Anti-claudin 18 antibodies and methods of use thereof
AssigneeNovarock Biotherapeutics, Ltd.
InventorsHan Li, Ming Lei, Yi Pei, Haichun Huang
Life of this patent
Estimating the term…
Abstract
Antibodies that specifically bind to the human tight junction molecule CLDN18.2 and have functional properties that make them suitable for use in antibody-based immunotherapies of a disease associated with aberrant expression of CLDN18.2 are disclosed.
Claims19
-10. (canceled)
A method of treating cancer in an individual comprising administering to the individual a therapeutically effective amount of an isolated fully human anti-human CLDN18.2, wherein the antibody does not bind to human CLDN18.1 and the antibody comprises:
- (a) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 221, CDR2:
- SEQ ID NO:
- 222, CDR3:
- SEQ ID NO:
- 223 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 224, CDR2:
- SEQ ID NO:
- 225, CDR3:
- SEQ ID NO:
- 226;
- (b) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 227, CDR2:
- SEQ ID NO:
- 228, CDR3:
- SEQ ID NO:
- 229 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 230, CDR2:
- SEQ ID NO:
- 231, CDR3:
- SEQ ID NO:
- 232;
- (c) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 233, CDR2:
- SEQ ID NO:
- 234, CDR3:
- SEQ ID NO:
- 235 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 236, CDR2:
- SEQ ID NO:
- 237, CDR3:
- SEQ ID NO:
- 238;
- (d) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 251, CDR2:
- SEQ ID NO:
- 252, CDR3:
- SEQ ID NO:
- 253 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 254, CDR2:
- SEQ ID NO:
- 255, CDR3:
- SEQ ID NO:
- 256;
- (e) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 257, CDR2:
- SEQ ID NO:
- 258, CDR3:
- SEQ ID NO:
- 259 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 260, CDR2:
- SEQ ID NO:
- 261, CDR3:
- SEQ ID NO:
- 262;
- (f) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 269, CDR2:
- SEQ ID NO:
- 270, CDR3:
- SEQ ID NO:
- 271 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 272, CDR2:
- SEQ ID NO:
- 273, CDR3:
- SEQ ID NO:
- 274;
- (g) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 275, CDR2:
- SEQ ID NO:
- 276, CDR3:
- SEQ ID NO:
- 277 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 278, CDR2:
- SEQ ID NO:
- 279, CDR3:
- SEQ ID NO:
- 280;
- or
- (h) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 287, CDR2:
- SEQ ID NO:
- 288, CDR3:
- SEQ ID NO:
- 289 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 290, CDR2:
- SEQ ID NO:
- 291, CDR3:
- SEQ ID NO:
- 292.
A method of treating cancer in an individual comprising administering to the individual a therapeutically effective amount of an isolated fully human anti-human CLDN18.2, wherein the antibody does not bind to human CLDN18.1 and the antibody comprises:
- (a) a heavy chain variable region sequence of SEQ ID NO:
- 185 and a light chain variable region sequence of SEQ ID NO:
- 186;
- (b) a heavy chain variable region sequence of SEQ ID NO:
- 187 and a light chain variable region sequence of SEQ ID NO:
- 188;
- (c) a heavy chain variable region sequence of SEQ ID NO:
- 189 and a light chain variable region sequence of SEQ ID NO:
- 190;
- (d) a heavy chain variable region sequence of SEQ ID NO:
- 195 and a light chain variable region sequence of SEQ ID NO:
- 196;
- (e) a heavy chain variable region sequence of SEQ ID NO:
- 197 and a light chain variable region sequence of SEQ ID NO:
- 198;
- (f) a heavy chain variable region sequence of SEQ ID NO:
- 201 and a light chain variable region sequence of SEQ ID NO:
- 202;
- (g) a heavy chain variable region sequence of SEQ ID NO:
- 203 and a light chain variable region sequence of SEQ ID NO:
- 204;
- or
- (h) a heavy chain variable region sequence of SEQ ID NO:
- 207 and a light chain variable region sequence of SEQ ID NO:
- 208.
