Anti-IL-6 monoclonal antibodies and uses thereof

• US 20080075726A1
• Filed: 08/03/2007
• Published: 03/27/2008
• Est. Priority Date: 08/03/2006
• Status: Active Grant

• Current Assignee: Vaccinex, Inc.
• Original Assignee: Vaccinex, Inc.
• Inventors: Smith, Ernest, Wang, Wei
• Granted Patent: US 7,919,095 B2
• Time in Patent Office: Days
• US Class Current: 424/141.1
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention provides novel monoclonal antibodies that bind specifically to IL-6. The antibodies of the invention comprise a variable heavy chain (VH) region selected from any of the VH regions disclosed herein as well as amino acid variants thereof, and/or a variable light chain (VL) region selected from any of the VL regions disclosed herein as well as amino acid variants thereof. The invention also provides methods of treating diseases and disorders associated with IL-6 expression and/or activity.

Claims

1. An isolated monoclonal antibody comprising:

(a) a variable heavy chain region (VH) comprising;

(i) a VH-CDR1 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

51, SEQ ID NO;

52, SEQ ID NO;

53, SEQ ID NO;

54, SEQ ID NO;

55, and an amino acid sequence that is identical to any one of SEQ ID NOs;

51-55 except for 1 to 5 amino acid substitutions;

(ii) a VH-CDR2 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

56, SEQ ID NO;

57, SEQ ID NO;

58, SEQ ID NO;

59, SEQ ID NO;

60, SEQ ID NO;

61, SEQ ID NO;

97, and an amino acid sequence that is identical to any one of SEQ ID NOs;

56 to 61 or 97 except for 1 to 5 amino acid substitutions;

(iii) a VH-CDR3 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

62, SEQ ID NO;

63, SEQ ID NO;

64, SEQ ID NO;

65, SEQ ID NO;

66, SEQ ID NO;

67, SEQ ID NO;

68, SEQ ID NO;

69, SEQ ID NO;

70, SEQ ID NO;

71, SEQ ID NO;

72, SEQ ID NO;

73, SEQ ID NO;

98, and an amino acid sequence that is identical to any one of SEQ ID NOs;

62 to 73 or 98 except for 1 to 5 amino acid substitutions; and

(b) a variable light chain region (VL) comprising;

(i) a VL-CDR1 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

74, SEQ ID NO;

75, SEQ ID NO;

76, SEQ ID NO;

77, SEQ ID NO;

78, SEQ ID NO;

79, and an amino acid sequence that is identical to any one of SEQ ID NOs;

74-79 except for 1 to 5 amino acid substitutions;

(ii) a VL-CDR2 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

80, SEQ ID NO;

81, SEQ ID NO;

82, SEQ ID NO;

83, SEQ ID NO;

84, SEQ ID NO;

85, and an amino acid sequence that is identical to any one of SEQ ID NOs;

80-85 except for 1 to 5 amino acid substitutions;

(iii) a VL-CDR3 comprising an amino acid sequence selected from the group consisting of;

SEQ ID NO;

86, SEQ ID NO;

87, SEQ ID NO;

88, SEQ ID NO;

89, SEQ ID NO;

90, SEQ ID NO;

91, SEQ ID NO;

92, SEQ ID NO;

93, SEQ ID NO;

94, SEQ ID NO;

95, SEQ ID NO;

96, and an amino acid sequence that is identical to any one of SEQ ID NOs;

86-96 except for 1 to 5 amino acid substitutions;

wherein said antibody binds specifically to an IL-6 antigen.

81. A method for treating an inflammatory disease, said method comprising administering an antibody of claim 1 to a patient in need thereof.

82. A method for treating an autoimmune disease, said method comprising administering an antibody of claim 1 to a patient in need thereof.

83. The method of claim 82, wherein the autoimmune disease is rheumatoid arthritis.

84. A method for treating a cancer, said method comprising administering an antibody of claim 1 to a patient in need thereof.

