STABILIZED IMMUNE MODULATORY RNA (SIMRA) COMPOUNDS

• US 20090053205A1
• Filed: 07/07/2008
• Published: 02/26/2009
• Est. Priority Date: 07/09/2007
• Status: Active Grant

• Current Assignee: Idera Pharmaceuticals, Inc. (Aceragen Incorporated)
• Original Assignee: Idera Pharmaceuticals, Inc. (Aceragen Incorporated)
• Inventors: Bhagat, Lakshmi, Kandimalla, Ekambar, Wang, Daqing, Agrawal, Sudhir, Lan, Tao
• Granted Patent: US 8,188,261 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C12N 15/117 Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• CPC Class Codes: C12N 2310/17 Immunomodulatory nucleic acids
• CPC Class Codes: C12N 2310/317 with an inverted bond, e.g. a cap structure
• CPC Class Codes: C12N 2310/3183 Diol linkers, e.g. glycols or propanediols
• CPC Class Codes: C12N 2310/51 in polymeric form, e.g. multimers, concatemers
• CPC Class Codes: C12N 2320/51 modulating the chemical stability, e.g. nuclease-resistance

Abstract

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.

Claims

1. A SIMRA compound selected from the group consisting of SIMRA#1 though SIMRA#189.

2. A composition comprising the SIMRA compound of claim 1 and a physiologically acceptable carrier.

3. A method for generating an immune response in a vertebrate, the method comprising administering to the vertebrate a SIMRA compound according to claim 1.

4. A method for therapeutically treating a vertebrate having a disease or disorder where modulating an immune response would be beneficial such method comprising administering to the vertebrate a SIMRA compound according to claim 1 in a pharmaceutically effective amount.

5. The method of claim 4 where in the disease or disorder is cancer, an autoimmune disorder, airway inflammation, inflammatory disorder, infectious disease, skin disorder, allergy, asthma or a disease caused by a pathogen.

6. The method according to claim 4, further comprising administering one or more chemotherapeutic compounds.

7. The method according to claim 4, further comprising administering a targeted therapeutic agent.

8. The method according to claim 4, further comprising administering an antibody.

9. The method according to claim 4, further comprising administering a DNA vaccine.

10. The method according to claim 4, further comprising administering a protein vaccine.

11. The method according to claim 4, further comprising administering a peptide vaccine.

12. The method according to claim 4, further comprising administering an antigen.

13. The method according to claim 4, further comprising an adjuvant.

14. A method for prophylactically treating a vertebrate having a disease or disorder where modulating an immune response would be beneficial such method comprising administering to the vertebrate a SIMRA compound according to claim 1 in a pharmaceutically effective amount.

15. The method of claim 14 wherein the disease or disorder is cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen in a vertebrate.

16. The method according to claim 15, further comprising administering one or more chemotherapeutic compounds.

17. The method according to claim 15, further comprising administering a targeted therapeutic agent.

18. The method according to claim 15, further comprising administering an antibody.

19. The method according to claim 15, further comprising administering a DNA vaccine.

20. The method according to claim 15, further comprising administering a protein vaccine.

21. The method according to claim 15, further comprising administering a peptide vaccine.

22. The method according to claim 15, further comprising administering an antigen.

23. The method according to claim 15, further comprising administering an adjuvant.