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Engineered polypeptides having enhanced duration of action and reduced immunogenicity

A technology of engineering and identity, applied in medical preparations containing active ingredients, fusion polypeptides, peptides, etc., can solve problems such as increased duration of action

Active Publication Date: 2014-07-30
安瑞特制药公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Without wishing to be bound by any theory, it is believed that because the engineered polypeptides described herein can bind albumin, the compounds can be sequestered (e.g., bound to albumin) when in circulation, due to, for example, renal clearance and / or decreased degradation resulting in increased duration of action

Method used

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  • Engineered polypeptides having enhanced duration of action and reduced immunogenicity
  • Engineered polypeptides having enhanced duration of action and reduced immunogenicity
  • Engineered polypeptides having enhanced duration of action and reduced immunogenicity

Examples

Experimental program
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Effect test

Embodiment approach 1

[0489] Embodiment 1. A method of treating obesity in a subject comprising peripherally administering therapeutically effective amounts of at least two different anti-obesity agents, wherein at least one of the anti-obesity agents is amylin, an amylin analog, an amylin Amylin-like polypeptide agonists or amylin derivatives (i.e., amylin agents), and at least one anti-obesity agent is an albumin-binding domain polypeptide (ABD) and is selected from leptin, leptin analogs or An engineered polypeptide of the first peptide hormone domain (HD1) of its active fragment, wherein ABD comprises any one of the peptides selected from SEQ ID NO: 301-452, 455-463 and 500-593.

Embodiment approach 2

[0490] Embodiment 2. A method of reducing body weight in a subject comprising peripherally administering therapeutically effective amounts of at least two different anti-obesity agents, wherein at least one of the anti-obesity agents is amylin, an amylin analog, an amylin Amylin-like polypeptide agonists or amylin derivatives (i.e., amylin agents), and at least one anti-obesity agent is an albumin-binding domain polypeptide (ABD) and is selected from leptin, leptin analogs or An engineered polypeptide of the first peptide hormone domain (HD1) of its active fragment, wherein ABD comprises any one of the peptides selected from SEQ ID NO: 301-452, 455-463 and 500-593.

Embodiment approach 3

[0491] Embodiment 3. The method of any one of Embodiments 1 or 2, wherein the at least one anti-obesity amylin agent is an amylin agonist.

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Abstract

Compounds are provided having inter alia good duration of action, high potency and / or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Description

[0001] sequence listing [0002] This application contains a Sequence Listing, filed in ASCII format via EFS-Web, which is incorporated by reference in its entirety. Said ASCII copy was created on July 3, 2012, named 1320USPR.txt, and was 450,377 bytes in size. Background of the invention [0003] The present application relates to compounds having good duration of action, high potency and / or convenient dosing regimens and methods of use thereof. Provided herein are engineered polypeptides comprising an albumin binding domain in combination with a biologically active peptide. Without wishing to be bound by any theory, it is believed that because the engineered polypeptides described herein can bind albumin, the compounds can be sequestered (e.g., bound to albumin) when in circulation, due to, for example, renal clearance and and / or reduced degradation resulting in increased duration of action. Diseases amenable to such treatment include lipodystrophy, dyslipidemia, hyperlip...

Claims

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Application Information

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IPC IPC(8): A61K38/22
CPCA61K38/22A61K38/2264C07K2319/70A61K38/00C07K14/5759A61P1/16A61P15/00A61P25/14A61P25/28A61P3/04A61P3/06A61P5/00A61P9/12A61P3/10C07K14/315C07K14/575C07K2319/31
Inventor M.埃里克森D.C.利青格尔S.S.高希Z.郭C.埃克布拉徳J.D.罗思
Owner 安瑞特制药公司
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