US 12,440,539 B2
Methods of using activin receptor type IIB variants
Jasbir S. Seehra, Lexington, MA (US); Jennifer Lachey, Lincoln, MA (US); and Elissa Furutani, Belmont, MA (US)
Assigned to Keros Therapeutics, Inc., Lexington, MA (US)
Filed by Keros Therapeutics, Inc., Lexington, MA (US)
Filed on Sep. 15, 2022, as Appl. No. 17/945,328.
Application 17/945,328 is a continuation of application No. PCT/US2021/023339, filed on Mar. 19, 2021.
Claims priority of provisional application 63/109,764, filed on Nov. 4, 2020.
Claims priority of provisional application 63/073,329, filed on Sep. 1, 2020.
Claims priority of provisional application 63/029,442, filed on May 23, 2020.
Claims priority of provisional application 62/992,879, filed on Mar. 20, 2020.
Prior Publication US 2023/0087128 A1, Mar. 23, 2023
Int. Cl. A61K 38/17 (2006.01); A61K 35/19 (2015.01); C07K 14/78 (2006.01)
CPC A61K 38/179 (2013.01) [A61K 35/19 (2013.01); C07K 14/78 (2013.01); C07K 2319/30 (2013.01)] 10 Claims
 
1. A method of treating a subject having or at risk of developing thrombocytopenia, 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 GRGEAETRECIYYNANWELERTNQSGLERCEGEQDKRLHCYASWRNSSGTIELVKKGC WLDDFNCYDRQECVATEENPQVYFCCCEGNFCNERFTHLPEAGGPEVTYEPPPTAPT (SEQ ID NO: 17) that impart reduced BMP9 binding relative to wild type extracellular ActRIIB, wherein the substitutions that reduce BMP9 binding comprise one or more of:
(a) an amino acid substitution E75K;
(b) amino acid substitutions Q69T and E70D; or
(c) amino acid substitutions Q69D and E70T, optionally wherein the variant is truncated from the N-terminus by deletion of 1, 2, 3, 4, 5, 6, or 7 amino acids.