US 11,702,461 B2
T-cell modulatory multimeric polypeptides comprising reduced-affinity immunomodulatory polypeptides
Ronald D. Seidel, III, Cambridge, MA (US); and Rodolfo J. Chaparro, Cambridge, MA (US)
Assigned to Cue Biopharma, Inc., Boston, MA (US)
Filed by Cue Biopharma, Inc., Cambridge, MA (US)
Filed on Jun. 23, 2020, as Appl. No. 16/909,323.
Application 16/909,323 is a continuation of application No. PCT/US2019/012688, filed on Jan. 8, 2019.
Claims priority of provisional application 62/782,109, filed on Dec. 19, 2018.
Claims priority of provisional application 62/782,214, filed on Dec. 19, 2018.
Claims priority of provisional application 62/713,408, filed on Aug. 1, 2018.
Claims priority of provisional application 62/615,253, filed on Jan. 9, 2018.
Claims priority of provisional application 62/615,225, filed on Jan. 9, 2018.
Prior Publication US 2020/0317747 A1, Oct. 8, 2020
Int. Cl. C07K 14/705 (2006.01); C07K 16/08 (2006.01); C12N 15/86 (2006.01); C07K 14/74 (2006.01)
CPC C07K 14/70539 (2013.01) [C07K 16/082 (2013.01); C12N 15/86 (2013.01); C07K 2317/34 (2013.01); C07K 2317/92 (2013.01); C12N 2730/10122 (2013.01)] 18 Claims
 
1. A T-cell modulatory multimeric polypeptide (TMMP) comprising:
at least one heterodimer comprising:
a) a first polypeptide comprising:
i) a hepatitis B virus (HBV) peptide epitope, wherein the HBV peptide has a length of at least 4 amino acids; and
ii) first major histocompatibility complex (MHC) polypeptide;
b) a second polypeptide comprising a second MHC polypeptide and an immunoglobulin (Ig) Fc polypeptide, and
c) one or more immunomodulatory polypeptides that modulates a CD8+T cell that is specific for the HBV epitope,
wherein the first and/or the second polypeptide comprises the immunomodulatory polypeptide, and
wherein the first MHC polypeptide is β2-microglobulin (β2M) polypeptide; and wherein the second MHC polypeptide is an MHC class I heavy chain polypeptide,
wherein at least one of the one or more immunomodulatory polypeptides is a variant immunomodulatory polypeptide that binds to a cognate co-immunomodulatory polypeptide and exhibits reduced affinity to the cognate co-immunomodulatory polypeptide compared to the affinity of a corresponding wild-type immunomodulatory polypeptide for the cognate co-immunomodulatory polypeptide.