MULTISPECIFIC ANTIBODIES COMPRISING FULL LENGTH ANTIBODIES AND SINGLE CHAIN FAB FRAGMENTS

• US 20100256338A1
• Filed: 03/31/2010
• Published: 10/07/2010
• Est. Priority Date: 04/02/2009
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Roche Glycart AG (Roche Holding AG)
• Inventors: Stracke, Jan Olaf, Schanzer, Juergen Michael, Croasdale, Rebecca, Umana, Pabio, Bruenker, Peter, Kopetzki, Erhard, Klein, Christian, Brinkmann, Ulrich, Moessner, Ekkehard, Regula, Joerg Thomas
• Granted Patent: US 9,382,323 B2
• Time in Patent Office: Days
• US Class Current: 530/387.300
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present invention relates to multispecific, especially bispecific antibodies comprising full length antibodies and single chain Fab fragments, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof.

Claims

1. A multispecific antibody comprising

a) a full length antibody consisting of two antibody heavy chains and two antibody light chains wherein the antibody specifically binds to a first antigen;

and

b) one or more single chain Fab fragments that specifically bind to one or more antigens different from the first antigen,

wherein each of the one or more single chain Fab fragments is fused to the full length antibody via a peptide connector at the C- or N-terminus of the heavy or light chain of the full length antibody.

2. The multispecific antibody according to claim 1, comprising one to four single chain Fab fragments that specifically bind to one to four antigens different from the first antigen,

wherein each of the one to four single chain Fab fragments is fused to the full length antibody via a peptide connector at the C- or N-terminus of the heavy or light chain of the full length antibody.

3. The multispecific antibody according to claim 2, wherein one or two single chain Fab fragments that specifically bind to a second antigen are each fused to the full length antibody via a peptide connector at the C-terminus of the heavy chains of the full length antibody.

4. The multispecific antibody according to claim 3, wherein one single chain Fab fragment that specifically binds to a second antigen is fused to the full length antibody via a peptide connector at the C-terminus of one heavy chain or one light chain of the full length antibody.

5. The multispecific antibody according to claim 2, wherein two identical single chain Fab fragments VL-CL-linker-VH-CH1 or VH-CH1-linker-VL-CL that specifically bind to a second antigen are fused at their N-termini to the full length antibody via a peptide connector at the two C-termini of the two heavy chains or at the two C-termini of the two light chains of the full length antibody.

6. The multispecific antibody according to claim 2, wherein two identical single chain Fab fragments VL-CL-linker-VH-CH1 or VH-CH1-linker-VL-CL that specifically bind to a second antigen are fused at their C-termini to the full length antibody via a peptide connector at the two N-termini of the two heavy chains or at the two N-termini the two light chains of the full length antibody.

7. A pharmaceutical composition comprising an antibody according to claim 1.

8. A pharmaceutical composition comprising an antibody according to claim 3.

9. A pharmaceutical composition comprising an antibody according to claim 4.

10. A pharmaceutical composition comprising an antibody according to claim 5.

11. A pharmaceutical composition comprising an antibody according to claim 6.

12. A nucleic acid encoding a multispecific antibody according to claim 1.