associated with expression of EMMPRIN is cell proliferative, a hyperpermeability, an inflammatory, an autoimmune, a heart, tissue regenerative, or an angiogenesis-related disease or disorder. 
     
     
         33 . The method of  claim 32 , wherein the cell proliferative disease is cancer and the method prevents or inhibits development of metastasis, treats tumor metastasis, increases the duration of survival, increases the progression free survival, increases the duration of response of a subject having cancer, or prevents tumor recurrence. 
     
     
         34 . A method for detecting or quantifying the presence of the protein EMMPRIN, the method comprising the steps of:
 i. incubating a sample with an antibody or an antibody fragment according to  claim 24 ;   ii. detecting the bound EMMPRIN using a detectable probe.   iii. comparing the amount of (ii) to a standard curve obtained from a reference sample containing a known amount of EMMPRIN via a processor; and   iv. calculating the amount of the EMMPRIN in the sample from the standard curve via a processor.