Actrii proteins and use in treating post-capillary pulmonary hypertension

Patent metadata

Field	Value
Publication number	US-12583906-B2
Application number	US-202418953973-A
Country	US
Kind code	B2
Filing date	Nov 20, 2024
Priority date	Apr 28, 2020
Publication date	Mar 24, 2026
Grant date	Mar 24, 2026

Abstract

In some aspects, the disclosure relates to compositions and methods comprising ActRII polypeptides to treat, prevent, or reduce the progression rate and/or severity of post-capillary pulmonary hypertension (PcPH), particularly treating, preventing or reducing the progression rate and/or severity of one or more PcPH-associated complications.

First claim

We claim:

1 . A method of treating combined pre- and postcapillary pulmonary hypertension (Cpc-PH) due to heart failure with preserved ejection fraction (HFpEF) in a apatient, comprising administering to the patient an effective amount of a fusion protein comprising:
(i) an ActRII polypeptide comprising the amino acid sequence of SEQ ID NO: 2; (ii) an Fc domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 32; and (iii) a linker domain positioned between the ActRII polypeptide and the Fc domain.

2 . The method of claim 1 , wherein the patient has a pulmonary vascular resistance (PVR) greater than 2 Woods Units.

3 . The method of claim 1 , wherein the Fc domain comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 32.

4 . The method of claim 3 , wherein the Fc domain comprises the amino acid sequence of SEQ ID NO: 32.

5 . The method of claim 3 , wherein the linker domain is selected from the group consisting of: TGGG (SEQ ID NO: 20), TGGGG (SEQ ID NO: 18), SGGGG (SEQ ID NO: 19), GGGGS (SEQ ID NO: 22), GGGG (SEQ ID NO: 17), and SGGG (SEQ ID NO: 21).

6 . The method of claim 5 , wherein the linker domain comprises SEQ ID NO: 20.

7 . The method of claim 1 , wherein the fusion protein comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NOs: 23 or 41.

8 . The method of claim 7 , wherein the fusion protein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 23.

9 . The method of claim 8 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 23.

10 . The method of claim 7 , wherein the fusion protein comprises an amino acid sequence that is at least 99% identical to the amino acid sequence of SEQ ID NO: 41.

11 . The method of claim 10 , wherein the fusion protein comprises the amino acid sequence of SEQ ID NO: 41.

12 . The method of claim 1 , wherein the patient has Group 2 pulmonary hypertension as recognized by the World Health Organization (WHO).

13 . The method of claim 1 , wherein the patient has a pulmonary vascular resistance (PVR) greater than or equal to 3 Wood Units.

14 . The method of claim 13 wherein the method reduces the PVR in the patient.

15 . The method of claim 14 , wherein the method reduces the PVR in the patient by at least 10%.

16 . The method of claim 1 , wherein the patient has preserved left ventricular ejection fraction.

17 . The method of claim 16 , wherein the preserved left ventricular ejection fraction is greater than 45%.

18 . The method of claim 1 , wherein the method increases the patient's 6-minute walk distance.

19 . The method of claim 18 , wherein the method increases the patient's 6-minute walk distance by at least 10 meters.

20 . The method of claim 1 , wherein the method delays clinical worsening of post-capillary pulmonary hypertension (PcPH).

21 . The method of claim 20 , wherein the method delays clinical worsening of PcPH in accordance with the World Health Organization's functional classification system for pulmonary hypertension.

22 . The method of claim 21 , wherein the method delays clinical worsening of PcPH in accordance with the New York Heart Association's functional classification system for pulmonary hypertension.

Assignees

• Acceleron Pharma Inc

Inventors

• Li Gang
• Kumar Ravindra
• Lu Jonathan Toshi
• Joshi Sachindra
• Andre Patrick

Classifications

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title

• A61P9/12 Primary

  Antihypertensives · CPC title

• C07K14/71 Primary

  for growth factors; for growth regulators · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61K45/06

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