Fc-free antibodies comprising two Fab-fragments and methods of use

Patent metadata

Field	Value
Publication number	US-2016130347-A1
Application number	US-201314434168-A
Country	US
Kind code	A1
Filing date	Oct 3, 2013
Priority date	Oct 8, 2012
Publication date	May 12, 2016
Grant date	—

Abstract

The present invention relates to bispecific antibodies comprising at least two Fab fragments, wherein the first Fab fragment comprises at least one antigen binding site specific for a first antigen; and the second Fab fragment comprises at least one antigen binding site specific for a second antigen, wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged and the two Fab fragments are connected to each other by two peptide linkers; and wherein the bispecific antibody is devoid of a Fc domain; methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

First claim

1 . A bispecific antibody comprising at least two Fab fragments, wherein
the first Fab fragment comprises at least one antigen binding site specific for a first antigen; and the second Fab fragment comprises at least one antigen binding site specific for a second antigen wherein either the variable regions or the constant regions of the second Fab heavy and light chain are exchanged; and the two Fab fragments are connected to each other by two peptide linkers and wherein the bispecific antibody is devoid of a Fc domain.

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

3 . The bispecific antibody of claim 2 , wherein the third Fab fragment comprises at least one antigen binding site specific for the first or second antigen.

4 . The bispecific antibody of claim 3 , wherein the third Fab fragment comprises at least one antigen binding site specific for the first antigen.

5 . The bispecific antibody of any of claims 2 to 4 , wherein the third Fab fragment is connected to the first Fab fragment by one or two peptide linkers.

6 . The bispecific antibody of claims 2 to 4 , wherein the third Fab fragment is connected to the second Fab fragment by one or two peptide linkers.

7 . The bispecific antibody of any of claims 1 to 6 , wherein the first Fab 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.

8 . The bispecific antibody of claim 7 , wherein the T-cell activating antigen is a CD3 T-Cell Co-Receptor (CD3) antigen.

9 . The bispecific antibody of any of claim 7 or 8 , wherein the Tumor Antigen is selected from the group of Melanoma-associated Chondroitin Sulfate Proteoglycan (MCSP), Epidermal Growth Factor Receptor (EGFR), Carcinoembryonic Antigen (CEA), Fibroblast Activation Protein (FAP) and CD33.

10 . The bispecific antibody of claim 9 , wherein the Tumor Antigen is MCSP.

11 . A pharmaceutical composition comprising a bispecific antibody of claims 1 to 10 .

12 . The bispecific antibody of claims 1 to 10 for the treatment of cancer.

13 . The bispecific antibody of claims 1 to 10 for use as a medicament.

14 . Use of the bispecific antibody of claims 1 to 10 in the manufacture of a medicament.

15 . The use of claim 14 , wherein the medicament is for treatment of cancer.

16 . A prokaryotic or eukaryotic host cell comprising vectors comprising nucleic acid molecules encoding the light chains and heavy chains of the bispecific antibody of any of claims 1 to 10 .

17 . A method of producing an antibody comprising culturing the host cell of claim 16 so that the antibody is produced.

18 . The invention as described herein, especially with reference to the foregoing examples.

Assignees

• Roche Glycart Ag

Inventors

• Bruenker Peter
• Fauti Tanja
• Jaeger Christiane
• Klein Christian
• Umaña Pablo

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• C07K16/468

  Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title

• A61K2039/505

  comprising antibodies · CPC title