Humanized affinity mature antibody against FcRH5 and method of use

Abstract

This invention provides an anti-FcRH5 antibody for the treatment of cell proliferation disorders (e.g., cancer, e.g., FcRH5-positive cancer, e.g., multiple myeloma). [Solution] An anti-FcRH5 antibody, including an anti-FcRH5 antibody containing an FcRH5-binding domain and a CD3-binding domain (for example, an FcRH5 T cell-dependent bispecificity (TDB) antibody), and a method for using the same are provided.

Claims

1. An anti-Fc receptor-like 5 (FcRH5) antibody, wherein the anti-FcRH5 antibody comprises the following six hypervariable regions (HVRs): (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 2 (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 3, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 4, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 5, (f) The anti-FcRH5 antibody comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

6.

2. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

23.

3. The anti-FcRH5 antibody according to claim 2, wherein the binding domain comprises (a) a heavy chain variable (VH) domain containing an amino acid sequence having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 104, (b) a light chain variable (VL) domain containing an amino acid sequence having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 105, or (c) a VH domain as in (a) and a VL domain as in (b).

4. The antibody has the following heavy chain variable region framework (FR): (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 2 or 3, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

5. The anti-FcRH5 antibody according to claim 4, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

104.

6. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 2 to 5, further comprising FR-L4 containing the amino acid sequence of SEQ ID NO:

51.

7. The anti-FcRH5 antibody according to claim 6, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

105.

8. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 104, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

105.

9. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 10, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 14, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

23.

10. The anti-FcRH5 antibody according to claim 9, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 106, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 107, or (c) a VH domain as in (a) and a VL domain as in (b).

11. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 53, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 9 or 10, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

12. The anti-FcRH5 antibody according to claim 11, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

106.

13. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 9 to 12, further comprising FR-L4 containing the amino acid sequence of SEQ ID NO:

51.

14. The anti-FcRH5 antibody according to claim 13, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

107.

15. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 106, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

107.

16. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 11, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 15, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

20.

17. The anti-FcRH5 antibody according to claim 16, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 82, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 83, or (c) a VH domain as in (a) and a VL domain as in (b).

18. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 16 or 17, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

19. The anti-FcRH5 antibody according to claim 18, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

82.

20. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 56, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 16 to 19, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

21. The anti-FcRH5 antibody according to claim 20, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

83.

22. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 82, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

83.

23. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

21.

24. The anti-FcRH5 antibody according to claim 23, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 84, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 85, or (c) a VH domain as in (a) and a VL domain as in (b).

25. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 23 or 24, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

26. The anti-FcRH5 antibody according to claim 25, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

84.

27. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 23 to 26, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

28. The anti-FcRH5 antibody according to claim 27, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

85.

29. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 84, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

85.

30. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 17, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

22.

31. The anti-FcRH5 antibody according to claim 30, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 86, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 87, or (c) a VH domain as in (a) and a VL domain as in (b).

32. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 30 or 31, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

33. The anti-FcRH5 antibody according to claim 32, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

86.

34. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 30 to 33, further comprising FR-L4 containing the amino acid sequence of SEQ ID NO:

51.

35. The anti-FcRH5 antibody according to claim 34, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

87.

36. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 86, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

87.

37. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 13, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

21.

38. The anti-FcRH5 antibody according to claim 37, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 88, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 89, or (c) a VH domain as in (a) and a VL domain as in (b).

39. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 37 or 38, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

40. The anti-FcRH5 antibody according to claim 39, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

88.

41. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 37 to 40, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

42. The anti-FcRH5 antibody according to claim 41, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

89.

43. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 88, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

89.

44. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

23.

45. The anti-FcRH5 antibody according to claim 44, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 90, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 91, or (c) a VH domain as in (a) and a VL domain as in (b).

46. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 44 or 45, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

47. The anti-FcRH5 antibody according to claim 46, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

90.

48. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 44 to 47, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

49. The anti-FcRH5 antibody according to claim 48, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

91.

50. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 90, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

91.

51. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 11, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 18, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

22.

52. The anti-FcRH5 antibody according to claim 51, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 92, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 93, or (c) a VH domain as in (a) and a VL domain as in (b).

53. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 51 or 52, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

54. The anti-FcRH5 antibody according to claim 53, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

92.

55. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 56, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 51 to 54, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

56. The anti-FcRH5 antibody according to claim 55, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

93.

57. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 92, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

93.

58. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 11, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 19, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

24.

59. The anti-FcRH5 antibody according to claim 58, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 94, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 95, or (c) a VH domain as in (a) and a VL domain as in (b).

60. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 58 or 59, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

61. The anti-FcRH5 antibody according to claim 60, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

94.

62. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 58 to 61, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

63. The anti-FcRH5 antibody according to claim 62, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

95.

64. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 94, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

95.

65. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 18, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

25.

66. The anti-FcRH5 antibody according to claim 65, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 96, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 97, or (c) a VH domain as in (a) and a VL domain as in (b).

67. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 53, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 65 or 66, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

68. The anti-FcRH5 antibody according to claim 67, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

96.

69. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 65 to 68, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

70. The anti-FcRH5 antibody according to claim 69, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

97.

71. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 96, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

97.

72. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 18, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

25.

73. The anti-FcRH5 antibody according to claim 72, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 98, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 99, or (c) a VH domain as in (a) and a VL domain as in (b).

74. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 55 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 72 or 73, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

75. The anti-FcRH5 antibody according to claim 74, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

98.

76. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 72 to 75, further comprising FR-L4 containing the amino acid sequence of SEQ ID NO:

51.

77. The anti-FcRH5 antibody according to claim 76, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

99.

78. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 98, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

99.

79. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 7, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 18, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

25.

80. The anti-FcRH5 antibody according to claim 79, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 100, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 101, or (c) a VH domain as in (a) and a VL domain as in (b).

81. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 79 or 80, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

82. The anti-FcRH5 antibody according to claim 81, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

100.

83. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 57, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 79 to 82, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

84. The anti-FcRH5 antibody according to claim 83, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

101.

85. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 100, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

101.

86. The aforementioned anti-FcRH5 antibody is effective against the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 11, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 15, and (f) The anti-FcRH5 antibody according to claim 1, comprising a binding domain containing HVR-L3 having the amino acid sequence of SEQ ID NO:

20.

87. The anti-FcRH5 antibody according to claim 86, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 102, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 103, or (c) a VH domain as in (a) and a VL domain as in (b).

88. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 52, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 54 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 46, and (d) The anti-FcRH5 antibody according to claim 86 or 87, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

47.

