IP Library Granted Patent US 10,293,020
Granted Patent B2
US 10,293,020 · App. 14/899,439 · Granted May 21, 2019

Peptide therapeutics and methods for using same

Inventor: D. Travis Wilson (Newton, MA)
Assignee: STEALTH BIOTHERAPEUTICS CORP.
A61K38/07A61K38/05A61K38/06A61K38/08A61K38/10A61K38/13
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 10,293,020
App. No.
14/899,439
Granted
May 21, 2019
Kind
B2
Abstract

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of an MPP, and/or naturally or artificially occurring variants or analogs of an MPP, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide such as D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ).

Claims (112)

1. A composition comprising the mitochondria penetrating peptide (MPP) Cha-Arg-Cha-Lys-NH 2 alone or in combination with one or more aromatic-cationic peptides selected from the group consisting of:

2′6′-Dmp-D-Arg-2′6′-Dmt-Lys-NH 2 ;

2′,6′-Dmt-D-Arg-Phe-Lys-NH 2 ;

2′6′-Dmp-D-Arg-Phe-Lys-NH 2 ;

2′6′-Dmt-D-Arg-PheOrn-NH 2 ;

2′6′-Dmt-D-Arg-Phe-Ahp(2-aminoheptanoicacid)-NH 2 ;

2′6′-Dmt-D-Arg-Phe-Lys-NH 2 ;

2′6′-Dmt-D-Cit-PheLys-NH 2 ;

Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe;

Arg-D-Dmt-Arg-NH 2 ;

Arg-D-Dmt-Lys-NH 2 ;

Arg-D-Dmt-NH 2 ;

Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly;

Arg-D-Tyr-Arg-NH 2 ;

Arg-D-Tyr-Lys-NH 2 ;

Arg-D-Tyr-NH 2 ;

Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe;

Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ;

D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ;

D-Arg-Arg-Dmt-Phe-NH 2 ;

D-Arg-Arg-Tyr-Phe-NH 2 ;

D-Arg-Cha-Lys-Cha-NH 2 ;

D-Arg-Cha-Lys-NH 2 ;

D-Arg-D-Dmt-NH 2 ;

D-Arg-Dmt-D-Lys-Phe-NH 2 ;

D-Arg-Dmt-Lys-Dmt-Lys-Met-NH 2 ;

D-Arg-Dmt-Lys-Dmt-Lys-Trp-NH 2 ;

D-Arg-Dmt-Lys-D-Phe-NH 2 ;

D-Arg-Dmt-Lys-NH 2 ;

D-Arg-Dmt-Lys-Phe-Lys-Met-NH 2 ;

D-Arg-Dmt-Lys-Phe-Lys-Trp-NH 2 ;

D-Arg-Dmt-Lys-Phe-Met-NH 2 ;

D-Arg-Dmt-Lys-Trp-NH 2 ;

D-Arg-Dmt-NH 2 ;

D-Arg-Dmt-Phe-NH 2 ;

D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 ;

D-Arg-D-Tyr-Lys-Phe-NH 2 ;

D-Arg-D-Tyr-NH 2 ;

D-Arg-Phe-Lys-NH 2 ;

D-Arg-Trp-Lys-NH 2 ;

D-Arg-Trp-Lys-Trp-NH 2 ;

D-Arg-Tyr-D-Lys-Phe-NH 2 ;

D-Arg-Tyr-Lys-D-Phe-NH 2 ;

D-Arg-Tyr-Lys-NH 2 ;

D-Arg-Tyr-Lys-Phe-NH 2 ;

D-Arg-Tyr-NH 2 ;

D-Arg-Tyr-Phe-NH 2 ;

D-Dmt-Arg-NH 2 ;

D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH 2 ;

D-His-Glu-Lys-Tyr-D-Phe-Arg;

D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-Asp-D-His-D-Lys-Arg-Trp-NH 2 ;

Dmt-D-Arg-NH 2 ;

Dmt-D-Phe-Arg-Lys-NH 2 ;

Dmt-Lys-D-Phe-NH 2 ;

Dmt-Lys-NH 2 ;

Dmt-Lys-Phe-NH 2 ;

D-Nle-Cha-Ahe-Cha-NH 2 ;

D-Nle-Dmt-Ahe-Phe-NH 2 ;

D-Phe-D-Arg-D-Phe-D-Lys-NH 2 ;

D-Tyr-Arg-NH 2 ;

D-Tyr-Trp-Lys-NH 2 ;

Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH 2 ;

Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp;

Gly-D-Phe-Lys-His-D-Arg-Tyr-NH 2 ;

