Aromatic-cationic peptides and uses of same

Patent metadata

Field	Value
Publication number	US-2016376309-A1
Application number	US-201615012286-A
Country	US
Kind code	A1
Filing date	Feb 1, 2016
Priority date	May 3, 2010
Publication date	Dec 29, 2016
Grant date	—

Abstract

The disclosure provides compositions and methods relating to aromatic-cationic peptides. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to subjects in need thereof. For example, the peptides may be administered to subjects in need of a mitochondrial-targeted antioxidant.

First claim

What is claimed is:

1 . An aromatic-cationic peptide selected from the group consisting of:
D-Arg-Tyr-Lys-Phe-NH 2 D-Arg-Dmt-D-Lys-Phe-NH 2 D-Arg-Dmt-Lys-D-Phe-NH 2 Phe-D-Arg-D-Phe-Lys-NH 2 Phe-D-Arg-Phe-D-Lys-NH 2 D-Phe-D-Arg-D-Phe-D-Lys-NH 2 Lys-D-Phe-Arg-Dmt-NH 2 D-Arg-Arg-Dmt-Phe-NH 2 Dmt-D-Phe-Arg-Lys-NH 2 Phe-D-Dmt-Arg-Lys-NH 2 D-Arg-Dmt-Lys-NH 2 Arg-D-Dmt-Lys-NH 2 D-Arg-Dmt-Phe-NH 2 Arg-D-Dmt-Arg-NH 2 Dmt-D-Arg-NH 2 D-Arg-Dmt-NH 2 D-Dmt-Arg-NH 2 Arg-D-Dmt-NH 2 D-Arg-D-Dmt-NH 2 D-Arg-D-Tyr-Lys-Phe-NH 2 D-Arg-Tyr-D-Lys-Phe-NH 2 D-Arg-Tyr-Lys-D-Phe-NH 2 D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 Lys-D-Phe-Arg-Tyr-NH 2 D-Arg-Arg-Tyr-Phe-NH 2 Tyr-D-Phe-Arg-Lys-NH 2 Phe-D-Tyr-Arg-Lys-NH 2 D-Arg-Tyr-Lys-NH 2 Arg-D-Tyr-Lys-NH 2 D-Arg-Tyr-Phe-NH 2 Arg-D-Tyr-Arg-NH 2 Tyr-D-Arg-NH 2 D-Arg-Tyr-NH 2 D-Tyr-Arg-NH 2 Arg-D-Tyr-NH 2 D-Arg-D-Tyr-NH 2 Dmt-Lys-Phe-NH 2 Lys-Dmt-D-Arg-NH 2 Phe-Lys-Dmt-NH 2 D-Arg-Phe-Lys-NH 2 D-Arg-Cha-Lys-NH 2 D-Arg-Trp-Lys-NH 2 Dmt-Lys-D-Phe-NH 2 Dmt-Lys-NH 2 Lys-Phe-NH 2 D-Arg-Cha-Lys-Cha-NH 2 D-Nle-Dmt-Ahe-Phe-NH 2 D-Nle-Cha-Ahe-Cha-NH 2
wherein Cha is cyclohexylalanine, Nle is norleucine, and Ahe is 2-amino-heptanoic acid.

2 . A pharmaceutical composition comprising one or more aromatic-cationic peptides of claim 1 and pharmaceutically acceptable salts thereof.

3 . The pharmaceutical composition of claim 2 further comprising a pharmaceutically acceptable carrier.

4 . A method of reducing the number of mitochondria undergoing mitochondrial permeability transition (MPT), or preventing mitochondrial permeability transitioning in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of claim 1 .

5 . A method for reducing oxidative damage in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of claim 1 .

6 . A method for increasing the ATP synthesis rate in a mammal in need thereof, the method comprising administering to the mammal an effective amount of one or more aromatic-cationic peptides of claim 1 .

7 . A method for determining the presence or amount of an administered aromatic-cationic peptide in a subject, the method comprising: detecting the administered aromatic-cationic peptide in a biological sample from the subject, wherein the aromatic-cationic peptide is selected from the group consisting of:
D-Arg-Tyr-Lys-Phe-NH 2 D-Arg-Dmt-D-Lys-Phe-NH 2 D-Arg-Dmt-Lys-D-Phe-NH 2 Phe-D-Arg-D-Phe-Lys-NH 2 Phe-D-Arg-Phe-D-Lys-NH 2 D-Phe-D-Arg-D-Phe-D-Lys-NH 2 Lys-D-Phe-Arg-Dmt-NH 2 D-Arg-Arg-Dmt-Phe-NH 2 Dmt-D-Phe-Arg-Lys-NH 2 Phe-D-Dmt-Arg-Lys-NH 2 D-Arg-Dmt-Lys-NH 2 Arg-D-Dmt-Lys-NH 2 D-Arg-Dmt-Phe-NH 2 Arg-D-Dmt-Arg-NH 2 Dmt-D-Arg-NH 2 D-Arg-Dmt-NH 2 D-Dmt-Arg-NH 2 Arg-D-Dmt-NH 2 D-Arg-D-Dmt-NH 2 D-Arg-D-Tyr-Lys-Phe-NH 2 D-Arg-Tyr-D-Lys-Phe-NH 2 D-Arg-Tyr-Lys-D-Phe-NH 2 D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 Lys-D-Phe-Arg-Tyr-NH 2 D-Arg-Arg-Tyr-Phe-NH 2 Tyr-D-Phe-Arg-Lys-NH 2 Phe-D-Tyr-Arg-Lys-NH 2 D-Arg-Tyr-Lys-NH 2 Arg-D-Tyr-Lys-NH 2 D-Arg-Tyr-Phe-NH 2 Arg-D-Tyr-Arg-NH 2 Tyr-D-Arg-NH 2 D-Arg-Tyr-NH 2 D-Tyr-Arg-NH 2 Arg-D-Tyr-NH 2 D-Arg-D-Tyr-NH 2 Dmt-Lys-Phe-NH 2 Lys-Dmt-D-Arg-NH 2 Phe-Lys-Dmt-NH 2 D-Arg-Phe-Lys-NH 2 D-Arg-Cha-Lys-NH 2 D-Arg-Trp-Lys-NH 2 Dmt-Lys-D-Phe-NH 2 Dmt-Lys-NH 2 Lys-Phe-NH 2 D-Arg-Cha-Lys-Cha-NH 2 D-Nle-Dmt-Ahe-Phe-NH 2 and D-Nle-Cha-Ahe-Cha-NH 2 .

8 . The method of claim 7 , wherein detecting is performed during administration of the peptide.

9 . The method of claim 7 , wherein detecting is performed after administration of the peptide.

10 . The method of any one of claim 7 , wherein detecting comprises HPLC.

11 . The method of claim 10 , wherein the HPLC comprises reverse phase HPLC.

12 . The method of claim 10 , wherein the HPLC comprises ion exchange HPLC.

13 . The method of claim 7 , wherein detecting comprises mass spectrometry.

14 . The method of claim 7 , wherein the biological sample comprises a fluid.

15 . The method of claim 7 , wherein the biological sample comprises a cell.

16 . The method of claim 7 , wherein the biological sample comprises a tissue.

17 . The method of any one of claims 7 , wherein the biological sample comprises a biopsy.

Assignees

• Stealth Biotherapeutics Corp

Inventors

• Liu Liping
• Gu Lawrence

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P5/50

  for increasing or potentiating the activity of insulin · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title