GITR antigen binding proteins and methods of use thereof

摘要

Antigen binding proteins that activate GITR are provided. Nucleic acids encoding the antigen binding proteins and vectors and cells containing such nucleic acids are also provided. The antigen binding proteins have value in therapeutic methods in which it is useful to stimulate GITR signaling, thereby inducing or enhancing an immune response in a subject. Accordingly, the antigen binding proteins have utility in a variety of immunotherapy treatments, including treatment of various cancers and infections.

主权项

1. An antigen binding protein, wherein said antigen binding protein is an antibody or a functional fragment thereof that agonizes human glucocorticoid-induced TNFR-related protein (“GITR”), said antigen binding protein comprising:
a) a variant VH comprising a CDRH1, a CDRH2 and a CDRH3, wherein one or more of CDRH1, CDRH2 and CDRH3 differ in sequence relative to the corresponding CDRH1, CDRH2 and CDRH3 of the VH of any single antigen binding protein selected from the group of Ab1 to Ab59 inclusive, provided however that the sequence differences in the CDRH1, CDRH2 and CDRH3 of the variant VH relative to the corresponding CDRs of the VH sequence collectively total no more than 1, 2, 3, 4 or 5 amino acids; and a variant VL comprising a CDRL1, a CDRL2 and a CDRL3, wherein one or more of CDRL1, CDRL2 and CDRL3 differ in sequence relative to the corresponding CDRL1, CDRL2 and CDRL3 of the VL of any single antigen binding protein selected from the group of Ab1 to Ab59 inclusive, provided however that the sequence differences in the CDRL1, CDRL2 and CDRL3 of the variant VL relative to the corresponding CDRs of the VL sequence collectively total no more than 1, 2, 3, 4 or 5 amino acids, provided that the variant VH and the variant VL are, respectively, variants of the VH and VL of the same antigen binding protein as specified in Table 1; b) a VH comprising a CDRH1, a CDRH2 and a CDRH3, wherein CDRH1 comprises the sequence X1YGMX2 (SEQ ID NO:436), wherein X1 is S or N; and X2 is H or Y;
CDRH2 comprises the sequence VIWYX1GSNKYYADSVX2G (SEQ ID NO:437), wherein X1 is E, V, A, P; and X2 is K or R;CDRH3 comprises the sequence GGX1LX2X3X4YYX5GMDV (SEQ ID NO:438), wherein X1 is Q, L, E, or R; X2 is G, R, or S; X3 is K, Y, L, F, or R; and X4 is Y or D; and X5 is Y or S; and a VL comprising a CDRL1, a CDRL2 and a CDRL3, wherein
CDRL1 comprises the sequence RASQX1IRNDLG (SEQ ID NO:439), wherein X1 is G or V;CDRL2 comprises the sequence X1X2SX3LQS (SEQ ID NO:440), wherein X1 is A or D; X2 is A or T; and X3 is S or T;CDRL3 comprises the sequence X1QX2X3X4YPX5T (SEQ ID NO:441), wherein X1 is L or Q; X2 is H or L; X3 is N or H; X4 is S, N or T, and X5 is W, L or I; c) a CDRH1, a CDRH2 and a CDRH3, each from the same VH of an antigen binding protein of Ab1 to Ab59 inclusive as specified in Table 1; and the CDRL1, a CDRL2, and a CDRL3, each from the same VL of an antigen binding protein of Ab1 to Ab59 inclusive as specified in Table 1, wherein the VH and the VL are from the same antigen binding protein; d) a VH that is at least 80%, 85%, 90%, 95%, 97% or 99% identical in amino acid sequence to the VH sequence of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1; and a VL that is at least 80%, 85%, 90%, 95%, 97% or 99% identical in amino acid sequence to the VL sequence of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the VH and the VL are from the same antigen binding protein as specified in Table 1; e) a VH comprising the amino acid sequence of the VH of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1; and a VL comprising the amino acid sequence of the VL of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the VH and the VL are from the same antigen binding protein as specified in Table 1; f) a full length heavy chain (HC) that is at least 90%, 95%, 97% or 99% identical in amino acid sequence to the full length heavy chain sequence of any one of antigen binding proteins Ab1 to AB59 inclusive as specified in Table 1; and a full length light chain (LC) that is at least 90%, 95%, 97% or 99% identical in amino acid sequence to the full length light chain sequence of any one of antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the full length heavy chain and the full length light chain are from the same antigen binding protein as specified in Table 1; or g) a full length heavy chain comprising the amino acid sequence of the full length heavy chain of any one of the antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1; and a full length light chain comprising the amino acid sequence of the full length light chain of any one of the antigen binding proteins Ab1 to Ab59 inclusive as specified in Table 1, wherein the full length heavy chain and the full length light chain are from the same antigen binding protein as specified in Table 1.