Modification of feeding behaviour

Abstract

Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering PYY or an agonist thereof and GLP-1 or an agonist thereof to the subject, simultaneously or sequentially, thereby decreasing the calorie intake of the subject.

1 . A method for decreasing calorie intake or food intake in a subject, for preventing or reducing weight gain or inducing weight loss in a subject, or controlling any one or more of appetite, satiety, and hunger in a subject comprising peripherally administering a therapeutically effective amount of Peptide YY (PYY) or an agonist thereof and a therapeutically effective amount of Glucagon-like peptide-1 (GLP-1) or an agonist thereof to the subject, wherein the amount of PYY or agonist thereof is administered in a molar equivalent amount of a PYY 3-36  dose of no more than 2.2 nmol per kg body weight of the subject. 
     
     
         2 - 8 . (canceled) 
     
     
         9 . A method as claimed in  claim 1 , wherein the PYY or agonist thereof and the GLP-1 or agonist thereof are administered simultaneously or sequentially. 
     
     
         10 . A method as claimed in  claim 1 , wherein the PYY and the GLP-1 are administered via different routes. 
     
     
         11 . A method as claimed in  claim 1 , wherein the subject is overweight, obese or diabetic. 
     
     
         12 . (canceled) 
     
     
         13 . A method as claimed in  claim 1 , wherein the subject has type II diabetes. 
     
     
         14 . A method as claimed in  claim 1 , wherein peripheral administration comprises subcutaneous, intravenous, intramuscular, intranasal, transdermal or sublingual administration. 
     
     
         15 . A method as claimed in  claim 1 , wherein peripherally administering PYY or the agonist thereof comprises administering about 45 to about 135 pmol per kilogram body weight of the subject or about 72 pmol per kilogram body weight of the subject. 
     
     
         16 . (canceled) 
     
     
         17 . A method as claimed in  claim 15 , wherein peripherally administering PYY or the agonist thereof comprises administering about 45 to about 135 pmol per kilogram body weight of the subject at least 30 minutes prior to a meal. 
     
     
         18 . A method as claimed in  claim 1 , wherein peripherally administering the therapeutically effective amount of PYY or the agonist thereof comprises administering PYY or an agonist thereof to the subject in a multitude of doses, wherein each dose in the multitude of doses comprises administration of about 0.5 to about 135 pmol per kilogram of body weight at least about 30 minutes prior to a meal. 
     
     
         19 . (canceled) 
     
     
         20 . A method as claimed in  claim 1 , wherein the PYY or the agonist thereof is administered in an amount sufficient to decrease calorie intake for a period of about 2 to 12 hours. 
     
     
         21 . A method as claimed in  claim 1 , wherein the PYY or agonist thereof is administered peripherally at a dose of 0.1 nmoles per kg body weight of the subject, 0.2 nmoles per kg body weight of the subject, 0.4 nmoles per kg body weight of the subject, 0.6 nmoles per kg body weight of the subject, 0.8 nmoles per kg body weight of the subject, 1.0 nmole per kg body weight of the subject, 1.2 nmoles per kg body weight of the subject, 1.4 nmoles per kg body weight of the subject, 1.6 nmoles per kg body weight of the subject, 1.8 nmoles per kg body weight of the subject, 2.0 nmoles per kg body weight of the subject, or 2.2 nmoles per kg body weight of the subject. 
     
     
         22 . (canceled) 
     
     
         23 . A method as claimed in  claim 1 , wherein the GLP-1 or agonist thereof is administered peripherally at a dose of 0.1 nmoles per kg body weight of the subject or more, for example, 0.2 nmoles or more, for example, 0.4 nmoles or more, for example, 0.6 nmoles or more, for example, 0.8 nmoles or more, for example, 1.0 nmole or more, for example, 1.2 nmoles or more, for example, 1.4 nmoles or more, for example, 1.6 nmoles or more, for example, 1.8 nmoles or more, for example, 2.0 nmoles or more, for example, 2.2 nmoles or more, for example, 2.4 nmoles or more, for example, 2.6 nmoles or more, for example, 2.8 nmoles, for example, 3.0 nmoles or more, for example, up to 3.2 nmoles per kg body weight. 
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . A method as claimed in  claim 1 , wherein the PYY or agonist thereof is modified by one or more of amidation, glycosylation, acylation, sulfation, phosphorylation, cyclization, lipidization, or pegylation. 
     
     
         27 . A method as claimed in  claim 1 , wherein the GLP-1 or agonist thereof comprises the amino acid sequence of GLP-1 (7-36) (SEQ ID NO:339) or a variant thereof that binds a GLP-1 receptor. 
     
     
         28 . A method as claimed in  claim 1 , wherein the PYY is PYY 3-36  or variant thereof. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A method as claimed in  claim 1 , wherein the GLP-1 agonist is exendin-4 or a derivative thereof that is a GLP-1 agonist. 
     
     
         32 . A method as claimed in  claim 1 , further comprising administering a therapeutically effective amount of amfepramone (diethylpropion), phentermine, mazindol, phenylpropanolamine, fenfluramine, dexfenfluramine, or fluoxetine. 
     
     
         33 . A method as claimed in  claim 1 , wherein the subject is human. 
     
     
         34 - 43 . (canceled) 
     
     
         44 . A pharmaceutical composition comprising PYY and an agonist thereof and GLP-1 or an agonist thereof, in admixture or in conjunction with a pharmaceutically suitable carrier, wherein the amount of PYY or agonist thereof present in the composition is sufficient to deliver a molar equivalent amount of PYY 3-36  of no more than 2.2 nmol per kg body weight of the subject. 
     
     
         45 . A pharmaceutical composition comprising PYY or an agonist thereof in admixture with a pharmaceutically suitable carrier, in a form suitable for subcutaneous, intravenous, intramuscular, intranasal, transdermal, or sublingual administration, wherein the amount of PYY or agonist thereof present in the composition is sufficient to deliver a molar equivalent amount of PYY 3-36  of no more than 2.2 nmol per kg body weight of the subject. 
     
     
         46 . A pharmaceutical composition as claimed in  claim 45 , which comprises 20 nmoles or more, for example, 30 nmoles or more, for example, 40 nmoles or more of PYY or an agonist thereof. 
     
     
         47 . (canceled) 
     
     
         48 . A pharmaceutical composition as claimed in  claim 45 , which comprises from PYY or an agonist thereof in an amount suitable for administration peripherally in an amount of up to 2.2 nmoles per kg body weight, for example, up to 2.0 nmoles, for example, up to 1.8 nmoles, for example, up to 1.4 nmoles, for example, up to 1.2 nmoles, for example, up to 1.0 nmoles, for example, up to 0.8 nmoles, for example, up to 0.6 nmoles, for example, up to 0.4 nmoles, for example, up to 0.2 nmoles, for example, up to 0.1 nmoles per kg body weight. 
     
     
         49 . (canceled) 
     
     
         50 . A pharmaceutical composition as claimed in  claim 48 , in unit dosage form. 
     
     
         51 . A method as defined in  claim 1 , which comprises administering PYY or an agonist thereof subcutaneously at a dose of 10 nmoles or more, for example, 20 nmoles or more, for example, 30 nmoles or more, for example, 40 nmoles or more to the subject of the method. 
     
     
         52 - 57 . (canceled) 
     
     
         58 . A method as claimed in  claim 1 , wherein the PYY or agonist thereof is administered in an amount of from 1 to 100 nmols, from 2 to 90 nmols, from 5 to 80 nmols, or from 5 to 50 nmols.