US 11,692,018 B2
TGF-β polypeptides
Ronald D. Seidel, III, Natick, MA (US); Rodolfo J. Chaparro, Cambridge, MA (US); John F. Ross, Cambridge, MA (US); and Chee Meng Low, Cambridge, MA (US)
Assigned to Cue Biopharma, Inc., Boston, MA (US)
Filed by Cue Biopharma, Inc., Cambridge, MA (US)
Filed on Apr. 16, 2022, as Appl. No. 17/722,328.
Application 17/722,328 is a continuation of application No. PCT/US2020/056937, filed on Oct. 22, 2020.
Claims priority of provisional application 62/925,227, filed on Oct. 23, 2019.
Prior Publication US 2022/0372093 A1, Nov. 24, 2022
Int. Cl. C07K 14/495 (2006.01); A61P 37/06 (2006.01); C07K 14/54 (2006.01); C07K 14/545 (2006.01); C07K 14/55 (2006.01); C07K 14/705 (2006.01); C12N 5/00 (2006.01); C12N 15/62 (2006.01); A61K 38/00 (2006.01)
CPC C07K 14/495 (2013.01) [A61P 37/06 (2018.01); C07K 14/54 (2013.01); C07K 14/545 (2013.01); C07K 14/5406 (2013.01); C07K 14/5412 (2013.01); C07K 14/5418 (2013.01); C07K 14/5428 (2013.01); C07K 14/5443 (2013.01); C07K 14/55 (2013.01); C07K 14/70532 (2013.01); C07K 14/70575 (2013.01); C12N 5/00 (2013.01); C12N 15/62 (2013.01); A61K 38/00 (2013.01); C07K 2318/10 (2013.01); C07K 2319/74 (2013.01)] 23 Claims
 
1. A heterodimer comprising a first polypeptide and a second polypeptide, wherein:
(i) the first polypeptide comprises, in the N-terminal to C-terminal direction,
a) a scaffold polypeptide sequence comprising an interspecific dimerization sequence and having at least 95% sequence identity to at least 175 contiguous amino acids of an IgG1 sequence selected from SEQ ID NOs:71 to 76,
b) a masking polypeptide sequence comprising a TGF-β receptor polypeptide sequence having at least 95% sequence identity to SEQ ID NO:122,
and
optionally, an independently selected linker polypeptide sequence comprising from 1 to 25 amino acids interposed between the scaffold polypeptide sequence and the masking polypeptide sequence of the first polypeptide; and
(ii) the second polypeptide comprises, in the N-terminal to C-terminal direction,
a) an IL-2 immunomodulatory polypeptide sequence having at least 95% sequence identity to 120 contiguous amino acids of SEQ ID NO:9,
b) a scaffold polypeptide sequence comprising a counterpart interspecific dimerization sequence to the interspecific dimerization sequence in the first polypeptide and having at least 95% sequence identity to at least 175 contiguous amino acids of an IgG1 sequence selected from SEQ ID NOs:71 to 76,
c) a TGF-β3 polypeptide sequence having at least 95% sequence identity to at least 100 contiguous amino acids of SEQ ID NO:111,
and
optionally independently selected linker polypeptide sequences comprising from 1 to 25 amino acids interposed
(A) between the IL-2 immunomodulatory polypeptide sequence and the scaffold polypeptide sequence of the second polypeptide, and/or
(B) between the scaffold polypeptide sequence and the TGF-β3 polypeptide sequence of the second polypeptide;
wherein the TGF-β receptor polypeptide sequence and the TGF-β3 polypeptide sequence interact with each other to reversibly mask the TGF-β3 polypeptide sequence; and
wherein the interspecific dimerization sequence and the counterpart interspecific dimerization sequence interact with each other to form the heterodimer.