US 11,746,359 B2
Helper-dependent adenoviral gene therapy delivery and expression system
Merry Ruan, South San Francisco, CA (US); Kilian Guse, Berlin (DE); and Brendan Lee, Houston, TX (US)
Assigned to Baylor College of Medicine, Houston, TX (US)
Filed by Baylor College of Medicine, Houston, TX (US)
Filed on Apr. 1, 2022, as Appl. No. 17/711,647.
Application 17/711,647 is a continuation of application No. 17/358,904, filed on Jun. 25, 2021.
Application 17/358,904 is a continuation of application No. 14/763,326, abandoned, previously published as PCT/IB2014/000071, filed on Jan. 27, 2014.
Claims priority of provisional application 61/756,516, filed on Jan. 25, 2013.
Prior Publication US 2022/0282280 A1, Sep. 8, 2022
Int. Cl. C12N 15/861 (2006.01); A61K 48/00 (2006.01); C07K 14/545 (2006.01); C12N 15/86 (2006.01)
CPC C12N 15/86 (2013.01) [A61K 48/0058 (2013.01); C12N 2710/10043 (2013.01); C12N 2710/10343 (2013.01); C12N 2800/24 (2013.01)] 6 Claims
 
1. A pharmaceutical composition, comprising a therapeutically effective amount of at least one helper-dependent adenoviral vector containing a nucleic acid sequence encoding proteoglycan 4 (PRG4), or a biologically active fragment thereof, which has chondoprotective activity, a left and a right adenoviral inverted terminal repeats (L ITR and R ITR), adenoviral packaging signal sequences and non-viral, non-coding stuffer nucleic acid sequences,
wherein
i. the at least one helper-dependent adenoviral vector additionally comprises a nucleic acid sequence encoding interleukin-1 receptor antagonist (II-1Ra), or
ii the composition comprises a second helper-dependent adenoviral vector comprising a nucleic acid sequence encoding Il-1Ra;
wherein PRG4 expression is controlled by an elongation factor 1 alpha (EF 1 alpha) promoter and expression of Il-1Ra is controlled by an NF-κB promoter, and
wherein the at least one helper-dependent adenoviral vector containing a nucleic acid sequence encoding PRG4, comprises a nucleic acid sequence which has at least 90% sequence homology with the nucleic acid sequence set forth in SEQ ID NO: 1, or SEQ ID NO: 2.