Methods and compositions to lower plasma cholesterol levels
AssigneeAtheroGenics, Inc.
InventorsRussell M. Medford, Uday Saxena
Life of this patent
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Abstract
A method is disclosed for determining whether a compound binds to a lipoprotein such as LDL or VLDL in a manner which will lower plasma cholesterol. The method provided includes assessing the ability of the compound to form a complex with the lipoprotein, and then determining whether the newly formed complex causes a change in the structure of apoB-100 that results in increased binding affinity to an LDL receptor.
Claims9
A method to determine if a compound causes a change in the structure of apolipoprotein B-100 in a cholesterol-containing low density lipoprotein thus increasing the binding of an epitope on the apolipoprotein B-100 to the LDL-receptor, comprising:
- (i) mixing the compound with and allowing it to bind to cholesterol-containing low density lipoprotein forming a complex;
- (ii) exposing the complex to a first capture antibody that is attached to a solid phase material and is directed to the epitope on apolipoprotein B-100 that binds to the LDL-receptor, forming a combination;
- (iii) adding a second antibody which binds to the combination;
- (iv) detecting the second antibody bound to the combination by the addition of a third antibody that binds the second antibody and to which is attached a label;
- (v) quantifying the amount of the captured complex by quantifying the amount of label;
- and
- (vi) comparing the amount of cholesterol-containing low density lipoprotein captured by the assay to a control, wherein an increase in the amount of cholesterol-containing low density lipoprotein captured indicates a change in the structure of apoB-100 in the cholesterol-containing low density lipoprotein, thus increasing binding to the low density lipoprotein receptor.
A method for assessing whether a compound first binds to a cholesterol-containing lipoprotein, enhancing the binding of the cholesterol-containing lipoprotein to a low density lipoprotein hepatic receptor and thus lowering plasma cholesterol, the method comprising:
- (a) allowing the compound to form a complex with a cholesterol-containing lipoprotein in vivo,
- (b) isolating the resulting complex, and
- (c) determining whether the formation of the complex causes a change in the three dimensional conformation of apoB-100 in the cholesterol-containing lipoprotein that enhances the binding of the lipoprotein to the LDL hepatic receptor.
A method to determine if a compound causes a change in the structure of apolipoprotein B-100 in a cholesterol-containing low density lipoprotein thus increasing the binding of an epitope on the apolipoprotein B-100 to an LDL-receptor, comprising:
- (i) mixing the compound with and allowing it to bind to cholesterol-containing low density lipoprotein forming a complex;
- (ii) exposing the complex to a first capture antibody that is attached to a solid phase material and is directed to the epitope on apolipoprotein B-100 that binds to the LDL-receptor, forming a combination;
- (iii) adding to the combination a second antibody which binds the apoB-100 in the combination and to which is attached a label;
- (iv) quantifying the amount of the captured complex by quantifying the amount of label;
- and
- (v) comparing the amount of cholesterol-containing low density lipoprotein quantified in step (iv) to a control, wherein an increase in the amount of cholesterol-containing low density lipoprotein captured indicates a change in the structure of apoB-100 in the cholesterol-containing low density lipoprotein, thus increasing binding to the low density lipoprotein receptor.
Dependencies are inferred from the claim text.