Bispecific antigen binding molecules comprising anti-FAP clone 212

Patent metadata

Field	Value
Publication number	US-11242396-B2
Application number	US-201916588780-A
Country	US
Kind code	B2
Filing date	Sep 30, 2019
Priority date	Oct 1, 2018
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

The invention relates to novel bispecific antigen binding molecules, comprising (a) at least one antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP) comprising FAP clone 212 or variants thereof, and (b) at least one antigen binding domain capable of specific binding to CD40, and to methods of producing these molecules and to methods of using the same.

First claim

The invention claimed is:

1. A bispecific antigen binding molecule, comprising
(a) at least one antigen binding domain capable of specific binding to CD40, and
(b) at least one antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP) comprising a heavy chain variable region (VHFAP) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:3, (ii) CDR-H2 comprising the amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:11 and SEQ ID NO:12, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:5, and a light chain variable region (V L FAP) comprising (iv) CDR-L1 comprising the amino acid sequence selected from the group consisting of SEQ ID NO:6, SEQ ID NO:13 and SEQ ID NO:14, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:7, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:8.

2. The bispecific antigen binding molecule of claim 1 , additionally comprising (c) a Fc region composed of a first and a second subunit capable of stable association.

3. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to FAP comprises a heavy chain variable region (V H FAP) comprising an amino acid sequence that is at least about 90% identical to the amino acid sequence of SEQ ID NO:9, and a light chain variable region (V L FAP) comprising an amino acid sequence that is at least about 90% identical to the amino acid sequence of SEQ ID NO:10.

4. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to FAP comprises a heavy chain variable region (V H FAP) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:20, and
a light chain variable region (V L FAP) comprising an amino acid sequence selected from the group consisting of SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26.

5. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to FAP comprises
(a) a heavy chain variable region (V H FAP) comprising the amino acid sequence of SEQ ID NO:15 and a light chain variable region (V L FAP) comprising the amino acid sequence of SEQ ID NO:21,
(b) a heavy chain variable region (V H FAP) comprising the amino acid sequence of SEQ ID NO:16 and a light chain variable region (V L FAP) comprising the amino acid sequence of SEQ ID NO:21,
(c) a heavy chain variable region (V H FAP) comprising the amino acid sequence of SEQ ID NO:16 and a light chain variable region (V L FAP) comprising the amino acid sequence of SEQ ID NO:22, or
(d) a heavy chain variable region (V H FAP) comprising the amino acid sequence of SEQ ID NO:19 and a light chain variable region (V L FAP) comprising the amino acid sequence of SEQ ID NO:25.

6. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises a heavy chain variable region (V H CD40) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:27, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:28, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:29, and a light chain variable region (V L CD40) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:30, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:31, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:32.

7. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises
(i) a heavy chain variable region (V H CD40) comprising the amino acid sequence selected from the group consisting of SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39 and SEQ ID NO:40, and
(ii) a light chain variable region (V L CD40) comprising the amino acid sequence selected from the group consisting of SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44.

8. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises
(i) a heavy chain variable region (V H CD40) comprising the amino acid sequence selected from the group consisting of SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49 and SEQ ID NO:50, and
(ii) a light chain variable region (V L CD40) comprising the amino acid sequence selected from the group consisting of SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, and SEQ ID NO:54.

9. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises
(a) a VH comprising the amino acid sequence of SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:41, or
(b) a VH comprising the amino acid sequence of SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:42, or
(c) a VH comprising the amino acid sequence of SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:43, or
(d) a VH comprising the amino acid sequence of SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:44, or
(e) a VH comprising the amino acid sequence of SEQ ID NO:38 and a VL comprising the amino acid sequence of SEQ ID NO:41, or
(f) a VH comprising the amino acid sequence of SEQ ID NO:38 and a VL comprising the amino acid sequence of SEQ ID NO:42, or
(g) a VH comprising the amino acid sequence of SEQ ID NO:38 and a VL comprising the amino acid sequence of SEQ ID NO:43, or
(h) a VH comprising the amino acid sequence of SEQ ID NO:38 and a VL comprising the amino acid sequence of SEQ ID NO:44, or
(i) a VH comprising the amino acid sequence of SEQ ID NO:39 and a VL comprising the amino acid sequence of SEQ ID NO:41, or
(j) a VH comprising the amino acid sequence of SEQ ID NO:39 and a VL comprising the amino acid sequence of SEQ ID NO:42, or
(k) a VH comprising the amino acid sequence of SEQ ID NO:39 and a VL comprising the amino acid sequence of SEQ ID NO:43, or
(l) a VH comprising the amino acid sequence of SEQ ID NO:39 and a VL comprising the amino acid sequence of SEQ ID NO:44, or
(m) a VH comprising the amino acid sequence of SEQ ID NO:40 and a VL comprising the amino acid sequence of SEQ ID NO:41, or
(n) a VH comprising the amino acid sequence of SEQ ID NO:40 and a VL comprising the amino acid sequence of SEQ ID NO:42, or
(o) a VH comprising the amino acid sequence of SEQ ID NO:40 and a VL comprising the amino acid sequence of SEQ ID NO:43, or
(p) a VH comprising the amino acid sequence of SEQ ID NO:40 and a VL comprising the amino acid sequence of SEQ ID NO:44.

10. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises a VH comprising the amino acid sequence of SEQ ID NO:37 and a VL comprising the amino acid sequence of SEQ ID NO:41.

11. The bispecific antigen binding molecule of claim 1 , wherein the antigen binding domain capable of specific binding to CD40 comprises
(a) a VH comprising the amino acid sequence of SEQ ID NO:45 and a VL comprising the amino acid sequence of SEQ ID NO:51, or
(b) a VH comprising the amino acid sequence of SEQ ID NO:46 and a VL comprising the amino acid sequence of SEQ ID NO:51, or
(c) a VH comprising the amino acid sequence of SEQ ID NO:47 and a VL comprising the amino acid sequence of SEQ ID NO:51, or
(d) a VH comprising the amino acid sequence of SEQ ID NO:48 and a VL comprising the amino acid sequence of SEQ ID NO:51, or
(e) a VH comprising the amino acid sequence of SEQ ID NO:45 an

Assignees

• Hoffmann La Roche

Inventors

• Bruenker Peter
• Duerr Harald
• Klein Christian
• Umana Pablo
• Bujotzek Alexander
• Zielonka Joerg
• Trumpfheller Christine
• Rapp Moritz
• Le Clech Marine

Classifications

• C07K2317/31

  multispecific · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/40

  against enzymes · CPC title

• C07K2317/526

  CH3 domain · CPC title