85. The method of claim 84, wherein said cancer is multiple myeloma.

86. The method of claim 84, wherein said cancer is selected from the group consisting of renal carcinoma, breast cancer, prostate cancer, lymphoma and post-transplant lymphoma.

87. A method for treating idiopathic juvenile arthritis, said method comprising administering an antibody of claim 1 to a patient in need thereof.

88. A method for producing the isolated monoclonal antibody of claim 1, said method comprising:

(i) culturing a host cell expressing one or more nucleic acid sequences encoding said antibody and (ii) recovering said antibody from the culture medium.

90. A pharmaceutical composition comprising the isolated monoclonal antibody of claim 1 and a pharmaceutically acceptable carrier.

92. The isolated monoclonal antibody of claim 1, wherein said antibody inhibits IL-6-induced proliferation of cells such as murine B9 (ECACC) or human U266 myeloma cells at a level of 80% or greater inhibition.

93. The isolated monoclonal antibody of claim 1, wherein said antibody binds specifically to IL-6, inhibiting the binding of IL-6 to its receptor at a level of 80% or greater inhibition.

2. An isolated human monoclonal antibody comprising a variable heavy chain CDR1 (VH-CDR1) having the amino acid sequence T-S-G-X₁-X₂-V-X₃ (SEQ ID NO:

99), wherein X₁, X₂ and X₃ can be any amino acid, and wherein said antibody binds specifically to an IL-6 antigen.

3. The antibody of claim 2, wherein X₁ is methionine (M) or valine (V).

4. The antibody of claim 3, wherein X₁ is valine (V).

5. The antibody of claim 2, wherein X₂ is cysteine (C), alanine (A), serine (S) or glycine (G).

6. The antibody of claim 2, wherein X₃ is serine (S) or glycine (G).

7. An isolated human monoclonal antibody comprising a variable heavy chain CDR2 (VH-CDR2) having the amino acid sequence X₁-X₂-X₃-W-D-D-D-X₄-X₅-Y-X₆-P-S-L-X₇-X₈ (SEQ ID NO:

100), wherein X₁, X₂, X₃, X₄, X₅, X₆, X₇ and X₈ can be any amino acid, and wherein said antibody binds specifically to an IL-6 antigen.

8. The antibody of claim 7, wherein X₁ is leucine (L), phenylalanine (F) or valine (V).

9. The antibody of claim 8, wherein X₁ is leucine (L).

10. The antibody of claim 7, wherein X₂ is isoleucine (I) or valine (V).

11. The antibody of claim 10, wherein X₂ is isoleucine (I).

12. The antibody of claim 7, wherein X₃ is tyrosine (Y) or phenyalanine (F).

13. The antibody of claim 7, wherein X₄ is lysine (K) or arginine (R).

14. The antibody of claim 7, wherein X₅ is arginine (R), tyrosine (Y), or histidine (H).

15. The antibody of claim 7, wherein X₆ is serine (S) or asparagine (N).

16. The antibody of claim 15, wherein X₆ is serine (S).

17. The antibody of claim 7, wherein X₇ is arginine (R), lysine (K), glutamic acid (E) or serine (S).

18. The antibody of claim 17, wherein X₇ is lysine (K).

19. The antibody of claim 7, wherein X₈ is serine (S) or asparagine (N).

20. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable heavy chain CDR1 (VH-CDR1) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

51, SEQ ID NO;

52, SEQ ID NO;

53, SEQ ID NO;

54, SEQ ID NO;

55, and an amino acid sequence that is identical to any one of SEQ ID NOs;

51-55 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VH-CDR1 binds specifically to an IL-6 antigen.

21. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable heavy chain CDR2 (VH-CDR2) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

56, SEQ ID NO;

57, SEQ ID NO;

58, SEQ ID NO;

59, SEQ ID NO;

60, SEQ ID NO;

61, SEQ ID NO;

97, and an amino acid sequence that is identical to any one of SEQ ID NOs;

56 to 61 or 97 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VH-CDR2 binds specifically to an IL-6 antigen.

22. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable heavy chain CDR3 (VH-CDR3) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

62, SEQ ID NO;

63, SEQ ID NO;

64, SEQ ID NO;

65, SEQ ID NO;

66, SEQ ID NO;

67, SEQ ID NO;

68, SEQ ID NO;

69, SEQ ID NO;

70, SEQ ID NO;

71, SEQ ID NO;

72, SEQ ID NO;

73, SEQ ID NO;

98, and an amino acid sequence that is identical to any one of SEQ ID NOs;

62 to 73 or 98 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VH-CDR3 binds specifically to an IL-6 antigen.

23. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable light chain CDR1 (VL-CDR1) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

74, SEQ ID NO;

75, SEQ ID NO;

76, SEQ ID NO;

77, SEQ ID NO;

78, SEQ ID NO;

79, and an amino acid sequence that is identical to any one of SEQ ID NOs;

74-79 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VL-CDR1 binds specifically to an IL-6 antigen.

24. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable light chain CDR2 (VL-CDR2) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

80, SEQ ID NO;

81, SEQ ID NO;

82, SEQ ID NO;

83, SEQ ID NO;

84, SEQ ID NO;

85, and an amino acid sequence that is identical to any one of SEQ ID NOs;

80-85 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VL-CDR2 binds specifically to an IL-6 antigen.

25. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a variable light chain CDR3 (VL-CDR3) comprising an amino acid sequence selected from the group consisting of:

SEQ ID NO;

86, SEQ ID NO;

87, SEQ ID NO;

88, SEQ ID NO;

89, SEQ ID NO;

90, SEQ ID NO;

91, SEQ ID NO;

92, SEQ ID NO;

93, SEQ ID NO;

94, SEQ ID NO;

95, SEQ ID NO;

96, and an amino acid sequence that is identical to any one of SEQ ID NOs;

86-96 except for 1 to 5 amino acid substitutions;

wherein an antibody molecule comprising said VL-CDR3 binds specifically to an IL-6 antigen.

26. An isolated monoclonal antibody comprising:

(a) a variable heavy chain region (VH) comprising an amino acid sequence selected from the group consisting of;

(1) H415 (SEQ ID NO;

19);

(2) H884 (SEQ ID NO;

20);

(3) H1077 (SEQ ID NO;

21)

(4) H1078 (SEQ ID NO;

22);

(5) H1079 (SEQ ID NO;

23);

(6) H1081 (SEQ ID NO;

24);

(7) H1089 (SEQ ID NO;

25); and

(8) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

19 to 25; and

(b) a variable light chain region (VL) comprising an amino acid sequence selected from the group consisting of;

(9) L112 (SEQ ID NO;

1);

(10) L151 (SEQ ID NO;

2);

(11) L158 (SEQ ID NO;

3);

(12) L159 (SEQ ID NO;

4);

(13) L164 (SEQ ID NO;

5);

(14) L165 (SEQ ID NO;

6);

(15) L166 (SEQ ID NO;

7);

(16) L167 (SEQ ID NO;

8);

(17) L168 (SEQ ID NO;

9);

(18) L169 (SEQ ID NO;

10);

(19) L170 (SEQ ID NO;

11);

(20) L171 (SEQ ID NO;

12)

(21) L172 (SEQ ID NO;

13);

(22) L173 (SEQ ID NO;

14);

(23) L174 (SEQ ID NO;

15);

(24) L175 (SEQ ID NO;

16);

(25) L189 (SEQ ID NO;

17);

(26) L198 (SEQ ID NO;

18); and

(27) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

1 to 18; and

wherein said antibody binds specifically to an IL-6 antigen.

27. The antibody of claim 26, wherein said VH comprises H415 (SEQ ID NO:

19) or an amino acid sequence that is at least 80% identical thereto.

28. The antibody of claim 26, wherein said VH comprises H884 (SEQ ID NO:

20) or an amino acid sequence that is at least 80% identical thereto.

