Idera Pharmaceuticals, Inc.

Lakshmi Bhagat

Sudhir Agrawal

Ekambar R Kandimalla

Dong Yu

Daqing Wang

Mallikarjuna Putta

Yukui Li

FuGang Zhu

Tao Lan

Rajendra K Pandey

Ekambar M Kandimalla

Millikarjuna Putta

The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response

The invention provides immunostimulatory oligonucleotides having at least one CpG dinucleotide and a secondary structure at the 5'- or 3&#x2032;-end. These oligonucleotides have either reduced or improved immunostimulatory properties. The invention establishes that 5&#x2032;-terminal secondary structures affect immunostimulatory activity significantly more than those at the 3&#x2032;-end. The invention also provides methods for increasing or decreasing the immunostimulatory activity of a CpG-containing nucleic acid.

Stabilized immunomodulatory oligonucleotides

The invention relates to TLR9 antagonist compounds and their therapeutic or prophylactic use. The invention provides novel immune regulatory oligonucleotides and immunomers as antagonist of TLRs and methods of use thereof. These immune regulatory oligonucleotides have unique sequences that suppress, without completely ablating, TLR-mediated signaling in response to a TLR ligand or TLR signaling agonist. The methods may have use in the prevention and treatment of autoimmunity, inflammation, inflammatory bowel disease, lupus, allergy, asthma, infection, sepsis, cancer and immunodeficiency.

Toll like receptor modulators

The inventors have examined the means for providing more efficacious gene expression blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of gene expression blocking molecules. These features include the presence of multiple 3' ends and a linker at the 5&#x2032; ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technologies.

Compositions for inhibiting gene expression and uses thereof

The invention provides the use of immune regulatory oligonucleotides (IRO) as antagonist of TLRs in the prevention and treatment of a disease caused by a pathogen, for example, a DNA or RNA virus.

The invention relates to the therapeutic use of novel stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides novel RNA-based oligoribonucleotides with improved nuclease and RNase stability and that have immune modulatory activity through TLR7 and/or TLR8.

Stabilized immune modulatory RNA (SIMRA) compounds

The invention relates to synthetic chemical compositions that are useful for modulation of Toll-Like Receptor (TLR)-mediated immune responses. In particular, the invention relates to agonists of Toll-Like Receptor 9 (TLR9) that generate unique cytokine and chemokine profiles.

Synthetic agonists of TLR9

The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3' ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5&#x2032; end.

Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends

The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3' ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5&#x2032; end.

Growing community of inventors

Framingham, MA, United States of America

Lakshmi Bhagat