Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Patent
1993-06-22
1996-04-23
Elliott, George C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
4352402, 4353201, 536 232, 536 235, C12P 2102, C12N 510, C12N 1511, C07H 2104
Patent
active
055102484
ABSTRACT:
An isolated polynucleotide which encodes human prothrombin is modified to encode amino acid substitutions at positions 155, 271 and 284 of the prothrombin polypeptide. A second polynucleotide is further modified to encode an additional amino acid substitution at residue 320.
The polypeptide encoded by the first polynucleotide is resistant to cleavage by thrombin and factor Xa, exhibits greatly reduced procoagulant activity towards fibrinogen and unchanged anticoagulant activity towards protein C. The polypeptide can be cleaved between amino acid positions 320 and 321 to produce an active serine protease which can activate protein C, thereby inhibiting coagulation and stimulating activated protein C fibrinolytic activity.
The polypeptide encoded by the second polynucleotide cannot be cleaved, mimics inactive prothrombin and thereby acts as a reversible inhibitor of coagulation by competing with Factor Xa and Factor Va for interaction at the phospholipid surface.
Methods of producing recombinant polypeptides using the two isolated, modified polynucleotides are described.
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Cote Helene C. F.
MacGillivray Ross T. A.
Nesheim Michael E.
Stevens Willem K.
Elliott George C.
The University of British Columbia
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