# US 11,998,549 B2 · Methods of treating a vascular leakage-associated disease or disorder

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- Number: US 11,998,549 B2
- Document ID: US11998549B2
- Status: Granted
- Kind: B2
- Application number: 16/755,008
- Filed: 2020-01-29
- Published: 2021-11-25
- Granted: 2024-06-04
- Earliest claimed: 2019-01-29
- Assignees: Unity Health Toronto
- Applicants: Unity Health Toronto
- Inventors: Xiao-Yan Wen; Anju Philip; Claudia Dossantos; John Marshall
- Web page: https://patentgrep.com/patent/US11998549B2

## CPC

- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/404: Indoles, e.g. pindolol
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/00: Drugs for disorders of the cardiovascular system
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure relates generally to treatment and diagnosis of diseases, disorders or conditions characterized by vascular leakage. More particularly, the present disclosure relates to methods for treating a vascular leakage-associated disease or disorder in a subject; for reducing vascular leakage in a subject; for reducing reactive oxygen species production in a subject; for inducing apoptosis of neutrophils in a subject; and for increasing survival of a subject having a vascular leakage-associated disease or disorder. The methods comprise administering a G9a and/or G9a-like protein (GLP) methyltransferase inhibitor to the subject. The present disclosure further relates to methods for developing a treatment plan for a subject with a vascular leakage-associated disease, disorder or condition, and for identifying a subject as a candidate for treatment of a vascular leakage-associated disease or disorder. The present disclosure relates to use of G9a and/or G9a-like protein (GLP) methyltransferase inhibitor in the treatment of vascular leakage-associated disease, disorder or condition.

## Claims

### Claim 1

A method of reducing vascular leakage in a subject in need thereof comprising administering an effective amount of a G9a and/or G9a-like protein (GLP) methyltransferase inhibitor.

### Claim 2 (depends on 1)

The method of claim 1, wherein the vascular leakage is associated with infection and/or inflammation.

### Claim 3 (depends on 1)

The method of claim 1, wherein the vascular leakage is associated with a disease, disorder or condition selected from sepsis, acute respiratory distress syndrome (ARDS), influenza virus infection, SARS virus infection, MERS-CoV virus infection, 2019-CoV virus infection, Dengue virus infection, Ebola virus infection, pancreatitis, trauma, post-transplant ischemia-reperfusion injury, and combinations thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein the vascular leakage is associated with sepsis.

### Claim 5

A method of treating a vascular leakage-associated disease, disorder or condition in a subject in need thereof comprising administering an effective amount of a G9a and/or G9a-like protein (GLP) methyltransferase inhibitor.

### Claim 6 (depends on 5)

The method of claim 5, wherein the vascular leakage-associated disease, disorder or condition is an infection and/or inflammation.

### Claim 7 (depends on 6)

The method of claim 6, wherein the vascular leakage-associated disease, disorder or condition is selected from sepsis, acute respiratory distress syndrome (ARDS), influenza virus infection, Dengue virus infection, Ebola virus infection, SARS virus infection, MERS-CoV virus infection, 2019-nCoV virus infection, pancreatitis, trauma, post-transplant ischemia-reperfusion injury, and a combination thereof.

### Claim 8 (depends on 5)

The method of claim 5, wherein the vascular leakage-associated disease, disorder or condition is sepsis.

### Claim 9 (depends on 5)

The method of claim 5, wherein the subject is a mammal.

### Claim 10 (depends on 9)

The method of claim 9, wherein the mammal is a human.

### Claim 11 (depends on 5)

The method of claim 5, wherein the G9a and/or G9a-like protein-(GLP) methyltransferase inhibitor is selected from
a pharmaceutically acceptable salt and/or solvate thereof, and a combination thereof.