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US 6,388,053 B1Granted
Glucagon-like insulinotropic peptides, compositions and methods
AssigneeEli Lilly and Company
InventorsJohn A. Galloway, James A. Hoffmann
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Abstract
The present invention provides novel complexes consisting of certain GLP-1 molecules associated with a divalent metal cation that is capable of co-precipitating with a GLP-1 molecule. Pharmaceutical compositions and methods of using such complexes for enhancing the expression of insulin in B-type islet cells is claimed, as is a method for treating maturity onset diabetes mellitus in mammals, particularly humans.
Claims13
A process of preparing a GLP-1 complex, which comprises steps of;
- a) mixing a GLP-1 molecule of the formula:
- R1-X-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Y-Gly-Gln-Ala-Ala-Lys-Z-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-R2
- wherein:
- R1 is selected from the group consisting of L-histidine, D-histidine, desamino-histidine, 2-amino-histidine, β-hydroxy-histidine, homohistidine, alpha-fluoromethyl-histidine, and alpha-methyl-histidine;
- X is selected from the group consisting of Gly, Val, Thr, Ile, and alpha-methyl-Ala;
- Y is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly;
- Z is selected from the group consisting of Glu, Gln, Ala, Thr, Ser, and Gly;
- R2 is selected from the group consisting of NH2, and Gly-OH;
- providing that the compound has an isoelectric point in the range from about 6.0 to about 9.0;
- with a divalent metal cation to form a mixture and;
- b) incubating for a time and a temperature sufficient to form a complex.
8 more elements
Dependencies are inferred from the claim text.