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1. WO2020117627 - ANTICORPS ANTI-IDO ET SES UTILISATIONS

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What is claimed:

1. An antibody that specifically binds to human Indoleamine 2,3-dioxygenase (IDO), comprising a heavy chain variable region (VH) and a light chain variable region (VL); wherein the VH comprises a VH complementarity determining region (CDR) 1 (VH-CDRl), a VH-CDR2, and a VH-CDR3 and the VL comprises a VL-CDR1, a VL-CDR2, and a VL-CDR3; wherein the VH-CDRl comprises the amino acid sequence set forth in SEQ ID NO:7, the VH-CDR2 comprises the amino acid sequence set forth in SEQ ID NO:8, the VH-CDR3 comprises the amino acid sequence set forth in SEQ ID NO:9, the VL-CDRl comprises the amino acid sequence set forth in SEQ ID NO: 10, the VL-CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 11, and the VL-CDR3 comprises the amino acid sequence set forth in SEQ ID NO: 12.

2. The antibody of claim 1, wherein the VH comprises an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4.

3. The antibody of claim 1 or 2, wherein the VH comprises an amino acid sequence having at least about 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4.

4. The antibody of any one of claims 1 to 3, wherein the VH comprises an amino acid sequence having at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 4.

5. The antibody of any one of claims 1 to 4, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO: 4.

6. The antibody of any one of claims 1 to 5, wherein the VL comprises an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

7. The antibody of any one of claims 1 to 6, wherein the VL comprises an amino acid sequence having at least about 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

8. The antibody of any one of claims 1 to 7, wherein the VL comprises an amino acid sequence having at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6.

9. The antibody of any one of claims 1 to 8, wherein the VL comprises the amino acid sequence set forth in SEQ ID NO: 6.

10. An antibody that specifically binds to human Indoleamine 2,3-dioxygenase (IDO), comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the amino acid sequence of SEQ ID NO: 4, and the VL comprises the amino acid sequence set forth in SEQ ID NO: 6.

11. The antibody of any one of claims 1 to 10, wherein the antibody comprises a heavy chain comprising an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 13.

12. The antibody of any one of claims 1 to 11, wherein the antibody comprises a heavy chain comprising an amino acid sequence having at least about 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 13.

13. The antibody of any one of claims 1 to 12, wherein the antibody comprises a heavy chain comprising an amino acid sequence having at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 13.

14. The antibody of any one of claims 1 to 13, wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 13.

15. The antibody of any one of claims 1 to 14, wherein the antibody comprises a light chain comprising an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 15.

16. The antibody of any one of claims 1 to 15, wherein the antibody comprises a light chain comprising an amino acid sequence having at least about 98% sequence identity to the amino acid sequence set forth in SEQ ID NO: 15.

17. The antibody of any one of claims 1 to 16, wherein the antibody comprises a light chain comprising an amino acid sequence having at least about 99% sequence identity to the amino acid sequence set forth in SEQ ID NO: 15.

18. The antibody of any one of claims 1 to 17, wherein the antibody comprises a light chain comprising the amino acid sequence set forth in SEQ ID NO: 15.

19. An antibody that specifically binds to human Indoleamine 2,3-dioxygenase (IDO), comprising a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 13 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 15.

20. The antibody of any one of claims 1 to 19, wherein the antibody is capable of specifically staining IDO in a biological sample by immuno histochemistry (IHC).

21. The antibody of any one of claims 1 to 20, wherein the antibody is capable of specifically staining IDO in a cancer sample by immunohistochemistry (IHC).

22. The antibody of any one of claims 1 to 21, wherein the antibody is capable of specifically staining IDO in a FFPE (formalin fixed paraffin embedded) cancer sample by IHC.

23. The antibody of any one of claims 1 to 22, wherein the antibody is an IgGl, an IgG2, an IgG3, an IgG4 or a variant thereof, or wherein the antibody is an IgGl, an IgG2a, an IgG2b, an IgG3 or a variant thereof.

24. The antibody of any one of claims 1 to 23, wherein the antibody is an IgGl antibody.

25. An antibody that binds to the same epitope on IDO as the antibody of any one of claims 1 to 24.

26. An antibody that cross-competes with the antibody of any one of claims 1 to 25 for binding to IDO.

27. A polynucleotide or a set of polynucleotides encoding the antibody of any one of claims 1 to 26.

28. A vector or a set of vectors comprising the polynucleotide or the set of polynucleotides of claim 27.

29. A host cell comprising the antibody of any one of claims 1 to 26, the polynucleotide or the set of polynucleotides of claim 27, or the vector or the set of vectors of claim 28.

