Optimized anti-CD30 antibodies
An antibody that targets CD30, wherein the antibody comprises at least one modification relative to a parent antibody and the antibody binds with altered affinity to an FcγR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the anti-CD30 antibody.
1 . An anti-CD30 antibody comprising at least one amino acid substitution in the Fc region at a position selected from the group consisting of 221, 222, 224, 227, 228, 230, 231, 223, 233, 234, 235, 236, 237, 238, 239, 240, 241, 243, 244, 245, 246, 247, 249, 250, 258, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 278, 280, 281, 283, 285, 286, 288, 290, 291, 293, 294, 295, 296, 297, 298, 299, 300, 302, 313, 317, 318, 320, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335 336 and 428 relative to a parent Fc region and said antibody binds with altered affinity to an FcγR as compared to the parent antibody, wherein numbering is according to the EU index as in Kabat.
2 . An antibody according to claim 1 , wherein said amino acid substitutions are selected from a group consisting of 230, 240, 244, 245, 247, 262, 263, 266, 273, 275, 299, 302, 313, 323, 325, 328, and 332.
3 . An antibody according to claim 1 , wherein said substitution is selected from the group consisting of H268E, A330Y, A330L and G236A.
4 . An antibody according to claim 1 , wherein said antibody is a humanized antibody.
5 . An antibody according to claim 4 , wherein said antibody comprises a variable heavy chain sequence selected from the group consisting of SEQ ID NOS: 2, 4, 7-9 and 11, and/or a variable light chain sequence selected from the group consisting of SEQ ID NOS: 1, 3, 5, 6 and 10.
6 . An antibody according to claim 5 , wherein said antibody comprises a variable heavy chain sequence selected from the group consisting of SEQ ID NOS: 2, 4, 7-9 and 11, and a variable light chain sequence selected from the group consisting of SEQ ID NOS: 1, 3, 5, 6 and 10.
7 . An antibody according to claim 1 , wherein said antibody comprises a heavy chain constant region selected from the group consisting of SEQ ID NOS: 13-19 and/or a light chain constant region SEQ ID NO: 12.
8 . An antibody according to claim 7 , wherein said antibody comprises a heavy chain constant region selected from the group consisting of SEQ ID NOS: 13-19 and a light chain constant region SEQ ID NO: 12.
9 . An antibody according to claim 1 , wherein said antibody comprises the heavy chain sequence of SEQ ID NO:19 and/or a light chain sequence of SEQ ID NO:20.
10 . An antibody according to claim 9 , wherein said antibody comprises the heavy chain sequence of SEQ ID NO:19 and a light chain sequence of SEQ ID NO:20.
11 . An antibody according to claim 1 , wherein said modification is an engineered glycoform.
12 . An antibody according to claim 11 , wherein said anti-CD30 antibody has reduced fucosylation relative to the parent antibody.
13 . An antibody according to claim 1 , wherein said FcγR is selected from the group consisting of human FcγRI, FcγRIIa, FcγRIIb, FcγRIIc and FcγRIIIa.
14 . An antibody according to claim 1 , wherein said antibody binds with greater affinity to said FcγR relative to the parent antibody.
15 . An antibody according to claim 1 , wherein said antibody has altered effector function as compared to the parent Fc region.
16 . An antibody according to claim 15 , wherein said effector function is ADCC.
17 . An antibody according to claim 16 , wherein said ADCC is enhanced relative to the parent antibody.
18 . A method of treating an indication selected from the group consisting of cancer, autoimmune disorder, infection disease, and an inflammatory disorder comprising administering the anti-CD30 antibody according to claim 1 .
19 . A method according to claim 18 wherein said indication is elected from the group consisting of small cell lung carcinoma and Hodgkin's lymphoma.
20 . A pharmaceutical composition comprising an anti-CD30 antibody according to claim 1 and a pharmaceutically acceptable carrier.
21 . A composition comprising the antibody of claim 1 , sodium chloride and a surfactant.
22 . The composition of claim 21 , wherein the surfactant is sorbitol.
23 . The composition of claim 22 , wherein said surfactant is polysorbate 20 or polysorbate 80.
24 . The composition of claim 21 , wherein said composition has at pH 6.0-7.0.