An antibody drug conjugate comprising an isolated fully human anti-human CLDN18.2 antibody or antigen-binding fragment thereof conjugated to one or more therapeutic agents, wherein the antibody does not bind to human CLDN18.1 and the antibody comprises:
- (a) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 221, CDR2:
- SEQ ID NO:
- 222, CDR3:
- SEQ ID NO:
- 223 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 224, CDR2:
- SEQ ID NO:
- 225, CDR3:
- SEQ ID NO:
- 226;
- (b) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 227, CDR2:
- SEQ ID NO:
- 228, CDR3:
- SEQ ID NO:
- 229 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 230, CDR2:
- SEQ ID NO:
- 231, CDR3:
- SEQ ID NO:
- 232;
- (c) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 233, CDR2:
- SEQ ID NO:
- 234, CDR3:
- SEQ ID NO:
- 235 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 236, CDR2:
- SEQ ID NO:
- 237, CDR3:
- SEQ ID NO:
- 238;
- (d) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 251, CDR2:
- SEQ ID NO:
- 252, CDR3:
- SEQ ID NO:
- 253 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 254, CDR2:
- SEQ ID NO:
- 255, CDR3:
- SEQ ID NO:
- 256;
- (e) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 257, CDR2:
- SEQ ID NO:
- 258, CDR3:
- SEQ ID NO:
- 259 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 260, CDR2:
- SEQ ID NO:
- 261, CDR3:
- SEQ ID NO:
- 262;
- (f) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 269, CDR2:
- SEQ ID NO:
- 270, CDR3:
- SEQ ID NO:
- 271 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 272, CDR2:
- SEQ ID NO:
- 273, CDR3:
- SEQ ID NO:
- 274;
- (g) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 275, CDR2:
- SEQ ID NO:
- 276, CDR3:
- SEQ ID NO:
- 277 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 278, CDR2:
- SEQ ID NO:
- 279, CDR3:
- SEQ ID NO:
- 280;
- or
- (h) a heavy chain variable region comprising CDR1:
- SEQ ID NO:
- 287, CDR2:
- SEQ ID NO:
- 288, CDR3:
- SEQ ID NO:
- 289 and a light chain variable region comprising CDR1:
- SEQ ID NO:
- 290, CDR2:
- SEQ ID NO:
- 291, CDR3:
- SEQ ID NO:
- 292.
An antibody drug conjugate comprising an isolated fully human anti-human CLDN18.2 antibody or antigen-binding fragment thereof conjugated to one or more therapeutic agents, wherein the antibody does not bind to human CLDN18.1 and the antibody comprises:
- (a) a heavy chain variable region sequence of SEQ ID NO:
- 185 and a light chain variable region sequence of SEQ ID NO:
- 186;
- (b) a heavy chain variable region sequence of SEQ ID NO:
- 187 and a light chain variable region sequence of SEQ ID NO:
- 188;
- (c) a heavy chain variable region sequence of SEQ ID NO:
- 189 and a light chain variable region sequence of SEQ ID NO:
- 190;
- (d) a heavy chain variable region sequence of SEQ ID NO:
- 195 and a light chain variable region sequence of SEQ ID NO:
- 196;
- (e) a heavy chain variable region sequence of SEQ ID NO:
- 197 and a light chain variable region sequence of SEQ ID NO:
- 198;
- (f) a heavy chain variable region sequence of SEQ ID NO:
- 201 and a light chain variable region sequence of SEQ ID NO:
- 202;
- (g) a heavy chain variable region sequence of SEQ ID NO:
- 203 and a light chain variable region sequence of SEQ ID NO:
- 204;
- or
- (h) a heavy chain variable region sequence of SEQ ID NO:
- 207 and a light chain variable region sequence of SEQ ID NO:
- 208.
Dependencies are inferred from the claim text.