Compositions and methods for treating pulmonary hypertension

Patent metadata

Field	Value
Publication number	US-11622992-B2
Application number	US-202016829642-A
Country	US
Kind code	B2
Filing date	Mar 25, 2020
Priority date	Jul 15, 2016
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

Abstract

In some aspects, the disclosure relates to GDF/BMP antagonists and methods of using GDF/BMP antagonists to treat, prevent, or reduce the progression rate and/or severity of pulmonary hypertension (PH), particularly treating, preventing or reducing the progression rate and/or severity of one or more PH-associated complications. The disclosure also provides methods of using a GDF/BMP antagonist to treat, prevent, or reduce the progression rate and/or severity of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. The disclosure further provides methods of using a GDF/BMP antagonist to reduce right ventricular systolic pressure in a subject in need thereof.

First claim

We claim:

1. A method of treating pulmonary arterial hypertension, comprising administering to a patient in need thereof an effective amount of a polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 39, wherein the polypeptide binds to activin and/or GDF11.

2. The method of claim 1 , wherein the patient has resting pulmonary arterial pressure (PAP) of at least 25 mm Hg.

3. The method of claim 1 , wherein the method reduces PAP in the patient; decreases ventricle hypertrophy in the patient; decreases smooth muscle hypertrophy in the patient; decreases pulmonary arteriole muscularity in the patient; decreases pulmonary vascular resistance in the patient; reduces pulmonary vascular resistance in the patient; increases pulmonary capillary wedge pressure; increases left ventricular end-diastolic pressure; increases exercise capacity of the patient; increases the patient's 6-minute walk distance; and/or reduces the patient's Borg dyspnea index (BDI).

4. The method of claim 1 , wherein the patient has Functional Class II or Class III pulmonary hypertension as recognized by the World Health Organization.

5. The method of claim 1 , wherein the method prevents or delays pulmonary hypertension Functional Class progression.

6. The method of claim 1 , wherein the method promotes or increases pulmonary hypertension Functional Class regression.

7. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 39.

8. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 39.

9. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 39.

10. The method of claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NO: 39.

11. The method of claim 1 , wherein the polypeptide is part of a homodimer protein complex.

12. The method of claim 1 , comprising further administering to the patient an additional active agent and/or supportive therapy for treating pulmonary hypertension.

13. The method of claim 12 , wherein the additional active agent and/or supportive therapy for treating pulmonary hypertension is selected from the group consisting of: prostacyclin or a derivative thereof; a prostacyclin receptor agonist; endothelin receptor; a calcium channel blocker; an anticoagulant; a diuretic; oxygen therapy; atrial septostomy; pulmonary thromboendarterectomy; a phosphodiesterase type 5 inhibitor; an activator of soluble guanylate cyclase; an ASK-1 inhibitor; an NF-.kappa.B antagonist; lung and/or heart transplantation.

14. The method of claim 1 , wherein the method further comprises administration of one or more agents selected from the group consisting of: a vasodilator, a phosphodiesterase type 5 inhibitor, a soluble guanylate cyclase stimulator, a prostacyclin receptor agonist, and an endothelin receptor antagonist.

15. The method of claim 14 , wherein the one or more agents is selected from the group consisting of: bosentan, sildenafil, beraprost, macitentan, selexipag, epoprostenol, treprostinil, iloprost, ambrisentan, and tadalafil.

16. The method of claim 1 , wherein the patient has been treated with one or more vasodilators.

17. The method of claim 16 , wherein the one or more vasodilators is selected from the group consisting of: bosentan, sildenafil, beraprost, macitentan, selexipag, epoprostenol, treprostinil, iloprost, ambrisentan, and tadalafil.

18. The method of claim 1 , wherein the polypeptide is glycosylated.

19. The method of claim 1 , wherein the polypeptide binds to one or more ligands selected from the group consisting of: activin A, activin B, and GDF11.

20. The method of claim 19 , wherein the polypeptide further binds to one or more ligands selected from the group consisting of: BMP10, GDF8, and BMP6.

Assignees

• Acceleron Pharma Inc

Inventors

• Kumar Ravindra
• Knopf John

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61K38/45

  Transferases (2) · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K38/1875 Primary

  Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title