89. The anti-FcRH5 antibody according to claim 88, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

102.

90. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 48, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 56, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 50, and (d) The anti-FcRH5 antibody according to any one of claims 86 to 89, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

51.

91. The anti-FcRH5 antibody according to claim 90, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

103.

92. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 102, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

103.

93. The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 32, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 33, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 34, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 35, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 36, and (f) An anti-FcRH5 antibody comprising a binding domain containing HVR-L3, which contains the amino acid sequence of SEQ ID NO:

37.

94. The anti-FcRH5 antibody according to claim 93, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 110, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 111, or (c) a VH domain as in (a) and a VL domain as in (b).

95. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 66, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 67, (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 68, and (d) The anti-FcRH5 antibody according to claim 93 or 94, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

69.

96. The anti-FcRH5 antibody according to claim 95, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

110.

97. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 70, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 71 (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 72, and (d) The anti-FcRH5 antibody according to any one of claims 93 to 96, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

73.

98. The anti-FcRH5 antibody according to claim 97, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

111.

99. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 110, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

111.

100. The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 38, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 39, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 40, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 41, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 42, (f) An anti-FcRH5 antibody containing a binding domain that includes HVR-L3 containing the amino acid sequence of SEQ ID NO:

43.

101. The anti-FcRH5 antibody according to claim 100, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 112, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 113, or (c) a VH domain as in (a) and a VL domain as in (b).

102. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 74, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 75 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 76, and (d) The anti-FcRH5 antibody according to claim 100 or 101, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

77.

103. The anti-FcRH5 antibody according to claim 102, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

112.

104. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 78, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 79 (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 80, and (d) The anti-FcRH5 antibody according to any one of claims 100 to 103, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

81.

105. The anti-FcRH5 antibody according to claim 104, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

113.

106. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 112, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

113.

107. The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 26, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 27, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 28, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 29, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 30, and (f) An anti-FcRH5 antibody comprising a binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO:

31.

108. The anti-FcRH5 antibody according to claim 107, wherein the binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 108, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 109, or (c) a VH domain as in (a) and a VL domain as in (b).

109. The antibody has the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 58, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 59 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 60, and (d) The anti-FcRH5 antibody according to claim 107 or 108, further comprising FR-H4 having the amino acid sequence of SEQ ID NO:

61.

110. The anti-FcRH5 antibody according to claim 109, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

108.

111. The antibody has the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 62, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 63 (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 64, and (d) The anti-FcRH5 antibody according to any one of claims 107 to 110, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

65.

112. The anti-FcRH5 antibody according to claim 111, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

109.

113. An anti-FcRH5 antibody comprising a binding domain, (a) a VH domain containing the amino acid sequence of SEQ ID NO: 108, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

109.

114. The anti-FcRH5 antibody according to any one of claims 1 to 113, wherein the anti-FcRH5 antibody binds to an epitope within the Ig-like domain 9 of FcRH5.

115. The anti-FcRH5 antibody according to claim 114, wherein the epitope comprises a portion of amino acids 743 to 850 of SEQ ID NO:

114.

116. The anti-FcRH5 antibody according to claim 114 or 115, wherein the binding domain binds to human FcRH5 or cynomolgus monkey (cyno) FcRH5, or both.

117. The anti-FcRH5 antibody according to claim 116, wherein the binding domain does not specifically bind to FcRH1, FcRH2, FcRH3, and / or FcRH4.

118. The anti-FcRH5 antibody has a K content of approximately 100 nM or less. Ｄ An anti-FcRH5 antibody according to claim 116 or 117, which binds to human FcRH5.

119. The aforementioned anti-FcRH5 antibody has a K content of approximately 10 pM to approximately 100 nM. Ｄ The anti-FcRH5 antibody according to claim 118, which binds to human FcRH5.

120. The aforementioned anti-FcRH5 antibody has a K content of approximately 100 pM to approximately 100 nM. Ｄ The anti-FcRH5 antibody according to claim 119, which binds to human FcRH5.

121. The anti-FcRH5 antibody has a K content of approximately 1 nM to approximately 20 nM. Ｄ An anti-FcRH5 antibody according to claim 120, which binds to human FcRH5.

122. The anti-FcRH5 antibody has a K content of approximately 1 nM to approximately 10 nM. Ｄ The anti-FcRH5 antibody according to claim 121, which binds to human FcRH5.

123. The anti-FcRH5 antibody has a K content of approximately 100 nM or less. Ｄ An anti-FcRH5 antibody according to any one of claims 118 to 122, which binds to cynomolgus monkey FcRH5.

124. The aforementioned anti-FcRH5 antibody has a K content of approximately 10 pM to approximately 100 nM. Ｄ The anti-FcRH5 antibody according to claim 123, which binds to cynomolgus monkey FcRH5.

125. The aforementioned anti-FcRH5 antibody has a K content of approximately 100 pM to approximately 100 nM. Ｄ The anti-FcRH5 antibody according to claim 124, which binds to cynomolgus monkey FcRH5.

126. The anti-FcRH5 antibody binds to cynomolgus monkey FcRH5 with a K of about 1 nM to about 50 nM Ｄ The anti-FcRH5 antibody according to claim 125, which binds to cynomolgus monkey FcRH5 with a K of Ｄ .

127. The anti-FcRH5 antibody according to any one of claims 1 to 126, wherein the anti-FcRH5 antibody comprises a non-glycosylation site mutation.

128. The anti-FcRH5 antibody according to claim 127, wherein the non-glycosylation site mutation is a substitution mutation.

129. The anti-FcRH5 antibody according to claim 127 or 128, wherein the non-glycosylation site mutation reduces the effector function of the anti-FcRH5 antibody.

130. The anti-FcRH5 antibody according to claim 128 or 129, wherein the substitution mutation is in amino acid residues N297, L234, L235, D265, and / or P329 (EU numbering).

131. The anti-FcRH5 antibody according to claim 130, wherein the substitution mutation is selected from the group consisting of N297G, N297A, L234A, L235A, D265A, and P329G.

132. The anti-FcRH5 antibody according to claim 131, wherein the substitution mutation is the N297G mutation.

133. The anti-FcRH5 antibody according to any one of claims 1 to 132, wherein the anti-FcRH5 antibody is a monoclonal antibody, a human antibody, a humanized antibody, or a chimeric antibody.

134. The anti-FcRH5 antibody according to any one of claims 1 to 133, wherein the anti-FcRH5 antibody is an IgG antibody.

135. The anti-FcRH5 antibody according to any one of claims 1 to 134, wherein the anti-FcRH5 antibody is an antibody fragment that binds to FcRH5.

