Bispecific antigen binding molecules capable of specific binding to CD40 and to fap

Patent metadata

Field	Value
Publication number	US-12145994-B2
Application number	US-202117179223-A
Country	US
Kind code	B2
Filing date	Feb 18, 2021
Priority date	Apr 4, 2017
Publication date	Nov 19, 2024
Grant date	Nov 19, 2024

Abstract

The invention relates to novel bispecific antigen binding molecules, 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 a target cell antigen, in particular Fibroblast Activation Protein (FAP), 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) (i) at least one antigen binding domain capable of specific binding to CD40, comprising a heavy chain variable region (VH-CD40) comprising the amino acid sequence of SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173, SEQ ID NO: 174, SEQ ID NO:179, SEQ ID NO:180, SEQ ID NO: 181, SEQ ID NO:182, SEQ ID NO: 183 or SEQ ID NO: 184,
and a light chain variable region (VL-CD40) comprising the amino acid sequence of SEQ ID NO: 175, SEQ ID NO:176, SEQ ID NO:177, SEQ ID NO: 178, SEQ ID NO:185, SEQ ID NO:186, SEQ ID NO: 187 or SEQ ID NO:188; or
(ii) a heavy chain variable region (VH-CD40) comprising the amino acid sequence of SEQ ID NO: 179, SEQ ID NO:180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO:183 or SEQ ID NO:184, and
a light chain variable region (VL-CD40) comprising the amino acid sequence of SEQ ID NO: 185, SEQ ID NO:186, SEQ ID NO: 187 or, SEQ ID NO: 188, and
(b) at least one antigen binding domain capable of specific binding to Fibroblast Activation Protein (FAP) comprising a heavy chain variable region (VH-FAP) comprising the amino acid sequence of SEQ ID NO:9 and a light chain variable region (VL-FAP) comprising the amino acid sequence of SEQ ID NO: 10, or a heavy chain variable region (VH-FAP) comprising the amino acid sequence of SEQ ID NO:17 and a light chain variable region (VL-FAP) comprising the amino acid sequence of SEQ ID NO:18; and
(c) an Fc region composed of a first and a second subunit capable of stable association.

2. 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 (VH-CD40) comprising the amino acid sequence of SEQ ID NO:171, SEQ ID NO:172, SEQ ID NO:173 or SEQ ID NO:174, and
(ii) a light chain variable region (VL-CD40) comprising the amino acid sequence of SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, or SEQ ID NO: 178.

3. 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 (VH-CD40) comprising the amino acid sequence of SEQ ID NO: 179, SEQ ID NO:180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183 or SEQ ID NO:184, and
(ii) a light chain variable region (VL-CD40) comprising the amino acid sequence of SEQ ID NO: 185, SEQ ID NO:186, SEQ ID NO: 187 or, SEQ ID NO: 188.

4. The bispecific antigen binding molecule of claim 2 , wherein the antigen binding domain capable of specific binding to CD40 comprises:
(a) a VH comprising the amino acid sequence of SEQ ID NO:171 and a VL comprising the amino acid sequence of SEQ ID NO:175, or
(b) a VH comprising the amino acid sequence of SEQ ID NO:173 and a VL comprising the amino acid sequence of SEQ ID NO:177, or
(c) a VH comprising the amino acid sequence of SEQ ID NO: 174 and a VL comprising the amino acid sequence of SEQ ID NO:178, or
(d) a VH comprising the amino acid sequence of SEQ ID NO:171 and a VL comprising the amino acid sequence of SEQ ID NO:177, or
(e) a VH comprising the amino acid sequence of SEQ ID NO:171 and a VL comprising the amino acid sequence of SEQ ID NO: 178, or
(f) a VH comprising the amino acid sequence of SEQ ID NO:173 and a VL comprising the amino acid sequence of SEQ ID NO:175, or
(g) a VH comprising the amino acid sequence of SEQ ID NO:173 and a VL comprising the amino acid sequence of SEQ ID NO:178, or
(h) a VH comprising the amino acid sequence of SEQ ID NO:174 and a VL comprising the amino acid sequence of SEQ ID NO:175, or
(i) a VH comprising the amino acid sequence of SEQ ID NO:174 and a VL comprising the amino acid sequence of SEQ ID NO: 177, or
(j) a VH comprising the amino acid sequence of SEQ ID NO:171 and a VL comprising the amino acid sequence of SEQ ID NO:176, or
(k) a VH comprising the amino acid sequence of SEQ ID NO:172 and a VL comprising the amino acid sequence of SEQ ID NO: 175, or
(l) a VH comprising the amino acid sequence of SEQ ID NO:172 and a VL comprising the amino acid sequence of SEQ ID NO:176, or
(m) a VH comprising the amino acid sequence of SEQ ID NO:172 and a VL comprising the amino acid sequence of SEQ ID NO:177, or
(n) a VH comprising the amino acid sequence of SEQ ID NO: 172 and a VL comprising the amino acid sequence of SEQ ID NO: 178, or
(o) a VH comprising the amino acid sequence of SEQ ID NO: 173 and a VL comprising the amino acid sequence of SEQ ID NO:176, or
(p) a VH comprising the amino acid sequence of SEQ ID NO:174 and a VL comprising the amino acid sequence of SEQ ID NO:176.

