CHIRAL NUCLEIC ACID ADJUVANT HAVING ANTI-ALLERGIC ACTIVITY, AND ANTI-ALLERGIC AGENT

• US 20160331835A1
• Filed: 01/14/2015
• Published: 11/17/2016
• Est. Priority Date: 01/15/2014
• Status: Active Grant

• Current Assignee: Wave Life Sciences Japan, Inc.
• Original Assignee: Shin Nippon Biomedical Laboratories Limited, Wave Life Sciences Japan, Inc.
• Inventors: Gemba, Takefumi, Nagata, Ryoichi
• Granted Patent: US 10,322,173 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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 2310/344 Position-specific modifications, e.g. on every purine, at the 3'-end

Abstract

An adjuvant which comprises oligonucleotides which comprise two to four CpG motifs each represented by 5′-X₁CpGX₂-3′ and has a length of 14 to 32 nucleotides, wherein a nucleic acid at 3′ end side of at least two CpG motifs is connected by phosphorothioate linkage, wherein each nucleic acids at 3′ end and 5′ end of the oligonucleotide is S type nucleic acids connected by phosphorothioate linkage, and wherein the oligonucleotide comprises at least one nucleic acid without phosphorothioate modification. The present invention relates to an adjuvant comprising the oligonucleotide represented by the sequence number 67. The present invention relates to an anti-allergic agent comprising these adjuvant.

Claims

1. An adjuvant which comprises an oligonucleotide comprising two to four CpG motifs each represented by 5′

-X₁CpGX₂-3′ and

has a length of 14 to 32 nucleotides,

wherein the CpG is non-methylated CpG without modified phosphate backbones,

wherein the X₁ is A or T,

wherein the X₂ is A or T,

wherein nucleic acids connected by phosphorothioate linkage are connected at 3′

end side of at least two CpG motifs,

wherein each nucleic acids at 5′

end and 3′

end of the oligonucleotide are S type nucleic acids connected by phosphorothioate linkage, and

wherein the oligonucleotide comprises at least one nucleic acid without phosphorothioate modification.

2. The adjuvant as claimed in claim 1,

wherein the X₁ is A,

wherein the X₂ is T, and

wherein the nucleic acids connected by phosphorothioate linkage are first phosphorothioated T bound by phosphorothioate linkage.

3. The adjuvant as claimed in claim 2,

wherein the oligonucleotide comprises a second phosphorothioated T at the 3′

end side of the first phosphorothioated T,

wherein a nucleic acid adjacent to 5′

end of the oligonucleotide is a S type nucleic acid bound by phosphorothioate linkage, and

wherein a nucleic acid adjacent to 3′

end of the oligonucleotide is a S type nucleic acid bound by phosphorothioate linkage.

4. The adjuvant as claimed in claim 1,

wherein the oligonucleotide has a nucleotide sequence represented by the sequence number 4, 5, 9, 10, 20, 22, 23, 29, 30, 31, 39, 53, 54, 55, 59, 64, 65, 66, 67, 68, 69, 70, 71, 74, 75, 76, 77, 78, 81 and 84.

5. The adjuvant as claimed in claim 1,

wherein the oligonucleotide is an oligonucleotide represented by the formula I below (an oligonucleotide represented by the sequence number 67) or an oligonucleotide where one or more nucleic acids are substituted, deleted, added or inserted in the oligonucleotide represented by the formula I, and has an anti-allergic activity.

T^SPC^SPGACGTT^SPT^SPT^SPGACGTT^SPT^SPT^SPGACG^SPT^SPT  

 

Formula (I)

6. An anti-allergic agent which comprises the adjuvant as claimed in any of claims 1 to 5.

7. The anti-allergic agent as claimed in claim 6,

wherein the agent is a therapeutic agent for allergic rhinitis.

8. An anti-allergic agent,

wherein the agent comprises the adjuvant as claimed in any of claims 1 to 5, and the oligonucleotide as an effective ingredient.

9. The anti-allergic agent as claimed in claim 8,

wherein the agent is a therapeutic agent for allergic rhinitis.