Novel anti-human gpvi antibodies and uses thereof

Abstract

The present invention relates to humanized anti-human GPVI antibodies and uses thereof.

1 - 16 . (canceled) 
     
     
         17 . An isolated humanized protein binding to human Glycoprotein VI (hGPVI), wherein said protein has a K D  for binding to hGPVI less than 15 nM, wherein said K D  is measured by surface plasmon resonance using 960 to 1071 RU of soluble human GPVI and using PBS pH 7.4 as running buffer, and wherein said isolated humanized protein does not induce a GPVI depletion phenotype in vivo. 
     
     
         18 . The isolated humanized protein binding to hGPVI according to  claim 17 , wherein said protein binds to an epitope comprising:
 at least one amino acid residue from amino acid residues 114 to 142 of hGPVI (SEQ ID NO: 13) or from a sequence sharing at least 60% of identity over amino acid residues 114 to 142 of hGPVI (SEQ ID NO: 13); and   at least one amino acid residue from amino acid residues 165 to 187 of hGPVI (SEQ ID NO: 13) or from a sequence sharing at least 60% of identity over amino acid residues 165 to 187 of hGPVI (SEQ ID NO: 13).   
     
     
         19 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising:
 an antibody molecule selected from the group consisting of a whole antibody, a humanized antibody, a single chain antibody, a Fv, and a Fab; or   an antibody fragment selected from the group consisting of a unibody, a domain antibody, and a nanobody; or   a monomeric antibody mimetic selected from the group consisting of an affibody, an affilin, an affitin, an adnectin, an atrimer, an evasin, a DARPin, an anticalin, an avimer, a fynomer, and a versabody.   
     
     
         20 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising a monovalent antibody. 
     
     
         21 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising an antibody wherein the variable region of the heavy chain comprises at least one of the following heavy chain CDRs: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 1) 
                 
                     
                   VH-CDR1: GYTFTSYNMH; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 2) 
                 
                     
                   VH-CDR2: GIYPGNGDTSYNQKFQG; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 3) 
                 
                     
                   VH-CDR3: GTVVGDWYFDV, 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or any CDR having an amino acid sequence that shares at least 60% of identity with SEQ ID NO: 1-3, and 
       wherein the variable region of the light chain comprises at least one of the following light chain CDRs: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 4) 
                 
                     
                   VL-CDR1: RSSQSLENSNGNTYLN; 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 5) 
                 
                     
                   VL-CDR2: RVSNRFS; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 6) 
                 
                     
                   VL-CDR3: LQLTHVPWT. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       or any CDR having an amino acid sequence that shares at least 60% of identity with SEQ ID NO: 4-6. 
     
     
         22 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising an antibody wherein the variable region of the heavy chain comprises the following CDRs: GYTFTSYNMH (SEQ ID NO: 1), GIYPGNGDTSYNQKFQG (SEQ ID NO: 2) and GTVVGDWYFDV (SEQ ID NO: 3), and the variable region of the light chain comprises the following CDRs: RSSQSLENSNGNTYLN (SEQ ID NO: 4), RVSNRFS (SEQ ID NO: 5) and LQLTHVPWT (SEQ ID NO: 6), or any CDR having an amino acid sequence that shares at least 60% of identity with said SEQ ID NO: 1-6. 
     
     
         23 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising an antibody wherein the amino acid sequence encoding the heavy chain variable region is SEQ ID NO: 7 and the amino acid sequence encoding the light variable region is SEQ ID NO: 8, or any sequence having an amino acid sequence that shares at least 60% of identity with said SEQ ID NO: 7 or 8. 
     
     
         24 . The isolated humanized protein binding to hGPVI according to  claim 17 , comprising an antibody wherein the amino acid sequence encoding the heavy chain variable region is SEQ ID NO: 7 and the amino acid sequence encoding the light variable region is SEQ ID NO: 9, or any sequence having an amino acid sequence that shares at least 60% of identity with said SEQ ID NO: 7 or 9. 
     
     
         25 . A method for treating a GPVI-related condition, wherein said method comprises administering an isolated humanized protein binding to hGPVI according to  claim 17 . 
     
     
         26 . The method according to  claim 25 , wherein said GPVI-related condition is a cardiovascular disease. 
     
     
         27 . The method according to  claim 25 , wherein said GPVI-related condition is a cardiovascular disease selected from the group consisting of arterial and venous thrombosis, restenosis and thromboembolic diseases. 
     
     
         28 . The method according to  claim 25 , wherein said GPVI-related condition is a cardiovascular disease selected from coronary artery diseases, cerebral artery diseases, peripheral artery diseases, and venous thrombosis. 
     
     
         29 . The method according to  claim 25 , wherein said GPVI-related condition is a cardiovascular disease selected from acute coronary syndrome, ischemic cerebrovascular accidents, myocardial infarction, stroke, acute phlebitis, and pulmonary embolism. 
     
     
         30 . An expression vector comprising at least one of SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12 or any sequence having a nucleic acid sequence that shares at least 60% of identity with said SEQ ID NO: 10-12.