Methods for treating pulmonary hypertension with a TGF-beta type II receptor-FC fusion protein

Patent metadata

Field	Value
Publication number	US-10682392-B2
Application number	US-201415037852-A
Country	US
Kind code	B2
Filing date	Nov 21, 2014
Priority date	Nov 21, 2013
Publication date	Jun 16, 2020
Grant date	Jun 16, 2020

Abstract

In some aspects, the invention teaches pharmaceutical compositions that include a TGF-beta ligand trap, and methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of pulmonary hypertension (PH). The invention also provides methods of using a TGF-beta ligand trap to treat, prevent, or reduce the progression rate of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, right ventricular hypertrophy, diseases associated with excessive TGF-beta signaling, diseases associated with excessive GDF15 signaling, and diseases associated with excessive PAI-1 signaling. The invention further provides methods of using a TGF-beta ligand trap to reduce right ventricular systolic pressure in a subject.

First claim

What is claimed is:

1. A method of treating pulmonary hypertension (PH) in a subject, comprising: administering a therapeutically effective amount of a fusion protein comprising a transforming growth factor β (TGF-β) ligand binding domain of a TGF-β type II receptor and an Fc domain of an immunoglobulin to the subject, thereby treating PH in the subject, and wherein the fusion protein comprises an amino acid sequence set forth in SEQ ID NO: 1.

2. The method of claim 1 , wherein PH is mediated by excessive TGF-β signaling.

3. The method of claim 1 , wherein the subject is a human.

4. The method of claim 1 , wherein the fusion protein comprises a linker between the TGF-β ligand binding domain and the Fc domain.

5. The method of claim 1 , wherein the fusion protein consists of the sequence set forth in SEQ ID NO: 1.

6. The method of claim 1 , wherein the amount of fusion protein administered to the subject is 0.1-10 mg/kg of body weight.

7. The method of claim 1 , wherein the fusion protein is administered to the subject orally, via inhalation, nasally, sublingually, buccally, subcutaneously, intradermally, intramuscularly, intravenously, intraperitoneally, or parenterally.

8. The method of claim 1 , wherein the fusion protein is administered before, during, or after the subject develops PH.

9. The method of claim 1 , wherein the fusion protein is part of a pharmaceutical composition.

10. The method of claim 9 , wherein the pharmaceutical composition is formulated for modified release, sustained release, or controlled release, or a combination thereof.

11. The method of claim 9 , wherein the pharmaceutical composition is formulated for oral, via inhalation, nasal, sublingual, buccal, subcutaneous, intradermal, intramuscular, intravenous, intraperitoneal, or parenteral administration.

Assignees

• Brigham & Womens Hospital Inc
• Acceleron Pharma Inc
• The Bringham And Womens Hospital Inc

Inventors

• Yu Paul
• Grinberg Asya
• Sako Dianne S
• Castonguay Roselyne
• Steeves Rita
• Kumar Ravindra

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07K14/71

  for growth factors; for growth regulators · CPC title

• C07K2319/32

  fusions with soluble part of a cell surface receptor, "decoy receptors" · CPC title

• A61K47/6811

  the drug being a protein or peptide, e.g. transferrin or bleomycin · CPC title

• A61K38/179 Primary

  for growth factors; for growth regulators · CPC title