BIVALENT, BISPECIFIC ANTIBODIES

• US 20090175851A1
• Filed: 12/11/2008
• Published: 07/09/2009
• Est. Priority Date: 12/21/2007
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Klein, Christian, Schaefer, Wolfgang
• Granted Patent: US 8,227,577 B2
• Time in Patent Office: Days
• US Class Current: 424/130.100
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 2317/31 multispecific
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/526 CH3 domain
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present invention relates to novel domain exchanged, bivalent, bispecific antibodies, their manufacture and use.

Claims

1. A bivalent, bispecific antibody, comprising:

a) the light chain and heavy chain of an antibody specifically binding to a first antigen, wherein heavy chain domain CH3 of the antibody specifically binding to a first antigen is replaced by a constant heavy chain domain CH1;

b) the light chain and heavy chain of an antibody specifically binding to a second antigen, wherein constant heavy chain domain CH3 of the antibody specifically binding to a second antigen is replaced by a constant light chain domain CL.

2. The antibody according to claim 1, wherein

the light chain and heavy chain of either of the first antibody specifically binding to a first antigen or said second antibody specifically binding the second antigen is altered by one or both of (1) the replacement of the variable domains VL and VH by each other and (2) the replacement of the variable domains CL and CH1 by each other.

3. A method for the preparation of an a bivalent, bispecific antibody according to claim 1 comprising the steps of

a) transforming a host cell with

vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a first antigen,

 

wherein heavy chain domain CH3 of the antibody specifically binding to a first antigen is replaced by a constant heavy chain domain CH1; and

vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a second antigen,

 

wherein constant heavy chain domain CH3 of the antibody specifically binding to a second antigen is replaced by a constant light chain domain CL;

b) culturing the host cell under conditions that allow synthesis of said antibody molecule; and

c) recovering said antibody molecule from said culture.

5. A composition comprising a bivalent, bispecific antibody according to claim 1 and at least one pharmaceutically acceptable excipient.

6. A composition comprising a bivalent, bispecific antibody according to claim 2 and at least one pharmaceutically acceptable excipient.

7. A method for the treatment of a patient in need of therapy, characterized by administering to the patient a therapeutically effective amount of a bivalent, bispecific antibody according to claim 1.

8. A method for the treatment of a patient in need of therapy, characterized by administering to the patient a therapeutically effective amount of a bivalent, bispecific antibody according to claim 2.

4. A host cell comprising:

vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a first antigen,

wherein the heavy chain domain CH3 of the antibody specifically binding to a first antigen is replaced by a constant heavy chain domain CH1; and

vectors comprising nucleic acid molecules encoding the light chain and heavy chain of an antibody specifically binding to a second antigen,

wherein the constant heavy chain domain CH3 of the antibody specifically binding to a second antigen is replaced by a constant light chain domain CL.