US 2017/0304444 A1Published application

Glucocorticoid-induced tumor necrosis factor receptor (gitr) antibodies and methods of use thereof

AssigneeDana-Farber Cancer Institute, Inc.

InventorsWayne A. MARASCO, Chen XU, De-Kuan CHANG

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Abstract

The present invention comprises human monoclonal antibodies that bind to GITR (also known as glucocorticoid-induced tumor necrosis factor receptor). Binding of the invented antibody to GITR inhibits binding of its ligand, GITR-L, and can be used to treat cancer.

Claims27

Dependent claims

An isolated humanized monoclonal antibody or antigen-binding fragment thereof that binds to the human-glucocorticoid-induced tumor necrosis factor receptor (GITR) comprising:

a. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
2, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
4;
b. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
6, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
8;
c. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
10, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
12;
d. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
14, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
16;
e. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
18, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
20;
f. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
22, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
24;
g. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
26, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
28;
h. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
30, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
32;
i. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
34, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
36;
j. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
38, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
40;
or
k. a variable heavy chain region comprising the amino acid sequence of SEQ ID NO:
42, and a variable light chain region comprising the amino acid sequence of SEQ ID NO:
44.

31 more elements

An isolated humanized monoclonal antibody or antigen-binding fragment thereof wherein the antibody or antigen-binding fragment comprises:

(a) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 45, 46 or 47, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 48, 49, or 50;
(b) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 51, 52, or 53, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 54, 55, or 56;
(c) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 57, 58, or 59, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 60, 61, or 62;
(d) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 63, 64, or 65, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 66, 67, or 68;
(e) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 69, 70, or 71, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 72, 73, or 74;
(f) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 75, 76, or 77, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 78, 79, or 80;
(g) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 81, 82, or 83, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 84, 85, or 86;
(h) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 87, 88, or 89, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 90, 91, or 92;
(i) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 93, 94, or 95, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 96, 97, or 98;
(j) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 99, 100, or 101, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 102, 103, or 104;
or
(k) a variable heavy chain complementarity determining region 1, 2, or 3 (VH-CDR) comprising the amino acid sequences of SEQ ID NO. 105, 106, or 107, respectively;
and, a variable light chain complementarity determining region 1, 2 or 3 (VL-CDR) comprising the amino acid sequences of SEQ ID NO. 108, 109, or 110
wherein said antibody or antibody binding fragment binds human-glucocorticoid-induced tumor necrosis factor receptor (GITR)

21 more elements

Dependencies are inferred from the claim text.

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