Anti-GD2 antibodies

Patent metadata

Field	Value
Publication number	US-9315585-B2
Application number	US-201113702319-A
Country	US
Kind code	B2
Filing date	Jun 20, 2011
Priority date	Jun 19, 2010
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

In this application are described chimeric, humanized, affinity matured, stability enhanced, and bispecific Anti-GD2 antibodies and fragments thereof. Also provided are methods of using individual antibodies or compositions thereof for the detection, prevention, and/or therapeutical treatment of GD2-related diseases, in particular, neuroblastoma.

First claim

What is claimed is:

1. A humanized or chimeric antibody or fragment thereof capable of binding to GD2, wherein the antibody or fragment thereof comprises any of the following:
(i) a variable heavy chain domain of SEQ ID NO: 1 and a variable light chain domain of SEQ ID NO:2;
(ii) a variable heavy chain domain of SEQ ID NO:3 and a variable light chain domain of SEQ ID NO:2;
(iii) a variable heavy chain domain of SEQ ID NO:4 and a variable light chain domain of SEQ ID NO:5;
(iv) a variable heavy chain domain of SEQ ID NO:6 and a variable light chain domain of SEQ ID NO:7;
(v) a variable heavy chain domain of SEQ ID NO:8 and a variable light chain domain of SEQ ID NO:5;
(vi) a variable heavy chain domain of SEQ ID NO:9 and a variable light chain domain of SEQ ID NO: 10; and
(vii) a variable heavy chain domain of SEQ ID NO:6 and a variable light chain domain of SEQ ID NO: 5.

2. The humanized or chimeric antibody or fragment of claim 1 , wherein the antibody or fragment is glycosylated with terminal mannose, N-acetylglucose or glucose, but no fucose.

3. A pharmaceutical composition comprising the humanized or chimeric antibody or fragment thereof of claim 1 , and further comprising a pharmaceutically acceptable carrier or diluent.

4. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment is conjugated to a cytotoxic agent.

5. A bispecific antibody having first and second antigen binding sites, one of which comprises antigen binding sequences of a light chain and a heavy chain of a humanized 3F8 antibody.

6. The bispecific antibody of claim 5 wherein the second antigen binding site is selected from the group consisting of scFv, scFab, Fab, and Fv.

7. The bispecific antibody of claim 5 wherein the second antigen binding site is associated with an immunological cell chosen from the group consisting of T-lymphocytes, NK cell, B-lymphocytes, dendritic cells, monocytes, macrophages, neutrophils, mesenchymal stem cells, and neural stem cells.

8. The bispecific antibody of claim 5 wherein the second antigen binding site is specific for CD3 or for a DOTA (metal).

9. The bispecific antibody of claim 6 , further comprising a peptide of SEQ ID NO:23 that includes the second antigen binding site.

10. The bispecific antibody of claim 6 , further comprising a peptide of SEQ ID NO:24 that includes the second antigen binding site.

11. A pharmaceutical composition comprising the bispecific antibody of claim 5 , and further comprising a pharmaceutically acceptable carrier or diluent.

12. A chimeric antigen receptor comprising an antigen binding domain of a humanized or chimeric antibody or fragment of claim 1 .

13. The chimeric antigen receptor of claim 12 , wherein the antigen binding domain is a scFv.

14. The chimeric antigen receptor of claim 13 , expressed by an immune effector cell.

15. A bispecific T-cell engaging monoclonal antibody comprising a first binding site comprising scFv from hu3F8 monoclonal antibody, and a second binding site binding to a T-cell.

16. A pharmaceutical composition comprising the antibody or fragment thereof of claim 2 , and further comprising a pharmaceutically acceptable carrier or diluent.

17. A pharmaceutical composition comprising the bispecific antibody of claim 6 , and further comprising a pharmaceutically acceptable carrier or diluent.

18. A pharmaceutical composition comprising the bispecific antibody of claim 7 , and further comprising a pharmaceutically acceptable carrier or diluent.

19. A pharmaceutical composition comprising the bispecific antibody of claim 8 , and further comprising a pharmaceutically acceptable carrier or diluent.

20. A pharmaceutical composition comprising the bispecific antibody of claim 9 , and further comprising a pharmaceutically acceptable carrier or diluent.

21. A pharmaceutical composition comprising the bispecific antibody of claim 10 , and further comprising a pharmaceutically acceptable carrier or diluent.

22. A pharmaceutical composition comprising the antibody or fragment thereof of claim 4 , and further comprising a pharmaceutically acceptable carrier or diluent.

23. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO: 1 and a variable light chain domain of SEQ ID NO:2.

24. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:3 and a variable light chain domain of SEQ ID NO:2.

25. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:4 and a variable light chain domain of SEQ ID NO:5.

26. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:6 and a variable light chain domain of SEQ ID NO:7.

27. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:8 and a variable light chain domain of SEQ ID NO:5.

28. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:9 and a variable light chain domain of SEQ ID NO: 10.

29. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the antibody or fragment comprises a variable heavy chain domain of SEQ ID NO:6 and a variable light chain domain of SEQ ID NO: 5.

30. The humanized or chimeric antibody or fragment thereof of claim 1 , wherein the humanized or chimeric antibody comprises a variant Fc region.

31. The humanized or chimeric antibody or fragment thereof of claim 30 , wherein the variant Fc region comprises a substitution of S239D, A330L and 1332E.

32. The humanized or chimeric antibody or fragment thereof of claim 30 , wherein the variant Fc region comprises a N297A substitution.

33. The humanized or chimeric antibody or fragment thereof of claim 2 , wherein the humanized or chimeric antibody comprises a variant Fc region.

34. The humanized or chimeric antibody or fragment thereof of claim 33 , wherein the variant Fc region comprises a substitution of S239D, A330L and 1332E.

35. The humanized or chimeric antibody or fragment thereof of claim 33 , wherein the variant Fc region comprises a N297A substitution.

Assignees

• Cheung Nai-Kong
• Ahmed Mahiuddin
• Xu Hong
• Sloan Kettering Inst Cancer

Inventors

• Cheung Nai-Kong
• Ahmed Mahiuddin
• Xu Hong

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

• C07K2317/72

  Increased effector function due to an Fc-modification · CPC title

• C07K16/28

  against receptors, cell surface antigens or cell surface determinants · CPC title

• A61K48/00

  Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy · CPC title