Activin receptor type IIB variants and methods of use thereof
AssigneeKeros Therapeutics, Inc.
InventorsJasbir S. Seehra, Jennifer Lachey
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Abstract
The invention features polypeptides that include an extracellular ActRIIB variant. In some embodiments, a polypeptide of the invention includes an extracellular ActRIIB variant fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions involving weakness and atrophy of muscles, bone damage, low red blood cell levels (e.g., anemia or blood loss), fibrosis, and/or pulmonary hypertension.
Claims13
A method of treating a subject having pulmonary hypertension (PH), the method comprising administering to the subject a therapeutically effective amount of a polypeptide comprising an extracellular activin receptor type IIB (ActRIIB) variant, the variant having one or more amino acid substitutions relative to the sequence of GRGEAETREC IYYNANWELE RTNQSGLERC EGEQDKRLHC YASWRNSSGT IELVKKGCWL DDFNCYDRQE CVATEENPQV YFCCCEGNFC NERFTHLPEA GGPEVTYEPP PTAPT (SEQ ID NO:
- 17),
- wherein the variant comprises one or more amino acid substitutions that impart reduced binding to bone morphogenetic protein 9 (BMP9) relative to wild type extracellular ActRIIB;
- wherein the variant comprises:
- (i) amino acid substitutions Q69T, E70D, I11L, L27V, Q34K, T50S, I51L, L53I, and F89M;
- (ii) amino acid substitutions Q69T, E70D, E75K, I11L, L27V, Q34K, T50S, I51L, L53I, and F89M;
- (iii) amino acid substitutions Q69D, E70T, I11L, L27V, Q34K, T50S, I51L, L53I, and F89M;
- or
- (iv) amino acid substitutions Q69D, E70T, E75K, I11L, L27V, Q34K, T50S, I51L, L53I, and F89M;
- and
- wherein the variant has at least 85% amino acid sequence identity to the sequence of SEQ ID NO:
- 17.
Dependencies are inferred from the claim text.