Treatment of hyperinsulinemic hypoglycemia with exendin-4 derivatives
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11116820-B2
Publication Date
2021-09-14
Expiration Date
Abstract
In one aspect, methods of treating hyperinsulinemic hypoglycemia comprising administration of an effective amount of a derivative of an exendin-4 peptide are provided. In some embodiments, the method comprises subcutaneously administering to a patient having hyperinsulinemic hypoglycemia a therapeutically effective amount of exendin(5-39).
Core Innovation
The invention relates to treating hyperinsulinemic hypoglycemia by administering an exendin-4 derivative to a patient in need thereof. The exendin-4 derivative is selected from exendin(3-39), exendin(4-39), exendin(5-39), exendin(6-39), exendin(7-39), and exendin(8-39). The treatment is directed to hyperinsulinemic hypoglycemia, including post-bariatric/post gastrointestinal surgery forms and congenital hyperinsulinism.
The described approach uses GLP-1 receptor antagonistic exendin-4 derivatives having N-terminal truncations, including exendin(3-39) to exendin(8-39), with an emphasis on exendin(5-39). The exendin-4 derivatives may be pegylated, and are administered subcutaneously in an immediate release or extended release formulation.
Pharmaceutical compositions and kit formats are also described, together with assay context for receptor antagonist behavior. The disclosed assays include prophetic, in vitro, animal, and cell-based assay contexts, including OGTT, MTT, CGM, and a cAMP functional assay using βTC6 cells for evaluating exendin(5-39) and pegylated exendin(5-39) versus exendin(9-39).
Claims Coverage
The independent claim coverage centers on treating hyperinsulinemic hypoglycemia with truncated exendin-4 derivatives, with at least five main inventive features specified across the provided claim content.
Truncated exendin-4 derivative for treating hyperinsulinemic hypoglycemia
Administering an exendin-4 derivative selected from exendin(3-39), exendin(4-39), exendin(5-39), exendin(6-39), exendin(7-39), and exendin(8-39) to a patient in need thereof for treating hyperinsulinemic hypoglycemia.
Specified exendin-4 derivative concentration
Administering the exendin-4 derivative at a concentration of 4–50 mg/mL.
Total injection volume range
Administering the exendin-4 derivative in a total volume of 0.25–2 mL.
Meal-timed twice-daily administration
Administering the exendin-4 derivative twice per day, before a morning meal and before an evening meal.
Pegylated exendin-4 derivative
Administering the exendin-4 derivative wherein the exendin-4 derivative is pegylated.
Bariatric surgery selection set
Where prior bariatric surgery is relevant, selecting the bariatric surgery from Roux-en-Y gastric bypass, vertical sleeve gastrectomy, placement of an endosleeve device, duodenal mucosal resurfacing, partial bypass of the duodenum, vagal nerve blockade, or pyloroplasty.
Overall, the claim coverage centers on using truncated exendin-4 derivatives (exendin(3-39) through exendin(8-39)) for treating hyperinsulinemic hypoglycemia, with quantitative coverage of derivative concentration and administration volume, and additional coverage for pegylation, meal-timed twice-daily administration, and a defined set of bariatric surgical histories.
Stated Advantages
Increased postprandial plasma glucose nadir.
Reduced hypoglycemic symptoms, including neuroglycopenic symptoms.
Documented Applications
Treatment of hyperinsulinemic hypoglycemia, including post-bariatric/post gastrointestinal surgery forms and congenital hyperinsulinism, using GLP-1 receptor antagonistic exendin-4 derivatives with N-terminal truncations.
Evaluation context for receptor antagonist behavior of exendin(5-39) and pegylated exendin(5-39) versus exendin(9-39) using prophetic, in vitro, animal, and cell-based assay contexts, including OGTT, MTT, CGM, and a cAMP functional assay in βTC6 cells with HTRF cAMP measurement.
Interested in licensing this patent?