IP Library › Granted Patent US 9,150,848
Granted Patent B2
US 9,150,848 · App. 14/272,726 · Granted Oct 6, 2015

Conjugated factor VIII molecules

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,150,848
App. No.
14/272,726
Granted
Oct 6, 2015
Kind
B2
Abstract

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.

Claims (12)

1. A B-domain truncated Factor VIII (FVIII) molecule, comprising: a heavy chain, a light chain, and a hydrophilic polymer; wherein (1) the heavy chain comprises a linker derived from the B-domain of a full-length FVIII molecule (SEQ ID NO:1) comprising a protease recognition site, (2) the hydrophilic polymer is covalently conjugated to the linker at Ser750 amino acid residue numbered relative to SEQ ID NO:1 via an O-linked oligosaccharide, (3) the length of the linker is 20-30 amino acids, and (4) activation of the molecule by thrombin results in removal of the linker and the hydrophilic polymer; wherein the B-domain truncated FVIII molecule has an increased circulatory half-life compared to a wild-type FVIII molecule.

2. The molecule according to claim 1 , wherein the hydrophilic polymer is polyethylene glycol (PEG).

3. The molecule according to claim 2 , wherein the size of the PEG is in a range of 10,000 to 160,000 Da.

4. The molecule according to claim 3 , wherein the size of the PEG is 40,000 Da.

5. The molecule according to claim 1 , wherein the hydrophilic polymer is a polysaccharide.

6. The molecule according to claim 5 , wherein the polysaccharide is polysialic acid.

7. A pharmaceutical composition comprising a molecule according to claim 1 .

8. A method of making a molecule according to claim 1 , wherein said method comprises conjugating a B-domain truncated Factor VIII molecule with a hydrophilic polymer via an O-linked oligosaccharide in the truncated B domain.

9. A molecule obtained by a method according to claim 8 .

10. A method of treating hemophilia comprising administering to a patient in need of such treatment a molecule according to claim 1 .

11. A method according to claim 10 , wherein said molecule is administered subcutaneously.

12. A method according to claim 10 , wherein said molecule is administered intravenously.