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1. WO2020210711 - COMPOSITIONS AND METHODS OF USING SENECA VALLEY VIRUS (SVV) FOR TREATING CANCER

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[ EN ]

CLAIMS

What is claimed:

1. A method of treating a cancer in a subject in need thereof, the method comprising

administering to the subject an effective amount of Seneca Valley Virus (SVV) or SVV derivative, wherein the cancer is characterized by:

a. an expression level of anthrax toxin receptor 1 (ANTXRl) higher than an ANTXRl reference value, and

b. an expression level of interferon type I (IFN-I) lower than an IFN-I reference value,

wherein the subject is also administered at least one IFN-I inhibiting agent comprising a JAK inhibitor.

2. The method of claim 1, wherein the expression level of ANTXR1 is determined based on the level of an ANTXR1 mRNA or an ANTXR1 protein.

3. The method of claim 1, wherein the expression level of IFN-I is determined based on the level of an IFN-I biomarker mRNA or an IFN-I biomarker protein.

4. The method of claim 3, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is at least one mRNA or protein selected from the group consisting of IFI35, IFN-a, IFN- b, IFN-k, IFN-d, IFN-e, IFN-t, IFN-w, and IFN-z, ADAR, IRF9, IFITM3, IFITM2, USP18, LOC144383, EGR1, IFI6, GBP2, HLA-A, HLA-B, HLA-C, HLA-F, HLA-G, IRF8, IFI27, IFI35, IFIT2, IFIT1, IFIT3, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA14, IFNA16, IFNA17, IFNA21, IFNAR1, IFNAR2, IFNB1, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, ISG20, JAK1, MX1, MX2, OAS1, OAS2, OAS3, IP6K2, XAF1, PSMB8, PTPN1, PTPN6, RNASEL, HLA-K, STAT1, STAT2, TYK2, HLA-B, IFITM1, OASL, SOCS1, SOCS3 and ISG15.

5. The method of claim 3, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is IFI35 mRNA or IFI35 protein.

6. The method of claim 1, wherein the subject is administered at least one anti-cancer therapeutic agent selected from the group consisting of: a checkpoint inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a cytokine, a growth factor, a photosensitizing agent, a toxin, a siRNA molecule, a signaling modulator, an anti-cancer antibiotic, an anti-cancer antibody, an angiogenesis inhibitor, a chemotherapeutic compound, anti-metastatic compound, an immunotherapeutic compound, a CAR therapy, a dendritic cell-based therapy, a cancer vaccine, an oncolytic virus, an engineered anti- cancer virus or virus derivative and a combination of any thereof.

7. The method of claim 5, wherein the least one anti-cancer therapeutic agent is

administered formerly, simultaneously or subsequently to the administering of the SVV.

8. The method of claim 1, wherein the least one IFN-I inhibiting agent comprises an HDAC inhibitor, an IFN inhibitor, an IFN antibody, an IFN-a Receptor 1 antibody, an IFN-a Receptor 2 antibody, a viral peptide or a combination of any thereof.

9. The method of claim 8, wherein the least one IFN-I inhibiting agent is administered

formerly, simultaneously or subsequently to the administering of the SVV.

10. The method of claim 1, wherein the administering comprises an administration route is selected from the group consisting of inhalation, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, intra-hepatic arterial, intrathecal, intra-tumoral, intravenal and any combination thereof.

11. The method of claim 1, wherein the cancer comprises a triple negative breast cancer, a small cell lung cancer, a non-small cell lung cancer, a non-small cell squamous carcinoma, an adenocarcinoma, a glioblastoma, a skin cancer, a hepatocellular carcinoma, a colon cancer, a cervical cancer, an ovarian cancer, an endometrial cancer, a neuroendocrine cancer, a pancreatic cancer, a thyroid cancer, a kidney cancer, a bone cancer, an oesophagus cancer or a soft tissue cancer.

12. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject an IFN-I inhibiting agent comprising a JAK inhibitor and an effective amount of SVV or SVV derivative, wherein the cancer is characterized by an expression level of ANTXRl higher than an ANTXRl reference value, and wherein the IFN-I inhibiting agent reduces the expression level of IFN-I in the cancer thereby favoring replication of the SVV or the SVV derivative and killing of the cancer.

13. The method of claim 12, wherein the IFN-I inhibiting agent comprises an HDAC

inhibitor, an IFN inhibitor, an IFN antibody, an IFN-a Receptor 1 antibody, an IFN-a Receptor 2 antibody, a viral peptide or a combination of any thereof.

14. The method of claim 12, wherein the IFN-I inhibiting agent is administered formerly, simultaneously or subsequently to the administering of the SVV.

