CD73 blockade
AssigneeInnate Pharma
InventorsIvan Perrot, Carine Paturel, Laurent Gauthier
Life of this patent
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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.
Claims21
A nucleic acid encoding a heavy and/or light chain of an antibody that specifically binds a human CD73 polypeptide at the surface of a cell and that is capable of neutralizing the 5′-ectonucleotidase activity thereof, wherein the antibody is selected from the group consisting of:
- (a) monoclonal antibody or antibody fragment comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 28 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 36 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO:
- 37.
A method for the treatment of cancer in a patient in need thereof, the method comprising administering to said patient an effective amount of an antibody that specifically binds a human CD73 polypeptide at the surface of a cell and that is capable of neutralizing the 5′-ectonucleotidase activity thereof, wherein the antibody is selected from the group consisting of:
- (a) monoclonal antibody or antibody fragment comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 28 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 36 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO:
- 37.
A method for relieving adenosine-mediated inhibition of T cell activity in a subject having a cancer, the method comprising administering to said subject an effective amount of an antibody that specifically binds a human CD73 polypeptide at the surface of a cell and that is capable of neutralizing the 5′-ectonucleotidase activity thereof, wherein the antibody is selected from the group consisting of:
- (a) monoclonal antibody or antibody fragment comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 28 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 36 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO:
- 37.
A method for increasing T cell activity in the tumor microenvironment of in a subject, the method comprising administering to said subject an effective amount of an antibody of an antibody that specifically binds a human CD73 polypeptide at the surface of a cell and that is capable of neutralizing the 5′-ectonucleotidase activity thereof, wherein the antibody is selected from the group consisting of:
- (a) monoclonal antibody or antibody fragment comprising (i) a heavy chain comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 3 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 28 and (ii) a light chain 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 comprising CDR 1, 2 and 3 of the heavy chain variable region of SEQ ID NO:
- 36 and (ii) a light chain comprising CDR 1, 2 and 3 of the light chain variable region of SEQ ID NO:
- 37.
Dependencies are inferred from the claim text.