Chimeric immunomodulatory compounds and methods of using the same-IV

• US 9,028,845 B2
• Filed: 09/18/2013
• Issued: 05/12/2015
• Est. Priority Date: 06/21/2001
• Status: Active Grant

• Current Assignee: Dynamax Technologies Limited
• Original Assignee: Dynamax Technologies Limited
• Inventors: Fearon, Karen L., Dina, Dino, Tuck, Stephen F.
• Primary Examiner(s): Minnifield, Nita M
• Application Number:
  US14/030,975
• Publication Number:
  US 20140127255A1
• Time in Patent Office: 601 Days
• Field of Search: None
• US Class Current: 424/278.1
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/292 Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• 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 37/04 Immunostimulants
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C07H 15/18 Acyclic radicals, substituted by carbocyclic rings
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• 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 2310/315 : Phosphorothioates
• CPC Class Codes: C12N 2310/332 : Abasic residue
• CPC Class Codes: C12N 2310/351 : Conjugate
• CPC Class Codes: C12N 2310/3519 : Fusion with another nucleic acid
• CPC Class Codes: C12N 2310/52 : branched
• CPC Class Codes: C12N 2730/10134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The invention provides immunomodulatory compounds and methods for immunomodulation of individuals using the immunomodulatory compounds.

Claims

1. A method of modulating an immune response in an individual comprising administering to an individual a linear chimeric immunostimulatory compound (CIC) comprising the structure N₁—

S₁—

N₂—

S₂—

N₃,

wherein N₁, N₂, and N₃ are independently selected nucleic acid moieties, at least one of N₁, N₂, and N₃ has the sequence 5′

-TCGY-3′

, where Y is selected from the group consisting of XCGX, XTCG, XXCG, and CGXX, where each X is an independently selected nucleotide;

wherein S₁ is a non-nucleic acid spacer moiety covalently bound to N₁ and N₂;

S₂ is a non-nucleic acid spacer moiety covalently bound to N₂ and N₃;

S₁ and S₂ are the same or different;

each of S₁ and S₂ comprises hexaethylene glycol (HEG), triethylene glycol (TEG), propyl, butyl, or hexyl; and

wherein said CIC has at least one immunostimulatory activity selected from the group consisting of (i) the ability to stimulate interferon-gamma (IFN-γ

) production by human peripheral blood mononuclear cells or (ii) the ability to stimulate interferon-alpha (IFN-α

) production by human peripheral blood mononuclear cells.

2. The method of claim 1 wherein at least one of N₁ and N₃ has a sequence 5′

-TCGXCGX-3′

.

3. The method of claim 1 wherein at least one of N₁ and N₂ has a sequence 5′

-TCGXCGX-3′

.

4. The method of claim 1 wherein at least one of N₂ and N₃ has a sequence 5′

-[(X)_0-2]TCG[(X)_2-4]-3′

, wherein the first X at the 5′

end of the CIC is an A and each following X is an independently selected nucleotide.

5. The method of claim 1, wherein said modulation comprises an increase in secretion of interferon-gamma (IFN-γ

) or interferon-alpha (IFN-α

) production by human peripheral blood mononuclear cells.

6. The method of claim 1, wherein at least one of S₁ and S₂ is a HEG spacer moiety.

7. The method of claim 6 wherein both S₁ and S₂ are HEG spacer moieties.

8. The method of claim 1 wherein at least one nucleic acid moiety comprises the sequence 5′

-TCGCCGG-3′

, 5′

-TCGGCGC-3′

or 5′

-TCGTCGT-3′

.

9. The method of claim 1 wherein at least one nucleic acid moiety comprises the sequence 5′

-TCGCCGG-3′

, 5′

-TCGGCGC-3′

or 5′

-TCGTCGT-3′

.