136. The antibody fragments are bis-Fab, Fab, Fab'-SH, Fv, scFv, and (Fab') ２ An anti-FcRH5 antibody according to claim 135, selected from the group consisting of fragments.

137. The anti-FcRH5 antibody according to claim 136, wherein the antibody fragment is a bis-Fab fragment.

138. The anti-FcRH5 antibody according to any one of claims 1 to 134, wherein the anti-FcRH5 antibody is a full-length antibody.

139. The anti-FcRH5 antibody according to any one of claims 1 to 138, wherein the anti-FcRH5 antibody is a monospecific antibody.

140. The anti-FcRH5 antibody according to any one of claims 1 to 138, wherein the anti-FcRH5 antibody is a multispecific antibody.

141. The anti-FcRH5 antibody according to claim 140, wherein the multispecific antibody is a bispecific antibody.

142. The anti-FcRH5 antibody according to claim 141, wherein the bispecific antibody includes a second binding domain that binds to surface antigen classification 3 (CD3).

143. The anti-FcRH5 antibody according to claim 142, wherein the second binding domain binds to an epitope of CD3 containing the amino acid residue Glu6 of CD3.

144. The anti-FcRH5 antibody according to claim 143, wherein the epitope further comprises one or more additional amino acid residues selected from the group consisting of Glun1, Asp2, and Met7 of CD3.

145. The anti-FcRH5 antibody according to claim 143 or 144, wherein the epitope comprises the amino acid residues Gln1, Asp2, and Glu6 of CD3.

146. The anti-FcRH5 antibody according to any one of claims 143 to 145, wherein the epitope comprises the amino acid residues Gln1, Asp2, Glu6, and Met7 of CD3.

147. The anti-FcRH5 antibody according to any one of claims 143 to 146, wherein the epitope does not contain the amino acid residue Glu5 of CD3.

148. The anti-FcRH5 antibody according to any one of claims 143 to 147, wherein the epitope does not contain the amino acid residues Gly3 and Glu5 of CD3.

149. The anti-FcRH5 antibody according to any one of claims 143 to 148, wherein the epitope consists of the amino acid residues Gln1, Asp2, Glu6, and Met7 of CD3.

150. The anti-FcRH5 antibody according to any one of claims 143 to 149, wherein the second binding domain can bind to a human CD3 polypeptide or a cynomolgus monkey CD3 polypeptide.

151. The anti-FcRH5 antibody according to claim 150, wherein the human CD3 polypeptide or the cynomolgus monkey CD3 polypeptide is, respectively, a human CD3ε polypeptide or a cynomolgus monkey CD3ε polypeptide.

152. The anti-FcRH5 antibody according to claim 150, wherein the human CD3 polypeptide or the cynomolgus monkey CD3 polypeptide is, respectively, a human CD3γ polypeptide or a cynomolgus monkey CD3γ polypeptide.

153. The second binding domain has a K of approximately 100 nM or less. Ｄ An anti-FcRH5 antibody according to any one of claims 142 to 152, wherein it binds to a human CD3ε polypeptide.

154. The second binding domain has a K2 concentration of approximately 10 pM to 100 nM. Ｄ The anti-FcRH5 antibody according to claim 153, which binds to a human CD3ε polypeptide.

155. The second binding domain has a K2 concentration of approximately 100 pM to approximately 50 nM. Ｄ The anti-FcRH5 antibody according to claim 154, which binds to a human CD3ε polypeptide.

156. The second binding domain has a K of approximately 1 nM to approximately 10 nM. Ｄ The anti-FcRH5 antibody according to claim 155, which binds to human CD3ε polypeptide.

157. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 117, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) An anti-FcRH5 antibody according to any one of claims 142 to 156, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

120.

158. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) The anti-FcRH5 antibody according to claim 157, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

123.

159. The anti-FcRH5 antibody according to claim 158, wherein the second binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 133, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 134, or (c) a VH domain as in (a) and a VL domain as in (b).

160. The second binding domain is the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 125, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 126, (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 127, and (d) The anti-FcRH5 antibody according to claim 158 or 159, comprising FR-H4 having the amino acid sequence of SEQ ID NO:

128.

161. The anti-FcRH5 antibody according to claim 160, wherein the second binding domain comprises a VH domain containing the amino acid sequence of SEQ ID NO:

133.

162. The second binding domain is the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 129, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 130, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 131, and (d) The anti-FcRH5 antibody according to any one of claims 158 to 161, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

132.

163. The anti-FcRH5 antibody according to claim 162, wherein the second binding domain comprises a VL domain containing the amino acid sequence of SEQ ID NO:

134.

164. The anti-FcRH5 antibody according to any one of claims 158 to 163, wherein the second binding domain comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 133, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

134.

165. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) The anti-FcRH5 antibody according to claim 157, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

124.

166. The anti-FcRH5 antibody according to claim 165, wherein the second binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 137, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 138, or (c) a VH domain as in (a) and a VL domain as in (b).

167. The second binding domain is the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 125, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 126, (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 127, and (d) The anti-FcRH5 antibody according to claim 165 or 166, comprising FR-H4 having the amino acid sequence of SEQ ID NO:

128.

168. The anti-FcRH5 antibody according to claim 167, wherein the second binding domain comprises a VH domain containing the amino acid sequence of SEQ ID NO:

137.

169. The second binding domain is the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 129, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 130, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 131, and (d) The anti-FcRH5 antibody according to any one of claims 165 to 168, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

132.

170. The anti-FcRH5 antibody according to claim 169, wherein the second binding domain comprises a VL domain having the amino acid sequence of SEQ ID NO:

138.

171. The anti-FcRH5 antibody according to any one of claims 165 to 170, wherein the second binding domain comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 137, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

138.

172. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 139, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 140, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 141, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 142, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 143, (f) An anti-FcRH5 antibody according to any one of claims 142 to 156, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

144.

173. The anti-FcRH5 antibody according to claim 172, wherein the second binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 153, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 154, or (c) a VH domain as in (a) and a VL domain as in (b).

174. The second binding domain is the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 145, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 146, (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 147, and (d) The anti-FcRH5 antibody according to claim 172 or 173, comprising FR-H4 having the amino acid sequence of SEQ ID NO:

148.

175. The anti-FcRH5 antibody according to claim 174, wherein the second binding domain comprises a VH domain containing the amino acid sequence of SEQ ID NO:

153.

176. The second binding domain is the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 149, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 150, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 151, and (d) The anti-FcRH5 antibody according to any one of claims 172 to 175, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

152.

