Activin receptor type iib variants and uses thereof
Assignee35PHARMA Inc.
InventorsMaureen O'CONNOR-MCCOURT, Vannakambadi K. GANESH, Gilles TREMBLAY, Gauthier SCHANG
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Abstract
There are provided polypeptides that include an Activin receptor type IIB (ActRIIB) ectodomain (ECD) variant. In some embodiments, a polypeptide of the disclosure includes an ActRIIB-ECD variant fused to an Fc domain moiety. The disclosure also provides pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions associated with TGFβ superfamily ligand signaling, such as pulmonary hypertension, fibrosis, muscle weakness and atrophy, metabolic disorders and/or cardiometabolic disease, bone damage, and/or low red blood cell levels (such as anemia).
Claims33
-23. (canceled)
A polypeptide comprising:
- (a) an Activin receptor type IIB (ActRIIB) ectodomain (ECD) variant comprising the amino acid substitution F58E relative to the human wild type ActRIIB-ECD of SEQ ID NO:
- 2;
- (b) a peptide linker comprising at least 10 amino acids;
- and
- (c) an Fc domain monomer.
A TGFβ superfamily ligand binding agent comprising a first polypeptide and a second polypeptide, wherein each of the first and second polypeptide comprise:
- (a) an Activin receptor type IIB (ActRIIB) ectodomain (ECD) variant comprising the amino acid substitution F58E relative to the human wild type ActRIIB-ECD of SEQ ID NO:
- 2;
- (b) a peptide linker comprising at least 10 amino acids;
- and
- (c) an Fc domain monomer,
- wherein the first and second polypeptides are linked by at least one disulfide bond between the Fc domain monomer of the first polypeptide and the Fc domain monomer of the second polypeptide.
Dependencies are inferred from the claim text.