Method for determining immunostimulatory activity of RNA...

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid

Reexamination Certificate

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Reexamination Certificate

active

08076068

ABSTRACT:
The present invention provides 4-nucleotide (4mer) RNA motifs that confer immunostimulatory activity, in particular, IFN-α-inducing activity to a RNA oligonucleotide. The present invention also provides RNA oligonucleotides, including siRNA, with high or low immunostimulatory activity. The present invention further provides the use of the RNA oligonucleotides of the invention for therapeutic purposes.

REFERENCES:
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patent: 2005/0070462 (2005-03-01), Schellack et al.
patent: 2006/0025366 (2006-02-01), MacLachlan et al.
patent: WO 03/086280 (2003-10-01), None
patent: WO 2004/004743 (2004-01-01), None
patent: WO 2005/021044 (2005-03-01), None
Barchet et al., “Dendritic cells respond to influenza virus through TLR7- and PKR-independent pathways,” Eur J Immunol 35: 236-242, 2005.
Heil et al., “Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8,” Science 303: 1526-1529, Mar. 5, 2004.
Hornung et al., “Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7,” Nature Medicine 11(3): 263-270, Mar. 2005.
Judge et al., “Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA,” Nature Biotechnology 23(4): 457-462, Apr. 2005.
Kaberdin, “Probing the substrate specificity ofEscherichia coliRNase E using a novel oligonucleotide-based assay,” Nucleic Acids Research 31(16): 4710-4716, Aug. 15, 2003.
Lochmann et al., “Drug delivery of oligonucleotides by peptides,” European Journal of Pharmaceutics and Biopharmaceutics 58: 237-251, 2004.
Schlee et al., “siRNA and isRNA: Two Edges of One Sword,” Molecular Therapy 14(4): 463-470, Oct. 2006.
Sioud, “Induction of Inflammatory Cytokines and Interferon Responses by Double-stranded and Single-stranded siRNAs is Sequence-dependent and Requires Endosomal Localization,” J Mol Biol 348: 1079-1090, 2005.

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