received by the International Bureau on 05 July 2016 (05.07.2016)

1. A binding molecule which binds to extracellular 3-phosphoinositide- dependent protein kinase- 1 (PDKl).

2. A binding molecule which binds to a cell expressing extracellular 3- phosphoinositide-dependent protein kinase- 1 (PDKl) and does not bind to a cell which does not express extracellular PDKl.

3. The binding molecule of claim 1 or 2, which inhibits migration of a cancer cell expressing extracellular PDKl .

4. The binding molecule of claim 1 or 2, wherein the binding molecule is capable of modulating a biological activity of PDKl.

5. The binding molecule of claim 1 or 2, which is an antigen binding protein or polypeptide.

6. The binding molecule of claim 1 or 2, which is an antibody, or antigen binding fragment thereof. 7. The binding molecule of claim 6, which is a recombinant human antibody, or antigen binding fragment thereof.

8. The binding molecule of claim 7, wherein the antibody, antigen binding fragment thereof, or polypeptide is expressed in a mammalian cell.

9. The binding molecule of claim 7, wherein the antibody, antigen binding fragment thereof, or polypeptide is expressed in a eukaryotic or prokaryotic cell.

10. The binding molecule of claim 7, wherein the antibody, antigen binding fragment thereof, or polypeptide is synthesized in a cell free system.

11. The binding molecule of claim 6, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising a CDR3 having the amino acid sequence of SEQ ID NO: 14.

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12. The binding molecule of claim 1 1, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 6 and a light chain variable region comprising a CDR2 having the amino acid sequence of SEQ ID NO: 13. 13. The binding molecule of claim 12, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 5 and a light chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO: 12.

14. The binding molecule of claim 13, wherein the antibody, or antigen binding fragment thereof, is an IgG isotype.

15. The binding molecule of claim 6, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 4.

16. The binding molecule of claim 6, wherein the antibody, or antigen binding fragment thereof, comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

17. The binding molecule of claim 16, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 4. 18. The binding molecule of claim 6, which is the antibody 2B9.

19. The binding molecule of claim 1 or 2, which is a small molecule.

20. The binding molecule of claim 1 or 2, which is conjugated to an imaging agent.

21. A pharmaceutical composition comprising the binding molecule of claim 1 or 2, and a pharmaceutically acceptable carrier.

22. A method of treating a cancer in a subject in need thereof comprising administering to the subject the binding molecule of claim 1 or 2, thereby treating the cancer in the subject.

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23. A method of treating a cancer in a subject comprising:

(a) selecting a subject having cancer, wherein the cancer is characterized by expression of extracellular 3-phosphoinositide-dependent protein kinase-1 (PDKl); and

(b) administering to the subject a therapeutically effective amount of the binding molecule of claim 1 or 2.

24. A method of treating a cancer in a subject in need thereof comprising:

(a) obtaining a sample from a subject having cancer;

(b) testing the sample for expression of extracellular 3-phosphoinositide-dependent protein kinase-1 (PDKl); and

(c) administering to the subject a therapeutically effective amount of the binding molecule of claim 1 or 2 when extracellular PDKl is present in the sample.

25. The method of claim 22, wherein the binding molecule is an antigen binding protein and does not cross the cell membrane.

26. A method of treating a cancer in a subject in need thereof comprising:

(a) obtaining a sample from a subject having cancer;

(b) testing the sample for expression of extracellular 3-phosphoinositide-dependent protein kinase-l(PDKl); and

(c) administering to the subject a therapeutically effective amount of a PDKl inhibitor.

27. The method of claim 23, wherein the cancer is metastatic or non-resectable.

28. The method of claim 23, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, prostate cancer, acute myeloid leukemia (AML), cervical cancer and squamous cell carcinoma.

29. The method of claim 23, further comprising administering to the subject at least one additional therapeutic agent.

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30. The method of claim 29, wherein the additional therapeutic agent is an agent selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic composition, a chemotherapeutic agent, and a cytotoxic agent.

31. A method for determining malignancy of a tumor from a subject comprising determining the presence of extracellular 3-phosphoinositide-dependent protein kinase- 1

(PDKl) in a sample from a tumor from the subject by contacting the sample with the binding molecule of claim 1 or 2, wherein the presence of extracellular PDKl as detected by the binding molecule in the sample indicates that the tumor is malignant.

32. A method for determining whether a cancer in a subject is metastatic, said method comprising determining the presence of extracellular 3-phosphoinositide-dependent protein kinase- 1 (PDKl) in a sample from the subject by contacting the sample with the binding molecule of claim 1 or 2, wherein the presence of extracellular PDKl as detected by the binding molecule in the sample indicates that the cancer is metastatic.

33. A method of identifying a subject having cancer which is responsive to anti- PDKl treatment comprising determining the presence of extracellular 3-phosphoinositide- dependent protein kinase-l (PDKl) in a sample from the subject by contacting the sample with the binding molecule of claim 1 or 2, wherein the presence of extracellular PDKl as detected by the binding molecule in the sample indicates that cancer will be responsive to an anti-PDKl treatment. 34. A method of identifying a subject having cancer which is responsive to the binding molecule of claim 1 or 2, said method comprising determining the presence of extracellular 3-phosphoinositide-dependent protein kinase-l (PDKl) in a sample from the subject, wherein the presence of extracellular PDKl in the sample indicates that cancer will be responsive to treatment with the antigen binding protein. 35. The method of claim 33 wherein the cancer is metastatic or non-resectable.

36. The method of claim 33, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, prostate cancer, acute myeloid leukemia (AML), cervical cancer and squamous cell carcinoma.

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37. A method of detecting extracellular 3-phosphoinositide-dependent protein kinase-1 (PDK1) in a sample, comprising contacting the sample with the binding molecule of claim 1 or 2.

38. An isolated anti-PDKl antibody, or antigen binding fragment thereof, comprising a heavy chain variable region comprising a CDRl having an amino acid sequence of SEQ ID NO: 5, a CDR2 having an amino acid sequence of SEQ ID NO: 6, and CDR3 having an amino acid sequences of SEQ ID NO: 7, and a light chain variable region comprising a CDRl having an amino acid sequence of SEQ ID NO: 12, a CDR2 having an amino acid sequence of SEQ ID NO: 13, and CDR3 having an amino acid sequences of SEQ ID NO: 14.

39. The antibody, or antigen binding fragment of claim 38, which is a recombinant human antibody.

40. The antibody, or antigen binding fragment of claim 39, wherein the antibody, or antigen binding fragment thereof, is an IgG isotype. 41. An isolated anti-PDKl antibody, or antigen binding fragment thereof, comprising a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 4, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 11.

42. The antibody, or antigen binding fragment of claim 41, which is a recombinant human antibody. 43. The antibody, or antigen binding fragment of claim 42, wherein the antibody, or antigen binding fragment thereof, is an IgG isotype.

44. The anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 38-43, wherein the antibody, or antigen binding fragment thereof, binds to

extracellular membrane bound 3-phosphoinositide-dependent protein kinase-1 (PDK1).

45. The anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 38-43, wherein the antibody, or antigen binding fragment thereof, binds to a cell expressing extracellular PDKl .

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46. The anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 36-41, wherein the antibody, or antigen binding fragment thereof, inhibits migration of a cell expressing extracellular PDKl .

47. The anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 38-43, wherein the antibody, or antigen binding fragment thereof, is capable of modulating a biological activity of PDKl .

48. The anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 38-43, which is conjugated to an imaging agent.

49. A pharmaceutical composition comprising the anti-PDKl antibody, or antigen binding fragment thereof, of any one of claims 38-43, and a pharmaceutically acceptable carrier.

50. A method for reducing cell migration and invasion, the method comprising the step of contacting a cell expressing extracellular PDKl with the antibody, or antigen-binding portion thereof, of any one of claims 36-41, such that cell migration and invasion is reduced. . 51. A method for reducing PDKl activity, the method comprising the step of contacting a cell expressing extracellular PDKl with the antibody, or antigen-binding portion thereof, of any one of claims 38-43, such that PDK activity is reduced.

52. The method of claim 50 or 51, wherein the method is in vivo.

53. A method for treating a human subject having a disorder in which extracellular expression of PDKl is detrimental comprising administering an effective amount of the anti- PDKl antibody, or antigen binding portion thereof, of any one of claims 38-43 to the subject.

54. The method of claim 53, wherein the disorder is cancer.

55. The method of claim 54, wherein the cancer is metastatic or non-resectable cancer.

56. The method of claim 54, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, prostate cancer, acute myeloid leukemia (AML), cervical cancer, and squamous cell carcinoma.

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57. The method of claim 53, wherein the disorder is a solid tumor or a hematopoietic cancer.

58. The method of any one of claims 53-57, further comprising administering an additional therapeutic agent to the subject. 59. The method of claim 58, wherein the additional therapeutic agent is an agent selected from the group consisting of an anti-angiogenic agent, an anti-neoplastic

composition, a chemotherapeutic agent, and a cytotoxic agent.

60. The method of any one of claims 53-57, further comprising administering radiation to the subject. 61. A method of treating a cancer in a subject comprising:

(a) selecting a subject having cancer, wherein the cancer is characterized by expression of extracellular PDK1; and

(b) administering to the subject a therapeutically effective amount of the anti-PDKl antibody, or antigen binding portion thereof, of any one of claims 38-43. 62. A nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular binding domain capable of binding to extracellular PDK1, a transmembrane domain, and an intracellular signaling domain.

63. The nucleic acid of claim 62, wherein the extracellular binding domain is an anti-PDKl antibody, or an antigen binding fragment thereof. 64. The nucleic acid of claim 63, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising a CDRl having an amino acid sequence of SEQ ID NO: 5, a CDR2 having an amino acid sequence of SEQ ID NO: 6, and CDR3 having an amino acid sequence of SEQ ID NO: 7, and comprises a light chain variable region comprising a CDRl having an amino acid sequence of SEQ ID NO: 12, a CDR2 having an amino acid sequences of SEQ ID NO: 13, and CDR3 having an amino acid sequence of SEQ ID NO: 14.

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65. The nucleic acid of claim 62, wherein the antibody, or antigen binding fragment thereof, comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 4, and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 11. 66. The nucleic acid of any one of claims 62-65, wherein the antigen binding fragment is an scFv.

67. The nucleic acid of any one of claims 60-63, wherein the intracellular signaling domain comprises a CD3 zeta signaling domain.

68. The nucleic acid of any one of claims 60-65, further comprising a co- stimulatory signaling domain.

69. A vector comprising the nucleic acid sequence of any one of claims 60-66.

70. The vector of claim 69, wherein the vector is a viral vector.

71. The vector of claim 70, wherein the viral vector is a lentiviral vector or a retroviral vector.

72. An immune effector cell comprising the vector of any one of claims 69-71.

73. The immune effector cell of claim 72, wherein the immune effector cell is a T lymphocyte.

74. The immune effector cell of claim 73, which is obtained from a subject having cancer. 75. A method of treating cancer in a subject in need thereof, comprising administering to the subject the immune effector cell of claim 72.

76. The method of claim 75, wherein the cancer is selected from the group consisting of breast cancer, lung cancer, prostate cancer, acute myeloid leukemia (AML), cervical cancer, and squamous cell carcinoma. 77. The method of claim 75, wherein the cancer is a solid tumor or a

hematopoietic cancer.

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78. An isolated anti-PDKl human antibody, or antigen binding portion thereof, produced by hybridoma cell line 2B9 (ATCC Accession No. PTA-122983).

79. The hybridoma cell line 2B9 deposited under ATCC Accession No. PTA- 122983.