29. The antibody of claim 26, wherein said VH comprises H1077 (SEQ ID NO:

21) or an amino acid sequence that is at least 80% identical thereto.

30. The antibody of claim 26, wherein said VH comprises H1078 (SEQ ID NO:

22) or an amino acid sequence that is at least 80% identical thereto.

31. The antibody of claim 26, wherein said VH comprises H1079 (SEQ ID NO:

23) or an amino acid sequence that is at least 80% identical thereto.

32. The antibody of claim 26, wherein said VH comprises H1081 (SEQ ID NO:

24) or an amino acid sequence that is at least 80% identical thereto.

33. The antibody of claim 26, wherein said VH comprises H1089 (SEQ ID NO:

25) or an amino acid sequence that is at least 80% identical thereto.

34. The antibody of claim 26, wherein said VH comprises H415 (SEQ ID NO:

19) and said VL comprises L112 (SEQ ID NO;

1).

35. The antibody of claim 26, wherein said VH comprises H415 (SEQ ID NO:

19) and said VL comprises L165 (SEQ ID NO;

6).

36. The antibody of claim 26, wherein said VH comprises H415 (SEQ ID NO:

19) and said VL comprises L172 (SEQ ID NO;

13).

37. The antibody of claim 26, wherein said VH comprises H1079 (SEQ ID NO:

23) and said VL comprises L159 (SEQ ID NO;

4).

38. The antibody of claim 26, wherein said VH comprises H415 (SEQ ID NO:

19) and said VL comprises L198 (SEQ ID NO;

18).

39. The antibody of claim 26, wherein said VH comprises H1079 (SEQ ID NO:

23) and said VL comprises L198 (SEQ ID NO;

18).

40. The antibody of claim 26, wherein said VH comprises H1081 (SEQ ID NO:

24) and said VL comprises L172 (SEQ ID NO;

13).

41. The antibody of claim 26, wherein said VH comprises H1077 (SEQ ID NO:

21) and said VL comprises L158 (SEQ ID NO;

3).

42. The antibody of claim 26, wherein said VH comprises H1078 (SEQ ID NO:

22) and said VL comprises L158 (SEQ ID NO;

3).

43. The antibody of claim 26, wherein said VH comprises H1081 (SEQ ID NO:

24) and said VL comprises L159 (SEQ ID NO;

4).

44. The antibody of claim 26, wherein said VH is a variant of H1079.

45. The antibody of claim 44, wherein said variant of H1079 comprises one or more amino acid differences in the CDR1, CDR2 or CDR3 of H1079.

46. The antibody of claim 45, wherein said variant of H1079 comprises one or more amino acid differences in CDR3 of H1079.

47. The antibody of claim 46, wherein said variant of H1079 is selected from the group consisting of H1511 (SEQ ID NO:

26);

H1420 (SEQ ID NO;

27);

H1432 (SEQ ID NO;

28);

H1515 (SEQ ID NO;

29);

H1362 (SEQ ID NO;

30);

H1437 (SEQ ID NO;

31); and

H1461 (SEQ ID NO;

32).

48. The antibody of claim 46, wherein said variant of H1079 is selected from the group consisting of H1519 (SEQ ID NO:

38);

H1520 (SEQ ID NO;

39);

H1521 (SEQ ID NO;

40); and

H1522 (SEQ ID NO;

41).

49. The antibody of claim 26, wherein said VL is a variant of L198.

50. The antibody of claim 49, wherein said variant of L198 comprises one or more amino acid differences in the CDR1, CDR2 or CDR3 of L198.

51. The antibody of claim 50, wherein said variant of L198 comprises one or more amino acid differences in the CDR3 of L198.

52. The antibody of claim 51, wherein said variant of L198 is selected from the group consisting of L314 (SEQ ID NO:

33);

L305 (SEQ ID NO;

34);

L303 (SEQ ID NO;

35);

L298 (SEQ ID NO;

36); and

L321 (SEQ ID NO;

37).

