Activatable fibrinolytic and anti-thrombotic proteins
AssigneeBritish Biotech Pharmaceuticals Limited
InventorsKeith Dawson, Richard M. Edwards, Joan M. Forman
Life of this patent
Estimating the term…
Abstract
Proteinaceous compounds are activatable by enzymes of the clotting cascade to have fibrinolytic or clot formation inhibition activity. For example, a plasminogen analogue is activatable to plasmin by thrombin or Factor Xa. Fibrinolytic or clot formation inhibition activity is therefore directed to the site of clot formation.
Claims24
A proteinaceous compound which is activatable by thrombin or Factor Xa enzyme to have fibrinolytic activity;
- characterized in that the compound is a plasminogen analogue, wherein the cleavage site Pro(559) to Val(562) of native plasminogen is altered by substitution of an amino acid sequence clearable by thrombin or Factor Xa, said plasminogen analogue being activatable by thrombin or Factor Xa cleavage to have plasmin activity.
A proteinaceous compound which is activatable by Factor Xa to have fibrinolytic activity;
- characterized in that the compound is a plasminogen analogue, wherein the cleavage site Pro(559) to Val(562) of native plasminogen is altered by substitution of an amino acid sequence clearable by Factor Xa;
- said amino acid sequence comprising a sequence P4-P3-Gly-Arg, wherein P4 represents a hydrophobic residue and P3 represents an acidic residue;
- said plasminogen analogue being activatable by Factor Xa cleavage to have plasmin activity.
A proteinaceous compound which is activatable by thrombin to have fibrinolytic activity;
- characterized in that the compound is a plasminogen analogue, wherein the cleavage site Pro(559) to Val(562) of native plasminogen is altered by substitution of an amino acid sequence clearable by thrombin;
- said amino acid sequence comprising a sequence P4-P3-Pro-Arg-P1'-P2', wherein each of P4 and P3 independently represents a hydrophobic residue and each of P1' and P2' independently represents a non-acidic residue;
- said plasminogen analogue being activatable by thrombin cleavage to have plasmin activity.
A proteinaceous compound which is activatable by thrombin to have fibrinolytic activity;
- characterized in that the compound is a plasminogen analogue, wherein the cleavage site Pro(559) to Val(562) of native plasminogen is altered by substitution of an amino acid sequence clearable by thrombin;
- said amino acid sequence comprising a sequence P2-Arg-P1', wherein one of the residues P2 and P1' represents glycine and the other represents any amino acid residue;
- said plasminogen analogue being activatable by thrombin cleavage to have plasmin activity.
A proteinaceous compound which is activatable by thrombin to have fibrinolytic activity;
- characterized in that the compound is a plasminogen analogue, wherein the cleavage site Pro(559) to Val(562) of native plasminogen is altered by substitution of an amino acid sequence clearable by thrombin;
- said amino acid sequence comprising a sequence Gly-Pro-Arg;
- said plasminogen analogue being activatable by thrombin cleavage to have plasmin activity.
Dependencies are inferred from the claim text.