Methods of identifying and treating a person having a predisposition to or afflicted with a cardiometabolic disease

Patent metadata

Field	Value
Publication number	US-12503733-B2
Application number	US-202318240789-A
Country	US
Kind code	B2
Filing date	Aug 31, 2023
Priority date	Nov 25, 2014
Publication date	Dec 23, 2025
Grant date	Dec 23, 2025

Abstract

The invention relates to method for identifying and selecting a subject with increased risk of developing a cardiometabolic disease and optionally, providing a personalized medicine method, which may involve sequencing at least part of a genome of one or more cells in a blood sample of the subject and identifying from said sequencing one or more mutations in one or more somatic mutations.

First claim

What is claimed is:

1 . A method of treating or preventing coronary heart disease (CHD) in a human subject, comprising the steps of:
(a) sequencing at least part of a genome of one or more cells from a blood sample of the subject, wherein the at least part of said genome comprises a JAK2 gene, (b) detecting an activating mutation in the JAK2 gene selected from N533D, N533Y, N533S, H538R, K539E, K539L, I540T, 1540V, R683S, R683G, del/ins537-539L, del/ins538-539L, del/ins540-543MK, del/ins540-544MK, del/ins541-543K, del542-543, del543-544 and ins11546-547; and (c) administering a lipid modifying medicine to the subject.

2 . The method according to claim 1 , wherein the one more cells in the blood sample are hematopoietic stem cells (HSCs), committed myeloid progenitor cells having long term self-renewal capacity or mature lymphoid cells having long term self-renewal capacity.

3 . The method according to claim 1 , wherein the sequencing is whole exome sequencing (WES).

4 . The method according to claim 1 , wherein the subject also exhibits one or more risk factors of being a smoker, having a high level of total cholesterol or having high level of high-density lipoprotein (HDL).

5 . The method of claim 1 , wherein the lipid-modifying medicine is a statin.

6 . The method of claim 1 , wherein the lipid-modifying medicine is a PCSK9 inhibitor.

7 . The method of claim 6 , wherein the PCSK9 inhibitor is a monoclonal antibody.

8 . A method of treating or preventing CHD in a human subject, wherein the genome of a blood cell in said subject comprises an activating mutation in a JAK2 gene selected from N533D, N533Y, N533S, H538R, K539E, K539L, I540T, 1540V, V1-7F R683S, R683G, del/ins537-539L, del/ins538-539L, del/ins540-543MK, del/ins540-544MK, del/ins541-543K, del542-543, del543-544 and ins11546-547, the method comprising administering a lipid-modifying medicine to the subject.

9 . The method according to claim 8 , wherein the subject also exhibits one or more risk factors of being a smoker, having a high level of total cholesterol or having high level of high-density lipoprotein (HDL).

10 . The method of claim 8 , wherein the lipid-modifying medicine is a statin.

11 . The method of claim 8 , wherein the lipid-modifying medicine is a PCSK9 inhibitor.

12 . The method of claim 11 , wherein the PCSK9 inhibitor is a monoclonal antibody.

Assignees

• Brigham & Womens Hospital Inc
• Massachusetts Gen Hospital

Inventors

• Ebert Benjamin Levine
• Jaiswal Siddhartha
• Kathiresan Sekar

Classifications

• G01N2800/32

  Cardiovascular disorders · CPC title

• G01N33/68

  involving proteins, peptides or amino acids {(involving lipoproteins G01N33/92)} · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title