Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment

• US 7,179,900 B2
• Filed: 03/31/2003
• Issued: 02/20/2007
• Est. Priority Date: 11/28/2000
• Status: Expired due to Fees

• Current Assignee: Medimmune LLC (Astrazeneca PLC)
• Original Assignee: Medimmune Incorporated (Astrazeneca PLC)
• Inventors: Wu, Herren, Johnson, Leslie S., Watkins, Jeffrey D., Koenig, Scott, Huse, William D., Young, James F.
• Primary Examiner(s): CHEN, STACY BROWN
• Application Number:
  US10/403,180
• Publication Number:
  US 20050196749A1
• Time in Patent Office: 1,422 Days
• Field of Search: 536/23.1, 536/23.53, 435/325, 435/320.1, 424/130.1, 424/147.1, 424/211.1
• US Class Current: 536/23.53
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 16/1027 Paramyxoviridae, e.g. respiratory syncytial virus
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• 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]

Abstract

The present invention encompasses novel antibodies and fragments thereof which immunospecifically bind to one or more RSV antigens and compositions comprising said antibodies and antibody fragments. The present invention encompasses methods preventing respiratory syncytial virus (RSV) infection in a human, comprising administering to said human a prophylactically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention also encompasses methods for treating or ameliorating symptoms associated with a RSV infection in a human, comprising administering to said human a therapeutically effective amount of one or more antibodies or fragments thereof that immunospecifically bind to one or more RSV antigens, wherein a certain serum titer of said antibodies or antibody fragments is achieved in said human subject. The present invention further encompasses compositions comprising antibodies or fragments thereof that immunospecifically bind to a RSV antigen, and methods using said compositions for detection or diagnosis of a RSV infection.

Claims

1. A nucleic acid molecule comprising a nucleotide sequence encoding a variable light (VL) chain of an antibody that immunospecifically binds to a respiratory syncytial virus (RSV) F antigen, wherein the VL chain comprises the amino acid sequence of SEQ ID NO:

255.

3. The nucleic acid molecule of claim 1 further comprising a nucleotide sequence encoding a VH chain of said antibody, wherein the VH chain comprises the amino acid sequence of SEQ ID NO:

254.

2. A nucleic acid molecule comprising a nucleotide sequence encoding a variable heavy (VH) chain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VH chain comprises the amino acid sequence of SEQ ID NO:

254.

4. A nucleic acid molecule comprising a nucleotide sequence encoding a VL domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VL domain comprises the amino acid sequence of SEQ ID NO:

11.

6. The nucleic acid molecule of claim 4 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

48.

5. A nucleic acid molecule comprising a nucleotide sequence encoding a VH domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VH domain comprises the amino acid sequence of SEQ ID NO:

48.

7. A nucleic acid molecule comprising a nucleotide sequence encoding a VH domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VH domain comprises a VH complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO:

10.

11. The nucleic acid molecule of claim 7, wherein the VH domain further comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

12. The nucleic acid molecule of claim 7, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

14. The nucleic acid molecule of claim 11, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

18. The nucleic acid molecule of claim 7 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

21. The nucleic acid molecule of claim 11 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

22. The nucleic acid molecule of claim 12 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

24. The nucleic acid molecule of claim 14 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

25. The nucleic acid molecule of claim 7 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

28. The nucleic acid molecule of claim 11 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

29. The nucleic acid molecule of claim 12 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

31. The nucleic acid molecule of claim 14 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

32. The nucleic acid molecule of claim 7 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

35. The nucleic acid molecule of claim 11 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

36. The nucleic acid molecule of claim 12 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

38. The nucleic acid molecule of claim 14 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

53. The nucleic acid molecule of claim 25, wherein the VL domain further comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

56. The nucleic acid molecule of claim 53, wherein the VH domain further comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

57. The nucleic acid molecule of claim 53, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

59. The nucleic acid molecule of claim 56, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

69. The nucleic acid molecule of claim 14, wherein the VH domain further comprises the framework regions depicted in FIG. 2B (SEQ ID NO:

263).