53. The antibody of claim 44, wherein said variant of H1079 is H1553 (SEQ ID NO:

42) or H1579 (SEQ ID NO;

43).

54. An isolated monoclonal antibody comprising:

(a) a variable heavy chain region (VH) comprising an amino acid sequence selected from the group consisting of;

(1) H1522 (SEQ ID NO;

41);

(2) H1553 (SEQ ID NO;

42);

(3) H1579 (SEQ ID NO;

43); and

(4) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

41 to 43; and

(b) a variable light chain region (VL) comprising an amino acid sequence selected from the group consisting of;

(5) L198 (SEQ ID NO;

18)

(6) L305 (SEQ ID NO;

34)

(7) L314 (SEQ ID NO;

33)

(8) L298 (SEQ ID NO;

36)

(9) L321 (SEQ ID NO;

37); and

(10) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

18, 33, 34, 36 or 37; and

wherein said antibody binds specifically to an IL-6 antigen.

55. The antibody of claim 54, wherein said VH comprises H1522 (SEQ ID NO:

41) or an amino acid sequence that is at least 80% identical thereto.

56. The antibody of claim 54, wherein said VH comprises H1553 (SEQ ID NO:

42) or an amino acid sequence that is at least 80% identical thereto.

57. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) or an amino acid sequence that is at least 80% identical thereto.

58. The antibody of claim 54, wherein said VH comprises H1522 (SEQ ID NO:

41) and said VL comprises L198 (SEQ ID NO;

18).

59. The antibody of claim 54, wherein said VH comprises H1522 (SEQ ID NO:

41) and said VL comprises L305 (SEQ ID NO;

34).

60. The antibody of claim 54, wherein said VH comprises H1522 (SEQ ID NO:

41) and said VL comprises L314 (SEQ ID NO;

33).

61. The antibody of claim 54, wherein said VH comprises H1553 (SEQ ID NO:

42) and said VL comprises L198 (SEQ ID NO;

18).

62. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) and said VL comprises L198 (SEQ ID NO;

18).

63. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) and said VL comprises L305 (SEQ ID NO;

34).

64. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) and said VL comprises L314 (SEQ ID NO;

33).

65. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) and said VL comprises L298 (SEQ ID NO;

36).

66. The antibody of claim 54, wherein said VH comprises H1579 (SEQ ID NO:

43) and said VL comprises L321 (SEQ ID NO;

37).

67. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an anti-IL-6 antibody variable heavy chain region (VH), wherein said VH comprises an amino acid sequence selected from the group consisting of:

(1) H415 (SEQ ID NO;

19);

(2) H884 (SEQ ID NO;

20);

(3) H11077 (SEQ ID NO;

21)

(4) H1078 (SEQ ID NO;

22);

(5) H1079 (SEQ ID NO;

23);

(6) H1081 (SEQ ID NO;

24);

(7) H1089 (SEQ ID NO;

25); and

(8) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

19 to 25.

73. An expression vector comprising a nucleic acid molecule of claim 67.

77. A host cell comprising an expression vector of claim 73.

68. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an anti-IL-6 antibody variable light chain region (VL), wherein said VL comprises an amino acid sequence selected from the group consisting of:

(1) L112 (SEQ ID NO;

1);

(2) L151 (SEQ ID NO;

2);

(3) L158 (SEQ ID NO;

3);

(4) L159 (SEQ ID NO;

4);

(5) L164 (SEQ ID NO;

5);

(6) L165 (SEQ ID NO;

6);

(7) L166 (SEQ ID NO;

7);

(8) L167 (SEQ ID NO;

8);

(9) L168 (SEQ ID NO;

9);

(10) L169 (SEQ ID NO;

10);

(11) L170 (SEQ ID NO;

11);

(12) L171 (SEQ ID NO;

12)

(13) L172 (SEQ ID NO;

13);

(14) L173 (SEQ ID NO;

14);

(15) L174 (SEQ ID NO;

15);

(16) L175 (SEQ ID NO;

16);

(17) L189 (SEQ ID NO;

17);

(18) L198 (SEQ ID NO;

18); and

(19) an amino acid sequence that is at least 80% identical to any one of SEQ ID NOs;

1 to 18.

