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Use of Sterically Stabilized Cationic Liposomes to Efficiently Deliver CpG Oligonucleotides in vivo

Immunostimulatory CpG oligonucleotides (ODN) show promise as immune adjuvants, anti-allergens, and immunoprotective agents. Increasing the bioavailability and duration of action of CpG ODN should improve their therapeutic utility. This invention claims use of Sterically Stabilized Cationic Liposomes (SSCL) to deliver CpG ODNs. In addition to use of SSCL to deliver CpG ODNs, SSCL-CpG compositions are also claimed in the patent application. The claimed SSCL comprise three distinct phospholipid elements, DC-CHOL (which increases liposome membrane stability while improving the uptake and encapsulation of DNA), DOPE (a pH-sensitive neutral lipid that improves the cytosolic delivery of CpG ODNs following internalization), and PEG-PE (which stabilizes the liposome and also facilitates cellular uptake). The inventors have conducted both in vivo and in vitro studies using the SSCL-CpG compositions, showing that in vitro, liposome-encapsulated CpG ODNs stimulated significantly more interferon-gamma (IFN-gamma) production than free CpG ODNs. The in vivo testing the inventors completed show that SSCL encapsulation of CpG ODNs increases the magnitude and duration of the activity of the CpG ODNs in vivo; when CpG-SSCLs were administered to mice infected with L. monocytogenes (listeria), one hundred percent of the infected mice survived four weeks post-treatment.

Inventors:
Dennis Klinman
Ihsan Gursel

Intellectual Property:
PCT Application No. PCT/US2002/024235
US Patent No. 7,666,674

Publications:
The invention is further described in Gursel I et al., "Sterically stabilized cationic liposomes improve the uptake and immunostimulatory activity of cpg oligonucleotides," J. Immunol. 2001 Sep 15;167(6):3324-8.

Licensing Contact:
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
Silver Spring, MD 20993
Email: FDAInventionlicensing@fda.hhs.gov
Phone: 240-402-4561

OTT Reference No: E-215-2001/0
Updated: August 7, 2015