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Human Amylin Analog

A technology of amyloid polypeptides and analogs, applied in the direction of animal/human proteins, hormone peptides, specific peptides, etc., can solve the problem of less calcitonin receptors and achieve the effect of improving selectivity

Active Publication Date: 2019-05-10
NOVO NORDISK AS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, apart from bone regulation, little is known about the physiology of calcitonin receptors in humans

Method used

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  • Human Amylin Analog
  • Human Amylin Analog
  • Human Amylin Analog

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0150] In one embodiment, the invention relates to a polypeptide comprising an amino acid sequence that is an analog of SEQ ID No: 1, wherein:

[0151] (a) said analog comprises a proline residue at position 21;

[0152] Wherein the amino acid sequence numbering of the analog corresponds to the amino acid numbering sequence of SEQ ID No: 1;

[0153] Optionally wherein (b) the IC of the polypeptide in a human amylin receptor binding assay 50 is about 1200 pM or less;

[0154] Optionally wherein the polypeptide has at least one substituent attached to at least one of its amino acid residues.

[0155] In a specific embodiment, the invention relates to a polypeptide comprising an amino acid sequence that is an analog of SEQ ID No: 1, wherein:

[0156] (a) said analog comprises a proline residue at position 21; and

[0157] (b) IC of the polypeptide in the human amylin receptor binding assay 50 is about 1200 pM or less;

[0158] Wherein the amino acid sequence numbering of th...

Embodiment

[0647] Acronym

[0648] Some abbreviations used in the examples are as follows:

[0649] Acm: acetamidomethyl

[0650] HATU: (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethylurea hexafluorophosphate )

[0651] HBTU: 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylurea hexafluorophosphate

[0652] Fmoc: 9 H-fluoren-9-ylmethoxycarbonyl

[0653] Boc: tert-butoxycarbonyl

[0654] Mtt: 4-Methyltrityl

[0655] DCM: dichloromethane

[0656] TIPS: Triisopropylsilane

[0657] TFA: Trifluoroacetic acid

[0658] NMP: 1-methyl-pyrrolidin-2-one

[0659] HOAt: 1-Hydroxy-7-azabenzotriazole

[0660] DIC: Diisopropylcarbodiimide

[0661] Trt: Triphenylmethyl

[0662] Assay

[0663] In the following examples, the following assays will be mentioned:

[0664] Assay (I) - Experimental Protocol for Efficacy Testing for Appetite Using the Ad libitum Rat Model

[0665] Assay (II)a- Functional Assay - Human Calcitonin and Amylin Receptor Assay

[0666] Assay (II)b- Functional Assay - Rat ...

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Abstract

The present invention relates to polypeptides comprising amino acid sequences which are analogs of human amylin, pharmaceutical compositions comprising these polypeptides and these polypeptides for use as medicaments.

Description

field of invention [0001] The present invention relates to polypeptides comprising an amino acid sequence which is an analogue of SEQ ID NO: 1 (human amylin), pharmaceutical compositions comprising these polypeptides and these polypeptides for use as medicaments. Background of the invention [0002] Numerous and increasing numbers of people suffer from diabetes and obesity. Diabetes mellitus is a metabolic disorder in which the ability to utilize glucose is partially or completely lost. [0003] Many treatment options target excess blood sugar, while others focus primarily on weight loss. The most effective antidiabetic drugs for lowering blood sugar are insulin and its analogs. It has long been known that when conventional insulin is used to treat diabetes, an accompanying weight gain occurs. Insulin has to be injected subcutaneously up to several times a day. [0004] Early-stage type 2 diabetes is generally treated with diet and exercise. As the disease progresses, v...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/575
CPCA61K38/00C07K14/575A61P1/04A61P1/14A61P3/04A61P3/06A61P3/10A61P9/10A61P9/12A61P25/28
Inventor K.达尔L.舍弗T.克鲁塞
Owner NOVO NORDISK AS
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