British Biotech Pharmaceuticals Limited

British Bio-Technology Limited

Richard James Gilbert

Michael George Hunter

Keith Martyn Dawson

Richard Mark Edwards

Stewart Craig

Lloyd George Czaplewski

Stem cell inhibiting proteins

Plasmin precursors are modified so that they exhibit resistance to inhibitors of plasmin. These modified plasmin precursors have fibrinolytic, thrombolytic or antithrombotic properties, which are useful in the treatment of blood clotting diseases or conditions.

Modified plasmin precursors with resistance to inhibitors of plasmin

Proteinaceous molecules with stem cell inhibition activity are analogues of LD78 or MIP-1.alpha. which have mutations to prevent or reduce multimer formation beyond certain stages (for example a dodecamer). Aggregate formation is therefore inhibited, and the resulting low molecular weight monomers (or oligomers) have improved solution properties leading to enhanced productivity and greater therapeutic utility as stem cell protective agents, which are useful in tumour therapy.

A plasminogen analogue activatable by thrombin to have plasmin activity which contains the cleavage site sequence (SEQ ID NO: 23): ##STR1## where Xaa at position 1 represents P4; Xaa at position 2 represents P3; Xaa at position 5 represents P1'; and Xaa at position 6 represents P2' where P3 is a basic amino acid residue, P4 is a hydrophobic amino acid residue and each of P1' and P2' is independently a non-acidic amino acid residue, said site being cleavable by thrombin between Arg and P1'.

Thrombin activatable plasminogen analogues

Inhibitor resistant serine proteases

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Oxford, United Kingdom

Richard James Gilbert