UNA single stranded oligomers for therapeutics

• US 9,944,929 B2
• Filed: 02/22/2016
• Issued: 04/17/2018
• 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:
  US15/050,065
• Publication Number:
  US 20160168567A1
• Time in Patent Office: 785 Days
• 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 single-stranded oligomers for therapeutics. The UNA oligomers can be composed of one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used for therapeutics that target oligonucleotides, nucleic acids, or RNAs to reduce their 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 oligomer and the 2′

-3′

-seco-nucleomonomers are monomer D

2. The oligomer of claim 1, wherein the oligomer is from 8 to 62 monomers in length.

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

-3′

-seco-nucleomonomers.

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

-O-alkyl-RNA nucleotide analogue.

5. The oligomer of claim 1, wherein one or more of the monomers are linked by a phosphorothioate linkage or a boranophosphate linkage.

6. The oligomer of claim 1, wherein the oligomer is from 14 to 26 monomers in length.

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

8. The oligomer of claim 1, wherein the oligomer has increased or prolonged stability towards enzymatic degradation in a cell as compared to an oligonucleotide having the same nucleobase sequence, wherein the oligonucleotide is composed of only natural RNA monomers.

9. The oligomer of claim 1, wherein the oligomer comprises two, three, four, or five 2′

-3′

-seco-nucleomonomers.