Novel mutated tissue plasminogen activators and uses thereof

A protein selected from the group consisting of:

• i) a protein comprising the sequence SEQ ID NO:
• 2 or SEQ ID NO:25, wherein said sequence comprises:
• a mutation A′ consisting of the replacement of any amino acid of the Lysine Binding Site of SEQ ID NO:
• 2 or SEQ ID NO:25 by a hydrophilic amino acid selected from the group consisting of arginine, aspartic acid, glutamic acid, lysine, asparagine, glutamine, serine, threonine, tyrosine and histidine, or
• a mutation B consisting of the replacement of arginine in position 275 of SEQ ID NO:
• 2 or SEQ ID NO:25 by serine, or
• a double mutation A′ and B consisting of the replacement of any amino acid of the Lysine Binding Site of SEQ ID NO:
• 2 or SEQ ID NO:25 by a hydrophilic amino acid chosen from arginine, aspartic acid, glutamic acid, lysine, asparagine, glutamine, serine, threonine, tyrosine and histidine, and the replacement of arginine in position 275 of SEQ ID NO:
• 2 or SEQ ID NO:25 by serine,
• ii) a protein comprising a sequence having at least 80% homology with SEQ ID NO:
• 2 or SEQ ID NO:25, said protein comprising mutation A′, mutation B, or mutation A′ and B, and
• iii) a protein comprising a fragment of SEQ ID NO:2, said fragment consisting of the Kringle 2 domain, the catalytic domain, and mutation A′ mutation B, or mutation A′ and B.