BISPECIFIC ANTIBODIES SPECIFIC FOR T-CELL ACTIVATING ANTIGENS AND A TUMOR ANTIGEN AND METHODS OF USE

• US 20150274845A1
• Filed: 05/05/2014
• Published: 10/01/2015
• Est. Priority Date: 08/23/2011
• Status: Active Grant

• Current Assignee: Roche Glycart AG (Roche Holding AG)
• Original Assignee: Roche Glycart AG (Roche Holding AG)
• Inventors: Bruenker, Peter, Fauti, Tanja, Jaeger, Christiane, Klein, Christian, Umana, Pablo
• Granted Patent: US 11,639,397 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3053 Skin, nerves, brain
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/66 comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1

Abstract

The present invention relates to bispecific antibodies that specifically bind a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and wherein the bispecific antibody does not comprise a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

Claims

1. A bispecific antibody that specifically binds a T-cell activating antigen and a Tumor Antigen (TA), comprising a first Fab fragment and a second Fab fragment, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged;

and wherein the bispecific antibody does not comprise a Fc domain.

2. The bispecific antibody of claim 1, wherein the first fragment comprises at least one antigen binding site specific for a Tumor Antigen;

and the second Fab fragment comprises at least one antigen binding site specific for a T-cell activating antigen.

3. The bispecific antibody of claim 1, wherein the T-cell activating antigen is a CD3 T-Cell Co-Receptor (CD3) antigen.

4. The bispecific antibody of claim 1, wherein the N-terminus of the second Fab fragment is connected to the C-terminus of the first Fab fragment.

5. The bispecific antibody of claim 1, additionally comprising a third Fab fragment.

6. The bispecific antibody of claim 5, wherein the third Fab fragment comprises at least one antigen binding site specific for a Tumor Antigen.

7. The bispecific antibody of claim 5, wherein the third Fab fragment is connected to the first Fab fragment.

8. The bispecific antibody of claim 7, wherein the C-terminus of the third Fab fragment is connected to the N-terminus of the first Fab fragment.

9. The bispecific antibody of claim 5, wherein the third Fab fragment is connected to the second Fab fragment.

10. The bispecific antibody of claim 9, wherein the N-terminus of the third Fab fragment is connected to the C-terminus of the second Fab fragment.

11. The bispecific antibody of claim 1 or claim 5, wherein the Fab fragments are connected via a peptide linker.

12. The bispecific antibody of claim 11, wherein the peptide linker is a (G4S)2 linker.

13. The bispecific antibody of any of claim 1 or claim 5, wherein the Tumor Antigen is selected from the group consisting of Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP), Epidermal Growth Factor Receptor (EGFR), Carcinoembryonic Antigen (CEA), Fibroblast Activation Protein (FAP) and CD33.

14. The bispecific antibody of claim 13, wherein the Tumor Antigen is MCSP.

15. A pharmaceutical composition comprising the bispecific antibody of claim 1 or claim 5.

18. A method of treating cancer comprising administering to a patient in need thereof an effective amount of the bispecific antibody of claim 1 or claim 5.

20. A prokaryotic or eukaryotic host cell comprising vectors comprising nucleic acid molecules encoding the light chains and heavy chains of the bispecific antibody of claim 1 or claim 5.

21. A method of producing an antibody comprising culturing the host cell of claim 20 so that the antibody is produced.

16. (canceled)

17. (canceled)

19. (canceled)