UNA oligomers for therapeutics

• US 9,051,570 B2
• Filed: 10/16/2012
• Issued: 06/09/2015
• Est. Priority Date: 05/22/2007
• Status: Active Grant

• Current Assignee: Arcturus Therapeutics, Inc. (Arcturus Therapeutics Holdings, Inc.)
• Original Assignee: Arcturus Therapeutics, Inc. (Arcturus Therapeutics Holdings, Inc.)
• Inventors: Wengel, Jesper
• Primary Examiner(s): Angell, Jon E
• Application Number:
  US13/652,965
• Publication Number:
  US 20130096289A1
• Time in Patent Office: 966 Days
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/31 of the backbone
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/323 modified ring structure
• CPC Class Codes: C12N 2310/3231 having an additional ring, e.g. LNA, ENA
• CPC Class Codes: C12N 2320/51 modulating the chemical stability, e.g. nuclease-resistance

Abstract

This invention is directed to oligomers composed of 2′-3′-seco-nucleomonomers and nucleotides or modified nucleotides, wherein the oligomer can be a microRNA and include from one to five 2′-3′-seco-nucleomonomers. The oligomers can have a sequence that is complementary to a target nucleotide sequence and be used for affecting the regulation of gene expression. Among other things, the oligomers can provide reduced off target effects.

Claims

1. An oligomer comprising an acyclic 2′

-3′

-seco-nucleomonomer, wherein the oligomer is a microRNA, wherein the oligomer comprises from one to five acyclic monomers, and wherein the acyclic monomer is monomer D

2. The oligomer of claim 1, further comprising a nucleotide analogue selected from the group consisting of 2′

-O-alkyl-RNA monomers, 2′

-amino-DNA monomers, 2′

-fluoro-DNA monomers, PNA monomers, HNA monomers, ANA monomers, FANA monomers, CeNA monomers, ENA monomers, DNA monomers, and INA monomers.

3. The oligomer of claim 1, further comprising one or more 2′

-O-alkyl-RNA nucleotide analogues.

4. The oligomer of claim 1, further comprising a phosphorothioate linkage or a boranophosphate linkage.

5. The oligomer of claim 1, wherein the oligomer has a sequence that is complementary to a target nucleotide sequence.

6. The oligomer of claim 1, wherein the oligomer has reduced off-target effects as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.

7. The oligomer of claim 1, wherein the oligomer has increased or prolonged potency for gene silencing as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.

8. The oligomer of claim 1, wherein the oligomer has improved stability towards enzymatic degradation as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.

9. The oligomer of claim 1, wherein the oligomer has reduced immune stimulation as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.