15. The method of claim 12, wherein the expression level of ANTXR1 is determined based on the level of an ANTXR1 mRNA or an ANTXR1 protein.

16. The method of claim 12, wherein the expression level of IFN-I is determined based on the level of an IFN-I biomarker mRNA or an IFN-I biomarker protein.

17. The method of claim 16, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is at least one mRNA or protein selected from the group consisting of IFI35, IFN-a, IFN- b, IFN-k, IFN-d, IFN-e, IFN-t, IFN-w, and IFN-z, ADAR, IRF9, IFITM3, IFITM2, USP18, LOC144383, EGR1, IFI6, GBP2, HLA-A, HLA-B, HLA-C, HLA-F, HLA-G, IRF8, IFI27, IFI35, IFIT2, IFIT1, IFIT3, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA14, IFNA16, IFNA17, IFNA21, IFNAR1, IFNAR2, IFNB1, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, ISG20, JAK1, MX1, MX2, OAS1, OAS2, OAS3, IP6K2, XAF1, PSMB8, PTPN1, PTPN6, RNASEL, HLA-K, STAT1, STAT2, TYK2, HLA-B, IFITM1, OASL, SOCS1, SOCS3 and ISG15.

18. The method of claim 16, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is IFI35 mRNA or IFI35 protein.

19. The method of claim 12, wherein the subject is administered at least one anti-cancer therapeutic agent selected from the group consisting of: a checkpoint inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a cytokine, a growth factor, a photosensitizing agent, a toxin, a siRNA molecule, a signaling modulator, an anti-cancer antibiotic, an anti-cancer antibody, an angiogenesis inhibitor, a chemotherapeutic compound, anti-metastatic compound, an immunotherapeutic compound, a CAR therapy, a dendritic cell-based therapy, a cancer vaccine, an oncolytic virus, an engineered anti- cancer virus or virus derivative a combination of any thereof.

20. The method of claim 18, wherein the least one anti-cancer therapeutic agent is

administered formerly, simultaneously or subsequently to the administering of the IFN-I inhibiting agent and SVV.

21. The method of claim 12, wherein the administering comprises an administration route is selected from the group consisting of inhalation, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, intra-hepatic arterial, intrathecal, intra-tumoral, intravenal and any combination thereof.

22. The method of claim 12, wherein the cancer comprises a triple negative breast cancer, a small cell lung cancer, a non-small cell lung cancer, a non-small cell squamous carcinoma, an adenocarcinoma, a glioblastoma, a skin cancer, a hepatocellular carcinoma, a colon cancer, a cervical cancer, an ovarian cancer, an endometrial cancer, a neuroendocrine cancer, a pancreatic cancer, a thyroid cancer, a kidney cancer, a bone cancer, an oesophagus cancer or a soft tissue cancer.

23. A method of predicting the efficacy of a cancer treatment comprising an Seneca Valley Virus (SVV), or an SVV derivative, combined with at least one IFN-I inhibiting agent comprising a JAK inhibitor, the method comprising determining the expression level of ANTXRl and the expression level of IFN-I in the cancer from a subject, wherein:

a. an expression level of ANTXRl higher than an ANTXRl reference value, and

b. an expression level of IFN-I lower than an IFN-I reference value are predictive that the treatment is effective, and wherein when the treatment is predicted to be effective, recommending treatment of the subject.

24. The method of claim 23, wherein the expression level of ANTXR1 is determined based on the level of an ANTXR1 mRNA or an ANTXR1 protein.

25. The method of claim 23, wherein the expression level of IFN-I is determined based on the level of an IFN-I biomarker mRNA or an IFN-I biomarker protein.

26. The method of claim 25, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is at least one mRNA or protein selected from the group consisting of IFI35, IFN-a, IFN- b, IFN-k, IFN-d, IFN-e, IFN-t, IFN-w, and IFN-z, ADAR, IRF9, IFITM3, IFITM2, USP18, LOC144383, EGR1, IFI6, GBP2, HLA-A, HLA-B, HLA-C, HLA-F, HLA-G, IRF8, IFI27, IFI35, IFIT2, IFIT1, IFIT3, IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA14, IFNA16, IFNA17, IFNA21, IFNAR1, IFNAR2, IFNB1, IRF1, IRF2, IRF3, IRF4, IRF5, IRF6, IRF7, ISG20, JAK1, MX1, MX2, OAS1, OAS2, OAS3, IP6K2, XAF1, PSMB8, PTPN1, PTPN6, RNASEL, HLA-K, STAT1, STAT2, TYK2, HLA-B, IFITM1, OASL, SOCS1, SOCS3 and ISG15.