5. The bispecific antigen binding molecule of claim 4 , wherein the antigen binding domain capable of specific binding to CD40 comprises a VH comprising the amino acid sequence of SEQ ID NO:171 and a VL comprising the amino acid sequence of SEQ ID NO: 175.

6. The bispecific antigen binding molecule of claim 3 , wherein the antigen binding domain capable of specific binding to CD40 comprises:
(a) a VH comprising the amino acid sequence of SEQ ID NO:179 and a VL comprising the amino acid sequence of SEQ ID NO:185, or
(b) a VH comprising the amino acid sequence of SEQ ID NO: 180 and a VL comprising the amino acid sequence of SEQ ID NO: 185, or
(c) a VH comprising the amino acid sequence of SEQ ID NO: 181 and a VL comprising the amino acid sequence of SEQ ID NO:185, or
(d) a VH comprising the amino acid sequence of SEQ ID NO:182 and a VL comprising the amino acid sequence of SEQ ID NO:185, or
(e) a VH comprising the amino acid sequence of SEQ ID NO:179 and a VL comprising the amino acid sequence of SEQ ID NO:186, or
(f) a VH comprising the amino acid sequence of SEQ ID NO:180 and a VL comprising the amino acid sequence of SEQ ID NO:186, or
(g) a VH comprising the amino acid sequence of SEQ ID NO:181 and a VL comprising the amino acid sequence of SEQ ID NO:186, or
(h) a VH comprising the amino acid sequence of SEQ ID NO:182 and a VL comprising the amino acid sequence of SEQ ID NO: 186, or
(i) a VH comprising the amino acid sequence of SEQ ID NO: 183 and a VL comprising the amino acid sequence of SEQ ID NO:187, or
(j) a VH comprising the amino acid sequence of SEQ ID NO:183 and a VL comprising the amino acid sequence of SEQ ID NO:188, or
(k) a VH comprising the amino acid sequence of SEQ ID NO:184 and a VL comprising the amino acid sequence of SEQ ID NO:187, or
(l) a VH comprising the amino acid sequence of SEQ ID NO:184 and a VL comprising the amino acid sequence of SEQ ID NO:188.

7. The bispecific antigen binding molecule of claim 6 , wherein the antigen binding domain capable of specific binding to CD40 comprises a VH comprising the amino acid sequence of SEQ ID NO:179 and a VL comprising the amino acid sequence of SEQ ID NO:185 or wherein the antigen binding domain capable of specific binding to CD40 comprises a VH comprising the amino acid sequence of SEQ ID NO:182 and a VL comprising the amino acid sequence of SEQ ID NO:185.

8. The bispecific antigen binding molecule of claim 1 , comprising:
(i) at least one antigen binding domain capable of specific binding to CD40, comprising a heavy chain variable region (VH-CD40) comprising the amino acid sequence of SEQ ID NO:171 and a light chain variable region (VL-CD40) comprising the amino acid sequence of SEQ ID NO: 175, and
(ii) at least one antigen binding domain capable of specific binding to FAP, comprising a heavy chain variable region (VH-FAP) comprising the amino acid sequence of SEQ ID NO:17 and a light chain variable region (VL-FAP) comprising the amino acid sequence of SEQ ID NO: 18.

9. The bispecific antigen binding molecule of claim 1 , wherein the Fc region is an IgG1 Fc region or an IgG4 Fc region and wherein the Fc region com

Assignees

• Hoffmann La Roche

Inventors

• Bruenker Peter
• Bujotzek Alexander
• Duerr Harald
• Georges Guy
• Klein Christian
• Leclair Stephane
• Rapp Moritz
• Sum Eva Carina
• Trumpfheller Christine
• Umaña Pablo

Classifications

• C07K2317/569

  Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61P35/00 Primary

  Antineoplastic agents · CPC title