Method and carrier complexes for delivering molecules to cells

• US 10,584,182 B2
• Filed: 03/11/2016
• Issued: 03/10/2020
• Est. Priority Date: 05/01/2003
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Szeto, Hazel H., Zhao, Kesheng, Robertson, Hugh, Birk, Alex V.
• Primary Examiner(s): Alstrum-Acevedo, James H
• Assistant Examiner(s): Martinez, Tara L
• Application Number:
  US15/067,726
• Publication Number:
  US 20170035899A1
• Time in Patent Office: 1,460 Days
• Field of Search: None
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 47/64 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 peptidic linkers A61K47/65
• 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: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: A61P 39/06 Free radical scavengers or antioxidants
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 17/00 Carrier-bound or immobilised peptides carrier-bound or immobilised enzymes C12N11/00; Preparation thereof
• CPC Class Codes: C07K 5/08 Tripeptides
• CPC Class Codes: C07K 5/1016 and aromatic or cycloaliphatic
• CPC Class Codes: C07K 5/1019 with the first amino acid being basic
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/87 : Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2310/3513 : Protein; Peptide
• CPC Class Codes: C12N 2320/32 : Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12N 9/2471 : Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase
• CPC Class Codes: C12N 9/96 : Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• CPC Class Codes: C12Y 302/01023 : Beta-galactosidase (3.2.1.23), i.e. exo-(1-->4)-beta-D-galactanase

Abstract

The invention relates to carrier complexes and methods for delivering molecules to cells. The carrier complexes comprises a molecule and an aromatic cationic peptide in accordance with the invention. In one embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a carrier complex. In another embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a molecule and an aromatic cationic peptide.

Claims

1. A carrier complex comprising a molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Phe-D-Arg-Phe-Lys-NH₂ (Phe¹-DALDA),

D-Arg-2′

,6′

Dmt-Lys-Phe-NH₂, and

2′

,6′

-Dmp-D-Arg-Phe-Lys-NH₂ (Dmp¹-DALDA),

and wherein the molecule is a lipid, an enzyme, an antibody, or a neurotrophic growth factor.

2. The carrier complex according to claim 1, wherein the molecule is conjugated to the aromatic cationic peptide by a linker.

3. The carrier complex according to claim 2, wherein the linker is a component of the aromatic-cationic peptide.

4. The carrier complex according to claim 2, wherein the linker is a component of the molecule.

5. The carrier complex according to claim 1, wherein the molecule and aromatic cationic peptide are chemically bonded.

6. The carrier complex according to claim 1, wherein the molecule and aromatic cationic peptide are physically bonded.

7. A method for delivering a molecule to a cell, the method comprising contacting the cell with a carrier complex, wherein the carrier complex comprises the molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Phe-D-Arg-Phe-Lys-NH₂ (Phe¹-DALDA),

D-Arg-2′

,6′

-Dmt-Lys-Phe-NH₂, and

2′

,6′

-Dmp-D-Arg-Phe-Lys-NH₂ (Dmp¹-DALDA);

and wherein the molecule is a lipid, an enzyme, an antibody, or a neurotrophic growth factor.

8. The method according to claim 7, wherein the molecule is conjugated to the aromatic cationic peptide by a linker.

9. The method according to claim 8, wherein the linker is a component of the aromatic-cationic peptide.

10. The method according to claim 8, wherein the linker is a component of the molecule.

11. The method according to claim 7, wherein the molecule and aromatic cationic peptide are chemically bonded.

12. The method according to claim 7, wherein the molecule and aromatic cationic peptide are physically bonded.