US 12,006,348 B2
T-cell modulatory multimeric polypeptide with conjugation sites and methods of use thereof
Ronald D. Seidel, III, Cambridge, 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 Mar. 6, 2020, as Appl. No. 16/812,125.
Application 16/812,125 is a continuation of application No. PCT/US2018/049803, filed on Sep. 6, 2018.
Claims priority of provisional application 62/615,402, filed on Jan. 9, 2018.
Claims priority of provisional application 62/609,082, filed on Dec. 21, 2017.
Claims priority of provisional application 62/555,559, filed on Sep. 7, 2017.
Prior Publication US 2020/0369745 A1, Nov. 26, 2020
Int. Cl. C07K 14/74 (2006.01); A61K 38/00 (2006.01); A61K 47/62 (2017.01); C07K 14/005 (2006.01); C12N 7/00 (2006.01); C12N 9/16 (2006.01)
CPC C07K 14/70539 (2013.01) [A61K 47/62 (2017.08); C07K 14/005 (2013.01); C12N 7/00 (2013.01); C12N 9/16 (2013.01); C12Y 301/06 (2013.01); A61K 38/00 (2013.01); C07K 2319/02 (2013.01); C07K 2319/30 (2013.01); C07K 2319/40 (2013.01); C12N 2710/16122 (2013.01); C12N 2710/16133 (2013.01); C12N 2730/10122 (2013.01); C12N 2730/10133 (2013.01)] 8 Claims
 
1. A T-cell modulatory multimeric polypeptide (T-Cell-MMP) comprising:
a) a first polypeptide comprising,
i) a first major histocompatibility complex (MHC) polypeptide having an N-terminus and a C-terminus, wherein the first MHC polypeptide comprises a beta-2-microglobulin (β2M) polypeptide;
b) a second polypeptide having an N-terminus and a C-terminus comprising, in order from N-terminus to C-terminus,
(i) a second MHC polypeptide, wherein the second MHC polypeptide comprises a class I MHC heavy chain polypeptide comprising a binding pocket;
(ii) optionally a peptide linker; and
(iii) optionally an immunoglobulin (Ig) Fc polypeptide or a non-Ig polypeptide scaffold;
c) (i) a first polypeptide chemical conjugation site that is part of a linker attached to the first polypeptide or is within the first polypeptide, or
(ii) a second polypeptide chemical conjugation site that is part of a linker attached to the second polypeptide or is within the second polypeptide;
wherein the first and second polypeptide chemical conjugation sites are sites at which a molecule comprising an epitope peptide may be covalently bound, either directly or indirectly through a linker, to the first or second polypeptide and positioned in the binding pocket of the T-Cell MMP for presentation to a cell bearing a T-cell receptor specific for the epitope presented by the epitope peptide; and
d) one or more immunomodulatory polypeptides (MODs), wherein at least one of the one or more MODs is
i) at the C-terminus of the first polypeptide,
ii) at the N-terminus of the second polypeptide,
iii) at the C-terminus of the second polypeptide, or
iv) at the C-terminus of the first polypeptide and at the N-terminus of the second polypeptide;
wherein each of the one or more MODs is an independently selected wild-type or variant MOD.