Compositions and methods for treating hypertension

Patent metadata

Field	Value
Publication number	US-9605047-B2
Application number	US-201314390408-A
Country	US
Kind code	B2
Filing date	Apr 3, 2013
Priority date	Apr 4, 2012
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

The technology described herein is directed to agents that reduce the level of oxidant-modified ET-B Cys405, Cys403, or Cys402 and the identification and use of such agents for, e.g. to treat hypertension.

First claim

What is claimed herein is:

1. A method of treating hypertension in a subject in need thereof, the method comprising administering to the subject an ET-B polypeptide comprising an oxidant-resistant mutation at Cys405, Cys403, or Cys402.

2. The method of claim 1 , wherein the subject is in need of treatment for a condition selected from the group consisting of:
systemic hypertension and pulmonary arterial hypertension.

3. The method of claim 1 , wherein the oxidant-resistant mutation is the substitution of a cysteine with an alanine, valine, leucine, or isoleucine.

4. The method of claim 1 , wherein the oxidant-resistant mutation at Cys405 is selected from: Cys405Ala; Cys405Val; Cys405Leu; and Cys405Ile.

5. A method of treating hypertension in a subject in need thereof, the method comprising administering to the subject a nucleic acid encoding an ET-B polypeptide comprising an oxidant-resistant mutation at Cys405, Cys403, or Cys402.

6. The method of claim 5 , wherein the oxidant-resistant mutation is the substitution of a cysteine with an alanine, valine, leucine, or isoleucine.

7. The method of claim 5 , wherein the oxidant-resistant mutation at Cys405 is selected from: Cys405Ala; Cys405Val; Cys405Leu; and Cys405Ile.

8. The method of claim 5 , wherein the subject is in need of treatment for a condition selected from the group consisting of:
systemic hypertension and pulmonary arterial hypertension.

Assignees

• Brigham & Womens Hospital Inc
• The Brigham And Womens'S Hospital Inc

Inventors

• Maron Bradley
• Loscalzo Joseph
• Leopold Jane

Classifications

• G01N33/502

  for testing non-proliferative effects · CPC title

• G01N2500/04

  Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A) · CPC title

• C07K14/705 Primary

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• G01N2333/726

  G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH · CPC title