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US 2020/0369758 A1Published application
Bispecific antigen binding proteins
AssigneeHoffmann-La Roche Inc.
InventorsSabine IMHOF-JUNG, Christian KLEIN, Joerg Thomas REGULA, Wolfgang SCHAEFER, Juergen Michael SCHANZER
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Abstract
The present invention relates to bispecific antigen binding proteins, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.
Claims10
1-10. (canceled)
11:
- A bispecific antigen binding protein, comprising:
- a) two light chains and two heavy chains of an antibody that comprises two Fab fragments and that specifically binds to a first antigen;
- and
- b) two additional Fab fragments of an antibody which specifically binds to a second antigen, wherein the additional Fab fragments are each fused at the C- or N-termini of the heavy chains of a);
- wherein the bispecific antigen binding protein also comprises a structural modification selected from the group consisting of:
- i) in both Fab fragments of a) or in both Fab fragments of b)
- the variable domains VL and VH are replaced by each other and the constant domains CL and CH1 are replaced by each other, or the constant domains CL and CH1 are replaced by each other;
- ii) in both Fab fragments of a)
- the variable domains VL and VH are replaced by each other, and
- the constant domains CL and CH1 are replaced by each other, and in both Fab fragments of b)
- the variable domains VL and VH are replaced by each other, or
- the constant domains CL and CH1 are replaced by each other;
- iii) in both Fab fragments of a)
- the variable domains VL and VH are replaced by each other, or
- the constant domains CL and CH1 are replaced by each other, and in both Fab fragments of b)
- the variable domains VL and VH are replaced by each other, and
- the constant domains CL and CH1 are replaced by each other;
- iv) in both Fab fragments of a)
- the variable domains VL and VH are replaced by each other, and
- in both Fab fragments of b)
- the constant domains CL and CH1 are replaced by each other;
- and
- v) in both Fab fragments of a)
- the constant domains CL and CH1 are replaced by each other, and in both Fab fragments of b) the variable domains VL and VH are replaced by each other.
21 more elements
12:
- The bispecific antigen binding protein according to claim 11, wherein in both Fab fragments of a) or in both Fab fragments of b) the variable domains VL and VH are replaced by each other and the constant domains CL and CH1 are replaced by each other.
13:
- The bispecific antigen binding protein according to claim 11, wherein in both Fab fragments of b) the variable domains VL and VH are replaced by each other and the constant domains CL and CH1 are replaced by each other.
14:
- The bispecific antigen binding protein according to claim 13, wherein each Fab fragment of b) is fused at the N-terminus of each of the heavy chains in a).
15:
- The bispecific antigen binding protein according to claim 14, wherein the CL of each Fab fragment of b) is fused to the VH of each of the heavy chains in a).
16:
- The bispecific antigen binding protein according to claim 13, wherein the antibody in a) is a full length antibody.
17:
- The bispecific antigen binding protein according to claim 14, wherein the antibody in a) is a full length antibody.
18:
- The bispecific antigen binding protein according to claim 15 comprising a heavy chain comprising in N to C terminal direction VL-CL-VH-CH1-CH2-CH3, comprising a light chain comprising in N to C terminal direction VH-CH, and comprising a light chain comprising in N to C terminal direction VL-CL.
19:
- A pharmaceutical composition comprising the bispecific antigen binding protein according to claim 13 and at least one pharmaceutically acceptable excipient.