30. A method of producing an antibody comprising culturing the host cell of claim 29 so that the antibody is produced.

31. An immunoconjugate comprising the antibody of any one of claims 1 to 26 and an agent.

32. The immunoconjugate of claim 31, wherein the agent is selected from the group consisting of a label, a cytotoxic agent, an imaging agent, a second antibody, an enzyme, and any combination thereof.

33. A pharmaceutical composition comprising the antibody of any one of claims 1 to 26, and a pharmaceutically acceptable carrier.

34. A method of detecting human IDO in a biological sample comprising contacting the biological sample with the antibody of any one of claims lto 26 under conditions permissive for binding of the antibody to human IDO, and detecting binding between the antibody and human IDO in the biological sample.

35. The method of claim 33, wherein the biological sample is cancer sample.

36. The method of claim 34 or 35, wherein the biological sample selected from a diffuse large B-cell lymphoma (DLBCL) sample; a head and neck squamous cell carcinoma (HNSCC) sample; a cervical carcinoma sample; a melanoma sample; a colorectal carcinoma (CRC) sample; a non small-cell lung carcinoma (NSCLC) sample; a bladder carcinoma sample; a pancreatic adenocarcinoma sample; a small cell lung cancer (SCLC) sample; and an ovarian adenocarcinoma sample.

37. A method of identifying a cancer patient having an IDO-positive cancer, comprising contacting a cancer sample from the patient with the anti-IDO antibody of any one of claims 1 to 26 under conditions permissive for binding of the anti-IDO antibody to human IDO, and detecting binding between the anti-IDO antibody and human IDO in the cancer sample.

38. A method of selecting a cancer patient for treatment with an IDO inhibitor, comprising determining the level of IDO expression in a cancer sample from the patient using immuno histochemistry (IHC), wherein an elevated level of IDO expression, as compared to a healthy subject or another cancer patient, indicates that the cancer patient is more likely to benefit from treatment with an IDO inhibitor, wherein IHC is performed using the antibody of any one of claims 1 to 26.

39. A method of selecting a cancer patient for treatment with an IDO inhibitor, comprising contacting a cancer sample from the patient with the anti-IDO antibody of any one of claims 1 to 26 under conditions permissive for binding of the anti-IDO antibody to human IDO, and detecting binding between the anti-IDO antibody and human IDO in the cancer sample.

40. A method of treating a cancer patient comprising administering to the patient a therapeutically effective amount of an IDO inhibitor, wherein a cancer sample from the patient has been determined to have an elevated level of IDO expression using immunohistochemistry (IHC), wherein IHC is performed using the antibody of any one of claims 1 to 26.

41. A method of treating a cancer patient with an IDO inhibitor comprising determining whether a cancer sample from the patient has an elevated level of IDO expression, compared to a healthy subject or another cancer patient, as detected by immunohistochemistry (IHC) using the antibody of any one of claims 1 to 26, and administering to the patient a therapeutically effective amount of the IDO inhibitor.

42. A method of treating a cancer patient with an IDO inhibitor comprising determining whether a cancer sample from the patient has an IDO-positive cancer, as detected by immunohistochemistry (IHC) using the antibody of any one of claims 1 to 26, and administering to the patient a therapeutically effective amount of the IDO inhibitor.

43. A method of treating a cancer patient with an IDO inhibitor comprising

a) determining the level of IDO expression in a cancer sample from the patient using immunohistochemistry (IHC) using the antibody of any one of claims 1 to 26, and

b) administering to the patient a therapeutically effective amount of the IDO inhibitor.

44. A method of treating a cancer patient with an IDO inhibitor comprising

a) determining the level of IDO expression in a cancer sample from the patient using immunohistochemistry (IHC), wherein an elevated level of IDO expression, as compared to a healthy subject or another cancer patient, indicates that the cancer patient is more likely to benefit from treatment with an IDO inhibitor, wherein IHC is performed using the antibody of any one of claims 1 to 26, and

b) administering to the patient a therapeutically effective amount of the IDO inhibitor.

45. A method of treating a cancer patient with an IDO inhibitor comprising

a) contacting a cancer sample from the patient with the anti-IDO antibody of any one of claims 1 to 26 under conditions permissive for binding of the anti-IDO antibody to human IDO,

b) detecting binding between the anti-IDO antibody and human IDO in the cancer sample, and

c) administering to the patient a therapeutically effective amount of the IDO inhibitor.

46. The method of any one of claims 37 to 45, where the cancer patient has one or more cancers selected from diffuse large B-cell lymphoma (DLBCL); head and neck squamous cell carcinoma (HNSCC); cervical carcinoma; melanoma; colorectal carcinoma (CRC); non small-cell lung carcinoma (NSCLC); bladder carcinoma; pancreatic adenocarcinoma; small cell lung cancer (SCLC); and ovarian adenocarcinoma.