Reconstituted hdl formulation
AssigneeCSL Limited
InventorsYvonne Vucica, Gary Lee Warren
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Abstract
The present invention relates to reconstituted high density lipoprotein (rHDL) formulations comprising an apolipoprotein, a lipid and a lyophilization stabilizer. Said formulations have reduced renal toxicity and good long-term stability, especially in lyophilized form.
Claims53
A reconstituted high density lipoprotein (rHDL) formulation comprising an apolipoprotein, a lipid and a lyophilization stabilizer, wherein the ratio between the apolipoprotein and the lipid is from about 1:20 to about 1:120 (mol:mol) and the lyophilization stabilizer is present in a concentration from about 1.0% to less than 6.0% (w/w of rHDL formulation).
The rHDL formulation according to any one of the preceding claims, wherein the lyophilization stabilizer is present in a concentration of from about 1.0 to 5.9% (w/w).
The rHDL formulation according to any one of the preceding claims, wherein the lyophilization stabilizer is present in a concentration from about 3.0 to 5:9% (w/w).
The rHDL formulation according to any one of the preceding claims, wherein the lyophilization stabilizer is present in a concentration from about 4.0 to 5.5% (w/w).
The rHDL formulation according to any one of the preceding claims, wherein the lyophilization stabilizer comprises a sugar, a sugar alcohol, an amino acid or a mixture thereof.
The rHDL formulation according to claim 26, wherein the sugar and the sugar alcohol are mixed in a ratio less than 2:1 (w:w).
The rHDL formulation according to any one of the preceding claims, wherein the formulation comprises additionally a detergent.
The rHDL formulation according to any one of the preceding claims, wherein the ratio between the apolipoprotein and the lipid is from about 1:20 to about 1:100 (mol:mol).
The rHDL formulation according to any one of the preceding claims, wherein the concentration of the apolipoprotein is from about 5 to about 50 mg/ml.
The rHDL formulation according to any one of the preceding claims, wherein the apolipoprotein comprises apolipoprotein A-I (Apo A-I).
The rHDL formulation according to any one of the preceding claims, wherein the apolipoprotein is a fragment of apolipoprotein.
The rHDL formulation according to any one of the preceding claims, wherein the lipid comprises at least one charged or non-charged phospholipid or a mixture thereof, preferably a phosphatidylcholine.
The rHDL formulation according to any one of the preceding claims, wherein the apolipoprotein is Apo A-I purified from plasma, the lipid is phosphatidylcholine, the lyophilization stabilizer is sucrose and the formulation further comprises sodium cholate detergent.
The rHDL formulation according to any one of the preceding claims, wherein the apolipoprotein is recombinant Apo A-I, the lipid is a mixture of sphingomyelin and phosphatidylglycerol and the lyophilization stabilizer is a mixture of sucrose and mannitol.
The rHDL formulation according to any one of the preceding claims, wherein the formulation has a pH in the range of 6 to 8.
A rHDL formulation according to any one of the preceding claims, wherein the formulation is lyophilized.
A method of producing a rHDL formulation comprising an apolipoprotein, a lipid, and a lyophilization stabilizer, the ratio between apolipoprotein and the lipid being from 1:20 to 1:120 (mol:mol), said method including the step of adding the lyophilization stabilizer to the solution comprising the lipid, and the apolipoprotein until a concentration from about 1.0% to less than 6.0% (w/w) is reached.
Dependencies are inferred from the claim text.