Glycoprotein VI fusion proteins

Abstract

The present invention relates to Glycoprotein VI (GPVI) fusion proteins (GPVI-fusion proteins) comprising a tag like myc, GST, HA, FLAG, STREP but preferably a Immunoglobulin molecule (Ig), more preferably a Fc portion of said Ig and a protein or oligopeptide having the biological activity of GPVI (GPVI-like protein) which is binding to collagen and their use in methods and kits for the screening of potential agonists or antagonists for GPVI-collagen and/or platelet-collagen interaction is disclosed. Further, pharmaceutical compositions and therapeutic methods are provided comprising such GPVI-fusion proteins for the treatment of thrombotic and cardiovascular events and disorders related to GPVI-collagen and/or platelet-collagen interactions.

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         23 . The method according to  claim 24  wherein the disorder related to GPVI-collagen and/or platelet-collagen interactions comprises increased platelet activation with collagen, atherosclerotic plaque rupture, or unstable angina and the event comprises Percutaneous Transluminal Coronary Angioplasty (PTCA). 
     
     
         24 . A method of treating a thrombotic or a cardiovascular event or a disorder related to platelet-collagen interactions comprising administering to a subject in need thereof a fusion protein comprising a tag molecule and a non immunoglobulin molecule, wherein the non-immunoglobulin molecule is a protein or oligopeptide having the biological activity of Glycoprotein VI (GPVI-like protein). 
     
     
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         34 . The method according to  claim 24 , wherein the fusion protein comprises a tag molecule which is an immunoglobulin molecule (Ig) or a fragment thereof. 
     
     
         35 . The method according to  claim 24 , wherein the fusion protein comprises a leader sequence. 
     
     
         36 . The method according to  claim 24 , wherein the fusion protein comprises a tag molecule which is covalently linked by its C-terminus to the N-terminus of the GPVI-like protein. 
     
     
         37 . The method according to  claim 24 , wherein the fusion protein comprises a tag molecule which is covalently linked by its N-terminus to the C-terminus of the GPVI-like protein. 
     
     
         38 . The method according to  claim 24 , wherein the fusion protein comprises a linker molecule which is fused between the tag molecule and the GPVI-like protein. 
     
     
         39 . The method according to  claim 24 , wherein the GPVI-like protein is the extracellular domain of human mature GPVI beginning with amino acid glutamine at position 21 and ending with amino acid asparagine at position 269. 
     
     
         40 . The method according to  claim 34 , wherein the fusion protein comprises a tag which is a Fc portion of said Ig molecule. 
     
     
         41 . The method according to  claim 34 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         42 . The method according to  claim 41 , wherein the fusion protein is without leader sequence. 
     
     
         43 . The method according to  claim 41 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         44 . A method of treating a thrombotic or a cardiovascular event or a disorder related to platelet-collagen interactions comprising administering to a subject in need thereof a pharmaceutical composition comprising fusion protein and an acceptable carrier, wherein said fusion protein comprises a tag molecule and a non immunoglobulin molecule, wherein the non-immunoglobulin molecule is a protein or oligopeptide having the biological activity of Glycoprotein VI (GPVI-like protein). 
     
     
         45 . The method according to  claim 44 , further comprising administering an active agent which is aspirin, heparin, saratin or streptokinase or a combination thereof. 
     
     
         46 . The method according to  claim 24 , further comprising administering an active agent which is aspirin, heparin, saratin or streptokinase or a combination thereof.