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Generated: August 19, 2017

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Title:High affinity nucleic acid ligands of complement system proteins
Abstract: Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention are specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.
Inventor(s): Biesecker; Gregory (Boulder, CO), Gold; Larry (Boulder, CO)
Assignee: Gilead Sciences, Inc. (Foster City, CA)
Filing Date:Nov 28, 2005
Application Number:11/288,622
Claims:1. A method for inhibiting inflammation or membrane attack vascular disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand of a C5 complement system protein wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 194, 195, or 196.

2. The method of claim 1 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 196.

3. The method of claim 1 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 194.

4. The method of claim 1 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 195.

5. A method for inhibiting activation of a membrane attack pathway in vivo, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand comprising the polynucleotide of SEQ ID NO: 194, 195 or 196.

6. The method of claim 5 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 194.

7. The method of claim 5 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 195.

8. The method of claim 5 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 196.

9. A method for inhibiting C5 complement activation, the method comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand comprising the polynucleotide of SEQ ID NO: 194, 195 or 196.

10. The method of claim 9 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 194.

11. The method of claim 9 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 195.

12. The method of claim 9 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 196.

13. The method of claim 1, wherein the ligand inhibits activation of the inflammation or the membrane attack pathway.

14. The method of claim 1, wherein the ligand is connected via a linker to a non-immunogenic, high molecular weight compound.

15. The method of claim 5, wherein the ligand is connected via a linker to a non-immunogenic, high molecular weight compound.

16. The method of claim 9, wherein the ligand is connected via a linker to a non-immunogenic, high molecular weight compound.

17. The method of claim 1, wherein inflammation is inhibited.

18. The method of claim 1, wherein membrane attack vascular disease is inhibited.

19. A method for inhibiting hemolysis, renal injury in autoimmune glomerulonephritis or leukocyte activation during extracorporeal circulation, comprising administering to a patient in need thereof a pharmaceutically effective amount of a nucleic acid ligand comprising the polynucleotide of SEQ ID NO: 194, 195 or 196.

20. The method of claim 19 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 194.

21. The method of claim 19 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 195.

22. The method of claim 19 wherein said nucleic acid ligand comprises the polynucleotide of SEQ ID NO: 196.

23. The method of claim 19, wherein the ligand is connected via a linker to a non-immunogenic, high molecular weight compound.

24. The method of claim 14, wherein the non-immunogenic, high molecular weight compound is polyethylene glycol.

25. The method of claim 15, wherein the non-immunogenic, high molecular weight compound is polyethylene glycol.

26. The method of claim 16, wherein the non-immunogenic, high molecular weight compound is polyethylene glycol.

27. The method of claim 23, wherein the non-immunogenic, high molecular weight compound is polyethylene glycol.
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