Treatment of myocardial infarction using TGF-β antagonists

Patent metadata

Field	Value
Publication number	US-10633437-B2
Application number	US-201615376358-A
Country	US
Kind code	B2
Filing date	Dec 12, 2016
Priority date	Sep 1, 2010
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Disclosed herein is a method of treating a patient suffering a myocardial infarction, particularly an acute myocardial infarction, or of reducing an adverse consequence of a myocardial infarction in a patient comprising administering an antagonist of TGF-β to the patient during the acute stage of the myocardial infarction.

First claim

What is claimed is:

1. A method of treating myocardial infarction in a patient in need thereof, comprising
administering to the patient an antibody or antigen-binding fragment that binds to one or more isoforms of transforming growth factor-β (TGF-β), wherein the antibody or antigen-binding fragment comprises the PET1073G12 VH domain (SEQ ID NO: 2) and the PET1073G12 VL domain (SEQ ID NO:7); and
measuring the patient's level of Snail1, or
measuring the patient's level of Snail2.

2. The method of claim 1 , wherein the myocardial infarction is an acute myocardial infarction.

3. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment is commenced within 120 hours of onset of myocardial ischemia.

4. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment is commenced within 12 hours of onset of myocardial ischemia.

5. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment is commenced prior to substantial macrophage and mononuclear infiltration of tissue affected by the myocardial infarction.

6. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment is commenced during a period characterized by neutrophilic infiltration of tissue affected by the myocardial infarction.

7. The method of claim 1 , wherein administration of the antibody or antigen-binding fragment is commenced during a period characterized by necrosis of tissue affected by the myocardial infarction.

8. The method of claim 1 , wherein the patient is a human or a non-human mammal.

9. The method of claim 1 , wherein the method preserves myocardium.

10. The method of claim 1 , wherein the method further comprises administering a compound that is capable of selectively restoring a desirable function of TGF-β to the patient.

11. The method of claim 10 , wherein the compound capable of selectively restoring a desirable function of TGF-β is an anti-inflammatory drug.

12. The method of claim 10 , wherein the compound capable of selectively restoring a desirable function of TGF-β is an antagonist of TNF-α.

13. The method of claim 1 , wherein the method further comprises administering an ACE inhibitor to the patient.

14. The method of claim 13 , wherein the ACE inhibitor is selected from the group consisting of benazepril, captopril, fosinopril, moexipril, perindopril, quinapril, transdolapril, lisinopril, enalapril, and ramipril.

15. The method of claim 1 , wherein the method further comprises administering an angiotensin II receptor antagonist to the patient.

16. The method of claim 15 , wherein the angiotensin II receptor antagonist is selected from the group consisting of eprosartan, telmisartan, losartan, irbesartan, olmesartan, candesartan, and valsartan.

17. The method of claim 1 , wherein the method further comprises administering a beta-adrenergic antagonist to the patient.

18. The method of claim 17 , wherein the beta-adrenergic antagonist is selected from the group consisting of alprenolol, bucindolol, carteolol, carvedilol, labetalol, nadolol, oxprenolol, penbutolol, pindolol, propranolol, sotalol, timolol, atenolol, betaxolol, bisoprolol, celiprolol, esmolol, metoprolol, and nebivolol.

19. The method of claim 1 , wherein the antibody or antigen-binding fragment is administered to the patient during an acute stage of myocardial infarction at a dose of about 1 mg per kilogram of patient body mass.

20. The method of claim 1 , wherein the antibody or antigen-binding fragment is administered to the patient during an acute stage of myocardial infarction at a dose of about 5 mg per kilogram of patient body mass.

Assignees

• Genzyme Corp

Inventors

• Akita Geoffrey Y
• Lonning Scott
• Gregory Jr Richard C
• Kudej Amelia B

Classifications

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• C07K14/495

  Transforming growth factor [TGF] · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• G01N33/50

  Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) · CPC title

• C07K16/22 Primary

  against growth factors {; against growth regulators} · CPC title