Oligonucleotide compositions with enhanced efficiency

Patent metadata

Field	Value
Publication number	US-10036025-B2
Application number	US-201715724224-A
Country	US
Kind code	B2
Filing date	Oct 3, 2017
Priority date	Feb 1, 2002
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

The oligonucleotide compositions of the present invention make use of combinations of oligonucleotides. In one aspect, the invention features an oligonucleotide composition including at least 2 different oligonucleotides targeted to a target gene. This invention also provides methods of inhibiting protein synthesis in a cell and methods of identifying oligonucleotide compositions that inhibit synthesis of a protein in a cell.

First claim

The invention claimed is:

1. A method of inhibiting protein synthesis in a cell comprising
contacting the cell with a composition comprising a combination of double-stranded oligonucleotides, the combination consisting of three or four different double-stranded oligonucleotides, wherein each double-stranded oligonucleotide is targeted to a different sequence within a single target gene, each double-stranded oligonucleotide consists of two separate strands, each strand is between 20 and 30 nucleomonomers in length, wherein the combination is capable of RNA interference (RNAi), and wherein at least one of the oligonucleotides comprises at least one modified internucleoside linkage or wherein at least one of the oligonucleotides comprises at least one modified sugar moiety.

2. The method of claim 1 wherein at least one of the oligonucleotides comprises at least one modified sugar moiety.

3. The method of claim 2 wherein at least one nucleomonomer of at least one strand comprises a pyrimidine and the pyrimidine is thymine or 5-methylcytosine.

4. The method of claim 1 , further comprising a pharmaceutically acceptable carrier.

5. The method of claim 1 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

6. The method of claim 2 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

7. The method of claim 3 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

8. The method of claim 1 , wherein at least one of the double-stranded oligonucleotides is covalently linked to an agent to facilitate cellular uptake.

9. The method of claim 1 , wherein the target gene is a mammalian gene.

10. A method of inhibiting protein synthesis in a cell comprising
contacting the cell with a composition comprising a combination of double-stranded oligonucleotides, the combination consisting of two different double-stranded oligonucleotides, wherein each double-stranded oligonucleotide is targeted to a different sequence within a single target gene, each double-stranded oligonucleotide consists of two separate strands, each strand is between 20 and 30 nucleomonomers in length, wherein the combination is capable of RNA interference (RNAi), and wherein at least one of the oligonucleotides comprises at least one modified internucleoside linkage or wherein at least one of the oligonucleotides comprises at least one modified sugar moiety.

11. The method of claim 10 wherein at least one of the oligonucleotides comprises at least one modified sugar moiety.

12. The method of claim 11 wherein at least one nucleomonomer of at least one strand comprises a pyrimidine and the pyrimidine is thymine or 5-methylcytosine.

13. The method of claim 10 , further comprising a pharmaceutically acceptable carrier.

14. The method of claim 10 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

15. The method of claim 11 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

16. The method of claim 12 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

17. The method of claim 10 , wherein at least one of the double-stranded oligonucleotides is covalently linked to an agent to facilitate cellular uptake.

18. The method of claim 10 , wherein the target gene is a mammalian gene.

19. A method of inhibiting protein synthesis in a cell comprising contacting the cell with a composition comprising a combination of double-stranded oligonucleotides, the combination consisting of five, six, seven or eight different double-stranded oligonucleotides, wherein each double-stranded oligonucleotide is targeted to a different sequence within a single target gene, each double-stranded oligonucleotide consists of two separate strands, each strand is between 20 and 30 nucleomonomers in length, wherein the combination is capable of RNA interference (RNAi), and wherein at least one of the oligonucleotides comprises at least one modified internucleoside linkage or wherein at least one of the oligonucleotides comprises at least one modified sugar moiety.

20. The composition of claim 19 wherein each double-stranded oligonucleotide comprises a nucleotide sequence that is at least 90% identical to a portion of the target gene.

Assignees

• Life Technologies Corp

Inventors

• Woolf Tod
• Taylor Margaret

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/20

  for DNA viruses · CPC title