초록 ▼

The invention provides GLP-1 compounds coupled to two polyethylene glycol molecule or derivative thereof, resulting in a biologically active peptide with an extended half-life and a slower clearance when compared to that of unPEGylated peptide. These PEGylated GLP-1 compounds and compositions are us

The invention provides GLP-1 compounds coupled to two polyethylene glycol molecule or derivative thereof, resulting in a biologically active peptide with an extended half-life and a slower clearance when compared to that of unPEGylated peptide. These PEGylated GLP-1 compounds and compositions are useful in treating conditions or disorders benefited by lowering blood glucose, decreasing food intake, decreasing gastric or intestinal emptying, increasing beta (β) cell population, or decreasing gastric or intestinal motility.

대표청구항 ▼

1. A di-PEGylated GLP-1 compound comprising amino acid sequence: Formula I(SEQ ID NO: 1)His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Xaa22-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Xaa33-Lys-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Cys45-Xaa46wherein Xaa8 is Val, Xaa22 is Glu, Xaa33 is

1. A di-PEGylated GLP-1 compound comprising amino acid sequence: Formula I(SEQ ID NO: 1)His-Xaa8-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Xaa22-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Xaa33-Lys-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Cys45-Xaa46wherein Xaa8 is Val, Xaa22 is Glu, Xaa33 is Ile, and Xaa46 is Cys-NH2 and wherein one PEG molecule is covalently attached to Cys45 and one PEG molecule is covalently attached to Cys46-NH2 and wherein each of the PEG molecules has a molecular weight of about 20,000 daltons. 2. The PEGylated GLP-1 compound of claim 1 wherein each of the PEG molecules is a linear methoxy PEG maleimide. 3. A method of treating non-insulin dependent diabetes in a subject in need thereof comprising administering an effective amount of the PEGylated GLP-1 compound of claim 1. 4. A method of treating obesity in a subject in need thereof comprising administering an effective amount of the PEGylated GLP-1 compound of claim 1.