Pharmaceutical composition comprising oxyntomodulin derivatives and a method for reducing body weight using the composition
View Patent ↗Modified oxyntomodulin derivatives. Such derivatives can be used for the treatment of metabolic diseases such as diabetes and obesity.
1. A polypeptide comprising the amino acid sequence
(SEQ ID NO: 97)
HSQGTFTSDYSKYLDSRRAQDFVQWLMNTK-CONH 2 ,
further comprising a substitution of Asp, Glu, Ile, Val, D-Ser, D-Ala, Trp, Asn, Leu, or α-aminoisobutyric acid for the Ser at position 2 and a pharmaceutically acceptable salt thereof.
2. The polypeptide of claim 1 , wherein the polypeptide further comprises a Lys(Palmitoyl), Cys, Cys(mPEG), or Cys(cholesteryl) at the carboxy terminus.
3. The polypeptide of claim 1 , wherein the polypeptide comprises α-aminoisobutyric acid for the Ser at position 2, Met(O) for the Met at position 27, and a Cys(mPEG) at the carboxy terminus.
4. The polypeptide of claim 1 , wherein the polypeptide comprises α-aminoisobutyric acid for the Ser at position 2, Asp for the Gln at position 3, Met(O) for the Met at position 27, and a Cys(cholesteryl) at the carboxy terminus.
5. The polypeptide of claim 1 , wherein the polypeptide comprises D-Ser for the Ser at position 2 and a Lys(palmitoyl) at the carboxy terminus.
6. The polypeptide of claim 1 , wherein the polypeptide is selected from a polypeptide comprising the amino acid sequence of SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, or SEQ ID NO:150.
7. A pharmaceutical composition comprising the polypeptide of claim 1 and a pharmaceutically suitable carrier.
8. A method for lowering glucose levels or reducing food intake and weight gain in a subject in need thereof comprising the step of administering to the subject a polypeptide comprising the amino acid sequence
(SEQ ID NO: 97)
HSQGTFTSDYSKYLDSRRAQDFVQWLMNTK-CONH 2 ,
further comprising a substitution of Asp, Glu, Ile, Val, D-Ser, D-Ala, Trp, Asn, Leu, or α-aminoisobutyric acid for the Ser at position 2 and a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the polypeptide further comprises a Lys(Palmitoyl), Cys, Cys(mPEG), or Cys(cholesteryl) at the carboxy terminus.
10. The method of claim 8 , wherein the polypeptide comprises α-aminoisobutyric acid for the Ser at position 2, Met(O) for the Met at position 27, and a Cys(mPEG) at the carboxy terminus.
11. The method of claim 8 , wherein the polypeptide comprises α-aminoisobutyric acid for the Ser at position 2, Asp for the Gln at position 3, Met(O) for the Met at position 27, and a Cys(cholesteryl) at the carboxy terminus.
12. The method of claim 8 , wherein the polypeptide comprises D-Ser for the Ser at position 2 and a Lys(palmitoyl) at the carboxy terminus.
13. The method of claim 8 , wherein the polypeptide is selected from a polypeptide comprising the amino acid sequence of SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ ID NO:145, SEQ ID NO:146, SEQ ID NO:147, SEQ ID NO:148, SEQ ID NO:149, or SEQ ID NO:150.
14. The method of claim 8 , wherein the treatment lowers glucose levels in the subject.