IP Library › Granted Patent US 7,083,949
Granted Patent B2
US 7,083,949 · App. 10/287,035 · Granted Aug 1, 2006

Receptor based antagonists and methods of making and using

Assignee: Regeneron Pharmaceuticals, Inc.
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Quick Facts
Patent No.
US 7,083,949
App. No.
10/287,035
Granted
Aug 1, 2006
Kind
B2
Abstract

The present invention provides a fusion polypeptide that forms a multimer that is capable of binding a cytokine to form a nonfunctional complex. It also provides a nucleic acid sequence encoding the fusion polypeptide and methods of making and uses for the fusion polypeptide.

Claims (81)

1. A fusion polypeptide having the amino acid sequence of SEQ ID NO: 30, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

2. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 1 .

3. The isolated nucleic acid of claim 2 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:29.

4. A fusion polypeptide having the amino acid sequence of SEQ ID NO: 32, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13to form a nonfunctional complex.

5. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 4 .

6. The isolated nucleic acid of claim 5 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:31.

7. A fusion polypeptide having the amino acid sequence of SEQ ID NO:34, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13to form a nonfunctional complex.

8. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 7 .

9. The isolated nucleic acid of claim 8 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:33.

10. The isolated nucleic acid of claim 9 , wherein nucleotide 311 is changed from C to T.

11. The isolated nucleic acid of claim 9 , wherein nucleotide 1105 is changed from A to G.

12. The isolated nucleic acid of claim 9 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952.

13. The isolated nucleic acid of claim 9 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952, nucleotide 311 is changed from C to T, and nucleotide 1105 is changed from A to G.

14. A fusion polypeptide having the amino acid sequence of SEQ ID NO:36, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13to form a nonfunctional complex.

15. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 14 .

16. The isolated nucleic acid of claim 15 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:35.

17. The isolated nucleic acid of claim 16 , wherein nucleotide 935 is changed from C to T.

18. The isolated nucleic acid of claim 16 , wherein nucleotides TCCGGA are inserted between nucleotides 624 and 625.

19. The isolated nucleic acid of claim 16 , wherein nucleotide 154 is changed from A to G.

20. The isolated nucleic acid of claim 16 , wherein nucleotide 935 is changed from C to T, nucleotides TCCGGA are inserted between nucleotides 624 and 625, and nucleotide 154 is changed from A to G.

21. A fusion polypeptide having the amino acid sequence of SEQ ID NO:38, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and IL-13to form a nonfunctional complex.

22. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 21 .

23. The isolated nucleic acid of claim 22 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:37.

24. The isolated nucleic acid of claim 23 , wherein nucleotide 311 is changed from C to T.

25. The isolated nucleic acid of claim 23 , wherein nucleotide 1105 is changed from A to G.

26. The isolated nucleic acid of claim 23 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952.

27. The isolated nucleic acid of claim 23 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952, nucleotide 311 is changed from C to T, and nucleotide 1105 is changed from A to G.

28. A fusion polypeptide having the amino acid sequence of SEQ ID NO:40, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13to form a nonfunctional complex.

29. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 28 .

30. The isolated nucleic acid of claim 29 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:39.

31. The isolated nucleic acid of claim 30 , wherein nucleotide 935 is changed from C to T.

32. The isolated nucleic acid of claim 30 , wherein nucleotides TCCGGA are inserted between nucleotides 624 and 625.

33. The isolated nucleic acid of claim 30 , wherein nucleotide 154 is changed from A to G.

34. The isolated nucleic acid of claim 30 , wherein nucleotide 935 is changed from C to T, nucleotides TCCGGA are inserted between nucleotides 624 and 625, and nucleotide 154 is changed from A to G.

35. A fusion polypeptide having the amino acid sequence of SEQ ID NO:42, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

36. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 35 .

37. The isolated nucleic acid of claim 36 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:41.

38. The isolated nucleic acid of claim 37 , wherein nucleotide 311 is changed from C to T.

39. The isolated nucleic acid of claim 37 , wherein nucleotide 1105 is changed from A to G.

40. The isolated nucleic acid of claim 37 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952.

41. The isolated nucleic acid of claim 37 , wherein nucleotides TCCGGA are inserted between nucleotides 951 and 952, nucleotide 311 is changed from C to T, and nucleotide 1105 is changed from A to G.

