公开(公告)号：US20220362408A1

公开(公告)日：2022-11-17

申请号：US17250712

申请日：2019-08-23

Applicant: SPARK THERAPEUTICS, INC.

Inventor： Xavier ANGUELA ,  Liron ELKOUBY

IPC: A61K48/00 ,  C07K14/755 ,  C12N15/86 ,  C12N7/00 ,  C07K14/775 ,  A61P7/04 ,  A61K9/00 ,  C07K14/81

Abstract: The invention provides expression cassettes. In certain embodiments, an expression cassette comprises (a) a regulatory element at least 90% identical to the sequence of any of SEQ ID NOs:2-67, and (b) a nucleic acid sequence encoding a Factor VIII protein having a B domain deletion (FVIII-BDD), where the nucleic acid sequence of (a) is at least 90% identical to the sequence of SEQ ID NO:77, where the regulatory element is operably linked to the nucleic acid sequence, and where no intron is present between the regulatory element and the nucleic acid sequence encoding FVIII-BDD, or where no more than 0-107 nucleotides of untranslated nucleic acid is between the regulatory element and the nucleic acid sequence encoding FVIII-BDD. In certain embodiments, expression cassettes contain sequence elements having CpG(s) substituted with CpT, CpA, TpG, or ApG at the same position(s) or has CpG reduced nucleic acid sequences.