Cell-penetrating compositions and methods using same

Patent metadata

Field	Value
Publication number	US-9908915-B2
Application number	US-201415036849-A
Country	US
Kind code	B2
Filing date	Nov 20, 2014
Priority date	Nov 26, 2013
Publication date	Mar 6, 2018
Grant date	Mar 6, 2018

Abstract

An isolated transport peptide, which crosses the cell membrane of a cell and/or binds to a target cell, is described. The transport peptide can be incorporated into a transport construct in which the transport peptide is linked to a cargo moiety to be delivered into a cell. Also described herein is a method of delivering a transport construct into and/or to a cell.

First claim

What is claimed is:

1. An isolated construct, or a salt or solvate thereof, comprising the transport peptide of amino acid sequence RRPPR (SEQ ID NO: 1) that is linked to a cargo moiety comprising a peptide of amino acid sequence selected from the group consisting of SEQ ID NOs: 3-6.

2. The construct of claim 1 , which is part of a pharmaceutical composition further comprising a pharmaceutically acceptable carrier.

3. An isolated construct, or a salt or solvate thereof, comprising the transport peptide of amino acid sequence RRPPR (SEQ ID NO: 1) that is linked to a cargo moiety selected from the group consisting of a nucleic acid; oligosaccharide; lipid; glycolipid; lipoprotein; small molecule compound; therapeutic drug; UV-vis, fluorescent or radioactive label; imaging agent; diagnostic agent; prophylactic agent; liposome; virus; and any combinations thereof.

4. The construct of claim 1 , wherein the cargo moiety is covalently linked to the transport peptide through a linker or a chemical bond.

5. The construct of claim 4 , wherein the linker comprises a disulfide bond or wherein the chemical bond between the cargo moiety and the transport peptide comprises a disulfide bond.

6. The construct of claim 4 , wherein the transport peptide is covalently linked through an amide bond to the cargo moiety.

7. The construct of claim 1 , which comprises a peptide of amino acid sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 3; SEQ ID NO: 1-SEQ ID NO: 4; SEQ ID NO: 1-SEQ ID NO: 5; SEQ ID NO: 1-SEQ ID NO: 6; SEQ ID NO: 3-SEQ ID NO: 1; SEQ ID NO: 4-SEQ ID NO: 1; SEQ ID NO: 5-SEQ ID NO: 1; and SEQ ID NO: 6-SEQ ID NO: 1.

8. The construct of claim 1 , which is a peptide of amino acid sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 3; SEQ ID NO: 1-SEQ ID NO: 4; SEQ ID NO: 1-SEQ ID NO: 5; SEQ ID NO: 1-SEQ ID NO: 6; SEQ ID NO: 3-SEQ ID NO: 1; SEQ ID NO: 4-SEQ ID NO: 1; SEQ ID NO: 5-SEQ ID NO: 1; and SEQ ID NO: 6-SEQ ID NO: 1.

9. A method of delivering a cargo moiety to or into a target cell, the method comprising contacting the target cell with a transport construct, wherein the transport construct comprises a transport peptide of amino acid sequence RRPPR (SEQ ID NO:1) that is linked to a cargo moiety comprising a peptide of amino acid sequence selected from the group consisting of SEQ ID NOs: 3-6, whereby the cargo moiety is delivered to or into the target cell.

10. The method of claim 9 , wherein the transport peptide is covalently linked to the cargo moiety through a linker or a chemical bond.

11. The method of claim 10 , wherein the linker comprises a disulfide bond or wherein the chemical bond between the cargo moiety and the transport peptide comprises a disulfide bond.

12. The method of claim 10 , wherein the transport peptide is covalently linked through an amide bond to the cargo moiety.

13. The method of claim 9 , wherein the transport construct comprises at least one peptide of amino acid sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 3; SEQ ID NO: 1-SEQ ID NO: 4; SEQ ID NO: 1-SEQ ID NO: 5; SEQ ID NO: 1-SEQ ID NO: 6; SEQ ID NO: 3-SEQ ID NO: 1; SEQ ID NO: 4-SEQ ID NO: 1; SEQ ID NO: 5-SEQ ID NO: 1; and SEQ ID NO: 6-SEQ ID NO: 1.

14. The method of claim 9 , wherein the target cell comprises at least one selected from the group consisting of an endothelial cell, cardiac cell, immune cell, skeletal muscle cell and brain cell.

15. The method of claim 9 , wherein the cell is mammalian.

16. The method of claim 15 , wherein the mammal is human.

17. A method of delivering a cargo moiety to or into a target cell of a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a transport construct, wherein the transport construct comprises a transport peptide of amino acid sequence RRPPR (SEQ ID NO:1) that is linked to a cargo moiety comprising a peptide of amino acid sequence selected from the group consisting of SEQ ID NOs: 3-6, whereby the cargo moiety is delivered to or into the target cell of the subject.

18. The method of claim 17 , wherein the transport peptide is covalently linked to the cargo moiety through a linker or a chemical bond.

19. The method of claim 18 , wherein the linker comprises a disulfide bond or wherein the chemical bond between the cargo moiety and the transport peptide comprises a disulfide bond.

20. The method of claim 18 , wherein the transport peptide is covalently linked through an amide bond to the cargo moiety.

21. The method of claim 17 , wherein the transport construct comprises at least one peptide of amino acid sequence selected from the group consisting of SEQ ID NO: 1-SEQ ID NO: 3; SEQ ID NO: 1-SEQ ID NO: 4; SEQ ID NO: 1-SEQ ID NO: 5; SEQ ID NO: 1-SEQ ID NO: 6; SEQ ID NO: 3-SEQ ID NO: 1; SEQ ID NO: 4-SEQ ID NO: 1; SEQ ID NO: 5-SEQ ID NO: 1; and SEQ ID NO: 6-SEQ ID NO: 1.

22. The method of claim 17 , wherein the target cell comprises at least one selected from the group consisting of an endothelial cell, cardiac cell, immune cell, skeletal muscle cell and brain cell.

23. The method of claim 17 , wherein the transport construct is administered to the subject by at least one route selected from the group consisting of oral, transmucosal, topical, transdermal, intradermal, subcutaneous, ophthalmic, intravitreal, subconjunctival, suprachoroidal, intracameral, inhalational, intrabronchial, pulmonary, intravenous, intra-arterial, intraduodenal, intravesical, parenteral, intrathecal, intramuscular and intragastrical.

24. The method of claim 17 , wherein the subject is a mammal.

25. The method of claim 24 , wherein the mammal is human.

Assignees

• Univ Yale

Inventors

• Sessa William C
• Giordano Frank J

Classifications

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• C07K14/4702

  Regulators; Modulating activity · CPC title

• C07K2319/01

  containing a localisation/targetting motif · CPC title

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• A61K47/645

  Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT · CPC title