Pharmaceutical Formulations, Methods, and Dosing Regimens for the Treatment and Prevention of Acute Coronary Syndromes

Abstract

The invention provides methods and formulations for treating and preventing acute coronary syndromes. The methods of the instant invention provide safe and effective doses of an Apolipoprotein A-I Milano: phospholipid complex to reduce and stabilize atherosclerotic plaque. Pharmaceutical formulations of the Apo A-I Milano:phospholipid complexes are also provided.

1 - 39 . (canceled) 
     
     
         40 . A pharmaceutical formulation comprising a recombinant Apo AI Milano or variant thereof/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine complex in a buffer. 
     
     
         41 . The pharmaceutical formulation of  claim 40  comprising about 6.0% to about 6.4% sucrose. 
     
     
         42 . The pharmaceutical formulation of  claim 40  comprising about 0.8% to about 1% mannitol. 
     
     
         43 . The pharmaceutical formulation of  claim 40  wherein the pH is about 7.0 to about 7.8. 
     
     
         44 . The pharmaceutical formulation of  claim 40  wherein the concentration of rApo A-I Milano is about 12 mg per ml to about 18 mg per ml of said buffer. 
     
     
         45 . The pharmaceutical formulation of  claim 40  wherein the recombinant Apo A-I Milano is a conservatively substituted Apo A-I Milano. 
     
     
         46 . The pharmaceutical formulation of  claim 40  wherein the recombinant Apo A-I Milano and POPC are complexed in a ratio of about 1:0.95 recombinant Apo A-I Milano:POPC (wt protein/wt lipid). 
     
     
         47 . The pharmaceutical formulation of  claim 40  comprising less than 6,000 particulates greater than 10 μm in size per 50 mL. 
     
     
         48 . The pharmaceutical formulation of  claim 40  comprising less than 600 particulates greater than 25 μm in size per 50 mL. 
     
     
         49 . The pharmaceutical formulation of  claim 40  wherein the Osmolality is about 280 to about 320 mOsm. 
     
     
         50 - 53 . (canceled) 
     
     
         54 . A pharmaceutical formulation comprising a recombinant Apo A-I Milano, or variant thereof, complexed with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, and a phosphate buffer having a pH of about 7.0 to about 7.8, said buffer comprising 2% glucose and 4 mM of sodium phosphate. 
     
     
         55 . The pharmaceutical formulation of  claim 54  comprising phosphate buffer to achieve a pH of about 7.5. 
     
     
         56 . The pharmaceutical formulation of  claim 54  wherein the recombinant Apo A-I Milano is a conservatively substituted Apo A-I Milano. 
     
     
         57 . The pharmaceutical formulation of  claim 54  wherein the recombinant Apo A-I Milano and POPC are complexed in a ratio of about 1:0.95 recombinant Apo A-I Milano:POPC (wt protein/wt lipid). 
     
     
         58 - 64 . (canceled) 
     
     
         65 . A lyophilized pharmaceutical formulation comprising: a) recombinant Apo A-I Milano, or variant thereof, complexed with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; b) about 6.0% to about 6.4% sucrose; and c) about 0.8 to about 1% mannitol. 
     
     
         66 - 67 . (canceled) 
     
     
         68 . The pharmaceutical formulation of  claim 65  further comprising a buffer, said buffer having a pH at about 7.5. 
     
     
         69 . The pharmaceutical formulation of  claim 65  wherein the recombinant Apo A-I Milano is a conservatively substituted Apo A-I Milano. 
     
     
         70 . The pharmaceutical formulation of  claim 65  wherein the concentration of POPC is about 11 mg/ml to about 17 mg/ml. 
     
     
         71 . The pharmaceutical formulation of  claim 65  wherein the recombinant Apo A-I Milano and POPC are complexed in a ratio of about 1:0.95 recombinant Apo A-I Milano:POPC (wt protein/wt lipid). 
     
     
         72 - 78 . (canceled)