IP Library › Granted Patent US 7,776,329
Granted Patent B2
US 7,776,329 · App. 10/583,795 · Granted Aug 17, 2010

Anti-glypican 3 antibody

Assignee: Chugai Seiyaku Kabushiki Kaisha
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Quick Facts
Patent No.
US 7,776,329
App. No.
10/583,795
Granted
Aug 17, 2010
Kind
B2
Abstract

An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.

Claims (100)

1. An isolated anti-glypican 3 antibody comprising a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 143, 144 and 158, respectively.

2. An isolated anti-glypican 3 antibody selected from the group consisting of the antibody of any one of (1)-(7):

(1) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 84 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92;

(2) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 85 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92;

(3) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 86 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92;

(4) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92;

(5) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92;

(6) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 89 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92; and

(7) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 90 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

3. The antibody as claimed in claim 1 or 2 , which is a humanized antibody.

4. An isolated monoclonal antibody capable of binding to an epitope of glypican 3 to which a second antibody is capable of binding, wherein said second antibody comprises a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 143, 144 and 158, respectively.

5. A pharmaceutical composition comprising the antibody as claimed in claim 1 .

6. A pharmaceutical composition comprising the antibody as claimed in claim 2 .

7. An isolated anti-glypican 3 antibody comprising any one of (1)-(15) below:

(1) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 174, 144 and 158, respectively;

(2) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 175, 144 and 158, respectively;

(3) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 176, 144 and 158, respectively;

(4) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 177, 144 and 158, respectively;

(5) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 178, 144 and 158, respectively;

(6) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 179, 144 and 158, respectively;

(7) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 180, 144 and 158, respectively;

(8) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 181, 144 and 158, respectively;

(9) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 182, 144 and 158, respectively;

(10) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 183, 144 and 158, respectively;

(11) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 184, 144 and 158, respectively;

(12) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124, and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 185, 144, and 158, respectively;

(13) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124, and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 186, 144 and 158, respectively;

(14) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 187, 144 and 158, respectively; and

(15) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 188, 144 and 158, respectively.

8. The antibody as claimed in claim 4 or 7 , which is a human antibody.

9. A pharmaceutical composition comprising the antibody as claimed in claim 4 .

10. A pharmaceutical composition comprising the antibody as claimed in claim 7 .

11. A pharmaceutical composition comprising the antibody as claimed in claim 8 .

12. A pharmaceutical composition comprising the antibody as claimed in claim 3 .

13. The antibody of claim 2 , wherein the antibody is:

(1) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 84 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

14. A pharmaceutical composition comprising the antibody as claimed in claim 13 .

15. The antibody of claim 2 , wherein the antibody is:

(2) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 85 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

16. A pharmaceutical composition comprising the antibody as claimed in claim 15 .

17. The antibody of claim 2 , wherein the antibody is:

(3) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 86 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

18. A pharmaceutical composition comprising the antibody as claimed in claim 17 .

19. The antibody of claim 2 , wherein the antibody is:

(4) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 87 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

20. A pharmaceutical composition comprising the antibody as claimed in claim 19 .

21. The antibody of claim 2 , wherein the antibody is:

(5) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 88 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

22. A pharmaceutical composition comprising the antibody as claimed in claim 21 .

23. The antibody of claim 2 , wherein the antibody is:

(6) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 89 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

24. A pharmaceutical composition comprising the antibody as claimed in claim 23 .

25. The antibody of claim 2 , wherein the antibody is:

(7) an antibody comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 90 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 92.

26. A pharmaceutical composition comprising the antibody as claimed in claim 25 .

27. The antibody of claim 7 , wherein the antibody comprises:

(1) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 174, 144 and 158, respectively.

28. A pharmaceutical composition comprising the antibody as claimed in claim 27 .

29. The antibody of claim 7 , wherein the antibody comprises:

(2) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 175, 144 and 158, respectively.

30. A pharmaceutical composition comprising the antibody as claimed in claim 29 .

31. The antibody of claim 7 , wherein the antibody comprises:

(3) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 176, 144 and 158, respectively.

32. A pharmaceutical composition comprising the antibody as claimed in claim 31 .

33. The antibody of claim 7 , wherein the antibody comprises:

(4) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 177, 144 and 158, respectively.

34. A pharmaceutical composition comprising the antibody as claimed in claim 33 .

35. The antibody of claim 7 , wherein the antibody comprises:

(5) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 178, 144 and 158, respectively.

36. A pharmaceutical composition comprising the antibody as claimed in claim 35 .

37. The antibody of claim 7 , wherein the antibody comprises:

(6) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 179, 144 and 158, respectively.

38. A pharmaceutical composition comprising the antibody as claimed in claim 37 .

39. The antibody of claim 7 , wherein the antibody comprises:

(7) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 180, 144 and 158, respectively.

40. A pharmaceutical composition comprising the antibody as claimed in claim 39 .

41. The antibody of claim 7 , wherein the antibody comprises:

(8) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 181, 144 and 158, respectively.

42. A pharmaceutical composition comprising the antibody as claimed in claim 41 .

43. The antibody of claim 7 , wherein the antibody comprises:

(9) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 182, 144 and 158, respectively.

44. A pharmaceutical composition comprising the antibody as claimed in claim 43 .

45. The antibody of claim 7 , wherein the antibody comprises:

(10) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 183, 144 and 158, respectively.

46. A pharmaceutical composition comprising the antibody as claimed in claim 45 .

47. The antibody of claim 7 , wherein the antibody comprises:

(11) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 184, 144 and 158, respectively.

48. A pharmaceutical composition comprising the antibody as claimed in claim 47 .

49. The antibody of claim 7 , wherein the antibody comprises:

(12) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124, and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 185, 144, and 158, respectively.

50. A pharmaceutical composition comprising the antibody as claimed in claim 49 .

51. The antibody of claim 7 , wherein the antibody comprises:

(13) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124, and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 186, 144 and 158, respectively.

52. A pharmaceutical composition comprising the antibody as claimed in claim 51 .

53. The antibody of claim 7 , wherein the antibody comprises:

(14) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 187, 144 and 158, respectively.

54. A pharmaceutical composition comprising the antibody as claimed in claim 53 .

55. The antibody of claim 7 , wherein the antibody comprises:

(15) a heavy chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 123, 124 and 125, respectively, and a light chain variable region having CDRs 1, 2 and 3 comprising the amino acid sequence set forth in SEQ ID NO: 188, 144 and 158, respectively.

56. A pharmaceutical composition comprising the antibody as claimed in claim 55 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 7, 2007
From: NAKANO, KIYOTAKA; YOSHINO, TAKESHI; NEZU, JUN-ICHI; TSUNODA, HIROYUKI; IGAWA, TOMOYUKI; KONISHI, HIROKO; TANAKA, MEGUMI; SUGO, IZUMI; KAWAI, SHIGETO; ISHIGURO, TAKAHIRO; KINOSHITA, YASUKO
To: CHUGAI SEIYAKU KABUSHIKI KAISHA
Reel/Frame 018978/0294 →
Priority Claims (1)
JP 2004-203637 · Jul 9, 2004 · national
Continuity (1)
Related Publication 20070190599A1 · Aug 16, 2007