177. The anti-FcRH5 antibody according to claim 176, wherein the second binding domain comprises a VL domain containing the amino acid sequence of SEQ ID NO:

154.

178. The anti-FcRH5 antibody according to any one of claims 172 to 177, wherein the second binding domain comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 153, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

154.

179. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 155, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 156, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 157, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 158, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 159, (f) An anti-FcRH5 antibody according to any one of claims 142 to 156, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

160.

180. The second binding domain is the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 155, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 162, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 157, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 158, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 159, (f) The anti-FcRH5 antibody according to claim 179, comprising HVR-L3 containing the amino acid sequence of SEQ ID NO:

160.

181. The anti-FcRH5 antibody according to claim 180, wherein the second binding domain comprises (a) a VH domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 172, (b) a VL domain having at least 95% sequence identity with respect to the amino acid sequence of SEQ ID NO: 173, or (c) a VH domain as in (a) and a VL domain as in (b).

182. The second binding domain is the following heavy chain variable region FR: (a) FR-H1 containing the amino acid sequence of SEQ ID NO: 164, (b) FR-H2 containing the amino acid sequence of SEQ ID NO: 165 (c) FR-H3 containing the amino acid sequence of SEQ ID NO: 166, and (d) The anti-FcRH5 antibody according to claim 180 or 181, comprising FR-H4 having the amino acid sequence of SEQ ID NO:

167.

183. The anti-FcRH5 antibody according to claim 182, wherein the second binding domain comprises a VH domain having the amino acid sequence of SEQ ID NO:

172.

184. The second binding domain is the following light chain variable region FR: (a) FR-L1 containing the amino acid sequence of SEQ ID NO: 168, (b) FR-L2 containing the amino acid sequence of SEQ ID NO: 169, (c) FR-L3 containing the amino acid sequence of SEQ ID NO: 170, and (d) The anti-FcRH5 antibody according to any one of claims 180 to 183, further comprising FR-L4 having the amino acid sequence of SEQ ID NO:

171.

185. The anti-FcRH5 antibody according to claim 184, wherein the second binding domain comprises a VL domain containing the amino acid sequence of SEQ ID NO:

173.

186. The anti-FcRH5 antibody according to any one of claims 180 to 185, wherein the second binding domain comprises (a) a VH domain containing the amino acid sequence of SEQ ID NO: 172, and (b) a VL domain containing the amino acid sequence of SEQ ID NO:

173.

187. The binding domain that binds to FcRH5 is a charged region (CR １ ) including VH domain (VH １ ), and the charged region (CR ２ ) including VL domain (VL １ ) including the VH １ The CR inside １ However, the VL １ The CR inside ２ An anti-FcRH5 antibody according to any one of claims 142 to 186, which forms a charge pair with the antibody.

188. The aforementioned CR １ However, it contains basic amino acid residues, and the CR ２ However, the anti-FcRH5 antibody according to claim 187, comprising an acidic amino acid residue.

189. The aforementioned CR １ However, the anti-FcRH5 antibody according to claim 188, comprising the Q39K substitution mutation (EU numbering).

190. The aforementioned CR １ However, the anti-FcRH5 antibody according to claim 189 comprises a Q39K substitution mutation.

191. The aforementioned CR ２ However, an anti-FcRH5 antibody according to any one of claims 187 to 190, comprising the Q38E substitution mutation (EU numbering).

192. The aforementioned CR ２ However, the anti-FcRH5 antibody according to claim 191 comprises a Q38E substitution mutation.

193. The second binding domain that binds to CD3 is a charged region (CR ３ ) including VH domain (VH ２ ), and the charged region (CR ４ ) including VL domain (VL ２ ) including the VL ２ The CR inside ４ However, the aforementioned VH ２ The CR inside ３ An anti-FcRH5 antibody according to any one of claims 187 to 192, which forms a charge pair with [the specified antibody].

194. The aforementioned CR ４ However, it contains basic amino acid residues, and the CR ３ However, the anti-FcRH5 antibody according to claim 193, comprising an acidic amino acid residue.

195. The aforementioned CR ４ However, the anti-FcRH5 antibody according to claim 194, comprising the Q38K substitution mutation (EU numbering).

196. The aforementioned CR ４ However, the anti-FcRH5 antibody according to claim 195 comprises a Q38K substitution mutation.

197. The aforementioned CR ３ However, an anti-FcRH5 antibody according to any one of claims 193 to 196, comprising the Q39E substitution mutation (EU numbering).

198. The aforementioned CR ３ However, the anti-FcRH5 antibody according to claim 197 comprises the Q39E substitution mutation.

199. Said VL １ The domain is a light chain stationary (CL) domain (CL １ ) is connected to the VH １ However, the first heavy chain constant (CH1) domain (CH1 １ ) is connected to the CL １ However, in the charged region (CR ５ ) including the CH1 １ However, in the charged region (CR ６ ) including the CL １ The CR inside ５ However, the aforementioned CH1 １ The CR inside ６ An anti-FcRH5 antibody according to any one of claims 187 to 198, which forms a charge pair with [the specified antibody].

200. The aforementioned CR ５ However, it contains basic amino acid residues, and the CR ６ The anti-FcRH5 antibody according to claim 199, wherein it contains an acidic residue.

201. The aforementioned CR ５ However, the anti-FcRH5 antibody according to claim 200, comprising the V133K substitution mutation (EU numbering).

202. The aforementioned CR ５ However, the anti-FcRH5 antibody according to claim 201, comprising a V133K substitution mutation.

203. The aforementioned CR ６ However, an anti-FcRH5 antibody according to any one of claims 199 to 202, comprising the S183E substitution mutation (EU numbering).

204. The aforementioned CR ６ However, the anti-FcRH5 antibody according to claim 203, comprising the S183E substitution mutation.

205. Said VL ２ The domain is a CL domain (CL ２ ) is connected to the VH ２ However, CH1 domain (CH1 ２ ) is connected to the CL ２ However, in the charged region (CR ７ ) including the CH1 ２ However, in the charged region (CR ８ ) including the CH1 ２ The CR inside ８ However, the CL ２ The CR inside ７ An anti-FcRH5 antibody according to any one of claims 199 to 204, which forms a charge pair with [the specified antibody].

206. The aforementioned CR ８ However, it contains basic amino acid residues, and the CR ７ However, the anti-FcRH5 antibody according to claim 205, comprising an acidic amino acid residue.

207. The aforementioned CR ８ However, the anti-FcRH5 antibody according to claim 206, comprising the S183K substitution mutation (EU numbering).

208. The aforementioned CR ８ However, the anti-FcRH5 antibody according to claim 207, comprising an S183K substitution mutation.

209. The aforementioned CR ７ However, an anti-FcRH5 antibody according to any one of claims 205 to 208, comprising the V133E substitution mutation (EU numbering).

210. The aforementioned CR ７ However, the anti-FcRH5 antibody according to claim 209 comprises a V133E substitution mutation.

211. Said VL ２ The domain is a CL domain (CL ２ ) is connected to the VH ２ However, CH1 domain (CH1 ２ (a) The CL ２ (b) The CH1 ２ The anti-FcRH5 antibody according to any one of claims 199 to 204, wherein the antibody comprises one or more mutations in amino acid residues A141, F170, S181, S183, and / or V185 (EU numbering).

212. The aforementioned CL ２ The anti-FcRH5 antibody according to claim 211, comprising one or more of the following substitutional mutations: F116A, L135V, S174A, S176F, and / or T178V.

213. The aforementioned CL ２ The anti-FcRH5 antibody according to claim 212, comprising the following substitutional mutations: F116A, L135V, S174A, S176F, and T178V.

214. The aforementioned CH1 ２ The anti-FcRH5 antibody according to any one of claims 211 to 213, comprising one or more of the following substitutional mutations: A141I, F170S, S181M, S183A, and / or V185A.

215. The aforementioned CH1 ２ The anti-FcRH5 antibody according to claim 214, comprising the following substitutional mutations: A141I, F170S, S181M, S183A, and V185A.

216. The binding domain that binds to FcRH5 comprises a VH domain (VH １ ) containing a charged region (CR １ ), and a VL domain (VL ２ ) containing a charged region (CR １ ), and the CR １ within the VL ２ forms a charge pair with the CR １ within the VH １ . The anti-FcRH5 antibody according to any one of claims 142 to 186.

217. The CR ２ contains a basic amino acid residue, and the CR １ contains an acidic amino acid residue, and the anti-FcRH5 antibody according to claim 216.

218. The aforementioned CR ２ However, the anti-FcRH5 antibody according to claim 217 includes a Q38K substitution mutation (EU numbering).

219. The aforementioned CR ２ However, the anti-FcRH5 antibody according to claim 218 comprises a Q38K substitution mutation.

220. The aforementioned CR １ However, an anti-FcRH5 antibody according to any one of claims 216 to 219, comprising the Q39E substitution mutation (EU numbering).

221. The aforementioned CR １ However, the anti-FcRH5 antibody according to claim 220 comprises the Q39E substitution mutation.

222. The second binding domain that binds to CD3 is a charged region (CR ３ ) including VH domain (VH ２ ), and the charged region (CR ４ ) including VL domain (VL ２ ) including the VH ２ The CR inside ３ However, the VL ２ The CR inside ４ An anti-FcRH5 antibody according to any one of claims 216 to 221, which forms a charge pair with the antibody.

223. The aforementioned CR ３ However, it contains basic amino acid residues, and the CR ４ However, the anti-FcRH5 antibody according to claim 222, comprising an acidic amino acid residue.

224. The aforementioned CR ３ However, the anti-FcRH5 antibody according to claim 223, comprising the Q39K substitution mutation (EU numbering).

225. The aforementioned CR ３ However, the anti-FcRH5 antibody according to claim 224, comprising a Q39K substitution mutation.

226. The aforementioned CR ４ However, an anti-FcRH5 antibody according to any one of claims 222 to 225, comprising the Q38E substitution mutation (EU numbering).

227. The aforementioned CR ４ However, the anti-FcRH5 antibody according to claim 225, comprising the Q38E substitution mutation.

228. Said VL １ The domain is a light chain stationary (CL) domain (CL １ ) is connected to the VH １ However, the first heavy chain constant (CH1) domain (CH1 １ ) is connected to the CL １ However, in the charged region (CR ５ ) including the CH1 １ However, in the charged region (CR ６ ) including the CH1 １ The CR inside ６ However, the CL １ The CR inside ５ An anti-FcRH5 antibody according to any one of claims 216 to 227, which forms a charge pair with the antibody.

229. The aforementioned CR ６ However, it contains basic amino acid residues, and the CR ５ However, the anti-FcRH5 antibody according to claim 228, comprising an acidic amino acid residue.

230. The aforementioned CR ６ However, the anti-FcRH5 antibody according to claim 229, comprising the S183K substitution mutation (EU numbering).

231. The aforementioned CR ６ However, the anti-FcRH5 antibody according to claim 230 comprises an S183K substitution mutation.

232. The aforementioned CR ５ The anti-FcRH5 antibody according to any one of claims 228 to 231, comprising the V133E substitution mutation (EU numbering).

233. The aforementioned CR ５ However, the anti-FcRH5 antibody according to claim 232 comprises a V133E substitution mutation.

234. Said VL ２ The domain is a CL domain (CL ２ ) is connected to the VH ２ However, CH1 domain (CH1 ２ ) is connected to the CL ２ However, in the charged region (CR ７ ) including the CH1 ２ However, in the charged region (CR ８ ) including the CL ２ The CR inside ７ However, the aforementioned CH1 ２ The CR inside ８ An anti-FcRH5 antibody according to any one of claims 228 to 233, which forms a charge pair with the antibody.

235. The aforementioned CR ７ However, it contains basic amino acid residues, and the CR ８ However, the anti-FcRH5 antibody according to claim 234, comprising an acidic residue.

236. The aforementioned CR ７ However, the anti-FcRH5 antibody according to claim 235 includes a V133K substitution mutation (EU numbering).

237. The aforementioned CR ７ However, the anti-FcRH5 antibody according to claim 236, comprising a V133K substitution mutation.

238. The aforementioned CR ８ However, an anti-FcRH5 antibody according to any one of claims 234 to 237, comprising the S183E substitution mutation (EU numbering).

239. The aforementioned CR ８ However, the anti-FcRH5 antibody according to claim 238, comprising the S183E substitution mutation.

240. Said VL ２ The domain is a CL domain (CL ２ ) is connected to the VH ２ However, CH1 domain (CH1 ２ (a) The CL ２ (b) The CH1 ２ The anti-FcRH5 antibody according to any one of claims 228 to 233, wherein it comprises one or more mutations in amino acid residues A141, F170, S181, S183, and / or V185 (EU numbering).

241. The aforementioned CL ２ The anti-FcRH5 antibody according to claim 240, comprising one or more of the following substitutional mutations: F116A, L135V, S174A, S176F, and / or T178V.

242. The aforementioned CL ２ The anti-FcRH5 antibody according to claim 241, comprising the following substitutional mutations: F116A, L135V, S174A, S176F, and T178V.

243. The aforementioned CH1 ２ The anti-FcRH5 antibody according to any one of claims 240 to 242, comprising one or more of the following substitutional mutations: A141I, F170S, S181M, S183A, and / or V185A.

244. The aforementioned CH1 ２ The anti-FcRH5 antibody according to claim 243, comprising the following substitutional mutations: A141I, F170S, S181M, S183A, and V185A.

245. The anti-FcRH5 antibody comprises one or more heavy chain constant domains, and the one or more heavy chain constant domains comprises a first CH2 domain (CH2 １ ), the first CH3 domain (CH3 １ ), the second CH2 domain (CH2 ２ ), and the second CH3 domain (CH3 ２ An anti-FcRH5 antibody according to any one of claims 187 to 244, selected from ).

246. The anti-FcRH5 antibody according to claim 245, wherein at least one of the one or more heavy chain constant domains is paired with another heavy chain constant domain.

247. The aforementioned CH3 １ and the CH3 ２ However, each has a raised area (P １ ) or cavity (C １ ) including the CH3 １ The P inside １ or C １ However, each of the above CH3 ２ C inside １ or P １ The anti-FcRH5 antibody according to claim 246, which can be positioned as follows.

248. The aforementioned CH3 １ and the CH3 ２ However, the aforementioned P １ and C １ The anti-FcRH5 antibody of claim 247, which intersects at the interface with the other.

249. The aforementioned CH2 １ and the CH2 ２ However, each of them, (P ２ ) or cavity (C ２ ) including the CH2 １ The P inside ２ or C ２ However, each of the above CH2 ２ C inside ２ or P ２ An anti-FcRH5 antibody according to any one of claims 245 to 249, which can be positioned as follows.

250. The aforementioned CH2 １ and the CH2 ２ However, the aforementioned P ２ and C ２ The anti-FcRH5 antibody according to claim 249, which intersects at the interface with the other.

251. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody binds to the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) an anti-FcRH5 arm comprising a first binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO: 23, The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) comprising an anti-CD3 arm comprising a second binding domain, which comprises HVR-L3 containing the amino acid sequence of SEQ ID NO: 123, The anti-FcRH5 arm and the anti-CD3 arm each contain the N297G substitution mutation (EU numbering), The anti-FcRH5 antibody wherein the anti-FcRH5 arm contains the T366W substitution mutation, and the anti-CD3 arm contains the T366S, L368A, and Y407V substitution mutations.

252. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody binds to the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) an anti-FcRH5 arm comprising a first binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO: 23, The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) comprising an anti-CD3 arm comprising a second binding domain, which comprises HVR-L3 containing the amino acid sequence of SEQ ID NO: 123, The anti-FcRH5 arm comprises a light chain containing Q38E and V133K substitution mutations, and a heavy chain containing Q39K, S183E, and N297G substitution mutations. The anti-CD3 arm of the anti-FcRH5 antibody comprises a light chain containing Q38K and V133E substitution mutations, and a heavy chain containing Q39E, S183K, and N297G substitution mutations (EU numbered).

253. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody is (a) An anti-FcRH5 arm comprising a first binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 104 and a VL domain comprising the amino acid sequence of SEQ ID NO: 105, wherein the anti-FcRH5 arm comprises a light chain comprising Q38E and V133K substitution mutations and a heavy chain comprising Q39K, S183E and N297G substitution mutations, (b) The anti-CD3 arm comprising a second binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 133 and a VL domain comprising the amino acid sequence of SEQ ID NO: 134, wherein the anti-CD3 arm comprises a light chain comprising Q38K and V133E substitution mutations and a heavy chain comprising Q39E, S183K and N297G substitution mutations (EU numbered), the anti-FcRH5 antibody.

254. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody binds to the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) an anti-FcRH5 arm comprising a first binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO: 23, The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) comprising an anti-CD3 arm comprising a second binding domain, which comprises HVR-L3 containing the amino acid sequence of SEQ ID NO: 123, The anti-FcRH5 arm comprises a light chain containing Q38K and V133E substitution mutations, and a heavy chain containing Q39E, S183K, and N297G substitution mutations. The anti-CD3 arm of the anti-FcRH5 antibody comprises a light chain containing Q38E and V133K substitution mutations, and a heavy chain containing Q39K, S183E, and N297G substitution mutations (EU numbered).

255. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody is (a) an anti-FcRH5 arm comprising a first binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 104 and a VL domain comprising the amino acid sequence of SEQ ID NO: 105, wherein the anti-FcRH5 arm comprises a light chain comprising Q38K and V133E substitution mutations and a heavy chain comprising Q39E, S183K and N297G substitution mutations, (b) The anti-CD3 arm comprising a second binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 133 and a VL domain comprising the amino acid sequence of SEQ ID NO: 134, wherein the anti-CD3 arm comprises a light chain comprising Q38E and V133K substitution mutations and a heavy chain comprising Q39K, S183E and N297G substitution mutations (EU numbered), the anti-FcRH5 antibody.

256. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody binds to the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) an anti-FcRH5 arm comprising a first binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO: 23, The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) comprising an anti-CD3 arm comprising a second binding domain, which comprises HVR-L3 containing the amino acid sequence of SEQ ID NO: 123, The anti-FcRH5 arm comprises a light chain containing Q38E and V133K substitution mutations, and a heavy chain containing Q39K, S183E, and N297G substitution mutations. The anti-CD3 arm comprises a light chain containing Q38K, F116A, L135V, S174A, S176F, and T178V substitution mutations, and a heavy chain containing Q39E, A141I, F170S, S181M, S183A, V185A, and N297G substitution mutations (EU numbered), wherein the anti-FcRH5 antibody.

257. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody is (a) An anti-FcRH5 arm comprising a first binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 104 and a VL domain comprising the amino acid sequence of SEQ ID NO: 105, wherein the anti-FcRH5 arm comprises a light chain comprising Q38E and V133K substitution mutations and a heavy chain comprising Q39K, S183E and N297G substitution mutations, (b) The anti-CD3 arm comprising a second binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 133 and a VL domain comprising the amino acid sequence of SEQ ID NO: 134, wherein the anti-CD3 arm comprises a light chain comprising Q38K, F116A, L135V, S174A, S176F, and T178V substitution mutations, and a heavy chain comprising Q39E, A141I, F170S, S181M, S183A, V185A, and N297G substitution mutations (EU numbered), the anti-FcRH5 antibody.

258. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody binds to the following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 1, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 8, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 9, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 12, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 16, and (f) an anti-FcRH5 arm comprising a first binding domain containing HVR-L3 containing the amino acid sequence of SEQ ID NO: 23, The following six HVRs: (a) HVR-H1 containing the amino acid sequence of SEQ ID NO: 115, (b) HVR-H2 containing the amino acid sequence of SEQ ID NO: 116, (c) HVR-H3 containing the amino acid sequence of SEQ ID NO: 121, (d) HVR-L1 containing the amino acid sequence of SEQ ID NO: 118, (e) HVR-L2 containing the amino acid sequence of SEQ ID NO: 119, and (f) comprising an anti-CD3 arm comprising a second binding domain, which comprises HVR-L3 containing the amino acid sequence of SEQ ID NO: 123, The anti-FcRH5 arm comprises a light chain containing Q38K and V133E substitution mutations, and a heavy chain containing Q39E, S183K, and N297G substitution mutations. The anti-CD3 arm comprises a light chain containing Q38E, F116A, L135V, S174A, S176F, and T178V substitution mutations, and a heavy chain containing Q39K, A141I, F170S, S181M, S183A, V185A, and N297G substitution mutations (EU numbered), wherein the anti-FcRH5 antibody.

259. An anti-FcRH5 antibody that binds to FcRH5 and CD3, wherein the anti-FcRH5 antibody is (a) an anti-FcRH5 arm comprising a first binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 104 and a VL domain comprising the amino acid sequence of SEQ ID NO: 105, wherein the anti-FcRH5 arm comprises a light chain comprising Q38K and V133E substitution mutations and a heavy chain comprising Q39E, S183K and N297G substitution mutations, (b) The anti-CD3 arm comprising a second binding domain comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 133 and a VL domain comprising the amino acid sequence of SEQ ID NO: 134, wherein the anti-CD3 arm comprises a light chain comprising Q38E, F116A, L135V, S174A, S176F, and T178V substitution mutations, and a heavy chain comprising Q39K, A141I, F170S, S181M, S183A, V185A, and N297G substitution mutations (EU numbered), the anti-FcRH5 antibody.

260. The anti-FcRH5 antibody according to any one of claims 1 to 8, 114 to 164, and 187 to 259, wherein the anti-FcRH5 antibody has a clearance after intravenous injection of about 10 ml / kg / day to about 35 ml / kg / day.

261. The anti-FcRH5 antibody according to claim 260, wherein the anti-FcRH5 antibody has a clearance in mice after intravenous injection of approximately 10 ml / kg / day to approximately 20 ml / kg / day.

262. The anti-FcRH5 antibody according to claim 261, wherein the anti-FcRH5 antibody has a clearance in mice after intravenous injection of approximately 12 ml / kg / day to approximately 16 ml / kg / day.

263. The anti-FcRH5 antibody according to any one of claims 260 to 262, wherein the anti-FcRH5 antibody has a clearance after intravenous injection of approximately 20 ml / kg / day to approximately 40 ml / kg / day in cynomolgus monkeys.

264. The anti-FcRH5 antibody according to claim 263, wherein the anti-FcRH5 antibody has a clearance after intravenous injection of approximately 25 ml / kg / day to approximately 35 ml / kg / day in cynomolgus monkeys.

265. The anti-FcRH5 antibody according to claim 264, wherein the anti-FcRH5 antibody has a clearance after intravenous injection of approximately 30 ml / kg / day to approximately 35 ml / kg / day in cynomolgus monkeys.

266. An isolated nucleic acid encoding an anti-FcRH5 antibody according to any one of claims 1 to 265, or a portion thereof comprising a binding domain that binds to FcRH5.

267. A vector comprising the isolated nucleic acid described in claim 266.

268. A host cell comprising the vector according to claim 267.

269. The host cell according to claim 268, wherein the host cell is a mammalian cell.

270. The host cell according to claim 269, wherein the mammalian cell is a Chinese hamster ovary (CHO) cell.

271. The host cell according to claim 268, wherein the host cell is a prokaryotic cell.

272. The host cell according to claim 271, wherein the prokaryotic cell is an E. coli cell.

273. A method for producing an anti-FcRH5 antibody according to any one of claims 1 to 265, comprising culturing the host cell described in claim 268 in a culture medium.

274. The method according to claim 273, further comprising recovering the anti-FcRH5 antibody from the host cells or the culture medium.

275. The method according to claim 273, further comprising culturing a second host cell comprising a second nucleic acid encoding an anti-CD3 antibody having a binding domain that binds to CD3.

276. The method according to claim 275, wherein the host cells are co-cultured.

277. The method according to claim 275 or 276, further comprising recovering the bispecific anti-FcRH5 antibody from the host cells or the culture medium.

278. An immune complex comprising an anti-FcRH5 antibody according to any one of claims 1 to 265 and a cytotoxic agent.

279. A composition comprising the anti-FcRH5 antibody according to any one of claims 1 to 265.

280. The composition according to claim 279, further comprising a pharmaceutically acceptable excipient or diluent.

281. The composition according to claim 280, wherein the pharmaceutically acceptable excipient is a buffer, carrier, stabilizer, or preservative.

282. The composition according to claim 281, wherein the composition is a pharmaceutical composition.

283. The composition according to any one of claims 279 to 282, wherein the composition further comprises a PD-1 axis-binding antagonist or an additional therapeutic agent.

284. An anti-FcRH5 antibody according to any one of claims 1 to 265, for use as a pharmaceutical product.

285. An anti-FcRH5 antibody according to any one of claims 1 to 265, for use in treatment or delay of progression in subjects requiring treatment or delay of progression of FcRH5-positive cancer.

286. An anti-FcRH5 antibody according to any one of claims 1 to 265, for use in enhancing immune function in subjects with FcRH5-positive cancer.

287. The anti-FcRH5 antibody according to claim 285 or 286, wherein the FcRH5-positive cancer is a B-cell carcinoma.

288. The anti-FcRH5 antibody according to claim 287, wherein the B-cell carcinoma is selected from the group consisting of multiple myeloma (MM), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL).

289. The anti-FcRH5 antibody according to claim 288, wherein the B-cell carcinoma is MM.

290. Use of an anti-FcRH5 antibody according to any one of claims 1 to 265, or a composition according to any one of claims 279 to 283, in the manufacture of a pharmaceutical product for the treatment or delaying the progression of FcRH5-positive cancer in a subject.

