BISPECIFIC ANTIBODIES WITH TETRAVALENCY FOR A COSTIMULATORY TNF RECEPTOR
First Claim
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1. A bispecific antigen binding molecule, comprising(a) four moities capable of specific binding to a costimulatory TNF receptor family member,(b) at least one moiety capable of specific binding to a target cell antigen, and(c) a Fc domain composed of a first and a second subunit capable of stable association.
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Abstract
The invention relates to novel bispecific antigen binding molecules, comprising (a) four moieties capable of specific binding to a costimulatory TNF receptor family member, (b) at least one moiety capable of specific binding to a target cell antigen, and (c) a Fc domain composed of a first and a second subunit capable of stable association, and to methods of producing these molecules and to methods of using the same.
36 Citations
41 Claims
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1. A bispecific antigen binding molecule, comprising
(a) four moities capable of specific binding to a costimulatory TNF receptor family member, (b) at least one moiety capable of specific binding to a target cell antigen, and (c) a Fc domain composed of a first and a second subunit capable of stable association.
- 10. The bispecific antigen binding molecule of claim 10, wherein the target cell antigen is Fibroblast Activation Protein (FAP).
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15. The bispecific antigen binding molecule of 13, comprising four moities capable of specific binding to 4-1BB, wherein each of said moities comprises a VH domain comprising
(i) a CDR-H1 comprising the amino acid sequence selected from the group consisting of SEQ ID NO: - 249 and SEQ ID NO;
250,(ii) a CDR-H2 comprising the amino acid sequence selected from the group consisting of SEQ ID NO;
251 and SEQ ID NO;
252, and(iii) a CDR-H3 comprising the amino acid sequence selected from the group consisting of SEQ ID NO;
253, SEQ ID NO;
254, SEQ ID NO;
255, SEQ ID NO;
256, and SEQ ID NO;
257,and a VL domain comprising (iv) a CDR-L1 comprising the amino acid sequence selected from the group consisting of SEQ ID NO;
258 and SEQ ID NO;
259,(v) a CDR-L2 comprising the amino acid sequence selected from the group consisting of SEQ ID NO;
260 and SEQ ID NO;
261, and(vi) a CDR-L3 comprising the amino acid sequence selected from the group consisting of SEQ ID NO;
262, SEQ ID NO;
263, SEQ ID NO;
264, SEQ ID NO;
265, and SEQ ID NO;
266.
- 249 and SEQ ID NO;
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16. The bispecific antigen binding molecule of 13, wherein each of the moieties capable of specific binding to 4-1BB comprises a heavy chain variable region VH comprising an amino acid sequence that is at least about 95%, 96%, 97%, 98%, 99% or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:
- 267, SEQ ID NO;
269, SEQ ID NO;
271, SEQ ID NO;
273, and SEQ ID NO;
275, and a light chain variable region VL comprising an amino acid sequence that is at least about 95%, 96%, 97%, 98%, 99% or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NO;
268, SEQ ID NO;
270, SEQ ID NO;
272, SEQ ID NO;
274, and SEQ ID NO;
276.
- 267, SEQ ID NO;
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17. The bispecific antigen binding molecule 13, wherein each of the moities capable of specific binding to 4-1BB comprises
(i) a heavy chain variable region VH comprising an amino acid sequence of SEQ ID NO: - 267 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
268,(ii) a heavy chain variable region VH comprising an amino acid sequence of SEQ ID NO;
269 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
270,(iii) a heavy chain variable region VH comprising an amino acid sequence of SEQ ID NO;
271 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
272,(iv) a heavy chain variable region VH comprising an amino acid sequence of SEQ ID NO;
273 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
274, or(v) a heavy chain variable region VH comprising an amino acid sequence of SEQ ID NO;
275 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
276.
- 267 and a light chain variable region VL comprising an amino acid sequence of SEQ ID NO;
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37. (canceled)
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38. (canceled)
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39. (canceled)
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40. (canceled)
Specification