42. A fusion polypeptide having the amino acid sequence of SEQ ID NO:44, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

43. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 42 .

44. The isolated nucleic acid of claim 43 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:43.

45. The isolated nucleic acid of claim 44 , wherein nucleotide 935 is changed from C to T.

46. The isolated nucleic acid of claim 44 , wherein nucleotides TCCGGA are inserted between nucleotides 624 and 625.

47. The isolated nucleic acid of claim 44 , wherein nucleotide 154 is changed from A to G.

48. The isolated nucleic acid of claim 44 , wherein nucleotide 935 is changed from C to T, nucleotides TCCGGA are inserted between nucleotides 624 and 625, and nucleotide 154 is changed from A to G.

49. A fusion polypeptide having the amino acid sequence of SEQ ID NO:46, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

50. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 49 .

51. The isolated nucleic acid of claim 50 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:45.

52. A fusion polypeptide having the amino acid sequence of SEQ ID NO:48, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

53. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 52 .

54. The isolated nucleic acid of claim 53 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:47.

55. A fusion polypeptide having the amino acid sequence of SEQ ID NO:50, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

56. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 55 .

57. The isolated nucleic acid of claim 56 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:49.

58. A fusion polypeptide having the amino acid sequence of SEQ ID NO:52, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

59. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 58 .

60. The isolated nucleic acid of claim 59 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:51.

61. A fusion polypeptide having the amino acid sequence of SEQ ID NO:54, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

62. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 61 .

63. The isolated nucleic acid of claim 62 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:53.

64. A fusion polypeptide having the amino acid sequence of SEQ ID NO:56, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

65. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 64 .

66. The isolated nucleic acid of claim 65 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:55.

67. A fusion polypeptide having the amino acid sequence of SEQ ID NO:58, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

68. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 67 .

69. The isolated nucleic acid of claim 68 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:57.

70. A fusion polypeptide having the amino acid sequence of SEQ ID NO:60, wherein the fusion polypeptide forms a multimer capable of binding interleukin-4 (IL-4) and/or IL-13 to form a nonfunctional complex.

71. An isolated nucleic acid molecule encoding the fusion polypeptide of claim 70 .

72. The isolated nucleic acid of claim 71 , wherein the nucleic acid molecule comprises the sequence of SEQ ID NO:59.

73. A pharmaceutical composition comprising a multimer of the fusion polypeptide of any one of claims 1 , 4 , 7 , 14 , 21 , 28 , 35 , 42 , 49 , 52 , 55 , 58 , 61 , 64 , 67 or 70 , and a pharmaceutically acceptable carrier.

74. The pharmaceutical composition of claim 73 , wherein the multimer is a dimer.

75. An isolated nucleic acid selected from the group consisting of SEQ ID NO: 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57 and 59.

76. A vector that comprises the isolated nucleic acid molecule of claim 75 .

77. The vector of claim 76 , wherein the isolated nucleic acid molecule is operatively linked to an expression control sequence.

78. A host-vector system for the production of a fusion polypeptide, comprising the vector of claim 77 , in a suitable host cell.

79. The host-vector system of claim 78 , wherein the suitable host cell is a bacterial cell, yeast cell, insect cell, or mammalian cell.

80. The host-vector system of claim 79 , wherein the suitable host cell is a CHO cell.

81. A method of producing a fusion polypeptide that comprises growing cells of the host-vector system of claim 78 , under conditions permitting production of the fusion polypeptide and recovering the fusion polypeptide so produced.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 6, 2003
From: STAHL, NEIL; YANCOPOULOS, GEORGE D.
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 014353/0634 →
Continuity (5)
Continuation In Part 0993586800 · Aug 23, 2001
Continuation In Part 0978783500
Continuation In Part 0931394200 · May 19, 1999
Provisional Application 6010185800 · Sep 25, 1998
Related Publication 20030104567A1 · Jun 5, 2003