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Calcitonin mimetics for treating diseases and disorders

A human calcitonin, drug technology, applied in the direction of calcitonin, calcitonin gene-related peptide, metabolic diseases, etc.

Inactive Publication Date: 2020-02-14
KEYBIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0021] However, a problem with peptide-driven therapeutics is the development of anti-drug antibodies (ADA) in response to host exposure to a given treatment (Wu B et al. AAPS J. 2016 Nov;18(6):1335-1350; Schellekens H , Clin Ther. 2002 Nov;24(11):1720-40)

Method used

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  • Calcitonin mimetics for treating diseases and disorders
  • Calcitonin mimetics for treating diseases and disorders
  • Calcitonin mimetics for treating diseases and disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0119] Example 1: β-Arrestin Assay

[0120] The PathHunter β-Arrestin GPCR Assay is a whole-cell functional assay that directly measures the ability of a ligand to activate a GPCR by detecting the interaction of β-arrestin with an activated GPCR. Since β-arrestin recruitment is independent of G protein signaling, these assays provide a powerful and versatile screening and analysis platform for virtually any Gi-, Gs or Gq-coupled receptor.

[0121] In this system, GPCR and small enzyme fragment ProLink TM were fused in frame and co-expressed in cells stably expressing a β-arrestin fusion protein and a larger N-terminal deletion mutant of β-gal, termed enzyme receptor or EA. Activation of the GPCR stimulates the binding of β-arrestin to the ProLink-tagged GPCR and forces complementarity of the two enzyme fragments, resulting in the formation of active β-gal enzyme. This interaction results in an increase in enzyme activity, which can be detected using chemiluminescence Det...

Embodiment 2

[0125] Example 2: Comparative effects of KBP-047 to KBP-063 on food intake in healthy Sprague Dawley rats.

[0126] Rats were single caged four days prior to individual testing. They were randomly divided into 7 groups by weight (vehicle (0.9% NaCl), KBP (dose: 2.5 μg / kg). They were fasted overnight and then treated with a single dose of peptide or vehicle subcutaneously in the morning. Following Food intake was monitored at serial intervals (0-4 hours and 4-24 hours).

[0127] Such as Figure 4 As shown in A, both KBP-047 and KBP-053 resulted in a reduction in food intake within a 4-hour interval, and the effect was maintained at 24 hours, with KBP-047 having the greatest reduction, followed by KBP-053.

[0128] Such as Figure 4 As shown in B, KBP-058, KBP-062 and KBP-063 all lead to a reduction in food intake within a 4-hour interval, and the effect is maintained at 24 hours, with KBP-062 having the largest reduction, followed by KBP-058 and KBP-063 In this order. An...

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Abstract

The present invention relates to humanized calcitonin mimetics and their use in treating diabetes (Type I and / or Type II), excess bodyweight, excessive food consumption, metabolic syndrome, rheumatoidarthritis, non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease, alcoholic fatty liver disease, osteoporosis, or osteoarthritis, poorly regulated blood glucose levels, poorly regulated response to glucose tolerance tests, or poor regulation of food intake.

Description

technical field [0001] The present invention relates to calcitonin mimetics, and extends to their use in the treatment of various diseases and conditions, including but not limited to diabetes (type I and type II), excess body weight, excess food consumption and metabolic syndrome, non Alcoholic steatohepatitis (NASH), alcoholic and nonalcoholic fatty liver disease, regulation of blood glucose levels, regulation of response to glucose tolerance test, regulation of food intake, treatment of osteoporosis and osteoarthritis treat. Background technique [0002] There are approximately 250 million diabetics worldwide and this number is expected to double in the next 20 years. More than 90% of patients in this group suffer from type 2 diabetes mellitus (T2DM). It is estimated that only 50-60% of people with T2DM or at a stage preceding overt T2DM are currently diagnosed. [0003] T2DM is a heterogeneous disease characterized by abnormal carbohydrate and fat metabolism. The cau...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/435A61K38/17
CPCA61K38/1706A61P1/16A61P3/10A61P19/02C07K14/435A61K38/00A61K47/12C07K14/57527A61K9/0019A61K9/0053A61K31/155A61K45/06A61K47/18C07K14/585
Inventor K·亨利克森M·卡尔斯达尔K·安德烈森
Owner KEYBIOSCI
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