Anti-cd137 molecules and use thereof
AssigneeAdagene Inc.
InventorsPeter Peizhi Luo, Fangyong Du, Yan Li, Guizhong Liu, Jun Chen, Xiaohong She, Peter Cheung
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Abstract
The present disclosure provides antibodies that bind to human CD137 or antigen binding fragments thereof, nucleic acid encoding the same, therapeutic compositions thereof, and their use to enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, such as tumor immunity, and for the treatment of cancer.
Claims57
An isolated antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CD137, wherein the antibody or the antigen-binding fragment thereof binds to one or more amino acid residues within amino acid residues 34-108 of SEQ ID NO:1.
An isolated antibody, or antigen-binding fragment thereof, that binds to an extracellular domain of human CD137, comprising a heavy chain variable region and a light chain variable region,
- a) wherein the heavy chain variable region comprises an HVR-H1, an HVR-H2, and an HVR-H3,
- wherein the HVR-H1 comprises an amino acid sequence according to a formula selected from the group consisting of:
- Formula (I):
- X1TFX2X3YX4IHWV (SEQ ID NO:2), wherein X1 is F or Y, X2 is S or T, X3 is G, N, or S, and X4 is A, G, or W;
- Formula (II):
- YSIX1SGX2X3WX4WI (SEQ ID NO:3), wherein X1 is S or T, X2 is H or Y, X3 is H or Y, and X4 is A, D, G, N, S, or T;
- and
- Formula (III):
- FSLSTX1GVX2VX3WI (SEQ ID NO:4), wherein X1 is G or S, X2 is A or G, and X3 is A, G, S, or T;
- wherein the HVR-H2 comprises an amino acid sequence according to a formula selected from the group consisting of:
- Formula (IV):
- LALIDWX1X2DKX3YSX4SLKSRL (SEQ ID NO:5), wherein X1 is A, D, or Y, X2 is D or G, X3 is R, S, or Y, and X4 is P or T;
- Formula (V):
- IGX1IYHSGX2TYYX3PSLKSRV (SEQ ID NO:6), wherein X1 is D or E, X2 is N or S, and X3 is N or S;
- and
- Formula (VI):
- VSX1ISGX2GX3X4TYYADSVKGRF (SEQ ID NO:7), wherein X1 is A, G, S, V, or Y, X2 is A, D, S, or Y, X3 is D, G, or S, and X4 is S or T;
- and
- wherein the HVR-H3 comprises an amino acid sequence according to Formula (VII):
- ARX1GX2X3X4VX5GDWFX6Y (SEQ ID NO:8), wherein X1 is E or G, X2 is E or S, X3 is D or T, X4 is A, T, or V, X5 is A, I, L, T, or V, and X6 is A, D, or G;
- and
- b) wherein the light chain variable region comprises an HVR-L1, an HVR-L2, and an HVR-L3,
- wherein the HVR-L1 comprises an amino acid sequence according to Formula (VIII):
- X1ASQX2X3X4X5X6X7X8 (SEQ ID NO:9), wherein X1 is Q or R, X2 is D, G, or S, X3 is I or V, X4 is G, R, S, or T, X5 is P, R, S, or T, X6 is A, D, F, S, V, or Y, X7 is L or V, and X8 is A, G, or N;
- wherein the HVR-L2 comprises an amino acid sequence according to Formula (IX):
- X1ASX2X3X4X5GX6 (SEQ ID NO:10), wherein X1 is A or D, X2 is N, S, or T, X3 is L or R, X4 is A, E, or Q, X5 is S or T, and X6 is I or V;
- and
- wherein the HVR-L3 comprises an amino acid sequence according to a formula selected from the group consisting of:
- Formula (X):
- YCQQX1YX2X3X4T (SEQ ID NO:11), wherein X1 is A, G, S, or Y, X2 is Q, S, or Y, X3 is I, L, T, or Y, and X4 is I, S, V, or W;
- and
- Formula (XI):
- YCX1QX2X3X4X5PX6T (SEQ ID NO:12), wherein X1 is E or Q, X2 is P, S, or Y, X3 is D, L, S, T, or Y, X4 is D, E, H, S, or T, X5 is D, L T, or W, and X6 is L, P, R, or V.
The antibody or antigen-binding fragment of 21, wherein the HVR-H1 comprises an amino acid sequence of SEQ ID NO:712, the HVR-H2 comprises an amino acid sequence of SEQ ID NO:736, the HVR-H3 comprises an amino acid sequence of SEQ ID NO:760, the HVR-L1 comprises an amino acid sequence of SEQ ID NO:784, the HVR-L2 comprises an amino acid sequence or SEQ ID NO:808, and the HVR-L3 comprises an amino acid sequence of SEQ ID NO:832.
A polynucleotide comprising a sequence selected from the group consisting of SEQ ID NOs:133-252.
Dependencies are inferred from the claim text.