Conjugated FVIII variants
The present invention relates to conjugated Factor VIII variants. The present invention in particular relates to conjugated FVIII variants comprising different polymeric groups as well as use thereof.
1. A Factor VIII (FVIII) variant comprising a FVIII molecule with a truncated B-domain, wherein the truncated B-domain is SEQ ID NO:2, wherein the FVIII variant is covalently heteroconjugated with: (1) at least one poly(ethylene glycol) (PEG) polymer via an O-linked oligosaccharide in the truncated B-domain; and (2) at least one poly(sialic acid) (PSA) polymer via an N-linked oligosaccharide.
2. The FVIII variant according to claim 1 , further comprising two to four PSA polymers linked to one double-branched N-linked oligosaccharide in the A1 domain and one double-branched N-linked oligosaccharide in the A3 domain.
3. The FVIII variant according to claim 1 , wherein said variant comprises one or two PSA polymers linked to one double-branched N-linked oligosaccharide in the A1 domain.
4. The FVIII variant according to claim 1 , wherein said variant comprises one or two PSA polymers linked to one double-branched N-linked oligosaccharide in the A3 domain.
5. The FVIII variant according to claim 1 , wherein the size of the PEG polymer is 30-50 kDa.
6. The FVIII variant according to claim 1 , wherein the size of the PSA polymer is 20-50 kDa.
7. A method of making a FVIII variant according to claim 1 , wherein said method comprises conjugating a FVIII molecule with at least one PEG polymer and at least one PSA polymer.
8. A pharmaceutical composition comprising a FVIII variant according to claim 1 and optionally one or more pharmaceutically acceptable excipients.
9. A method for treating hemophilia A comprising administering the FVIII variant according to claim 1 to a patient in need thereof.