The present invention comprises ligands and methods of manufacture thereof
as well as pharmaceutical preparations including the ligands. The ligands
may be human or humanized monoclonal antibodies and fragments,
derivatives and homologs thereof. These may exhibit an unforeseen
"plateau effect", i.e. the achievement of only a partial inactivation of
a factor involved in hemostasis, in particular in the coagulation
cascade, either individually or in combination even in molar excess. The
ligands may bind to a factor or a complex of factors resulting in only
partially impairing the function of a physiologically functional site of
the said factor or factor complex even in molar excess. This makes the
ligands particularly suitable for treating coagulation disorders and
resulting thrombotic pathologic conditions while minimizing the risk of
bleeding. Particularly useful is a property of ligands in accordance with
the present invention to allow some physiological function of the
affected site even when the ligand is in molar excess. The ligands may be
anti-factor VIII antibodies or antibodies against a factor VIII complex,
in particular human or human hybrid monoclonal antibodies which bind to
factor VIII or a factor VIII complex and at least partially inhibit the
activity of factor VIII.