Cell lines, ligands and antibody fragments for use in pharmaceutical compositions for preventing and treating haemostasis disorders

Abstract

A ligand derived from, e.g., a Fab fragment of a monoclonal antibody obtainable from the cell line deposited with the Belgian Coordinated Collections of Micro-Organisms under accession number LMBP 5108CB binds to the human platelet glycoprotein GPIb and prevents the binding of von Willebrand factor to said GPIb without inducing thrombocytopenia. The said ligand is useful, in admixture with a pharmaceutically acceptable carrier, in a pharmaceutical composition, optionally further comprising a thrombolytic agent, for preventing and/or treating haemostasis disorders.

1 . A method for treating patients suffering from or at risk of developing a platelet-dependent disorder, which comprises administering to said patient a therapeutically effective amount of an inhibitory anti-GPIb monovalent antibody fragment which binds in vivo to human glycoprotein GPIb and prevents the binding of von Willebrand factor to said human glycoprotein GPIb, wherein administration of said monovalent antibody fragment does not incur thrombocytopenia in said patient. 
     
     
         2 . The method according to  claim 1 , wherein said monovalent antibody fragment is a Fab fragment or a single variable domain. 
     
     
         3 . The method according to  claim 2 , wherein said monovalent antibody fragment comprises SEQ ID NO: 4. 
     
     
         4 . The method according to  claim 1 , wherein said monovalent antibody fragment is an antibody fragment from a monoclonal antibody produced by the cell line deposited with the Belgian Coordinated Collections of Microorganisms, under accession number LMBP 5108CB. 
     
     
         5 . The method according to  claim 1 , wherein said monovalent antibody fragment is a humanized antibody fragment. 
     
     
         6 . The method according to  claim 1 , wherein said platelet-dependent disorder is a hemostasis disorder. 
     
     
         7 . The method according to  claim 1 , wherein said platelet-dependent disorder is platelet-dependent thrombus formation. 
     
     
         8 . The method according to  claim 1 , wherein said platelet-dependent disorder is caused by angioplasty, coronary stenting, or thrombolysis. 
     
     
         9 . The method according to  claim 1 , wherein said method further comprises administering to said patient, simultaneously or sequentially, a thrombolytic agent. 
     
     
         10 . The method according to  claim 9 , wherein said thrombolytic agent is selected from the group consisting of tissue plasminogen activator (t-Pa), streptokinase, reptilase, TNK-t-Pa, and staphylokinase. 
     
     
         11 . The method according to  claim 1 , wherein said method further comprises administering to said patient in adjunctive therapy one or more other anti-thrombotic agents. 
     
     
         12 . The method according to  claim 11 , wherein said other anti-thrombotic agent is aspirin or heparin.