Clinical parameters by expression of factor VIII
AssigneeSangamo Therapeutics, Inc.
InventorsEdward R. Conner, Brigit E. Riley, Didier Rouy
Life of this patent
Estimating the term…
Abstract
Described herein are constructs used for liver-specific expression of a transgene.
Claims19
A method of increasing Factor VIII (FVIII) protein in a human subject, comprising intravenously administering to the human subject a dose of 1×1013 to 5×1013 vg/kg of an Adenovirus-Associated Virus serotype 6 (AAV6) vector that encodes a FVIII protein, wherein administration of the AAV6 vector results in a clinically relevant 20% to 172% increase in the level of circulating FVIII activity, and wherein the AAV6 vector comprises an expression cassette that comprises
- a first insulator sequence comprising nucleotides 14-32 of SEQ ID NO:5,
- an enhancer sequence of SEQ ID NO:2,
- a promoter sequence of SEQ ID NO:3,
- a coding sequence that encodes an FVIII protein of SEQ ID NO:1, and
- a second insulator sequence comprising nucleotides 4869-4885 of SEQ ID NO:5.
A method of decreasing spontaneous bleeding episodes in a human subject receiving FVIII therapy, comprising intravenously administering to the human subject a dose of 1×1013 to 5×1013 vg/kg of an Adenovirus-Associated Virus serotype 6 (AAV6) vector that encodes a FVIII protein, wherein no more than one spontaneous bleeding episode occurs from 3 to 12 months after the intravenous administration, and wherein the AAV6 vector comprises an expression cassette that comprises
- a first insulator sequence comprising nucleotides 14-32 of SEQ ID NO:5,
- an enhancer sequence of SEQ ID NO:2,
- a promoter sequence of SEQ ID NO:3,
- a coding sequence that encodes an FVIII protein of SEQ ID NO:1, and
- a second insulator sequence comprising nucleotides 4869-4885 of SEQ ID NO:5.
Dependencies are inferred from the claim text.