74. An expression vector comprising a nucleic acid molecule of claim 68.

78. A host cell comprising an expression vector of claim 74.

69. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a complementary determining region (CDR) of an anti-IL-6 antibody variable heavy chain region (VH) selected from the group consisting of:

(1) H415 (SEQ ID NO;

19);

(2) H884 (SEQ ID NO;

20);

(3) H1077 (SEQ ID NO;

21)

(4) H1078 (SEQ ID NO;

22);

(5) H1079 (SEQ ID NO;

23);

(6) H1081 (SEQ ID NO;

24); and

(7) H1089 (SEQ ID NO;

25).

70. The nucleic acid molecule of claim 69, wherein said nucleotide sequence encodes a CDR3 of an anti-IL-6 antibody variable heavy chain region (VH) selected from the group consisting of:

(1) H415 (SEQ ID NO;

19);

(2) H884 (SEQ ID NO;

20);

(3) H1077 (SEQ ID NO;

21)

(4) H1078 (SEQ ID NO;

22);

(5) H1079 (SEQ ID NO;

23);

(6) H1081 (SEQ ID NO;

24); and

(7) H1089 (SEQ ID NO;

25).

75. An expression vector comprising a nucleic acid molecule of claim 69.

79. A host cell comprising an expression vector of claim 75.

71. An isolated nucleic acid molecule comprising a nucleotide sequence that encodes a complementary determining region (CDR) of an anti-IL-6 antibody variable light chain region (VL) selected from the group consisting of:

(1) L112 (SEQ ID NO;

1);

(2) L151 (SEQ ID NO;

2);

(3) L158 (SEQ ID NO;

3);

(4) L159 (SEQ ID NO;

4);

(5) L164 (SEQ ID NO;

5);

(6) L165 (SEQ ID NO;

6);

(7) L166 (SEQ ID NO;

7);

(8) L167 (SEQ ID NO;

8);

(9) L168 (SEQ ID NO;

9);

(10) L169 (SEQ ID NO;

10);

(11) L170 (SEQ ID NO;

11);

(12) L171 (SEQ ID NO;

12)

(13) L172 (SEQ ID NO;

13);

(14) L173 (SEQ ID NO;

14);

(15) L174 (SEQ ID NO;

15);

(16) L175 (SEQ ID NO;

16);

(17) L189 (SEQ ID NO;

17); and

(18) L198 (SEQ ID NO;

18).

72. The nucleic acid molecule of claim 71, wherein said nucleotide sequence encodes a CDR3 of an anti-IL-6 antibody variable light chain region (VL) selected from the group consisting of:

(1) L112 (SEQ ID NO;

1);

(2) L151 (SEQ ID NO;

2);

(3) L158 (SEQ ID NO;

3);

(4) L159 (SEQ ID NO;

4);

(5) L164 (SEQ ID NO;

5);

(6) L165 (SEQ ID NO;

6);

(7) L166 (SEQ ID NO;

7);

(8) L167 (SEQ ID NO;

8);

(9) L168 (SEQ ID NO;

9);

(10) L169 (SEQ ID NO;

10);

(11) L170 (SEQ ID NO;

11);

(12) L171 (SEQ ID NO;

12)

(13) L172 (SEQ ID NO;

13);

(14) L173 (SEQ ID NO;

14);

(15) L174 (SEQ ID NO;

15);

(16) L175 (SEQ ID NO;

16);

(17) L189 (SEQ ID NO;

17); and

(18) L198 (SEQ ID NO;

18).

76. An expression vector comprising a nucleic acid molecule of claim 71.

80. A host cell comprising an expression vector of claim 76.

89. (canceled)

91. (canceled)