Aptamer therapeutics useful in the treatment of complement-related disorders
The invention provides nucleic acid therapeutics and methods for using these nucleic acid therapeutics in the treatment of complement-related disorders.
1. A compound having the formula:
or a pharmaceutically acceptable salt thereof,
where indicates a linker
where Aptamer=fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCfUmGmAmGfUfUfUAfCf CfUmGfCmG-3T (SEQ ID NO: 4),
wherein fC and fU=2′-fluoro nucleotides, and mG and mA=2′-OMe nucleotides and all other nucleotides are 2′-OH and 3T indicates an inverted deoxy thymidine.
2. The compound or pharmaceutically acceptable salt of the compound of claim 1 , wherein the linker is an alkyl linker.
3. The compound or pharmaceutically acceptable salt of the compound of claim 2 , wherein the alkyl linker comprises 2 to 18 consecutive CH 2 groups.
4. The compound or pharmaceutically acceptable salt of the compound of claim 3 , wherein the alkyl linker comprises 2 to 12 consecutive CH 2 groups.
5. The compound or pharmaceutically acceptable salt of the compound of claim 4 , wherein the alkyl linker comprises 3 to 6 consecutive CH 2 groups.
6. The compound or pharmaceutically acceptable salt of the compound of claim 2 , wherein the alkyl linker comprises 6 consecutive CH 2 groups.
7. A compound having the structure:
or a pharmaceutically acceptable salt thereof,
where Aptamer=fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCfUmGmAmGfUfUfUAfCf CfUmGfCmG-3T (SEQ ID NO: 4),
wherein fC and fU=2′-fluoro nucleotides, and mG and mA=2′-OMe nucleotides and all other nucleotides are 2′-OH and 3T indicates an inverted deoxy thymidine.
8. A composition comprising a therapeutically effective amount of the compound or pharmaceutically acceptable salt of claim 1 .
9. The composition of claim 8 , wherein the alkyl linker comprises 2 to 18 consecutive CH 2 groups.
10. The composition of claim 9 , wherein the alkyl linker comprises 2 to 12 consecutive CH 2 groups.
11. The composition of claim 10 , wherein the alkyl linker comprises 3 to 6 consecutive CH 2 groups.
12. The composition of claim 11 , wherein the alkyl linker comprises 6 consecutive CH 2 groups.
13. The composition of claim 8 , further comprising a pharmaceutically acceptable carrier or diluent.
14. The composition of claim 8 , wherein the compound has the structure set forth below:
where Aptamer=fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCfUmGmAmGfUfUfUAfCf CfUmGfCmG-3T (SEQ ID NO: 4),
wherein fC and fU=2′-fluoro nucleotides, and mG and mA=2′-OMe nucleotides and all other nucleotides are 2′-0′-1 and 3T indicates an inverted deoxy thymidine.
15. The composition of claim 14 , further comprising a pharmaceutically acceptable carrier or diluent.