Conjugated Factor VIII Molecules
The present invention relates to B-domain truncated Factor VIII molecules with a modified circulatory half-life, said molecule being covalently conjugated with a hydrophilic polymer. The invention furthermore relates to methods for obtaining such molecules as well as use of such molecules.
1 . A Factor VIII molecule with a modified circulatory half-life comprising a FVIII molecule with a truncated B-domain consisting of amino acids 741-760 of SEQ ID N0:2, wherein the FVIII molecule is covalently conjugated to a hydrophilic polymer via an O-linked oligosaccharide on a serine residue corresponding to position 750 of SEP ID N0:2.
2 . The FVIII molecule of claim 1 made by a process comprising: a) transfecting a mammalian host cell with a vector encoding the FVIII molecule of claim 1 ; b) culturing the host cell of step (a) under conditions suitable to express the FVIII molecule in the host cell; c) harvesting the FVIII molecule from the host cell culture of step (b); and d) covalently conjugating the FVIII molecule with the hydrophilic polymer via an O-linked oligosaccharide on the serine residue corresponding to position 750 of SEQ ID N0:2.
3 . The FVIII molecule of claim 1 , wherein the hydrophilic polymer is a polysaccharide.
4 . The FVIII molecule of claim 1 , wherein the hydrophilic polymer is heparin.
5 . The FVIII molecule of claim 2 , wherein the mammalian host cell is a CHO cell.
6 . A pharmaceutical composition comprising the FVIII molecule of claim 1 .
7 . A pharmaceutical composition comprising the FVIII molecule of claim 2 .
8 . A method of treating a haemophilic disease comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 6 .
9 . A method of treating a haemophilic disease comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 7 .
10 . A method according to claim 8 , wherein the pharmaceutical composition is administered subcutaneously.
11 . A method according to claim 9 , wherein the pharmaceutical composition is administered intravenously.
12 . The FVIII molecule of claim 2 , wherein the hydrophilic polymer is a polysaccharide.
13 . The FVIII molecule of claim 2 , wherein the hydrophilic polymer is heparin.