H-D-Arg(NαMe)-Dmt(NMe)-Lys(NαMe)-Phe(NMe)-NH 2 ;

H-D-Arg-Dmt-Lys(NαMe)-Phe(NMe)-NH 2 ;

H-D-Arg-Dmt-Lys(NαMe)-Phe-NH 2 ;

H-D-Arg-Dmt-Lys-Phe(NMe)-NH 2 ;

H-D-Arg-Dmt-Lys-Phe-Sar-Gly-Cys-NH 2 ;

H-D-Arg-Dmt-LysΨ[CH2-NH]Phe-NH 2 ;

H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Phe-NH 2 ;

H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Ψ[CH2-NH]Phe-NH 2 ;

H-D-Arg-Ψ[CH2-NH]Dmt-Lys-Phe-NH 2 ;

His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH 2 ;

Lys-D-Arg-Tyr-NH 2 ;

Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ;

Lys-Dmt-D-Arg-NH 2 ;

Lys-D-Phe-Arg-Dmt-NH 2 ;

Lys-D-Phe-Arg-Tyr-NH 2 ;

Lys-Phe-NH 2 ;

Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ;

Met-Tyr-D-Arg-Phe-Arg-NH 2 ;

Met-Tyr-D-Lys-Phe-Arg;

Phe-Arg-D-His-Asp;

Phe-D-Arg-2′6′-Dmt-Lys-NH 2 ;

Phe-D-Arg-D-Phe-Lys-NH 2 ;

Phe-D-Arg-His;

Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His;

Phe-D-Arg-Phe-D-Lys-NH 2 ;

Phe-D-Arg-Phe-Lys-NH 2 ;

Phe-D-Dmt-Arg-Lys-NH 2 ;

Phe-D-Tyr-Arg-Lys-NH 2 ;

Phe-Lys-Dmt-NH 2 ;

Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH 2 ;

Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr;

Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys;

Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ;

Trp-D-Lys-Tyr-Arg-NH 2 ;

Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys;

Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys;

Tyr-D-Arg-NH 2 ;

Tyr-D-Arg-Phe-Lys-Glu-NH 2 ;

Tyr-D-Arg-Phe-Lys-NH 2 ;

Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe;

Tyr-D-Phe-Arg-Lys-NH 2 ;

Tyr-His-D-Gly-Met; and

Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,

and further comprising one or more additional active agents selected from the group consisting of cyclosporine, a cardiac drug, an anti-inflammatory, an anti-hypertensive drug, an antibody, an ophthalmic drug, an antioxidant, a metal complexer, and an antihistamine.

2. The composition of claim 1 , wherein the MPP further comprises a modification selected from the group consisting of inclusion of one or more D-amino acids, inclusion of one or more sites of N-methylation, and inclusion of one or more reduced amide bonds (Ψ[CH2-NH]).

3. The composition of claim 1 , further comprising at least one pharmaceutically acceptable pH-lowering agent and at least one absorption enhancer comprising an absorbable or biodegradable surface active agent selected from the group consisting of an acylcarnitine, a phospholipid, a bile acid, and a sucrose ester.

4. The composition of claim 3 , wherein the pH-lowering agent is selected from the group consisting of citric acid, tartaric acid, and an acid salt of an amino acid.

5. The composition of claim 3 , wherein the composition comprises a lamination having a first layer comprising the at least one pharmaceutically acceptable pH-lowering agent and a second layer comprising the MPP alone or in combination with one or more aromatic-cationic peptides and further comprising the at least one absorption enhancer, wherein the first and second layers are united with each other, but wherein the layers prevent interaction between the pH-lowering agent and the peptide(s).

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 17, 2021
From: STEALTH BIOTHERAPEUTICS CORP
To: STEALTH BIOTHERAPEUTICS INC.
Reel/Frame 058164/0305 →
CHANGE OF NAME Recorded Mar 23, 2017
From: STEALTH PEPTIDES INTERNATIONAL, INC.
To: STEALTH BIOTHERAPEUTICS CORP
Reel/Frame 042157/0448 →
CHANGE OF NAME Recorded Sep 21, 2016
From: STEALTH PEPTIDES INTERNATIONAL, INC.
To: STEALTH BIOTHERAPEUTICS CORP
Reel/Frame 040098/0114 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 21, 2016
From: WILSON, D. TRAVIS
To: STEALTH PEPTIDES INTERNATIONAL, INC.
Reel/Frame 039819/0712 →
Continuity (2)
Provisional Application 61840317 · Jun 27, 2013
Related Publication 20160151446A1 · Jun 2, 2016
Cited By (2)
US 12,337,000 US 12,410,143