Composition exhibiting a von willebrand factor (vWF) protease activity comprising a polypeptide chain with the amino acid sequence AAGGILHLELLV
The invention relates to vWF cleaving entities having a molecular weight of 180 kD, 170 kD, 160 kD, 120 kD or 110 kD and an N-terminal amino acid sequence of AAGGILHLELLV, vWF cleaving complexes and methods for their production.
1. A composition comprising an effective dose of an isolated polypeptide for the treatment of a disease in which the patient has a supranormal vWF content or an increased level of high-molecular weight vWF, wherein the polypeptide has vWF protease activity and comprises at least one single isolated peptide chain that has a molecular weight from about 180 kD to about 120 kD as determined by SDS-PAGE under reducing conditions and comprises the amino acid sequence AAGGILHLELLV (SEQ ID NO: 1), and wherein the polypeptide is obtained from human plasma or is encoded by a nucleic acid present in a human cDNA library.
2. The composition according to claim 1 , wherein the polypeptide comprises the amino acid sequence:
(SEQ ID NO: 4)
AAGGILHLELLVAVGPDVFQAHQEDTERYVLTNLNIGAELLRDPSLGAQF
RVHLVKMVILTEPEGAPNITANLTSSLLSVCGWSQTINPEDDTDPGHADL
VLYITRFDLELPDGNRQVRGVTQLGGACSPTWSCLITEDTGFDLGVTI.
3. The composition according to claim 1 , wherein the polypeptide has a molecular weight of about 170 kD.
4. The composition according to claim 1 , wherein the polypeptide has a molecular weight of about 160 kD.
5. The composition according to claim 1 , wherein the polypeptide has a molecular weight of about 120 kD.
6. The composition according to claim 1 , wherein the disease is thrombotic thrombocytopenic purpura (TTP), Henoch-Schönlein purpura, preeclampsia, neonatal thrombocytopenia or hemolytic-uremic syndrome.