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US 2024/0181007 A1Published application
Compositions and methods for treating pulmonary hypertension
AssigneeAcceleron Pharma Inc.
InventorsGang Li, Ravindra Kumar, Jonathan Toshi Lu, Sachindra Joshi, Patrick Andre
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Abstract
In some aspects, the disclosure relates to compositions and methods comprising variant ActRIIB polypeptides or heteromultimers thereof 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.
Claims23
1-177. (canceled)
A method of treating post-capillary pulmonary hypertension (PcPH), comprising administering to a patient in need thereof an effective amount of a fusion protein comprising:
- (i) a variant ActRIIB polypeptide comprising an amino acid sequence that is at least 90% identical to an amino acid sequence that begins at any one of amino acids 20-29 of SEQ ID NO:
- 2 and ends at any one of amino acids 109-134 of SEQ ID NO:
- 2, and wherein the polypeptide comprises one or more amino acid substitutions at a position of SEQ ID NO:
- 2 selected from the group consisting of:
- A24, S26, N35, E37, L38, R40, S44, L46, E50, E52, Q53, D54, K55, R56, L57, Y60, R64, N65, S67, G68, K74, W78, L79, D80, F82, N83, T93, E94, Q98, V99, E105, F108, E111, R112, A119, G120, E123, P129, P130, and A132;
- (ii) an Fc domain of an immunoglobulin;
- (iii) a linker domain positioned between the ActRIM polypeptide domain and the one or more heterologous domains or Fc domain.
4 more elements
Dependencies are inferred from the claim text.