Use of oligonucleotides for inhibition of complement activation

• US 20020082227A1
• Filed: 02/27/2001
• Published: 06/27/2002
• Est. Priority Date: 09/30/1999
• Status: Abandoned Application

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Henry, Scott
• Application Number:
  US09/794,824
• Publication Number:
  US 20020082227A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters

Abstract

Methods for inhibiting complement activation using antisense oligonucleotides, preferably modified oligonucleotides. These compounds may be used therapeutically to treat undesirable complement-mediated events such as inflammation.

Claims

1. A method for inhibiting complement activation in a human cell, tissue or bodily fluid comprising administering an oligonucleotide to said cell, tissue or bodily fluid.

2. The method of claim 1, wherein said oligonucleotide comprises one or more modifications.

3. The method of claim 2, wherein said modification is an internucleoside linkage.

4. The method of claim 3, wherein said linkage is a phosphorothioate linkage.

5. The method of claim 1, wherein said modification is a modification at the 2′

-position of a sugar.

6. The method of claim 5, wherein said modification is a 2′

-O-methoxyethyl modification.

7. The method of claim 4, wherein said oligonucleotide consists of phosphorothioate linkages.

8. The method of claim 1, wherein said oligonucleotide is selected from the group consisting of ISIS 13650, ISIS 15839, ISIS 12854 and ISIS 14725.

9. The method of claim 1, wherein said oligonucleotide is selected from the group consisting of ISIS 5132 and ISIS 2302.

10. The method of claim 1, wherein the concentration of said oligonucleotide is at least about 50 μ

g/ml.

11. The method of claim 10, wherein the concentration of said oligonucleotide is between about 50 μ

g/ml and about 250 μ

g/ml.

13. The composition of claim 12 wherein said complement activation inhibitory molecule is Factor H.

12. A composition comprising an oligonucleotide and a complement activation inhibitory molecule, wherein said oligonucleotide comprises one or more phosphorothioate modifications and one or more 2′

-methoxyethoxy modifications.