UNA oligomers targeting micro-RNA for therapeutics

• US 9,297,009 B2
• Filed: 05/04/2015
• Issued: 03/29/2016
• 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:
  US14/703,016
• Publication Number:
  US 20150232851A1
• Time in Patent Office: 330 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 provides UNA oligomers for therapeutics that can be used to target micro-RNAs. The UNA oligomers can be composed of one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a single stranded oligomer. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used to target micro-RNAs to reduce micro-RNA activity.

Claims

1. An oligomer comprising one or more 2′

-3′

-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, wherein the oligomer is a single-stranded RNA targeting a microRNA, and wherein the 2′

-3′

-seco-nucleomonomers are monomer D

2. The oligomer of claim 1, wherein the nucleobase is adenine, thymine, uracil, guanine, cytosine, inosine, or a nucleobase of a non-natural nucleotide.

3. The oligomer of claim 1, comprising from 8 to 62 monomers in length.

4. The oligomer of claim 1, comprising from one to five 2′

-3′

-seco-nucleomonomers.

5. The oligomer of claim 1, wherein one or more of the nucleotide monomers is selected from the group consisting of 2′

-O-alkyl-RNA monomers, 2′

-amino-DNA monomers, 2′

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

6. The oligomer of claim 1, wherein one or more of the nucleotide monomers is 2′

-O-alkyl-RNA nucleotide analogues.

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

8. The oligomer of claim 1, comprising a monomer sequence that is complementary to a target nucleotide sequence.

9. The oligomer of claim 1, wherein the oligomer has increased or prolonged potency as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.