US 2005/0239733 A1 · Sequence requirements for inhibitory oligonucleotides

Abstract

Novel oligonucleotides having immune inhibitory effects, and methods for their use, are provided. The inhibitory oligonucleotides include those that specifically inhibit certain Toll-like receptors, including TLR7, TLR8, and TLR9. Certain of the immunoinhibitory oligonucleotides inhibit a combination of TLRs selected from TLR7, TLR8, and TLR9. Inhibitors of TLR9 are characterized by a 5′ CC dinucleotide appropriately spaced upstream of a G-rich oligomer. Inhibitors of TLR8 include specific simple dinucleotides and oligonucleotides ending at their 3′ termini with the specific dinucleotides. TLR7 inhibitors include oligonucleotides having a phosphorothioate backbone. Also provided are combinations and conjugates involving the inhibitory oligonucleotides of the invention and other agents, where the other agents include TLR agonists and antigens. Compositions of the invention can be used to shape an immune response, reduce unwanted specific TLR-mediated immunostimulation, and to treat conditions including allergy, asthma, infection, and cancer.

Claims46

Dependent claims

A composition comprising an isolated immunoinhibitory nucleic acid molecule comprising a sequence

XaCCN1N2N3YbN4GGGZc (SEQ ID NO:1)
wherein:
each C is cytidine or a derivative thereof, wherein at least one C is a cytidine derivative;
each G is guanosine or a deaza derivative thereof;
Xa is any nucleotide sequence a nucleotides long, wherein a is an integer between 0-12, inclusive, and each nucleotide is selected independently of any other in Xa;
Yb is any nucleotide sequence b nucleotides long, wherein b is an integer between 0-21, inclusive, and each nucleotide is selected independently of any other in Yb;
Zcis any nucleotide sequence c nucleotides long, wherein c is an integer between 0-12, inclusive, and each nucleotide is selected independently of any other in Zc;
and
N1, N2, N3, and N4 are each independently any nucleotide:

6 more elements

Dependencies are inferred from the claim text.

Sequence requirements for inhibitory oligonucleotides

Life of this patent

Sequence requirements for inhibitory oligonucleotides

Life of this patent

Abstract

Claims46