Target-specific delivery of therapeutic agents

Patent metadata

Field	Value
Publication number	US-2018360755-A1
Application number	US-201615737047-A
Country	US
Kind code	A1
Filing date	Jun 15, 2016
Priority date	Jun 15, 2015
Publication date	Dec 20, 2018
Grant date	—

Abstract

Isolated peptides targeting cardiovascular disease are described herein or one or more conservative amino acid substitutions, deletions or additions of such peptides and methods of use thereof for delivering payloads to specific cell types or tissues.

First claim

1 . An isolated peptide comprising the amino acid sequence selected from peptides in Table 1 or wherein the peptide has one 1 or more conservative amino acid substitutions, deletions or additions as compared to a peptide of Table 1.

2 . The peptide of claim 1 , wherein one or more of the amino acids are D-amino acids or other peptidomimetic derivative.

3 . The peptide of claim 1 , wherein the peptide is conjugated to a payload.

4 . The peptide of claim 3 , wherein the payload is conjugated to the peptide directly or indirectly.

5 . The peptide of claim 3 wherein the payload is conjugated to the peptide with the use of one or more linkers and/or spacers.

6 . The peptide of claim 1 further comprising a delivery vehicle.

7 . The peptide of claim 6 , wherein the delivery vehicle is a liposome.

8 . The peptide of claim 1 , wherein a payload is encapsulated by the delivery vehicle.

9 . The peptide of claim 8 , wherein the peptide is associated covalently or non-covalently with the delivery vehicle.

10 . A composition comprising one or more of the peptides of claim 1 and a pharmaceutically acceptable carrier.

11 . A method of delivering a payload to cardiovascular tissue or cell of a subject in need thereof comprising administering to the subject the peptide of claim 1 , wherein the peptide targets the payload to the cardiovascular tissue or cell thereby delivering the payload to the cardiovascular tissue or cell.

12 . The method of claim 11 , wherein the administration is systemic or subcutaneous.

13 . The method of claim 11 , wherein the peptide is selective for dysfunctional, ischemic and/or peri-infarct region of mammalian cardiovascular tissue.

14 . A method of treating a cardiomyopathy in a subject comprising: administering systemically to a subject in need thereof an effective amount of the peptide of claim 3 , wherein the effective amount is effective to cause functional improvement in at least one of the following parameters: left ventricular strain, left ventricular volume, left ventricular area, left ventricular dimension, cardiac function, 6-minute walk test, or New York Heart Association (NYHA) functional classification.

15 . A method of delivering a payload to a cardiovascular cell comprising contacting said cell with a peptide of claim 3 .

16 . A method of treating a cardiovascular disease or disorder comprising administering to a subject in need thereof an effective amount of the peptide of claim 3 , wherein the effective amount treats the disease or disorder.

17 . The method of claim 11 comprising two or more peptides having different amino acid sequences.

18 . The method of claim 11 comprising two or more different payloads.

19 . The method of claim 18 , wherein the two or more payloads are therapeutic agents and imaging agents.

20 . The method of claim 18 , wherein each payload is delivered to a different cell type.

21 . The method of claim 20 , wherein the different cell types are located within the same tissue.

Assignees

• Univ Virginia Patent Foundation

Inventors

• Klibanov Alexander L
• French Brent A
• Kelly Kimberly A
• Dasa Siva Sai Krishna

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K9/127 Primary

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61K47/6913

  the liposome being modified on its surface by an antibody · CPC title