Therapeutic combinations comprising anti-cd73 antibodies and uses thereof

Patent metadata

Field	Value
Publication number	US-2016129108-A1
Application number	US-201514937565-A
Country	US
Kind code	A1
Filing date	Nov 10, 2015
Priority date	Nov 11, 2014
Publication date	May 12, 2016
Grant date	—

Abstract

The present invention provides therapeutic combinations featuring anti-CD73 antibodies (e.g., MEDI9447) and A2A receptor inhibitors and methods of using such combinations for reducing tumor-mediated immunosuppression.

First claim

What is claimed is:

1 . A method of inhibiting tumor growth in a subject comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor for inhibiting tumor growth to the subject.

2 . A method of increasing an anti-tumor immune response comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor to a subject in need thereof.

3 . A method of treating a tumor in a subject comprising administering an anti-CD73 antibody, or an antigen-binding fragment thereof, and an A2A receptor inhibitor for treating a tumor to a subject.

4 . The method any one of claims 1 - 3 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.

5 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.

6 . The method of any one of claims 1 - 3 , wherein the A2A receptor inhibitor is SCH58261.

7 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

8 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

9 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody or antigen-binding fragment thereof and the adenosine receptor inhibitor (A2ARi) are administered concurrently.

10 . The method of any one of claims 1 - 3 , wherein the anti-CD73 antibody or antigen-binding fragment thereof is administered prior to the adenosine receptor inhibitor (A2ARi).

11 . The method of any one of claims 1 - 3 , wherein the adenosine receptor inhibitor (A2ARi) is administered prior to the anti-CD73 antibody or antigen-binding fragment thereof.

12 . The method of any one of claims 1 - 3 , wherein the tumor is a breast cancer, hormonally mediated breast cancer, triple negative breast cancer, colon carcinoma, colorectal cancer, lung cancer, melanoma, non-small cell carcinoma, lymphoma, Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, and sarcoma.

13 . The method of any one of claims 1 - 3 , wherein said method results in an increase in overall survival as compared to the administration of any one of the anti-CD73 antibody or the A2A receptor inhibitor alone.

14 . The method of any one of claims 1 - 3 , wherein the said method induces or increases a tumor-specific immune response.

15 . The method of any one of claims 1 - 3 , wherein the said method reduces the immunosuppressive effects of a AMP/CD73/adenosine pathway.

16 . The method of any one of claims 1 - 3 , wherein the said method reduces metastasis or reduces the propensity of the tumor to metastasize relative to the administration of either the anti-CD73 antibody or the adenosine receptor inhibitor (A2ARi) alone.

17 . The method of any one of claims 1 - 3 , wherein the said method reduces the number of metastases within the subject.

18 . The method of any one of claims 1 - 3 , wherein the subject is a human patient.

19 . The method of any one of claims 1 - 3 , wherein the tumor is a CD73 overexpres sing tumor.

20 . The method of any one of claims 1 - 3 , wherein the cancer has a prometastatic phenotype.

21 . A kit for increasing anti-tumor activity, the kit comprising an anti-CD73 antibody or antigen-binding fragment thereof and an A2A receptor inhibitor.

22 . The kit of claim 21 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.

23 . The kit of claim 21 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.

24 . The kit of claim 21 , wherein the A2A receptor inhibitor is SCH58261.

25 . The kit of claim 21 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

26 . The kit of claim 21 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

27 . A pharmaceutical formulation comprising an effective amount an anti-CD73 antibody or antigen-binding fragment thereof and an A2A receptor inhibitor.

28 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof.

29 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof.

30 . The pharmaceutical formulation of claim 27 , wherein the A2A receptor inhibitor is SCH58261.

31 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is MEDI9447 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

32 . The pharmaceutical formulation of claim 27 , wherein the anti-CD73 antibody is Phen0203 hIgG1 or an antigen-binding fragment thereof and the A2A receptor inhibitor is SCH58261.

Assignees

• Medimmune Ltd

Inventors

• Sachsenmeier Kris
• Sult Erin
• Hay Carl
• Poon Edmund

Classifications

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• C07K16/2896

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

• C07K16/2818

  against CD28 or CD152 · CPC title

• C07K16/40

  against enzymes · CPC title

• C07K2317/33

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