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 or salt thereof, wherein the compound comprises the sequence fCmGfCfCGfCmGmGfUfCfUfCmAmGmGfCGfCfUmGmAmGfUfCf UmGmAmGfUfUfUAfCfCfUmGfCmG-3T (SEQ ID NO:4) and 1,3-bis(mPEG)-propyl-2-(4-butamide);
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; and
wherein the compound binds specifically to complement system protein C5.
2. A compound of claim 1 , wherein the mPEG has a molecular weight greater than 10 kDA.
3. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier or vehicle.
4. A method for treating a C5 complement protein, C5a and/or C5b-9-mediated disorder, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt of the compound of claim 1 .
5. The method of claim 4 , wherein the disorder is myocardial injury relating to CABG surgery, myocardial injury relating to balloon angioplasty, myocardial injury relating to restenosis, C5, C5a and/or C5b-9-complement protein mediated complications relating to CABG surgery, percutaneous coronary intervention, paroxysomal nocturnal hemoglobinuria, acute transplant rejection, hyperacute transplant rejection, subacute transplant rejection, or chronic transplant rejection.
6. The method of claim 4 , wherein the disorder is complement mediated ocular tissue damage.
7. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 2 and a pharmaceutically acceptable carrier or vehicle.
8. A method for treating a C5 complement protein, C5a and/or C5b-9-mediated disorder, the method comprising administering to a patient in need thereof a therapeutically effective amount of the compound or pharmaceutically acceptable salt of the compound of claim 2 .
9. The method of claim 8 , wherein the disorder is myocardial injury relating to CABG surgery, myocardial injury relating to balloon angioplasty, myocardial injury relating to restenosis, C5, C5a and/or C5b-9-complement protein mediated complications relating to CABG surgery, percutaneous coronary intervention, paroxysomal nocturnal hemoglobinuria, acute transplant rejection, hyperacute transplant rejection, subacute transplant rejection, or chronic transplant rejection.
10. The method of claim 8 , wherein the disorder is complement-mediated ocular tissue damage.