Antibodies specific for DR5 and methods of use

Patent metadata

Field	Value
Publication number	US-11214622-B2
Application number	US-201815913713-A
Country	US
Kind code	B2
Filing date	Mar 6, 2018
Priority date	Apr 3, 2013
Publication date	Jan 4, 2022
Grant date	Jan 4, 2022

Abstract

The present invention relates to bispecific antibodies comprising at least one antigen binding site specific for DR5 and at least one antigen binding site specific for FAP, antibodies specific for DR5, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

First claim

We claim:

1. A method of treating cancer in an individual, the method comprising administering to the individual an effective amount of an antibody that specifically binds to DR5, wherein the antibody comprises at least one antigen binding site specific for DR5, and wherein the antigen binding site specific for DR5 comprises:
(a) a heavy chain complementarity determining region 1 (CDR1) comprising an amino acid sequence of SEQ ID NO.:1;
(b) a heavy chain complementarity determining region 2 (CDR2) comprising an amino acid sequence of SEQ ID NO.:2;
(c) a heavy chain complementarity determining region 3 (CDR3) comprising an amino acid sequence of SEQ ID NO.:3;
(d) a light chain CDR1 comprising an amino acid sequence of SEQ ID NO.:4;
(e) a light chain CDR2 comprising an amino acid sequence of SEQ ID NO.:5; and
(f) a light chain CDR3 comprising an amino acid sequence of SEQ ID NO.:6.

2. The method of claim 1 , wherein the cancer is pancreatic cancer or colorectal carcinoma.

3. The method of claim 1 , wherein the antigen binding site specific for DR5 comprises a variable heavy chain comprising an amino acid sequence of SEQ ID NO.:7 and a variable light chain comprising an amino acid sequence of SEQ ID NO.:8.

4. The method of claim 1 , wherein the antibody is human.

5. The method of claim 1 , wherein the antibody is monovalent for DR5.

6. The method of claim 1 , wherein the antibody is bivalent for DR5.

7. The method of claim 1 , wherein the antibody is trivalent for DR5.

8. The method of claim 1 , wherein the antibody comprises an Fc domain and at least one Fab fragment comprising the antigen binding site specific for DR5.

9. The method of claim 8 , wherein at least one of the Fab fragments is connected to the Fc domain via a peptide linker.

10. The method of claim 8 , wherein the Fc domain comprises one or more amino acid substitutions that reduce binding to an Fc receptor and/or that reduce effector function.

11. The method of claim 10 , wherein the one or more amino acid substitutions are at one or more residues selected from the group consisting of L234, L235, and P329 according to EU numbering.

12. The method of claim 10 , wherein the one or more amino acid substitutions are L234A, L235A, and P329G.

13. The method of claim 1 , wherein the antibody is administered to the individual in a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable carrier.

Assignees

• Roche Glycart Ag

Inventors

• Bruenker Peter
• Daouti Sherif
• Feng Ningping
• Ferrara Koller Claudia
• Georges Guy
• Grau-Richards Sandra
• Hosse Ralf
• Klein Christian
• Koenig Maximiliane
• Moelleken Joerg
• Moessner Ekkehard
• Niu Huifeng
• Packman Kathryn E
• Runza Valeria
• Seeber Stefan
• Umana Pablo
• Waldhauer Inja
• Wang Huisheng
• Weiser Barbara

Classifications

• C07K16/2875 Primary

  against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241) · CPC title

• C07K16/2878 Primary

  against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title