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.
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