Glp-1 analog fusion protein formulations

A technology of GLP-1 and analogues, which is applied in the field of glucagon-like peptide analogues, and can solve problems such as large and complex technologies

Active Publication Date: 2007-09-26
ELI LILLY & CO
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Technically too large and complex for synthetically produced or recombinantly produced fusion proteins of this nature in bacterial cells

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0068] GLP-1 receptor activation assay in vitro

[0069] HEK-293 cells expressing human GLP-1 receptor were seeded into poly-d-lysine-coated 96 wells at 20,000 to 40,000 cells / well / 100 μl DMEM medium containing 10% FBS using the CRE-BLAM system Available in black transparent bottom tablet. One day after inoculation, the medium was gently poured off, and 80 μl of serum-free DMEM medium was added. On the third day after inoculation, 20 μl of serum-free DMEM medium containing 0.5% BSA containing various GLP-1-Fc fusion proteins at various concentrations was added to each well to prepare a dose-response curve. Typically, 14 dilutions containing 3 nanomolar to 30 nanomolar GLP-1 Fc fusion protein were used to generate dose response curves from which EC50 values ​​could be determined. After 5 hours of incubation with the fusion protein, 20 μl of β-lactamase substrate (CCF2 / AM, PanVera LLC) was added and incubation was continued for 1 hour, at which time fluorescence was measured o...

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PUM

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Abstract

The invention provides a stable solution formulation comprising a GLP-1-Fc fusion at a pH between about pH 6 and about pH 8.5. analogs fused to specific IgG4-Fc derivatives. These formulations provide unexpected and considerably greater chemical stability than when compared to GLP-1-Fc fusions at a pH outside the described ranges. The formulations comprising a GLP-1-Fc fusion are useful in treating diabetes, obesity, irritable bowel syndrome and other conditions that would be benefited by lowering plasma glucose, inhibiting gastric and / or intestinal motility and inhibiting gastric and / or intestinal emptying, or inhibiting food intake.

Description

technical field [0001] The present invention relates to glucagon-like peptide analogs which are fused to a protein which has the effect of stabilizing the fused protein. These formulations are useful in the treatment of diabetes and a variety of other diseases or disorders. Background technique [0002] Glucagon-like peptide-1 (GLP-1) analogs and derivatives hold promise for the treatment of type 2 diabetes in clinical trials. GLP-1 induces various biological effects such as stimulation of insulin secretion, inhibition of glucagon secretion, inhibition of gastric emptying, inhibition of gastric or intestinal motility, and induction of weight loss. A notable feature of GLP-1 is its ability to stimulate insulin secretion without the associated risks of hypoglycemia seen with insulin therapy or certain types of oral therapy that act by increasing insulin expression. [0003] GLP-1(1-37) activity is very low, and GLP-1(7-37)OH and GLP-1(7-36)NH 2 The fact that these two natur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/50C12N15/62C07K14/605C07K14/435A61K38/26A61K38/00A61P3/10
CPCC07K2319/30C07K14/605A61P1/00A61P1/04A61P3/00A61P3/04A61P43/00A61P9/10A61P3/10C07K14/435A61K38/00
Inventor W·格莱斯纳R·L·小米利肯
Owner ELI LILLY & CO
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