Conjugated factor VIII molecules
View Patent ↗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 NO: 2, wherein the FVIII molecule is covalently conjugated to a PEG via an O-linked oligosaccharide on a serine residue corresponding to position 750 of SEQ ID NO: 2, wherein the size of the PEG is about 40,000 Da.
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 PEG via an O-linked oligosaccharide on the serine residue corresponding to position 750 of SEQ ID NO: 2, wherein the size of the PEG is about 40,000 Da.
3. The FVIII molecule of claim 2 , wherein the mammalian host cell is a CHO cell.
4. A pharmaceutical composition comprising the FVIII molecule of claim 1 .
5. A pharmaceutical composition comprising the FVIII molecule of claim 2 .
6. 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 4 .
7. 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 5 .