CD73 blockade

Patent metadata

Field	Value
Publication number	US-10766966-B2
Application number	US-201515517991-A
Country	US
Kind code	B2
Filing date	Oct 9, 2015
Priority date	Oct 10, 2014
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

This disclosure relates to antibodies that bind an epitope present on CD73 expressed at the surface of cells, including tumor cells, and that inhibit the enzymatic (ecto-5′ nucleotidase) activity of the CD73 enzyme. Such agents can be used for the treatment of diseases such as cancers.

First claim

The invention claimed is:

1. An isolated antibody or antibody fragment that specifically binds a human CD73 polypeptide at the surface of a cell and that is capable of neutralizing the 5′-ectonucleotidase activity thereof, selected from the group consisting of:
(a) monoclonal antibody or antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 4;
(b) monoclonal antibody or antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 21;
(c) monoclonal antibody or antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 28 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 29; and
(d) monoclonal antibody or antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 36 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 37.

2. The isolated antibody of claim 1 , wherein the antibody is a human IgG4 antibody or an antibody having a human Fc domain that is modified to reduce binding between the Fc domain and an Fcγ receptor.

3. The isolated antibody of claim 1 , wherein the antibody is an IgG1 and comprises one, two or three substitutions at residues 234, 235 and 331 or at 234, 235 and 322 (EU numbering).

4. A pharmaceutical composition comprising an antibody or antibody fragment according to claim 1 , and a pharmaceutically acceptable carrier.

5. The isolated antibody or antibody fragment of claim 1 , said monoclonal antibody or antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 4.

6. The isolated antibody or antibody fragment of claim 1 , said monoclonal antibody comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 21.

7. The isolated antibody or antibody fragment of claim 1 , said monoclonal antibody comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 28 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 29.

8. The isolated antibody or antibody fragment of claim 1 , said monoclonal antibody comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 36 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 37.

9. The isolated antibody or antibody fragment of claim 1 , said antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 4.

10. The isolated antibody or antibody fragment of claim 1 , said antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 3 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 21.

11. The isolated antibody or antibody fragment of claim 1 , said antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 28 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 29.

12. The isolated antibody or antibody fragment of claim 1 , said antibody fragment comprising (i) a heavy chain variable region comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO: 36 and (ii) a light chain variable region comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO: 37.

Assignees

• Innate Pharma

Inventors

• Perrot Ivan
• Paturel Carine
• Gauthier Laurent

Classifications

• C07K16/40

  against enzymes · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K16/2896 Primary

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title