Una single stranded oligomers for therapeutics

Patent metadata

Field	Value
Publication number	US-2016168567-A1
Application number	US-201615050065-A
Country	US
Kind code	A1
Filing date	Feb 22, 2016
Priority date	May 22, 2007
Publication date	Jun 16, 2016
Grant date	—

Abstract

The present invention is directed to RNA oligonucleotides or complexes of RNA oligonucleotides, denoted herein together as RNA complexes, containing at least one, but optionally more that one, hydroxymethyl substituted nucleotide monomer(s). By a hydroxymethyl substituted nucleotide monomer is understood a nucleotide monomer containing a hydroxymethyl group (that may be unsubstituted, O-substituted for example with a conjugating group, or converted into an optionally substituted or conjugated aminomethyl group). This hydroxymethyl group is not partaking in formation of an internucleotide linkage and is not the hydroxymethyl group (containing the 5′-hydroxy group) of a natural RNA monomer. The RNA complexes of the invention may be useful for therapeutic applications, diagnostic applications or research applications. The complexes include short interfering RNA complexes (siRNA duplexes) comprising an antisense strand and a continued or a discontinued passenger strand (“sense strand”) capable of regulating gene expression. At least one of these strands, possible more than one of these strands, are modified with one or more hydroxymethyl substituted nucleotide monomer(s) of this invention, that can be positioned at the 3′-end, at the 5′-end or internally. The RNA complexes of the invention can also be single stranded RNA oligonucleotides (“RNA strands”) that are modified with at least one, but optionally more that one, hydroxymethyl substituted nucleotide monomer(s). Such single stranded RNA strands are to be considered included whenever the term RNA complexes is used in this patent application. The complexes of the invention display enhanced stability towards nucleolytic degradation relative to the corresponding complexes comprised entirely from natural RNA monomers.

First claim

1 - 24 . (canceled)

25 . An oligomer comprising one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, wherein the oligomer is single stranded and the 2′-3′-seco-nucleomonomers are monomer D

wherein Base is a nucleobase.

26 . The oligomer of claim 25 , wherein the nucleobase is adenine, thymine, uracil, guanine, cytosine, inosine, or a nucleobase of a non-natural nucleotide.

27 . The oligomer of claim 25 , wherein the oligomer is from 8 to 62 monomers in length.

28 . The oligomer of claim 25 , comprising from one to five 2′-3′-seco-nucleomonomers.

29 . The oligomer of claim 25 , 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.

30 . The oligomer of claim 25 , wherein one or more of the nucleotide monomers is a 2′-O-alkyl-RNA nucleotide analogue.

31 . The oligomer of claim 25 , wherein one or more of the monomers are linked by a phosphorothioate linkage or a boranophosphate linkage.

32 . The oligomer of claim 25 , wherein the oligomer is from 14 to 26 monomers in length.

33 . The oligomer of claim 25 , comprising a monomer nucleobase sequence that is complementary to a target nucleotide sequence.

34 . The oligomer of claim 25 , 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.

Assignees

• Arcturus Therapeutics Inc

Inventors

• Wengel Jesper

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/113 Primary

  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 title

• C12N2310/323

  modified ring structure · CPC title

• C12N2310/321

  2'-O-R Modification · CPC title

• C12N2320/51

  modulating the chemical stability, e.g. nuclease-resistance · CPC title