US 12,103,959 B2
Multispecific binders of TGFBeta-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., Cambridge, MA (US)
Appl. No. 17/052,785
Filed by Acceleron Pharma Inc., Cambridge, MA (US)
PCT Filed May 2, 2019, PCT No. PCT/US2019/030469
§ 371(c)(1), (2) Date Nov. 3, 2020,
PCT Pub. No. WO2019/213442, PCT Pub. Date Nov. 7, 2019.
Claims priority of provisional application 62/666,547, filed on May 3, 2018.
Claims priority of provisional application 62/779,998, filed on Dec. 14, 2018.
Prior Publication US 2022/0372107 A1, Nov. 24, 2022
Int. Cl. C07K 14/705 (2006.01); A61K 38/00 (2006.01); C07K 14/71 (2006.01); C07K 16/22 (2006.01)
CPC C07K 14/70578 (2013.01) [C07K 14/71 (2013.01); C07K 16/22 (2013.01); A61K 38/00 (2013.01); C07K 2319/02 (2013.01); C07K 2319/30 (2013.01)] 8 Claims
 
1. A heteromultimer comprising an ActRIIA fusion protein and a TβRII fusion protein, wherein the ActRIIA fusion protein comprises an ActRIIA polypeptide comprising:
a. a sequence beginning at any one of positions 21 to 30 of SEQ ID NO: 50, and ending at any one of positions 110 to 135 of SEQ ID NO: 50;
b. a sequence beginning at position 21 of SEQ ID NO: 50, and ending at position 135 of SEQ ID NO: 50;
c. a sequence beginning at position 30 of SEQ ID NO: 50 and ending at position 110 of SEQ ID NO: 50;
d. the sequence of SEQ ID NO: 51; or
e. the sequence of SEQ ID NO: 52;
wherein the TβRII fusion protein comprises a TβRII polypeptide comprising:
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, activin A, activin B, TGFβ1, and TGFβ3; and
wherein the ActRIIA fusion protein and the TβRII fusion protein comprise a heterologous portion.