Notch inhibition in the treatment and prevention of obesity

Abstract

The present invention is directed to methods of treating or preventing obesity by administering agents that inhibit the NOTCH signaling pathway. Antibodies that inhibit the binding of Delta like 4 ligand (Dll4) to NOTCH receptors may be used for this purpose.

What is claimed is: 
     
         1 . A method of treating or preventing obesity in a patient, comprising administering to said patient a therapeutically effective amount of a compound that inhibits the NOTCH signaling pathway. 
     
     
         2 . The method of  claim 1 , wherein said compound inhibits the binding of a NOTCH ligand to a NOTCH receptor. 
     
     
         3 . The method of  claim 2 , wherein said compound is an antibody. 
     
     
         4 . The method of  claim 1 , wherein said antibody inhibits the binding of Delta like 4 ligand (Dll4) to a NOTCH receptor. 
     
     
         5 . The method of  claim 4 , wherein said compound is an antibody that binds to Dll4 and inhibits its binding to a NOTCH 3 receptor. 
     
     
         6 . The method of  claim 1 , wherein said method is used to treat an obese patient with a body mass index (BMI) of 30 kg/m 2  or higher. 
     
     
         7 . The method of  claim 6 , wherein said compound is an antibody that inhibits the binding of Dll4 to a NOTCH receptor. 
     
     
         8 . The method of  claim 7 , wherein said patient is treated by administering a pharmaceutical composition comprising said antibody and a pharmaceutically acceptable carrier. 
     
     
         9 . The method of  claim 8  wherein a sufficient amount of antibody is administered at regular intervals over a period of 12-36 months to reduce the BMI of said patient to below 25 kg/m 2  and/or to reduce the weight of said patient by at least 20%. 
     
     
         10 . The method of  claim 9 , wherein said compound is an antibody that binds to Dll4 and inhibits its binding to NOTCH-3 receptors. 
     
     
         11 . The method of  claim 1 , wherein said compound is a is a gamma-secretase inhibitor. 
     
     
         12 . The method of  claim 11 , wherein said patient is treated by administering a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier. 
     
     
         13 . The method of  claim 12 , wherein said pharmaceutical composition is in unit dosage form. 
     
     
         14 . The method of  claim 13  wherein a sufficient amount of compound is administered at regular intervals over a period of 12-36 months to reduce the BMI of said patient to below 25 kg/m 2  and/or reduce the weight of said patient by at least 20%. 
     
     
         15 . The method of  claim 1 , wherein said method is used to prevent a patient from becoming obese. 
     
     
         16 . The method of  claim 15 , wherein said compound is an antibody that inhibits the binding of Dll4 to a NOTCH receptor. 
     
     
         17 . The method of  claim 15 , wherein said compound is an antibody that binds to Dll4 and inhibits its binding to a NOTCH 3 receptor. 
     
     
         18 . The method of  claim 17 , wherein said subject is treated by administering a pharmaceutical composition comprising said antibody and a pharmaceutically acceptable carrier. 
     
     
         19 . The method of  claim 18 , wherein said pharmaceutical composition is in unit dosage form. 
     
     
         20 . The method of  claim 15 , wherein said patient has been identified as being at increased risk of becoming obese by a method comprising:
 a) assaying a test biological sample derived from said patient for the amount, function, or activity of a NOTCH component;   b) comparing the results obtained in step a) with those from one or more samples from a control group, wherein a higher amount, function, or activity of said NOTCH component in said test biological sample is an indication that said patient is at increased risk of becoming obese.