Methods for treating metabolic disorders and obesity with GIP and GLP-1 receptor-active glucagon-based peptides

A GLP-1, therapeutic agent technology, applied in metabolic diseases, organic active ingredients, pharmaceutical formulations, etc.

Inactive Publication Date: 2013-11-20
MARCADIA BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although GLP-1 therapeutics are associated with weight loss, it is also associated with nausea, which occurs in more than 20% of patients treated with GLP-1 analogs

Method used

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  • Methods for treating metabolic disorders and obesity with GIP and GLP-1 receptor-active glucagon-based peptides
  • Methods for treating metabolic disorders and obesity with GIP and GLP-1 receptor-active glucagon-based peptides
  • Methods for treating metabolic disorders and obesity with GIP and GLP-1 receptor-active glucagon-based peptides

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0170] In an exemplary embodiment, the half-life extended GLP-1 / GIP co-agonist peptide of the present disclosure is an analog of native glucagon comprising (i) an amino acid comprising an imidazole side chain at position 1, (ii) A DPP-IV protected amino acid at position 2, (iii) optionally an acylated amino acid or an alkylated amino acid at any of positions 9, 10, 12, 16, 20 or 37-43, wherein an acyl or an alkyl group is optionally (iv) an alpha-helix stabilizing amino acid at one or more of positions 16-21, and (v) up to ten (e.g., up to 2, 3, 4, 5, 6, 7, 8, 9 or 10) other amino acid modifications that retain the desired GIP and GLP-1 activity.

[0171] In any of the exemplary embodiments of this section, the amino acid at position 1 may be His or a derivative of His. In any of the exemplary embodiments, the amino acid at position 2 is an α,α-disubstituted amino acid. In any exemplary embodiment, the α,α-disubstituted amino acid comprises R1 and R2 (each of which is bonded...

Embodiment 1

[0174] Example 1: Half-life extended GLP-1 / GIP co-agonist peptides with an extended half-life of about 5 days are well tolerated

[0175] A phase I, randomized, placebo-controlled, continuous, single-ascending, two-period study in healthy male subjects to assess the safety, tolerability, pharmacokinetics of GLP-1 / GIP co-agonist peptides with extended half-life ( PK) and pharmacodynamic (PD) properties. Select a body mass index of 20 kg / m based on history, physical examination, ECG, and routine laboratory tests (eg, blood, chemistry, blood count, urinalysis, and drug screen) 2 with 30kg / m 2 Healthy adult male subjects (approximately 18 to 55 years of age) were used in the study. The half-life extended GLP-1 / GIP co-agonist peptide tested in all examples was SEQ ID NO:153.

[0176] The subjects were randomly divided into several teams. Cohorts 1, 2, 3, 4, 5, and 6 each consisted of 6 patients receiving 0.1 mg, 0.3 mg, 1 mg, 2 mg, 4 mg, and 8 mg of the half-life-extended GLP-1...

Embodiment 2

[0182] Example 2: GLP-1 / GIP co-agonist peptides with extended half-life increase insulin secretion in a dose-dependent manner

[0183] Phase I, randomized, placebo-controlled, active-controlled two-arm study in healthy male and female subjects to assess the effect of a range of doses on the β-cell response to a glucose load and to assess the effect of these doses on gastric emptying . β-cell function was assessed by calculating prehepatic insulin secretion in response to gradient glucose infusion. Gastric emptying was assessed by measuring the plasma profile of absorbed acetaminophen.

[0184] Subjects in Group 1 (Cohort 1) received two abdominal subcutaneous (SC) injections of placebo 2 hours apart on Day 1, followed by BYETTA (Amylin Pharmaceuticals) two 5 μg abdominal subcutaneous injections (SC). In Arm 2, subjects in Cohort 2 received placebo on day 1, followed by 8 mg of a half-life-extended GLP-1 / GIP co-agonist peptide on day 2. Subjects in Cohort 3 received placebo...

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Abstract

Methods are provided for administering an extended half-life GLP-1 / GIP coagonist peptide to a patient in need thereof for reducing weight gain, inducing weight loss, treating hyperglycemia, reducing blood glucose levels, or normalizing blood glucose levels in said patient.

Description

[0001] priority statement [0002] This application claims priority to US Provisional Application No. 61 / 500,229, filed June 23, 2011, and US Provisional Application No. 61 / 426,338, filed December 22, 2010. [0003] Incorporation by Reference of Electronically Submitted Materials [0004] Incorporated by reference in its entirety is the computer-readable nucleotide / amino acid sequence listing filed concurrently with this application and identifying the sequence listing as follows: a file entitled "45708A_SeqListing.txt" created on December 22, 2011 285,688 byte ASCII (text) file. Background technique [0005] Field of the Disclosure [0006] The present disclosure generally relates to methods of administering half-life-extended GLP-1 / GIP co-agonist peptides. More specifically, the present disclosure relates to methods of reducing weight gain or inducing weight loss via administration of a GLP-1 / GIP co-agonist peptide with an extended half-life, and treating hypertensive dis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/26A61K38/08A61K31/195A61K31/198A61P3/04A61P3/10
CPCA61K31/198A61K38/26A61K31/195A61K45/06A61K38/17A61K47/60A61P1/16A61P3/00A61P3/04A61P3/10A61P43/00A61K2300/00A61K9/0021A61K9/0019
Inventor 路易斯·维格纳提理查德·D·狄马区
Owner MARCADIA BIOTECH
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