Title: Peptides having reduced toxicity that stimulate cholesterol efflux

Abstract

The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia, or inflammation; or diseases involving abnormal glucose metabolism, e.g., diabetes, metabolic syndrome; or Alzheimer's Disease or frontotemporal dementia.

Inventors:

Bielicki, John K.; Johansson, Jan; Danho, Waleed

Issue Date:

2018-07-10

Research Org.:

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:

USDOE

OSTI Identifier:

1463293

Patent Number(s):

10017551

Application Number:

14/774,682

Assignee:

The Regents of the University of California (Oakland, CA)

Patent Classifications (CPCs):

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES

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A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P3/10 - for hyperglycaemia, e.g. antidiabetics
A61P13/12 - of the kidneys
A61P9/00 - Drugs for disorders of the cardiovascular system
A61P3/06 - Antihyperlipidemics
A61P29/00 - Non-central analgesic, antipyretic or anti-inflammatory agents, e.g antirheumatic agents
A61P9/04 - Inotropic agents, i.e. stimulants of cardiac contraction

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES

C07K14/435 - from animals

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A61K47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
A61K45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P25/28 - for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61K - PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

A61K47/544 - {Phospholipids}
A61K38/17 - from animals

C - CHEMISTRY C07 - ORGANIC CHEMISTRY C07K - PEPTIDES

C07K14/775 - Apolipopeptides

A - HUMAN NECESSITIES A61 - MEDICAL OR VETERINARY SCIENCE A61P - SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

A61P9/10 - for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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DOE Contract Number:  

AC02-05CH11231

Resource Type:

Patent

Resource Relation:

Patent File Date: 2014 Mar 14

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES