Patents.us
Patents/USRE050631

USRE050631No. USRE050631reissueGranted 10/14/2025

Claims (99)

Claim 1 (Independent)

1. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-A, having the structure

Claim 8 (Independent)

8. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-E, having the structure

Claim 15 (Independent)

15. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-H, having the structure,

Claim 22 (Independent)

22. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-J, having the structure

Claim 29 (Independent)

29. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-K, having the structure

Claim 36 (Independent)

36. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-L, having the structure

Claim 43 (Independent)

43. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-M, having the structure

Claim 50 (Independent)

50. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-N, having the structure

Claim 57 (Independent)

57. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-O, having the structure

Claim 64 (Independent)

64. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-P, having the structure

Claim 71 (Independent)

71. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-Q, having the structure

Claim 78 (Independent)

78. An immunoconjugate comprising an antibody conjugated to a cytotoxic drug moiety, wherein the V H and V L of the antibody comprise the amino acid sequences of SEQ ID NOs: 5 and 6, respectively, and the immunoconjugate is ADC-R, having the structure

Claim 87 (Independent)

87. A method of treating a human receptor tyrosine kinase like orphan receptor 1 (ROR1) expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 1.

Show 86 dependent claims
Claim 2 (depends on 1)

2. The immunoconjugate of claim 1 , wherein the heavy chain and light chain of the antibody Ab comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 3 (depends on 2)

3. The immunoconjugate of claim 2 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7 n is an integer from 1 to 5 .

Claim 4 (depends on 1)

4. A pharmaceutical composition comprising the immunoconjugate of claim 1 and a pharmaceutically acceptable excipient.

Claim 5 (depends on 4)

5. The pharmaceutical composition of claim 4 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine rapamycin (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 6 (depends on 1)

6. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 1 .

Claim 7 (depends on 1)

7. A method of making the immunoconjugate of claim 1 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 9 (depends on 8)

9. The immunoconjugate of claim 8 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 10 (depends on 8)

10. The immunoconjugate of claim 8 , wherein the ratio of the cytoxic drug moiety to the antibody is 1 to 7.

Claim 11 (depends on 8)

11. A pharmaceutical composition comprising the immunoconjugate of claim 8 and a pharmaceutically acceptable excipient.

Claim 12 (depends on 11)

12. The pharmaceutical composition of claim 11 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 13 (depends on 8)

13. A method of treating a ROR 1 -expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 8 .

Claim 14 (depends on 8)

14. A method of making the immunoconjugate of claim 8 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:5.

Claim 16 (depends on 15)

16. The immunoconjugate of claim 15 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 17 (depends on 16)

17. The immunoconjugate of claim 16 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 18 (depends on 15)

18. A pharmaceutical composition comprising the immunoconjugate of claim 15 and a pharmaceutically acceptable excipient.

Claim 19 (depends on 18)

19. The pharmaceutical composition of claim 18 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton'tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2(Bcl-2) inhibitor, mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 20 (depends on 15)

20. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 15 .

Claim 21 (depends on 15)

21. A method of making the immunoconjugate of claim 15 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating azonafide to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO: 6.

Claim 23 (depends on 22)

23. The immunoconjugate of claim 22 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 24 (depends on 23)

24. The immunoconjugate of claim 23 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 25 (depends on 22)

25. A pharmaceutical composition comprising the immunoconjugate of claim 22 and a pharmaceutically acceptable excipient.

Claim 26 (depends on 25)

26. The pharmaceutical composition of claim 25 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (MTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 27 (depends on 22)

27. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 22 .

Claim 28 (depends on 22)

28. A method of making the immunoconjugate of claim 22 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating Duocarmycin TM to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 30 (depends on 29)

30. The immunoconjugate of claim 29 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 31 (depends on 30)

31. The immunoconjugate of claim 30 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 32 (depends on 29)

32. A pharmaceutical composition comprising the immunoconjugate of claim 29 and a pharmaceutically acceptable excipient.

Claim 33 (depends on 32)

33. The pharmaceutical composition of claim 32 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 34 (depends on 29)

34. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 29 .

Claim 35 (depends on 29)

35. A method of making the immunoconjugate of claim 29 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating pyrrolobenzodiazepine (PBD) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 37 (depends on 36)

37. The immunoconjugate of claim 36 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 38 (depends on 37)

38. The immunoconjugate of claim 37 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 39 (depends on 36)

39. A pharmaceutical composition comprising the immunoconjugate of claim 36 and a pharmaceutically acceptable excipient.

Claim 40 (depends on 39)

40. The pharmaceutical composition of claim 39 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 41 (depends on 36)

41. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 36 .

Claim 42 (depends on 36)

42. A method of making the immunoconjugate of claim 36 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 44 (depends on 43)

44. The immunoconjugate of claim 43 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 45 (depends on 44)

45. The immunoconjugate of claim 44 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 46 (depends on 43)

46. A pharmaceutical composition comprising the immunoconjugate of claim 43 and a pharmaceutically acceptable excipient.

Claim 47 (depends on 46)

47. The pharmaceutical composition of claim 46 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 48 (depends on 43)

48. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 43 .

Claim 49 (depends on 43)

49. A method of making the immunoconjugate of claim 43 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 51 (depends on 50)

51. The immunoconjugate of claim 50 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 52 (depends on 51)

52. The immunoconjugate of claim 51 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 53 (depends on 50)

53. A pharmaceutical composition comprising the immunoconjugate of claim 50 and a pharmaceutically acceptable excipient.

Claim 54 (depends on 53)

54. The pharmaceutical composition of claim 53 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 55 (depends on 50)

55. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 50 .

Claim 56 (depends on 50)

56. A method of making the immunoconjugate of claim 50 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 58 (depends on 57)

58. The immunoconjugate of claim 57 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 59 (depends on 58)

59. The immunoconjugate of claim 58 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 60 (depends on 57)

60. A pharmaceutical composition comprising the immunoconjugate of claim 57 and a pharmaceutically acceptable excipient.

Claim 61 (depends on 60)

61. The pharmaceutical composition of claim 60 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 62 (depends on 57)

62. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 57 .

Claim 63 (depends on 57)

63. A method of making the immunoconjugate of claim 57 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 65 (depends on 64)

65. The immunoconjugate of claim 64 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 66 (depends on 65)

66. The immunoconjugate of claim 65 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 67 (depends on 64)

67. A pharmaceutical composition comprising the immunoconjugate of claim 64 and a pharmaceutically acceptable excipient.

Claim 68 (depends on 67)

68. The pharmaceutical composition of claim 67 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 69 (depends on 64)

69. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 64 .

Claim 70 (depends on 64)

70. A method of making the immunoconjugate of claim 64 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 72 (depends on 71)

72. The immunoconjugate of claim 71 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 73 (depends on 72)

73. The immunoconjugate of claim 72 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 74 (depends on 71)

74. A pharmaceutical composition comprising the immunoconjugate of claim 71 and a pharmaceutically acceptable excipient.

Claim 75 (depends on 74)

75. The pharmaceutical composition of claim 74 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 76 (depends on 71)

76. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 71 .

Claim 77 (depends on 71)

77. A method of making the immunoconjugate of claim 71 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating monomethyl auristatin E (MMAE) to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 79 (depends on 78)

79. The immunoconjugate of claim 78 , wherein the heavy chain and light chain of the antibody comprise the amino acid sequences of SEQ ID NOs: 3 and 4, respectively.

Claim 80 (depends on 79)

80. The immunoconjugate of claim 79 , wherein the ratio of the cytotoxic drug moiety to the antibody is 1 to 7.

Claim 81 (depends on 78)

81. A pharmaceutical composition comprising the immunoconjugate of claim 78 and a pharmaceutically acceptable excipient.

Claim 82 (depends on 81)

82. The pharmaceutical composition of claim 81 , further comprising an additional therapeutic agent selected from the group consisting of a Bruton's tyrosine kinase (BTK) inhibitor, a B-cell lymphoma 2 (Bcl-2) inhibitor, a mammalian target of rapamycine (mTOR) inhibitor, and a phosphoinositide 3-kinase (PI3K) inhibitor.

Claim 83 (depends on 78)

83. A method of treating a ROR1-expressing cancer in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the immunoconjugate of claim 78 .

Claim 84 (depends on 78)

84. A method of making the immunoconjugate of claim 78 , comprising: providing an antibody that specifically binds to human receptor tyrosine kinase like orphan receptor 1 (ROR1); and conjugating PNU-159682 to the antibody; wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO:5 and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:6.

Claim 85 (depends on 3)

85. The immunoconjugate of claim 3 , wherein n is 4.

Claim 86 (depends on 1)

86. The immunoconjugate of claim 1 , wherein Ab comprises: a heavy chain comprising an amino acid sequence at least 95% identical to that of SEQ ID NO: 3, and a light chain comprising an amino acid sequence at least 95% identical to that of SEQ ID NO: 4.

Claim 88 (depends on 1)

88. A method of making the immunoconjugate of claim 1 , comprising the steps: (i) reducing the cysteine residues of Ab of claim 1 by contacting Ab with a reducing agent; and (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).

Claim 89 (depends on 87)

89. The method of claim 87 , wherein the human receptor tyrosine kinase like orphan receptor 1 (ROR1) expressing cancer is a lymphoma.

Claim 90 (depends on 89)

90. The method of claim 89 , wherein the lymphoma is selected from diffuse large β-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL).

Claim 91 (depends on 87)

91. The method of claim 87 , further comprising administering to the patient one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are selected from rituximab, cyclophosphamide, vincristine, prednisone, gemcitabine, daunorubicin hydrochloride, and a Bruton's tyrosine kinase (BTK) inhibitor.

Claim 92 (depends on 86)

92. The immunoconjugate of claim 86 , wherein Ab comprises: a V H comprising the amino acid sequence of SEQ ID NO: 5, and a V L comprising the amino acid sequence of SEQ ID NO: 6.

Claim 93 (depends on 3)

93. A method of making the immunoconjugate of claim 3 , comprising the steps: (i) reducing the cysteine residues of Ab of claim 3 by contacting Ab with a reducing agent; and (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).

Claim 94 (depends on 86)

94. A method of making the immunoconjugate of claim 86 , comprising the steps: (i) reducing the cysteine residues of Ab of claim 86 by contacting Ab with a reducing agent; and (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).

Claim 95 (depends on 92)

95. A method of making the immunoconjugate of claim 92 , comprising the steps: (i) reducing the cysteine residues of Ab of claim 92 by contacting Ab with a reducing agent; and (ii) conjugating one or more thiol groups of the reduced cysteine moieties of the product of step (i) with the maleimide group of the following linker/payload moiety: 6-maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl-monomethyl auristatin E (MC-VC-PAB-MMAE).

Claim 96 (depends on 86)

96. The immunoconjugate of claim 86 , wherein n is 4.

Claim 97 (depends on 92)

97. The immunoconjugate of claim 92 , wherein n is 4.

Claim 98 (depends on 90)

98. The method of claim 90 , wherein the lymphoma is diffuse large β-cell lymphoma (DLBCL).

Claim 99 (depends on 98)

99. The method of claim 98 , further comprising administering to the patient one or more additional therapeutic agents, wherein the one or more additional therapeutic agents are selected from rituximab, cyclophosphamide, vincristine, prednisone, daunorubicin hydrochloride, and gemcitabine.

Full Description

No description text available for this patent.

Citations

This patent cites (85)

  • US6821783
  • US6884869
  • US7498298
  • US7659241
  • US7829531
  • US7851437
  • US8212009
  • US8288352
  • US8609105
  • US8697688
  • US8742076
  • US8900589
  • US8936910
  • US9150647
  • US9089614
  • US9217040
  • US9228023
  • US9242014
  • US9266952
  • US9316646
  • US9523695
  • US9758591
  • US9933434
  • US9938350
  • US10316080
  • US2008/0050310
  • US2009/0258442
  • US2009/0311249
  • US2011/0178070
  • US2012/0058051
  • US2012/0282177
  • US2013/0028919
  • US2013/0101607
  • US2013/0131139
  • US2013/0251642
  • US2013/0309256
  • US2014/0127239
  • US2014/0286970
  • US2014/0294851
  • US2015/0037360
  • US2015/0232569
  • US2016/0022833
  • US2016/0193355
  • US2016/0208018
  • US2017/0014311
  • US2017/0319709
  • US2017/0368173
  • US2022/0133901
  • US2022/0152214
  • US103429618
  • US105473616
  • US105813655
  • US154613
  • US1545613
  • US2353611
  • US2019509021
  • US7245239
  • USWO 2010/124188
  • USWO 2011/159847
  • USWO 2012/045085
  • US2014031174
  • USWO 2014/031171
  • USWO 2014/080251
  • USWO 2014/145090
  • USWO 2014/167022
  • USWO 2014/177042
  • USWO 2014/197854
  • USWO 2015/038426
  • USWO 2015/057699
  • US2015198332
  • USWO 2015/198332
  • USWO 2016/055592
  • USWO 2016/055593
  • US2016094873
  • USWO 2016/094873
  • USWO 2016/115559
  • US2016187220
  • USWO 2016/187220
  • USWO 2017/072361
  • US2017127664
  • USWO 2017/127499
  • USWO 2017/127664
  • USWO 2018/119314
  • US2018237335
  • US2020160527