Compositions and methods for treating heart disease and/or injury

Patent metadata

Field	Value
Publication number	US-10786541-B2
Application number	US-201916279621-A
Country	US
Kind code	B2
Filing date	Feb 19, 2019
Priority date	Apr 9, 2012
Publication date	Sep 29, 2020
Grant date	Sep 29, 2020

Abstract

A method of treating heart disease and/or injury in a subject includes administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ.

First claim

Having described the invention, we claim:

1. A method of treating heart disease or injury in a subject in need thereof, the method comprising:
administering to the subject a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ, wherein the therapeutic agent comprises a therapeutic peptide comprising an amino acid sequence with at least 70% identity to SEQ ID NO:32.

2. The method of claim 1 , wherein the therapeutic peptide comprises an amino acid sequence with at least 75%, at least 80%, or at least 85% identity to SEQ ID NO:32.

3. The method of claim 1 , wherein the therapeutic peptide comprises a substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32 for another amino acid.

4. The method of claim 3 , wherein the amino acid residue 4E is substituted with D or Q, amino acid residue 5R is substituted with H, L or K, amino acid residue 6L is substituted with I, V or M, amino acid residue 7K is substituted with R or H, amino acid residue 9N is substituted with E or D, amino acid residue 10D is substituted with E or N, amino acid residue 12L is substituted with I, V or M, and/or amino acid residue 13K is substituted with R or H.

5. The method of claim 1 , wherein the therapeutic agent includes a transport moiety that is linked to the therapeutic peptide and facilitates uptake of the therapeutic peptides by a cell of the heart being treated.

6. The method of claim 5 , wherein the transport moiety is an HIV Tat transport moiety.

7. The method of claim 1 , wherein the therapeutic agent is administered systemically to the subject being treated.

8. The method of claim 1 , wherein the heart disease or injury comprises at least one of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac denervation hypersensitivity, and arrhythmia.

9. The method of claim 8 , wherein the heart injury is a myocardial infarction and the therapeutic agent is administered to the infarct or peri-infarct region of the heart.

10. A method of treating arrhythmia in a subject in need thereof, the method comprising:
administering to the cardiac tissue of the subject a therapeutically effective amount of a therapeutic agent that inhibits one or more of catalytic activity, signaling, and function of PTPσ, wherein the therapeutic agent comprises a therapeutic peptide comprising an amino acid sequence with at least 70% identity to SEQ ID NO:32.

11. The method of claim 10 , wherein the therapeutic peptide comprises an amino acid sequence with at least 75%, at least 80%, or at least 85% identity to SEQ ID NO:32.

12. The method of claim 10 , wherein the therapeutic peptide comprises a substitution of an amino acid of at least one of residue 4, 5, 6, 7, 9, 10, 12, or 13 of SEQ ID NO: 32 for another amino acid.

13. The method of claim 12 , wherein the amino acid residue 4E is substituted with D or Q, amino acid residue 5R is substituted with H, L or K, amino acid residue 6L is substituted with I, V or M, amino acid residue 7K is substituted with R or H, amino acid residue 9N is substituted with E or D, amino acid residue 10D is substituted with E or N, amino acid residue 12L is substituted with I, V or M, and/or amino acid residue 13K is substituted with R or H.

14. The method of claim 10 , wherein the therapeutic agent includes a transport moiety that is linked to the therapeutic peptide and facilitates uptake of the therapeutic peptides by a cell of the heart being treated.

15. The method of claim 14 , wherein the transport moiety is an HIV Tat transport moiety.

16. The method of claim 10 , wherein the therapeutic agent is administered systemically to the subject being treated.

Assignees

• Univ Case Western Reserve
• Univ Oregon Health & Science

Inventors

• Lang Bradley T
• Silver Jerry
• Gardner Ryan
• Habecker Beth

Classifications

• A61K38/005 Primary

  Enzyme inhibitors (protease inhibitors A61K38/55) · CPC title

• C12Y301/03048

  Protein-tyrosine-phosphatase (3.1.3.48) · CPC title

• A61K38/465 Primary

  acting on ester bonds (3.1), e.g. lipases, ribonucleases · CPC title

• C07K14/00

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof · CPC title