27. The method of claim 25, wherein the IFN-I biomarker mRNA or IFN-I biomarker protein is IFI35 mRNA or IFI35 protein.

28. The method of claim 23, wherein the SVV or SVV derivative treatment further comprises a treatment with at least one anti-cancer therapeutic agent selected from the group consisting of: a checkpoint inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a cytokine, a growth factor, a photosensitizing agent, a toxin, a siRNA molecule, a signaling modulator, an anti-cancer antibiotic, an anti-cancer antibody, an angiogenesis inhibitor, a chemotherapeutic compound, anti-metastatic compound, an immunotherapeutic compound, a CAR therapy, a dendritic cell-based therapy, a cancer

vaccine, an oncolytic virus, an engineered anti-cancer virus or virus derivative and a combination of any thereof.

29. The method of claim 27, wherein the treatment with at least one anti-cancer therapeutic agent is performed formerly, simultaneously or subsequently to the SVV or SVV derivative treatment.

30. The method of claim 23, wherein the at least one IFN-I inhibiting agent comprises an HDAC inhibitor, a JAK inhibitor, an IFN inhibitor, an IFN antibody, an IFN-a Receptor 1 antibody, an IFN-a Receptor 2 antibody, a viral peptide or a combination of any thereof.

31. The method of claim 30, wherein the least one IFN-I inhibiting agent is administered formerly, simultaneously or subsequently to the SVV or SVV derivative treatment.

32. The method of claim 23, wherein SVV or SVV derivative treatment comprises an

administration route selected from the group consisting of inhalation, oral, rectal, vaginal, parenteral, topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, intra-hepatic arterial, intrathecal, intra-tumoral, intravenal and any combination thereof.

33. The method of claim 23, wherein the cancer comprises a triple negative breast cancer, a small cell lung cancer, a non-small cell lung cancer, a non-small cell squamous carcinoma, an adenocarcinoma, a glioblastoma, a skin cancer, a hepatocellular carcinoma, a colon cancer, a cervical cancer, an ovarian cancer, an endometrial cancer, a neuroendocrine cancer, a pancreatic cancer, a thyroid cancer, a kidney cancer, a bone cancer, an oesophagus cancer or a soft tissue cancer.

34. A pharmaceutical composition for treating a cancer in a subject, the pharmaceutical

composition comprising an IFN-I inhibiting agent comprising a JAK inhibitor, an SVV or an SVV derivative and a pharmaceutical acceptable carrier.

35. The composition of claim 34, wherein the IFN-I inhibiting agent is at least one agent selected from the group consisting of: HDAC inhibitor, JAK inhibitor, IFN inhibitor, IFN antibody, IFN-a Receptor 1 antibody, IFN-a Receptor 2 antibody and viral peptide and a combination of any thereof.

36. The composition of claim 34, further comprises at least one anti-cancer therapeutic agent selected from the group consisting of: a checkpoint inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, a cytokine, a growth factor, a photosensitizing agent, a toxin, a siRNA molecule, a signaling modulator, an anti-cancer antibiotic, an anti-cancer antibody, an angiogenesis inhibitor, a chemotherapeutic compound, anti-metastatic compound, an immunotherapeutic compound, a CAR therapy, a dendritic cell-based therapy, a cancer vaccine, an oncolytic virus, an engineered anti-cancer virus or virus derivative and a combination of any thereof.

37. The composition of claim 34, wherein the cancer comprises a triple negative breast

cancer, small cell lung cancer, a non-small squamous cell carcinoma, a skin cancer, a hepatocellular carcinoma, a colon cancer, a cervical cancer, an ovarian cancer, an endometrial cancer, a pancreatic cancer, a thyroid cancer, a kidney cancer, a bone cancer, an oesophagus cancer or a soft tissue cancer.

38. A kit for determining a predisposition of an efficacious response to a cancer treatment comprising an Seneca Valley Virus (SVV), or an SVV derivative, combined with at least one IFN-I inhibiting agent comprising a JAK inhibitor, the kit comprising a reagent for determining the expression level of ANTXRl and a reagent for determining the expression level of IFN-I in the cancer from a subject.

39. The method or kit of any one of claims 1, 12, 23, 34 and 38, wherein the subject is a human.

40. A Seneca Valley Virus (SVV) or SVV derivative in combination with at least one IFN-I inhibiting agent comprising a JAK inhibitor for use in the manufacture of a medicament for treatment of a cancer, wherein the cancer is characterized by an expression level of anthrax toxin receptor 1 (ANTXRl) higher than an ANTXRl reference value, and an expression level of interferon type I (IFN-I) lower than an IFN-I reference value.