HEAVY-CHAIN ​​ANTI-IL-2RBG AGONIST ANTIBODIES

Claims

This document discloses heavy chain antibodies with activity as agonists of the dimeric interleukin-2 receptor, pharmaceutical compositions comprising the heavy chain antibodies, and methods for treating certain disorders, such as cancer, including, but not limited to, small cell lung cancer. It also describes methods for treating cancers expressing DLL3, comprising the administration of a DLL3-binding T-cell docking molecule and IL-2-based therapy.

1. A heavy chain antibody comprising: a first heavy chain variable region (HV) that binds to IL2RB, comprising: (a) a complementarity-determining region of HV one (CDR1) comprising the amino acid sequence: GGSISSSX 1 W (SEQ ID No. 26), wherein X1 is D or N; (b) a HV CDR2 comprising the amino acid sequence: IX 2 HSGST (SEQ ID No. 27), wherein X2 is D or S; and (c) a HV CDR3 comprising the amino acid sequence: X3 RGX4 WELX5 DAFDI (SEQ ID No. 28), wherein X3 is G or A; X4 is S or Q; and X5 is S or T; a second heavy chain variable region that binds to IL2RG, comprising: (a) a VH CDR1 comprising the amino acid sequence: GFX 1 X 2 X 3 X 4 YY (SEQ ID No. 32), wherein X 1 is T or I; X 2 is F or V; X 3 is S, N, or G; and X 4 is D or N; (b) a VH CDR2 comprising the amino acid sequence: ISX 5 SGX 6 X 7 I (SEQ ID No. 33), wherein X 5 is S or N; X 6 is D, S, G, or N; and X 7 is T or I;and (c) a VH CDR3 comprising the amino acid sequence ARGDAVSITGDY (SEQ ID No. 20); and an Fc region comprising an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID No. 34, wherein the amino acid sequence comprises a glycine at position 297, a cysteine ​​at position 292, and a cysteine ​​at position 302, all according to EU numbering.

30. A pharmaceutical composition comprising: a heavy chain antibody of any one of claims 1-29; and a pharmaceutically acceptable excipient.