Clinical parameters by expression of factor VIII
Inventors
Conner, Edward R. • Riley, Brigit E. • Rouy, Didier
Assignees
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Publication Number
US-12497632-B2
Publication Date
2025-12-16
Expiration Date
Abstract
Described herein are constructs used for liver-specific expression of a transgene.
Core Innovation
The invention provides an AAV6 vector encoding human Factor VIII (FVIII) under the control of a liver-specific enhancer and a minimal promoter. The vector contains an expression cassette with insulator sequences, an enhancer, a promoter, and an FVIII coding sequence. The methods administer the vector to increase circulating FVIII activity or to decrease spontaneous bleeding episodes in a human subject receiving FVIII therapy.
Reported clinical data describe dose-dependent increases in circulating FVIII activity in patients with severe hemophilia A, accompanied by fewer spontaneous bleeding episodes and reduced or discontinued FVIII replacement therapy in higher-dose patients. The data also indicate generally acceptable tolerability across treated patients. Because the background section is omitted from the supplied content, the specific problem identified there is not explicitly described in patent.
Claims Coverage
The claims identify two inventive features across two independent claims, directed to increasing circulating FVIII activity and decreasing spontaneous bleeding episodes.
Increasing circulating FVIII activity
Claim 1 covers intravenous administration of an AAV6 vector encoding an FVIII protein to a human subject to produce an increase in circulating FVIII activity, wherein the vector comprises an expression cassette with insulator, enhancer, promoter, and FVIII coding sequences.
Decreasing spontaneous bleeding episodes
Claim 11 covers intravenous administration of an AAV6 vector encoding an FVIII protein to a human subject receiving FVIII therapy, resulting in no more than one spontaneous bleeding episode during the specified post-administration period, wherein the vector comprises an expression cassette with insulator, enhancer, promoter, and FVIII coding sequences.
The two independent claims cover AAV6 vector administration methods comprising an expression cassette with insulator, enhancer, promoter, and FVIII coding sequences, directed respectively to increasing circulating FVIII activity and decreasing spontaneous bleeding episodes.
Stated Advantages
Produces increases in circulating FVIII activity in patients with severe hemophilia A.
Decreases spontaneous bleeding episodes, with higher-dose patients generally experiencing no spontaneous bleeding episodes after the initial post-infusion period and claim 11 specifying no more than one episode during the stated post-administration period.
Markedly reduces or discontinues FVIII replacement therapy after the initial post-infusion period in higher-dose patients.
Demonstrates generally acceptable tolerability in treated patients.
Documented Applications
AAV6 vector gene therapy for human subjects with hemophilia A to increase FVIII protein or circulating FVIII activity.
Administration in human subjects receiving FVIII therapy to decrease spontaneous bleeding episodes.
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