Non-antagonistic EGFR-binding molecules and immunoconjugates thereof

Patent metadata

Field	Value
Publication number	US-9238690-B2
Application number	US-201113882059-A
Country	US
Kind code	B2
Filing date	Oct 28, 2011
Priority date	Oct 29, 2010
Publication date	Jan 19, 2016
Grant date	Jan 19, 2016

Abstract

Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to EGFR are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.

First claim

What is claimed is:

1. An antibody or antigen binding fragment thereof that specifically binds to human EGFR, wherein said antibody or antigen binding fragment thereof comprises:
a) a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:7, 9, or 10, and the heavy chain CDR3 of SEQ ID NO:8; and
b) a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

2. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises:
a) a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:7, and the heavy chain CDR3 of SEQ ID NO:8; and
b) a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

3. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises:
a) a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:10, and the heavy chain CDR3 of SEQ ID NO:8; and
b) a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

4. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises:
a) a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:9, and the heavy chain CDR3 of SEQ ID NO:8; and
b) a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

5. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises the heavy chain variable region of SEQ ID NO:20 and the light chain variable region of SEQ ID NO:24.

6. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises the heavy chain variable region of SEQ ID NO:19 and the light chain variable region of SEQ ID NO:23.

7. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof is murine, non-human, humanized, chimeric, resurfaced, or human.

8. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises the full length heavy chain of SEQ ID NO:27 and the full length light chain of SEQ ID NO:28.

9. The antibody or antigen binding fragment thereof of claim 1 , which is a full length antibody.

10. The antibody or antigen binding fragment thereof of claim 1 , which is an antigen binding fragment.

11. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof comprises a Fab, Fab′, F(ab′)2, single chain Fv or scFv, disulfide linked Fv, intrabody, IgGΔCH2, minibody, F(ab′)3, tetrabody, triabody, diabody, DVD-Ig, mAb2, (scFv)2, or scFv-Fc.

12. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof binds both human and macaque EGFR with a substantially similar binding affinity.

13. The antibody or antigen binding fragment thereof of claim 12 , wherein the binding affinity is measured by flow cytometry, Biacore, or radioimmunoassay.

14. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof binds to human or macaque EGFR with a Kd of about 1.0 to about 10 nM.

15. The antibody or antigen binding fragment thereof of claim 1 , wherein said antibody or antigen binding fragment thereof binds to human or macaque EGFR with a Kd of about 1.0 nM or better.

16. The antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is produced by the hybridoma deposited with the ATCC on Oct. 21, 2010 and having ATCC deposit no. PTA-11423.

17. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

18. A kit comprising the antibody or antigen binding fragment thereof of claim 1 .

19. A diagnostic reagent comprising the antibody or antigen binding fragment thereof of claim 1 .

20. An immunoconjugate having the formula (A)-(L)-(C), wherein:
(A) is an antibody or antigen binding fragment thereof that specifically binds to human EGFR comprising a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:7, 9, or 10, and the heavy chain CDR3 of SEQ ID NO:8; and a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16;
(L) is a linker;
(C) is a cytotoxic agent; and
wherein said linker (L) links (A) to (C).

21. The immunoconjugate of claim 20 , wherein (A) comprises a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:7, and the heavy chain CDR3 of SEQ ID NO:8; and a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

22. The immunoconjugate of claim 20 , wherein (A) comprises a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:10, and the heavy chain CDR3 of SEQ ID NO:8; and a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

23. The immunoconjugate of claim 20 , wherein (A) comprises a heavy chain variable region comprising the heavy chain CDR1 of SEQ ID NO:6, the heavy chain CDR2 of SEQ ID NO:9, and the heavy chain CDR3 of SEQ ID NO:8; and a light chain variable region comprising the light chain CDR1 of SEQ ID NO:14, the light chain CDR2 of SEQ ID NO:15, and the light chain CDR3 of SEQ ID NO:16.

24. The immunoconjugate of claim 20 , wherein (A) comprises an antibody or antigen binding fragment thereof comprising the heavy chain variable domain of SEQ ID NO:20 and the light chain variable domain of SEQ ID NO:24.

25. The immunoconjugate of claim 20 , wherein (A) comprises an antibody or antigen binding fragment thereof comprising the heavy chain variable domain of SEQ ID NO:19 and the light chain variable domain of SEQ ID NO:23.

26. The immunoconjugate of claim 20 , wherein (L) is selected from the group consisting of: a cleavable linker, a non-cleavable linker, a hydrophilic linker, and a dicarboxylic acid based linker.

27. The immunoconjugate of claim 26 , wherein (L) comprises a linker selected from the group consisting of: N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP), N-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB), N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB), N-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC), N-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfoSMCC), N-succinimidyl-4-(iodoacetyl)-aminobenzo

Assignees

• Setiady Julianto
• Singh Rajeeva
• Park Peter U
• Rui Lingyun
• Chittenden Thomas
• Immunogen Inc

Inventors

• Setiady Julianto
• Singh Rajeeva
• Park Peter U
• Rui Lingyun
• Chittenden Thomas

Classifications

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• G01N2333/71

  for growth factors; for growth regulators · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• G01N33/74

  involving hormones {or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors} · CPC title