Therapeutic compositions including frataxin, lactoferrin, and mitochondrial energy generating enzymes, and uses thereof

• US 10,576,124 B2
• Filed: 05/27/2015
• Issued: 03/03/2020
• Est. Priority Date: 05/28/2014
• Status: Active Grant

• Current Assignee: Stealth BioTherapeutics, Inc. (Morningside Group Ltd.)
• Original Assignee: Stealth BioTherapeutics Corp. (Morningside Group Ltd.)
• Inventors: Wilson, D. Travis
• Primary Examiner(s): Audet, Maury A
• Application Number:
  US15/313,767
• Publication Number:
  US 20170196933A1
• Time in Patent Office: 1,742 Days
• Field of Search: None
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/06 Tripeptides
• CPC Class Codes: A61K 38/07 Tetrapeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/40 Transferrins, e.g. lactoferrins, ovotransferrins
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 38/443 acting on CH-OH groups as donors, e.g. glucose oxidase, lactate dehydrogenase (1.1)
• CPC Class Codes: A61K 38/45 Transferases (2)
• CPC Class Codes: A61K 38/46 Hydrolases (3)
• CPC Class Codes: A61K 38/51 Lyases (4)
• CPC Class Codes: A61K 38/53 Ligases (6)
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: C07K 5/06078 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/06095 Arg-amino acid
• CPC Class Codes: C07K 5/06156 and Trp-amino acid; Derivatives thereof
• CPC Class Codes: C07K 5/0812 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/0815 with the first amino acid being basic
• CPC Class Codes: C07K 5/0817 : the first amino acid being Arg
• CPC Class Codes: C07K 5/0821 : with the first amino acid being heterocyclic, e.g. His, Pro, Trp
• CPC Class Codes: C07K 5/1016 : and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1021 : with the first amino acid being acidic
• CPC Class Codes: C12Y 101/01037 : Malate dehydrogenase (1.1.1.37)
• CPC Class Codes: C12Y 101/01042 : Isocitrate dehydrogenase (NADP+) (1.1.1.42)
• CPC Class Codes: C12Y 102/04002 : Oxoglutarate dehydrogenase (succinyl-transferring) (1.2.4.2), i.e. alpha-ketoglutarat dehydrogenase
• CPC Class Codes: C12Y 103/05001 : Succinate dehydrogenase (ubiquinone) (1.3.5.1)
• CPC Class Codes: C12Y 106/05003 : NADH dehydrogenase (ubiquinone) (1.6.5.3)
• CPC Class Codes: C12Y 109/03001 : Cytochrome-c oxidase (1.9.3.1)
• CPC Class Codes: C12Y 110/02002 : Ubiquinol-cytochrome-c reductase (1.10.2.2), i.e. electron-transport-complex-III
• CPC Class Codes: C12Y 203/03001 : Citrate (Si)-synthase (2.3.3.1)
• CPC Class Codes: C12Y 306/03014 : H+-transporting two-sector ATPase (3.6.3.14), i.e. F1 ATPase
• CPC Class Codes: C12Y 402/01002 : Fumarate hydratase (4.2.1.2)
• CPC Class Codes: C12Y 402/01003 : Aconitate hydratase (4.2.1.3)
• CPC Class Codes: C12Y 602/01004 : Succinate-CoA ligase (GDP-forming) (6.2.1.4)
• CPC Class Codes: C12Y 604/01001 : Pyruvate carboxylase (6.4.1.1)

Abstract

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2′,6′-dimethyl-Tyr-D-Arg-Phe-Lys-NH₂, Phe-D-Arg-Phe-Lys-NH₂, or D-Arg-2′,6′-Dmt-Lys-Phe-NH₂.

Claims

1. A peptide conjugate comprising a therapeutic biological molecule conjugated to an aromatic-cationic peptide, wherein the aromatic-cationic peptide is 2′

, 6′

dimethyl-Tyr-D-Arg-Phe-Lys-NH₂, and wherein the therapeutic biological molecule is frataxin.

2. A peptide conjugate according to claim 1, wherein the therapeutic biological molecule is conjugated to the aromatic-cationic peptide by a linker.

3. A peptide conjugate according to claim 1, wherein the therapeutic biological molecule and aromatic-cationic peptide are chemically bonded.

4. A peptide conjugate according to claim 1, wherein the therapeutic biological molecule and aromatic-cationic peptide are physically bonded.

5. A peptide conjugate according to claim 1, wherein the aromatic-cationic peptide and the therapeutic biological molecule are linked using a labile linkage that is hydrolyzed in vivo to uncouple the aromatic-cationic peptide and the therapeutic biological molecule.

6. A peptide conjugate according to claim 5, wherein the labile linkage comprises an ester linkage.