CD73 blocking antibodies

Patent metadata

Field	Value
Publication number	US-12528876-B2
Application number	US-202117451835-A
Country	US
Kind code	B2
Filing date	Oct 22, 2021
Priority date	Apr 23, 2019
Publication date	Jan 20, 2026
Grant date	Jan 20, 2026

Abstract

The present invention relates to antibodies, and fragments thereof, that bind and inhibit CD73. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g., cancer.

First claim

We claim:

1 . An antibody or antibody fragment that binds to a human CD73 protein and neutralizes enzymatic 5′-ectonucleotidase activity of said human CD73 protein, wherein the antibody or antibody fragment comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 42 (2H4+ chain), and a light chain variable region (VL) comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 43 (2L1 chain), 44 (2L2 chain), 45 (2L3 chain) and 46 (2L4 chain).

2 . The antibody of claim 1 , wherein the antibody is a full-length antibody.

3 . The antibody or antibody fragment of claim 1 , wherein the antibody is an antibody fragment.

4 . A pharmaceutical composition comprising the antibody or antibody fragment according to claim 1 .

5 . A nucleic acid or set of nucleic acids encoding a heavy and light chains or a variable heavy (VH) and variable light (VL) domains of the antibody or antibody fragment according to claim 1 .

6 . A recombinant host cell comprising a vector encoding the antibody or antibody fragment according to claim 1 .

7 . An expression vector comprising one or more nucleic acid according to claim 5 .

8 . An antibody or antibody fragment that binds to a human CD73 protein and neutralizes its enzymatic 5′-ectonucleotidase activity, comprising a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 42 (2H4+ chain), and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 43.

9 . An antibody or antibody fragment that binds to a human CD73 polypeptide, comprising a heavy chain comprising SEQ ID NO: 47, and a light chain comprising SEQ ID NO: 48.

10 . A pharmaceutical composition comprising the antibody or antibody fragment according to claim 8 .

11 . A pharmaceutical composition comprising the antibody or antibody fragment according to claim 7 .

12 . A method for the treatment of a disease associated with the presence of CD73 or comprising CD73-expressing cells in a patient in need thereof, the method comprising administering a therapeutically effective amount of the antibody or antibody fragment according to claim 1 or a composition comprising said antibody or antibody fragment to said patient.

13 . The method of claim 12 , wherein said disease is cancer or infectious disease.

14 . The method of claim 13 , wherein the cancer is a leukemia, bladder cancer, glioma, glioblastoma, ovarian cancer, melanoma, prostate cancer, thyroid cancer, stomach cancer, esophageal cancer, pancreatic cancer or a breast cancer.

15 . A method for treating a cancer comprising CD73-expressing cells in a patient in need thereof, the method comprising administering to the patient the antibody or antibody fragment of claim 1 in an amount that achieves or maintains for a specified period of time a concentration in circulation or in an extravascular tissue of interest characterized by an EC50 for inhibition of the 5′-ectonucleotidase activity of CD73 expressed by a cell of no more than 1 μg/ml and wherein said cancer comprising CD-73 expressing cells is selected from the group consisting of leukemia, bladder cancer, glioma, glioblastoma, ovarian cancer, melanoma, prostate cancer, thyroid cancer, stomach cancer, esophageal cancer, pancreatic cancer or breast cancer.

16 . A method of administering an antibody to a patient for the treatment of a cancer comprising CD73-expressing cells in a patient in need thereof, the method comprising administering the antibody or antibody fragment according to claim 1 for at least one administration cycle, in which at least 2, 3, 4, 5, 6, 7 or 8 doses of the anti-CD73 antibody is administered and wherein the cancer comprising CD73-expressing cells is selected from the group consisting of leukemia, bladder cancer, glioma, glioblastoma, ovarian cancer, melanoma, prostate cancer, thyroid cancer, stomach cancer, esophageal cancer, pancreatic cancer or breast cancer.

17 . A method for the treatment of a disease associated with the presence of CD73 or CD73- expressing cells in a patient in need thereof, the method comprising administering to said patient a therapeutically effective amount of the antibody or antibody fragment according to claim 1 and one or more other therapeutic agents, wherein the other therapeutic agent is a chemotherapeutic agent, an anti-PD-1 antibody or antibody fragment, or an anti-PD-L1 antibody or antibody fragment.

18 . A method for the treatment of a cancer comprising CD73-expressing cells in a patient in need thereof, comprising administering to said patient an effective amount of the antibody or antibody fragment according to claim 1 and an anti-PD-1 antibody or an anti-PD-L1 antibody.

19 . A method of producing a human anti-CD73 antibody or antibody fragment thereof, comprising culturing a cell according to claim 6 under conditions suitable for expression of the anti-CD73 antibody or antibody fragment.

20 . A method of manufacturing a pharmaceutical preparation, comprising admixing the antibody or antibody fragment according to claim 1 with a pharmaceutically acceptable carrier.

21 . A method for decreasing adenosine production by a CD73-expressing cell, said method comprising bringing the CD73-expressing cell into contact the antibody or antibody fragment according to claim 1 .

22 . A method for reducing the production of adenosine by a CD73-expressing lymphocyte, the method comprising administering to the subject an effective amount of the antibody or antibody fragment according to claim 1 , thereby relieving the adenosine-mediated inhibition of lymphocyte activity in the subject.

23 . An antibody or antibody fragment that comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 47, and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 48, wherein the antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 42, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 43, said antibody or antibody fragment binds to a human CD73 protein and neutralizes its enzymatic 5′-ectonucleotidase activity.

24 . A pharmaceutical composition comprising the antibody or antibody fragment according to claim 23 .

25 . A nucleic acid or set of nucleic acids encoding a heavy and light chains or a VH and VL domains of the antibody or antibody fragment according to claim 23 .

26 . An expression vector comprising one or more nucleic acid according to claim 25 .

27 . A recombinant host cell comprising a vector encoding the antibody or antibody fragment of claim 23 .

28 . A method of producing a human anti-CD73 antibody or antibody fragment thereof, comprising culturing a cell according to claim 27 under conditions suitable for expression of the anti-CD73 antibody or antibody fragment.

29 . A method of manufacturing a pharmaceutical preparation, comprising admixing the antibody or antibody fragment according to claim 23 with a pharmaceutically acceptable carrier.

30 . A method for decreasing adenosine production by a CD73-expressing cell, said method comprising bringing the CD73-expressing cell into contact the antibody or antibody fragment according to claim

Assignees

• Innate Pharma

Inventors

• Gauthier Laurent
• Paturel Carine
• Perrot Ivan

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/74

  Inducing cell proliferation · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/55

  Fab or Fab' · CPC title