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 method of treating a disease in which a patient has a supranormal vWF content or an increased level of high-molecular weight vWF, wherein the method comprises administering a pharmaceutical composition comprising an effective dose of an isolated polypeptide that has vWF protease activity and comprises a 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 purified from human plasma or is encoded by a nucleic acid present in a human cDNA library.
2. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence:
(SEQ ID NO: 4)
AAGGILHLELLVAVGPDVFQAHQEDTERYVLTNLNIGAELLRDPSLGAQF
RVHLVKMVILTEPEGAPNITANLTSSLLSVCGWSQTINPEDDTDPGHADL
VLYITRFDLELPDGNRQVRGVTQLGGACSPTWSCLITEDTGFDLGVTI.
3. The method of claim 1 , wherein the polypeptide has a molecular weight of about 170kD.
4. The method of claim 1 , wherein the polypeptide has a molecular weight of about 160kD.
5. The method of claim 1 , wherein the polypeptide has a molecular weight of about 120kD.
6. The method of claim 1 , wherein the disease is thrombotic throbocytic purpura (TTP), Henoch-Schonlein purpura, preeclampsia, neonatal thrombocytopenia or hemolyticuremic syndrome.