291. Use of an anti-FcRH5 antibody according to any one of claims 1 to 265, or a composition according to any one of claims 279 to 283, in the manufacture of a pharmaceutical product for enhancing immune function in a subject having FcRH5-positive cancer.

292. The use according to claim 290 or 291, wherein the FcRH5-positive cancer is a B-cell carcinoma.

293. The use according to claim 292, wherein the B-cell carcinoma is selected from the group consisting of MM, CLL, MCL, DLBCL, and FL.

294. The use according to claim 293, wherein the B-cell carcinoma is MM.

295. A method for treating or delaying the progression of FcRH5-positive cancer in a subject requiring treatment or delaying the progression of the cancer, comprising administering an anti-FcRH5 antibody according to any one of claims 1 to 265 to the subject.

296. A method for enhancing immune function in a subject having FcRH5-positive cancer, comprising administering an effective amount of an anti-FcRH5 antibody according to any one of claims 1 to 265 to the subject.

297. The method according to claim 295 or 296, wherein the FcRH5-positive cancer is a B-cell carcinoma.

298. The method according to claim 297, wherein the B-cell carcinoma is selected from the group consisting of MM, CLL, MCL, DLBCL, and FL.

299. The method according to claim 298, wherein the B-cell carcinoma is MM.

300. The method according to any one of claims 295 to 299, wherein the anti-FcRH5 antibody binds to (a) an FcRH5 molecule located on a target cell and (b) a CD3 molecule located on an immunoeffector cell.

301. The method according to claim 300, wherein the anti-FcRH5 antibody activates the immunoeffector cells after binding to the FcRH5 molecule and the CD3 molecule.

302. The method according to claim 301, wherein the activated immune effector cells can exert cytotoxic and / or apoptotic effects on the target cells.

303. The method according to any one of claims 300 to 302, wherein the target cell is a plasma cell.

304. The method according to claim 303, wherein the plasma cells are short-lived plasma cells.

305. The method according to claim 303, wherein the plasma cells are long-lived plasma cells.

306. The method according to any one of claims 303 to 305, wherein the plasma cells are myeloma cells.

307. The method according to any one of claims 295 to 306, wherein the method comprises administering the anti-FcRH5 antibody to the subject at a dosage of about 0.01 mg / kg / week to about 50 mg / kg / week.

308. The method according to claim 307, wherein the method comprises administering the anti-FcRH5 antibody to the subject at a dosage of approximately 0.1 mg / kg / week to approximately 10 mg / kg / week.

309. The method according to claim 308, wherein the method comprises administering the anti-FcRH5 antibody to the subject at a dosage of approximately 1 mg / kg / week.

310. The method according to any one of claims 295 to 309, further comprising administering a PD-1 axis-binding antagonist and / or an additional therapeutic agent to the subject.

311. The method according to claim 310, wherein the PD-1 axis-binding antagonist or additional therapeutic agent is administered before or after the administration of the anti-FcRH5 antibody.

312. The method according to claim 311, wherein the PD-1 axis-binding antagonist or additional therapeutic agent is administered simultaneously with the anti-FcRH5 antibody.

313. The method according to any one of claims 310 to 312, wherein the PD-1 axis binding antagonist is selected from the group consisting of PD-L1 binding antagonists, PD-1 binding antagonists, and PD-L2 binding antagonists.

314. The method according to claim 313, wherein the PD-1 axis binding antagonist is a PD-L1 binding antagonist.

315. The method according to claim 314, wherein the PD-L1 binding antagonist is selected from the group consisting of MPDL3280A (atezolizumab), YW243.55.S70, MDX-1105, MEDI4736 (durvalumab), and MSB0010718C (avelumab).

316. The method according to claim 315, wherein the PD-L1 binding antagonist is MPDL3280A (atezolizumab).

317. The method according to claim 313, wherein the PD-1 axis binding antagonist is a PD-1 binding antagonist.

318. The method according to claim 317, wherein the PD-1 binding antagonist is selected from the group consisting of MDX 1106 (nivolumab), MK-3475 (pembrolizumab), CT-011 (pidilizumab), MEDI-0680 (AMP-514), PDR001, REGN2810, and BGB-108.

319. The method according to claim 313, wherein the PD-1 axis binding antagonist is a PD-L2 binding antagonist.

320. The method according to claim 319, wherein the PD-L2 binding antagonist is an antibody or an immunoadhesin.

321. The method according to any one of claims 295 to 320, further comprising administering a steroid, an immunomodulator (IMiD), a proteosome inhibitor (PI), or a combination thereof to the subject.

322. The method according to claim 321, wherein the steroid is a glucocorticoid.

323. The method according to claim 322, wherein the glucocorticoid is dexamethasone.

324. The method according to claim 321, wherein the IMiD is lenalidomide.

325. The method according to claim 321, wherein the PI is bortezomib.

326. The method according to any one of claims 295 to 325, wherein the method comprises administering the anti-FcRH5 antibody, PD-1 axis-binding antagonist, steroid, IMiD, PI, or a combination thereof intravenously, subcutaneously, intramuscularly, locally, orally, percutaneously, intraperitoneally, intraorbitally, by implantation, by inhalation, intrathecally, intravenously, or intranasally.

327. The method according to claim 326, wherein the method comprises administering intravenously the anti-FcRH5 antibody, PD-1 axis-binding antagonist, steroid, IMiD, PI, or a combination thereof.

328. The method according to claim 326, wherein the method comprises subcutaneously administering the anti-FcRH5 antibody, PD-1 axis-binding antagonist, steroid, IMiD, PI, or a combination thereof.

329. The method according to any one of claims 295 to 328, wherein the subject is a human.

330. A method for detecting FcRH5 in a biological sample from a subject, wherein the method is (a) Contacting the biological sample with the anti-FcRH5 antibody described in any one of claims 1 to 265 under conditions that allow the anti-FcRH5 antibody to bind to naturally occurring FcRH5 in the biological sample, (b) The method comprising detecting whether a complex of the anti-FcRH5 antibody and spontaneously occurring FcRH5 is formed in the biological sample.

331. The method according to claim 330, wherein the biological sample is a blood sample.

332. The method according to claim 330 or 331, wherein the subject is a human.

333. A kit comprising an antibody according to any one of claims 1 to 265, and a package insert containing instructions for using the antibody for the treatment or delaying the progression of FcRH5-positive cancer in a subject.

334. A kit comprising an antibody according to any one of claims 1 to 265, and an accompanying document containing instructions for using the antibody to enhance immune function in a subject having FcRH5-positive cancer.

335. The kit according to claim 333 or 334, wherein the subject is a human.

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