IP Library › Granted Patent US 11,369,569
Granted Patent B2
US 11,369,569 · App. 15/737,047 · Granted Jun 28, 2022

Target-specific delivery of therapeutic agents

Inventors: Alexander L. Klibanov (Charlottesville, VA); Brent A. French (Charlottesville, VA); Kimberly A. Kelly (Crozet, VA); Siva Sai Krishna Dasa (Charlottesville, VA)
Assignee: University of Virginia Patent Foundation
A61K9/127A61K9/0019A61K47/62A61K47/64A61K47/6911A61K47/6913A61P9/00C07K7/06
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Quick Facts
Patent No.
US 11,369,569
App. No.
15/737,047
Granted
Jun 28, 2022
Kind
B2
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.

Claims (238)

1. An isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO: 10)

B-11

TMQHDG (SEQ ID NO: 14)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a delivery vehicle containing a payload, wherein said delivery vehicle is a liposome, micelle, non-liposomal nanoparticle, nanoparticle made of drug, microbubble, dendrimer, adeno-associated virus (AAV) vector, or nanoparticle of polymer, metal oxide and/or lipid, wherein said payload is a therapeutic agent or a diagnostic agent, wherein said therapeutic agent is a small molecule, protein, peptide, cytokine, nucleic acid, hormone, steroid, enzyme, or mixtures thereof.

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

3. The isolated peptide of claim 1 , wherein the delivery vehicle is a liposome.

4. The isolated peptide of claim 1 , wherein the isolated peptide is associated non-covalently with the delivery vehicle.

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

6. A method of delivering a payload to cardiovascular tissue or cell of a subject in need thereof comprising administering to the subject an isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-26

SHPASHD (SEQ ID NO: 7)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO: 10)

B-11

TMQHDG (SEQ ID NO: 14)

B-12

SAPGSSP (SEQ ID NO: 15)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a payload or a delivery vehicle containing a payload, wherein said payload is a therapeutic agent or a diagnostic agent, wherein said therapeutic agent is a small molecule, protein, peptide, cytokine, nucleic acid, hormone, steroid, enzyme or mixtures thereof, wherein the isolated peptide targets the payload to the cardiovascular tissue or cell thereby delivering the payload to the cardiovascular tissue or cell.

7. The method of claim 6 , wherein the administration is systemic or subcutaneous.

8. The method of claim 6 , wherein the isolated peptide is selective for a dysfunctional, ischemic and/or peri-infarct region of mammalian cardiovascular tissue.

9. A method of treating a cardiomyopathy in a subject comprising:

administering systemically to a subject in need thereof an effective amount of an isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-26

SHPASHD (SEQ ID NO: 7)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO: 10)

B-11

TMQHDG (SEQ ID NO: 14)

B-12

SAPGSSP (SEQ ID NO: 15)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a payload or a delivery vehicle containing a payload, wherein said payload is a therapeutic agent, wherein said therapeutic agent is a small molecule, protein, peptide, cytokine, nucleic acid, hormone, steroid, enzyme or mixtures thereof, 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 or 6-minute walk test.

10. A method of delivering a payload to a cardiovascular cell comprising contacting said cell with an isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-26

SHPASHD (SEQ ID NO: 7)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO: 10)

B-11

TMQHDG (SEQ ID NO: 14)

B-12

SAPGSSP (SEQ ID NO: 15)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a payload or a delivery vehicle containing a payload, wherein said payload is a therapeutic agent or a diagnostic agent, wherein said therapeutic agent is a small molecule, protein, peptide, cytokine, nucleic acid, hormone, steroid, enzyme or mixtures thereof.

11. A method of treating a cardiovascular disease or disorder comprising administering to a subject in need thereof an effective amount of an isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-26

SHPASHD (SEQ ID NO: 7)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO:10)

B-11

TMQHDG (SEQ ID NO: 14)

B-12

SAPGSSP (SEQ ID NO: 15)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a payload or a delivery vehicle containing a payload, wherein said payload is a therapeutic agent, wherein said therapeutic agent is a small molecule, protein, peptide, cytokine, nucleic acid, hormone, steroid, enzyme or mixtures thereof, wherein the effective amount treats the disease or disorder.

12. The method of claim 6 wherein two or more isolated peptides having different amino acid sequences are administered.

13. The method of claim 6 , wherein two or more isolated peptides comprising two or more different payloads are administered.

14. The method of claim 13 , wherein the two or more different payloads are therapeutic agents and imaging agents.

15. The method of claim 13 , wherein each payload is delivered to a different cell type.

16. The method of claim 15 , wherein the different cell types are located within the same tissue.

17. An isolated peptide selected from the group consisting of:

B-29

RPPALAP (SEQ ID NO: 6)

B-26

SHPASHD (SEQ ID NO: 7)

B-43

ESRQVTP (SEQ ID NO: 8)

B-18

DPRATMY (SEQ ID NO: 9)

B-22/B-40*

SLLNRMP (SEQ ID NO: 10)

B-11

TMQHDG (SEQ ID NO: 14)

B-12

SAPGSSP (SEQ ID NO: 15)

B-17

YATQSSP (SEQ ID NO: 17)

B-42

AMRPPLN (SEQ ID NO: 31)

B-47

ATMSRAP (SEQ ID NO: 35)

B-49

TPGGKSP (SEQ ID NO: 36)

B-50

GLSQLQR (SEQ ID NO: 38)

B-6

YPNHASP (SEQ ID NO: 39)

B-7

SDTWSSR (SEQ ID NO: 40)

B-8

TLAQIHH (SEQ ID NO: 41)

I-1

TALPRLN (SEQ ID NO: 42)

I-12

SALPNLY (SEQ ID NO: 45)

I-8

TSLSDSQ (SEQ ID NO: 65)

wherein said isolated peptide is conjugated to a payload, wherein said payload is a diagnostic agent, wherein said diagnostic agent is a rare earth metal, a radioisotope, a radionuclide or a contrast agent.

18. The isolated peptide of claim 17 , wherein the payload is conjugated to the isolated peptide indirectly.

19. The isolated peptide of claim 17 wherein the payload is conjugated to the isolated peptide with one or more linkers and/or spacers.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 7, 2019
From: KLIBANOV, ALEXANDER L.; FRENCH, BRENT A.; KELLY, KIMBERLY A.; DASA, SIVA SAI KRISHNA
To: UNIVERSITY OF VIRGINIA
Reel/Frame 049402/0965 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 7, 2019
From: UNIVERSITY OF VIRGINIA
To: UNIVERSITY OF VIRGINIA PATENT FOUNDATION
Reel/Frame 049403/0001 →
CONFIRMATORY LICENSE Recorded Apr 18, 2018
From: UNIVERSITY OF VIRGINIA
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 045968/0109 →
Continuity (2)
Provisional Application 62175922 · Jun 15, 2015
Related Publication 20180360755A1 · Dec 20, 2018