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US 11,896,652 B2Granted
Modified factor IX, and compositions, methods and uses for gene transfer to cells, organs, and tissues
AssigneeThe Children's Hospital of Philadelphia
InventorsKatherine A. High, Xavier Anguela
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Abstract
The invention relates to modified Factor IX coding sequence, expression cassette, vectors such as viral (e.g., lenti- or adeno-associated viral) vectors, and gene transfer methods and uses. In particular, to target Factor IX nucleic acid to cells, tissues or organs for expression (transcription) of Factor IX.
Claims23
A method of treating a human subject with hemophilia B comprising:
- administering to said subject a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) vector comprising a vector genome encapsidated by an AAV5 capsid,
- wherein said vector genome comprises at least two AAV inverted terminal repeats (ITR), an expression control element conferring liver tissue-specific expression operably linked with a nucleic acid sequence encoding human Factor IX (FIX) protein, and a polyadenylation signal sequence, wherein said nucleic acid sequence encoding human FIX protein is at least 70% identical to SEQ ID NO:10, has a reduced number of CpG di-nucleotides compared to wild-type nucleic acid sequence encoding human FIX protein and encodes the same human FIX protein encoded by SEQ ID NO:10, and wherein said therapeutically effective amount of said rAAV vector is a dose ranging from 1×1013 to 1×1014 vector genomes per kilogram (vg/kg) human subject body weight.
A method of treating a human subject with hemophilia B comprising:
- administering to said human subject a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) vector comprising a vector genome encapsidated by an AAV5 capsid,
- wherein said vector genome comprises at least two AAV inverted terminal repeats (ITR), an expression control element conferring liver tissue-specific expression operably linked with a nucleic acid sequence encoding human Factor IX (FIX) protein, and a polyadenylation signal sequence, wherein said nucleic acid sequence encoding human FIX protein is at least 70% identical to SEQ ID NO:10 and encodes the same human FIX protein encoded by SEQ ID NO:10, and
- wherein said therapeutically effective amount of said rAAV vector is a dose ranging from 1×1013 to 1×1014 vector genomes per kilogram (vg/kg) human subject body weight.
A method of treating a human subject with hemophilia B comprising:
- administering to said human subject a therapeutically effective amount of a recombinant adeno-associated virus (rAAV) vector comprising a vector genome encapsidated by an AAV5 capsid,
- wherein said vector genome comprises at least two AAV inverted terminal repeats (ITR), an expression control element conferring liver tissue-specific expression operably linked with a nucleic acid sequence encoding human Factor IX (FIX) protein, and a polyadenylation signal sequence, wherein said nucleic acid sequence encoding human FIX protein is at least 70% identical to SEQ ID NO:10 and encodes a human FIX protein variant having an amino acid sequence at least 99% identical to that encoded by SEQ ID NO:10, amino acid number 338 thereof being leucine and invariant, and
- wherein said therapeutically effective amount of said rAAV vector is a dose ranging from 1×1013 to 1×1014 vector genomes per kilogram (vg/kg) human subject body weight.
Dependencies are inferred from the claim text.