US 12,168,683 B2
Binders of TGFβ-superfamily ligands and uses thereof
Ravindra Kumar, Acton, MA (US); Dianne S. Sako, Medford, MA (US); Roselyne Castonguay, Watertown, MA (US); and Tzu-Hsing Kuo, Chestnut Hill, MA (US)
Assigned to Acceleron Pharma Inc., Rahway, NJ (US)
Appl. No. 17/052,783
Filed by Acceleron Pharma Inc., Cambridge, MA (US)
PCT Filed May 2, 2019, PCT No. PCT/US2019/030475
§ 371(c)(1), (2) Date Nov. 3, 2020,
PCT Pub. No. WO2019/213446, PCT Pub. Date Nov. 7, 2019.
Claims priority of provisional application 62/666,548, filed on May 3, 2018.
Claims priority of provisional application 62/779,992, filed on Dec. 14, 2018.
Prior Publication US 2021/0380663 A1, Dec. 9, 2021
Int. Cl. C07K 14/71 (2006.01); A61K 38/00 (2006.01); C07K 14/47 (2006.01); C07K 16/22 (2006.01)
CPC C07K 14/71 (2013.01) [C07K 14/4703 (2013.01); C07K 16/22 (2013.01); A61K 38/00 (2013.01); C07K 2317/52 (2013.01); C07K 2319/02 (2013.01); C07K 2319/30 (2013.01)] 14 Claims
 
1. A heteromultimer comprising an ActRIIB fusion protein and a TβRII fusion protein, wherein the ActRIIB fusion protein comprises an ActRIIB polypeptide comprising an amino acid sequence that is at least 98% identical to:
a. a sequence beginning at any one of positions 20 to 29 of SEQ ID NO: 50, and ending at any one of positions 109 to 134 of SEQ ID NO: 50;
b. a sequence beginning at position 20 of SEQ ID NO: 50, and ending at position 134 of SEQ ID NO: 50;
c. a sequence beginning at position 29 of SEQ ID NO: 50 and ending at position 109 of SEQ ID NO: 50;
d. a sequence beginning at position 25 of SEQ ID NO: 50 and ending at position 131 of SEQ ID NO: 50;
e. the sequence of SEQ ID NO: 51;
f. the sequence of SEQ ID NO: 52;
g. the sequence of SEQ ID NO: 54;
h. the sequence of SEQ ID NO: 55; or
i. the sequence of SEQ ID NO: 109;
wherein the TβRII fusion protein comprises a TβRII polypeptide comprising an amino acid sequence that is at least 98% identical to:
a. a sequence beginning at any one of positions 23 to 35 of SEQ ID NO: 1, and ending at any one of positions 153 to 159 of SEQ ID NO: 1;
b. a sequence beginning at any one of positions 23 to 60 of SEQ ID NO: 2, and ending at any one of positions 178 to 184 of SEQ ID NO: 2;
c. the sequence of SEQ ID NO: 18;
d. the sequence of SEQ ID NO: 27; or
e. the sequence of any one of SEQ ID NOs: 20, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38; and 39;
wherein the heteromultimer binds to and/or inhibits one or more of: GDF11, GDF8, activin A, activin B, BMP10, TGFβ1, and TGFβ3; and
wherein the ActRIIB fusion protein and the TβRII fusion protein further comprise a heterologous portion.