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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         11 . A polynucleotide which encodes 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). 
     
     
         12 . A polynucleotide according to  claim 11  comprising:
 (a) a leader sequence   (b) a sequence encoding an tag molecule   (c) a sequence encoding said fusion protein.   
     
     
         13 . An expression vector comprising the polynucleotide according to  claim 11 . 
     
     
         14 . An expression vector according to  claim 13 , wherein the vector is the pdC-Fc-X vector. 
     
     
         15 . An expression vector according to  claim 13 , wherein the vector is the pcDNA3.1+ vector. 
     
     
         16 . A host cell comprising a vector according to  claim 13 . 
     
     
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         34 . The polynucleotide according to  claim 11 , wherein the fusion protein comprises a tag molecule which is an immunoglobulin molecule (Ig) or a fragment thereof. 
     
     
         35 . The polynucleotide according to  claim 11 , wherein the fusion protein comprises a leader sequence. 
     
     
         36 . The polynucleotide according to  claim 11 , wherein the tag molecule is covalently linked by its C-terminus to the N-terminus of the GPVI-like protein. 
     
     
         37 . The polynucleotide according to  claim 11 , wherein the tag molecule is covalently linked by its N-terminus to the C-terminus of the GPVI-like protein. 
     
     
         38 . The polynucleotide according to  claim 11 , wherein a linker molecule is fused between the tag molecule and the GPVI-like protein. 
     
     
         39 . The polynucleotide according to  claim 11 , 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 polynucleotide according to  claim 11 , wherein the Ig molecule is a Fc portion. 
     
     
         41 . The polynucleotide according to  claim 11 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         42 . The polynucleotide according to  claim 11 , wherein the fusion protein comprises amino acids 22-501 of SEQ ID NO: 1 or amino acids 26-512 of SEQ ID NO: 2. 
     
     
         43 . The polynucleotide according to  claim 11 , wherein the fusion protein consists of the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         44 . The polynucleotide according to  claim 11 , wherein the fusion protein consists of amino acids 22-501 of SEQ ID NO: 1 or amino acids 26-512 of SEQ ID NO: 2.