Clusterin for use in the treatment of thrombotic microangiopathies

Patent metadata

Field	Value
Publication number	US-2020138902-A1
Application number	US-201816632684-A
Country	US
Kind code	A1
Filing date	Jul 20, 2018
Priority date	Jul 21, 2017
Publication date	May 7, 2020
Grant date	—

Abstract

The present invention concerns clusterin for use in the treatment of thrombotic microangiopathies, and a pharmaceutical composition comprising clusterin for use in the treatment of thrombotic microangiopathies, said composition not comprising von Willebrand factor protease. The present invention also concerns an ex vivo method for stratifying a patient suffering, or likely to be suffering, from TMA, comprising the following steps: 1) measuring, in a biological sample from said patient, the amount L C of clusterin, and 2) comparing the amount L c measured in step 1) with an amount L ref of clusterin by calculating the score S1=L C /L ref , in which: •If S1≤1, the patient is considered to be likely to benefit from a treatment of the TMA with clusterin, •If S1>1, the patient is not considered to be likely to benefit from treatment of TMA with clusterin.

First claim

1 . A method of treating a thrombotic microangiopathy comprising administering a therapeutically effective amount of clusterin to a subject in need of such treatment.

2 . The method of claim 1 , wherein said clusterin is a human clusterin of sequence SEQ ID No.: 1.

3 . The method of claim 1 , wherein said clusterin has a peptide sequence which has at least 70% identity with the sequence SEQ ID No.: 1.

4 . The method of claim, wherein said clusterin is a recombinant clusterin, a plasma clusterin, or a synthetic clusterin.

5 . The method of claim 1 , wherein the thrombotic microangiopathy is thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) associated or not associated with bacteria, HELLP syndrome, or a secondary thrombotic microangiopathy.

6 . The method of claim 1 , comprising oral or parenteral administration of said clusterin.

7 . The method of claim 6 , wherein said parenteral administration is intravenous administration, intramuscular administration, or subcutaneous administration.

8 . A pharmaceutical composition comprising clusterin, said composition not comprising von Willebrand factor of protease.

9 . The pharmaceutical composition as claimed in claim 8 , wherein said clusterin is a human clusterin of sequence SEQ ID No.: 1, or a peptide sequence which has at least 70% identity with the sequence SEQ ID No.: 1.

10 . The pharmaceutical composition as claimed in claim 8 , said pharmaceutical composition being in the form of an injectable solution.

11 . An ex vivo method for stratification of a patient who is or who may be suffering from a thrombotic microangiopathy (TMA), comprising the following steps:
1) measuring, in a biological sample from said patient, the clusterin level L C , and 2) comparing the level L C measured in step 1) with a clusterin level L ref by calculating the score S1=L C /L ref , wherein:
if S1≤1, the patient is considered to be liable to receive a benefit from a TMA treatment with clusterin,
if S1>1, the patent is not considered to be liable to receive a benefit from a TMA treatment with clusterin.

12 . The method of claim 11 , further comprising administering clusterin to the subject.

Assignees

• Univ Bordeaux
• Centre Nat Rech Scient
• Centre Hospitalier Univ Bordeaux
• Inst Nat Sante Rech Med
• Univ Angers
• Centre Hospitalier Univ Dangers

Inventors

• Augusto Jean-Francois
• Contin-Bordes Cecile
• Delmas Yahsou
• Blanco Patrick
• Delneste Yves
• Jeannin Pascale
• Beauvillain Celine

Classifications

• G01N33/92

  involving lipids, e.g. cholesterol {, lipoproteins, or their receptors (steroid hormones G01N33/743)} · CPC title

• G01N2800/226

  Thrombotic disorders, i.e. thrombo-embolism irrespective of location/organ involved, e.g. renal vein thrombosis, venous thrombosis · CPC title

• G01N2800/22

  Haematology · CPC title

• A61K38/1709 Primary

  from mammals · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title