IP Library › Granted Patent US 12,655,448
Granted Patent B2
US 12,655,448 · App. 17/358,904 · Granted Jun 16, 2026

Helper-dependent adenoviral gene therapy delivery and expression system

Inventors: Zhechao Ruan (Houston, TX); Kilian Guse (Hamburg, DE); Brendan Lee (Houston, TX)
Assignee: Baylor College of Medicine
C12N15/86A61K48/0058C12N2710/10043C12N2710/10343C12N2800/24
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Quick Facts
Patent No.
US 12,655,448
App. No.
17/358,904
Granted
Jun 16, 2026
Kind
B2
Abstract

The present invention relates to gene therapy delivery and expression systems comprising at least one helper-dependent adenoviral vector containing a nucleic acid sequence encoding for proteoglycan 4 (PRG4) or a biologically active fragment thereof. The invention further relates to a pharmaceutical composition comprising a therapeutically effective amount of at least one helper-dependent adenoviral vector containing said nucleic acid sequence encoding for proteoglycan 4 (PRG4), or a homolog thereof from any other species, or a biologically active fragment thereof. The invention also relates to the use of the novel gene therapy delivery and expression system according to the invention for use in the prevention and/or treatment of camptodactyly-arthropathy-coxa vara-pericarditis (CACP), or a musculoskeletal disorder such as a joint disorder or joint disease.

Claims (26)

1 . A method for the treatment of osteoarthritis in a subject in need thereof, comprising administering to a joint of the subject a helper-dependent adenoviral vector comprising a nucleic acid sequence encoding proteoglycan 4 (PRG4), a left inverted terminal repeat (LITR) and a right adenoviral inverted terminal repeat (RITR), adenoviral packaging signal sequences and non-viral, non-coding stuffer nucleic acid sequences, wherein PRG4 expression is controlled by an elongation factor 1 alpha (EF 1 alpha) promoter,

wherein the helper-dependent adenoviral vector does not comprise a nucleic acid sequence encoding interleukin-1 receptor antagonist (II-1Ra) and

wherein the subject is not administered a second helper-dependent adenoviral vector comprising a nucleic acid sequence encoding II-1Ra.

2 . The method of claim 1 , wherein the osteoarthritis is age-related osteoarthritis.

3 . The method of claim 1 , wherein the osteoarthritis is post-traumatic osteoarthritis.

4 . The method of claim 1 , wherein the nucleic acid sequence encoding PRG4 comprises a nucleic acid having at least 90% identity to the sequence set forth in SEQ ID NO: 3.

5 . The method of claim 1 , wherein the nucleic acid sequence encoding PRG4 comprises the nucleic acid sequence set forth in SEQ ID NO: 3.

6 . The method of claim 1 , wherein the helper-dependent adenoviral vector comprises a nucleic acid sequence which is at least 90% identical to the nucleic acid sequence set forth in SEQ ID NO: 1.

7 . The method of claim 1 , wherein the helper-dependent adenoviral vector comprises the nucleic acid sequence set forth in SEQ ID NO: 1.

8 . The method of claim 1 , wherein the amino acid sequence of PRG4 comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO: 5.

9 . The method of claim 1 , wherein the amino acid sequence of PRG4 comprises the sequence set forth in SEQ ID NO: 5.

10 . The method of claim 1 , where the administering to a joint of the subject comprises administration not more frequently than once in six weeks.

11 . The method of claim 1 , wherein the helper-dependent adenoviral vector comprises a nucleic acid sequence which is at least 90% identical to the nucleic acid sequence set forth in SEQ ID NO: 1 and the amino acid sequence of PRG4 encoded by the nucleic acid sequence encoding PRG4 comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO: 5.

12 . The method of claim 11 , wherein the amino acid sequence of PRG4 encoded by the nucleic acid sequence encoding PRG4 comprises an amino acid sequence that is at least identical to the sequence set forth in SEQ ID NO: 5.

13 . A method for the prevention of post-traumatic osteoarthritis in a subject in need thereof, comprising administering to a joint of the subject a helper-dependent adenoviral vector comprising a nucleic acid sequence encoding PRG4, a LITR and a RITR, adenoviral packaging signal sequences and non-viral, non-coding stuffer nucleic acid sequences, wherein PRG4 expression is controlled by an elongation factor 1 alpha (EF 1 alpha) promoter, and

wherein the helper-dependent adenoviral vector does not comprise a nucleic acid sequence encoding interleukin-1 receptor antagonist (II-1Ra) and

wherein the subject is not administered a second helper-dependent adenoviral vector comprising a nucleic acid sequence encoding II-1Ra.

14 . The method of claim 13 , wherein the nucleic acid sequence encoding PRG4 comprises a nucleic acid having at least 90% identity to the sequence set forth in SEQ ID NO: 3.

15 . The method of claim 13 , wherein the nucleic acid sequence encoding PRG4 comprises the nucleic acid sequence set forth in SEQ ID NO: 3.

16 . The method of claim 13 , wherein the helper-dependent adenoviral vector comprises a nucleic acid sequence which is at least 90% identical to the nucleic acid sequence set forth in SEQ ID NO: 1.

17 . The method of claim 13 , wherein the helper-dependent adenoviral vector comprises the nucleic acid sequence set forth in SEQ ID NO: 1.

18 . The method of claim 13 , wherein the amino acid sequence of PRG4 comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO: 5.

19 . The method of claim 13 , wherein the amino acid sequence of PRG4 comprises the sequence set forth in SEQ ID NO: 5.

20 . The method of claim 13 , where the administering to a joint of the subject comprises administration not more frequently than once in four weeks.

21 . The method of claim 13 , wherein the helper-dependent adenoviral vector comprises a nucleic acid sequence which is at least 90% identical to the nucleic acid sequence set forth in SEQ ID NO: 1 and the amino acid sequence of PRG4 encoded by the nucleic acid sequence encoding PRG4 comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO: 5.

22 . The method of claim 21 , wherein the amino acid sequence of PRG4 encoded by the nucleic acid sequence encoding PRG4 comprises an amino acid sequence that is at least identical to the sequence set forth in SEQ ID NO: 5.

Assignments (2)
SECURITY INTEREST Recorded Jul 4, 2025
From: PACIRA THERAPEUTICS, INC.
To: WELLS FARGO BANK, NATIONAL ASSOCIATION, AS ADMINISTRATIVE AGENT
Reel/Frame 071609/0342 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2021
From: RUAN, ZHECHAO; GUSE, KILIAN; LEE, BRENDAN
To: BAYLOR COLLEGE OF MEDICINE
Reel/Frame 056747/0920 →
Continuity (3)
Continuation 14763326
Provisional Application 61756516 · Jan 25, 2013
Related Publication 20220017923A1 · Jan 20, 2022
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