公开(公告)号：US20210038744A1

公开(公告)日：2021-02-11

申请号：US16965895

申请日：2019-01-31

Applicant: BIOVERATIV THERAPEUTICS INC.

Inventor： Andrea ANNONI ,  Alessio CANTORE ,  Douglas DRAGER ,  Tongyao LIU ,  Michela MILANI ,  Jeff MOFFIT ,  Luigi NALDINI ,  Susannah PATARROYO-WHITE ,  Robert T. PETERS ,  Alexey SEREGIN

IPC: A61K48/00 ,  A61K38/37

Abstract: The present disclosure provides lentiviral vectors comprising codon optimized Factor VIII sequences, and methods of using such lentiviral vectors. The liver-targeted lentiviral vectors disclosed herein can be used for gene therapy, wherein the lentiviral gene delivery enables stable integration of the transgene expression cassette into the genome of targeted cells (e.g., hepatocytes) of pediatric (e.g., neonatal) or adult subjects, achieving an improvement in FVIII expression (for example, a 100-fold improvement) at low lentiviral vector doses (e.g., 5×1010 or lower, such as 1.5×109 or lower, or 1×108 TU/kg or lower). The present disclosure also provides methods of treating bleeding disorders such as hemophilia (e.g., hemophilia A) comprising administering to a subject in need thereof a liver-targeted lentiviral vector comprising a codon optimized Factor VIII nucleic acid sequence at low dosages (1×108 TU/kg or lower to 1.5×1010 TU/kg).

公开(公告)号：US20200069817A1

公开(公告)日：2020-03-05

申请号：US16537192

申请日：2019-08-09

Applicant: BIOVERATIV THERAPEUTICS INC.

Inventor： Tongyao LIU ,  Alexey SEREGIN ,  Robert T. PETERS ,  Jiayun LIU ,  Philip ZAKAS ,  Douglas DRAGER ,  Susannah PATARROYO-WHITE

IPC: A61K48/00 ,  C12N15/86 ,  C12N7/00 ,  C07K14/755 ,  A61P7/04 ,  A61K9/00

Abstract: The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the target sequence encodes a miRNA and/or a therapeutic protein. In certain embodiments, the therapeutic protein comprises a clotting factor, a growth factor, a hormone, a cytokine, an antibody, a fragment thereof, and a combination thereof. In some embodiments, the first ITR and/or the second ITR is an ITR of a non-adeno-associated virus (AAV). The present disclosure also provides methods of treating a metabolic disorder of the liver in a subject comprising administering to the subject the nucleic acid molecule or a polypeptide encoded thereby.

公开(公告)号：US20210163986A1

公开(公告)日：2021-06-03

申请号：US16636583

申请日：2018-08-09

Applicant: BIOVERATIV THERAPEUTICS INC.

Inventor： Alexey SEREGIN ,  Tongyao LIU ,  Susannah PATARROYO-WHITE ,  Douglas DRAGER ,  Robert T. PETERS ,  Jiayun LIU

IPC: C12N15/86 ,  C07K14/755

Abstract: The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a miRNA and/or a therapeutic protein. In certain embodiments, the therapeutic protein comprises a clotting factor, e.g., a FVIII polypeptide, a FIX polypeptide, or a fragment thereof. In some embodiments, the first ITR and/or the second ITR is an ITR of a non-adeno-associated virus (AAV). The present disclosure also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject the nucleic acid molecule or a polypeptide encoded thereby.