Short interfering ribonucleic acid (siRNA) for oral administration

Patent metadata

Field	Value
Publication number	US-9493771-B2
Application number	US-201414177640-A
Country	US
Kind code	B2
Filing date	Feb 11, 2014
Priority date	May 4, 2006
Publication date	Nov 15, 2016
Grant date	Nov 15, 2016

Abstract

Short interfering ribonucleic acid (siRNA) for oral administration, said siRNA comprising two separate RNA strands that are complementary to each other over at least 15 nucleotides, wherein each strand is 49 nucleotides or less, and wherein at least one of which strands contains at least one chemical modification.

First claim

We claim:

1. Short interfering ribonucleic acid (siRNA), comprising two strands that are complementary to each other over at least 15 nucleotides,
wherein each strand comprises 49 nucleotides or less,
wherein the first two base-pairing nucleotides at the 3′ end of each strand are 2′-methoxyethyl ribonucleotide residues, and
wherein a 3′-terminus of at least one strand containing a 2′-methoxyethyl ribonucleotide comprises a modification at the 3′ carbon, wherein the modification is selected from the group consisting of:

2. The siRNA according to claim 1 , wherein at least one additional nucleotide is modified with a modification.

3. The siRNA of claim 2 , wherein the modification is selected from 2′-OMe, 2′-F, 2′-Oallyl, 2′-MOE, Locked Nucleic Acid, phosphorothioate, and boranophosphate.

4. The siRNA of claim 1 , wherein each strand is 19 nucleotides.

5. The siRNA according to claim 1 , wherein said siRNA comprises modified nucleotides selected from among nucleotides having a modified internucleoside linkage selected from among phosphorothioate, phosphorodithioate, phosphoramidate, boranophosphonoate, and amide linkages.

6. The siRNA according to claim 1 , wherein said two RNA strands are fully complementary to each other.

7. The siRNA according to claim 1 , comprising a 1 to 9 nucleotide overhang on at least one of the 5′ end or 3′ end.

8. The siRNA according to claim 1 , wherein the two strands are complementary to each other for 19 nucleotides.

9. The siRNA according to claim 1 , wherein one end of the siRNA is blunt-ended.

10. The siRNA according to claim 1 , wherein both ends of the siRNA are blunt-ended.

11. The siRNA according to claim 1 , wherein both ends are blunt-ended, and the two strands are complementary to each other for 19 nucleotides.

12. A composition comprising a siRNA of claim 1 and a pharmaceutically acceptable carrier.

13. Short interfering ribonucleic acid (siRNA) comprising two strands that are complementary to each other over at least 15 nucleotides, wherein each strand comprises 49 nucleotides or less, and wherein the first two base-pairing nucleotides at the 3′ end of each strand are 2′-methoxyethyl (2′-MOE) ribonucleotide residues, and
wherein at least one additional nucleotide is modified with a modification selected from 2′-OMe, 2′-F, 2′-O-allyl, 2′-MOE, Locked Nucleic Acid, phosphorothioate, and boranophosphate, and
wherein a 3′-terminus of at least one strand containing a 2′-methoxyethyl ribonucleotide comprises a modification at the 3′ carbon, wherein the modification is selected from the group consisting of triethylene glycol, cyclohexyl, phenyl, and adamantane.

Assignees

• Natt Francois Jean-Charles
• Billy Eric
• Hunziker Juerg
• Schnell Christian Rene
• Novartis Ag

Inventors

• Natt Francois Jean-Charles
• Billy Eric
• Hunziker Juerg
• Schnell Christian Rene

Classifications

• A61P7/04

  Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P7/10

  Antioedematous agents; Diuretics · CPC title