Conjugates of small-interfering nucleic acids

Patent metadata

Field	Value
Publication number	US-9433684-B2
Application number	US-73783309-A
Country	US
Kind code	B2
Filing date	Aug 19, 2009
Priority date	Aug 19, 2008
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

The present invention relates to conjugates of small-interfering nucleic acids (siNA). Compositions of siNA suited for administration to a patient are described. Methods for delivering the compositions are also described.

First claim

What is claimed is:

1. A conjugate comprising a residue of a siNA having a 5′ amino linker with a terminal amino group having the structure

covalently attached at the terminal amino group to a single polymeric reagent having the following structure,

wherein: R 2 is H and each of R 1 and R 3 is

R 2 is H and each of R 1 and R 3 is

R 1 is H, R 2 is

 and R 3 is

R 1 is H, R 2 is

 and R 3 is

where each m-PEG represents CH 3 O(CH 2 CH 2 O) n —CH 2 CH 2 ˜ and (n) is defined to provide CH 3 O(CH 2 CH 2 O) n —CH 2 CH 2 ˜ with a weight-average molecular weight of from 10,000 Daltons to 40,000 Daltons
, and wherein the siNA is selected from the group consisting of double stranded siNA that is blunt ended, double stranded siNA that has a 5′overhang, and double stranded siNA that has a 3′ overhang.

2. The conjugate of claim 1 , wherein the siNA is a siRNA.

3. The conjugate of claim 1 , wherein the siNA has a length of from 10 to 30 nucleotides.

4. The conjugate of claim 1 , wherein the siNA has a length of from 15 to 25 nucleotides.

5. The conjugate of claim 1 , wherein the siNA is double stranded siNA that is blunt ended.

6. The conjugate of claim 1 , wherein the siNA is double stranded siNA that has a 5′overhang.

7. The conjugate of claim 6 , wherein the 5′overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.

8. The conjugate of claim 1 , wherein the siNA is a double stranded siNA that has a 3′overhang.

9. The conjugate of claim 8 , wherein the 3′overhang is an overhang of a number of nucleotides selected from the group consisting of 1, 2, 3 and 4.

10. The conjugate of claim 1 , wherein the siNA includes one or more modified nucleotides selected from the group consisting of 2′O-methyl nucleotides, 2′F nucleotides, 2′deoxynucleotides, 2′OMOE nucleotides, locked nucleic acids and unlocked nucleic acids.

Assignees

• Mcmanus Samuel P
• Riley Timothy A
• Culbertson Sean M
• Kozlowski Antoni
• Fry Dennis G
• Yuan Xuejun
• Sheng Dawei
• Dixit Vidula R
• Nektar Therapeutics

Inventors

• Mcmanus Samuel P
• Riley Timothy A
• Culbertson Sean M
• Kozlowski Antoni
• Fry Dennis G
• Yuan Xuejun
• Sheng Dawei
• Dixit Vidula R

Classifications

• C08G65/329 Primary

  with organic compounds · CPC title

• C08L2203/02

  for biomedical use · CPC title

• A61K47/549

  Sugars, nucleosides, nucleotides or nucleic acids · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title