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Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (GIPR) in combination with GLP-1 agonists

A technology for binding proteins and metabolic disorders, applied in the field of treating or improving metabolic disorders

Pending Publication Date: 2020-02-21
AMGEN INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Rapid degradation by DPP-IV enzymes limits the function of GLP-1, resulting in a half-life of approximately 2 minutes

Method used

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  • Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (GIPR) in combination with GLP-1 agonists
  • Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (GIPR) in combination with GLP-1 agonists
  • Method of treating or ameliorating metabolic disorders using binding proteins for gastric inhibitory peptide receptor (GIPR) in combination with GLP-1 agonists

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example 1

[0610] Materials and methods - Yeast demonstration

[0611] Construction of yeast display molecules and libraries used gBlock and degenerate codon primers (IDT DNA). Standard PCR and overlap assembly PCR were done using Q5HotStart polymerase (NEB). Yeast strain BJ5464 (ATCC) was transformed by electroporation using inserts previously purified by a PCR purification kit (Qiagen) and homologous recombination of the digested vector. Briefly, BJ5464 cells were picked from YPD agar plates and grown overnight in YPD medium at 30°C. Cells were then expanded to a starting OD of 0.2 and grown at 30°C for 6 hrs. After precipitation and resuspension at room temperature, 10 mM Tris, 100 mM LiOAc, 0.6M sorbitol, 10 mM DTT were added, followed by incubation for 30 min at room temperature with gentle shaking at 220 rpm. In cold 1M sorbitol, 1mM CaCl 2 Pellet and wash cells in 2x 10 10 cells / mL for resuspension. Electroporation of 0.5ug DNA was performed with 120uL of cells in a 5uL volu...

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Abstract

Methods of treating metabolic diseases and disorders using an antigen binding protein specific for the GIPR polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the antigen binding protein is administered in combination with a GLP-1 receptor agonist.

Description

technical field [0001] The present disclosure relates to the use of gastric inhibitory peptide receptor (GIPR) specific antigen binding proteins to treat or ameliorate metabolic disorders, for example, type 2 diabetes, elevated glucose levels, elevated insulin levels, obesity, non-alcoholic fatty liver disease or heart disease Vascular disease. Background technique [0002] Glucose-dependent insulinotropic polypeptide (GIP) is a single 42-amino acid peptide secreted from K cells in the small intestine (duodenum and jejunum). Human GIP is derived from the processing of proGIP, a 153-amino acid precursor encoded by a gene located on chromosome 17q (Inagaki et al., Mol Endocrinol 1989; 3:1014-1021; Fehmann et al., Endocr Rev. 1995;16:390-410). Previously, GIP was known as gastric inhibitory polypeptide. [0003] Food intake induces GIP secretion. In tissues, GIP has multiple physiological roles, including promoting fat storage in adipocytes and promoting islet β-cell functi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28
CPCC07K16/2869C07K2317/55C07K2317/75C07K2317/92C07K2317/94A61K9/0019A61K38/26C07K2317/21C07K2317/54
Inventor D·L·贝茨D·史D·J·劳埃德P·邦达伦科M·L·米切尔斯T·海格X·闵A·梅田I·陈Z·王
Owner AMGEN INC
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