8. A nucleic acid molecule comprising a nucleotide sequence encoding a VH domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VH domain comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

13. The nucleic acid molecule of claim 8, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

19. The nucleic acid molecule of claim 8 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

23. The nucleic acid molecule of claim 13 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

26. The nucleic acid molecule of claim 8 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

30. The nucleic acid molecule of claim 13 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

33. The nucleic acid molecule of claim 8 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

37. The nucleic acid molecule of claim 13 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

54. The nucleic acid molecule of claim 26, wherein the VL domain further comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

58. The nucleic acid molecule of claim 54, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

9. A nucleic acid molecule comprising a nucleotide sequence encoding a VH domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VH domain comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

20. The nucleic acid molecule of claim 9 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

27. The nucleic acid molecule of claim 9 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

34. The nucleic acid molecule of claim 9 further comprising a nucleotide sequence encoding a VL domain of said antibody, wherein the VL domain comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

55. The nucleic acid molecule of claim 27, wherein the VL domain further comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

10. A nucleic acid molecule comprising a nucleotide sequence encoding a VL domain of an antibody that immunospecifically binds to a RSV F antigen, wherein the VL domain comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:

39.

15. The nucleic acid molecule of claim 10, wherein the VL domain further comprises a VL CDR2 comprising the amino acid sequence of SEQ ID NO:

5.

16. The nucleic acid molecule of claim 10, wherein the VL domain further comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

17. The nucleic acid molecule of claim 15, wherein the VL domain further comprises a VL CDR3 comprising the amino acid sequence of SEQ ID NO:

6.

39. The nucleic acid molecule of claim 15 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO:

10.

40. The nucleic acid molecule of claim 15 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

41. The nucleic acid molecule of claim 15 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

42. The nucleic acid molecule of claim 39, wherein the VH domain further comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

43. The nucleic acid molecule of claim 39, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

44. The nucleic acid molecule of claim 40, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

45. The nucleic acid molecule of claim 42, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

46. The nucleic acid molecule of claim 16 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO:

10.

47. The nucleic acid molecule of claim 16 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

48. The nucleic acid molecule of claim 16 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

49. The nucleic acid molecule of claim 46, wherein the VH domain further comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

50. The nucleic acid molecule of claim 46, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

51. The nucleic acid molecule of claim 47, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

52. The nucleic acid molecule of claim 49, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

60. The nucleic acid molecule of claim 17 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR1 comprising the amino acid sequence of SEQ ID NO:

10.

61. The nucleic acid molecule of claim 17 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

62. The nucleic acid molecule of claim 17 further comprising a nucleotide sequence encoding a VH domain of said antibody, wherein the VH domain comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

63. The nucleic acid molecule of claim 60, wherein the VH domain further comprises a VH CDR2 comprising the amino acid sequence of SEQ ID NO:

19.

64. The nucleic acid molecule of claim 60, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

65. The nucleic acid molecule of claim 61, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

66. The nucleic acid molecule of claim 63, wherein the VH domain further comprises a VH CDR3 comprising the amino acid sequence of SEQ ID NO:

20.

67. The nucleic acid molecule of claim 7, 8, 9, 10 or 66, wherein the antibody is a monoclonal antibody, a human antibody, a humanized antibody, a multispecific antibody, a chimeric antibody, a single chain antibody, a Fab fragment or a single chain Fv.

68. The nucleic acid molecule of claim 17, wherein the VL domain further comprises the framework regions depicted in FIG. 2A (SEQ ID NO:

262).

70. The nucleic acid molecule of claim 66, wherein the VL domain further comprises the framework regions depicted in FIG. 2A (SEQ ID NO:

262) and the VH domain further comprises the framework regions depicted in FIG. 2B (SEQ ID NO;

263).

71. The nucleic acid molecule of claim 3, 7, 8, 9, 10, 66, 68, 69 or 70 further comprising a heterologous nucleotide sequence which regulates the expression of the nucleic acid molecule.

72. The nucleic acid molecule of claim 3, 7, 8, 9, 10, 66, 68, 69 or 70, wherein the nucleic acid molecule is isolated.

73. A vector comprising the nucleic acid molecule of claim 3, 7, 8, 9, 10, 66, 68, 69 or 70.

74. The vector of claim 73 further comprising a nucleotide sequence which regulates the expression of the nucleic acid molecule.

75. An isolated, purified, or cultured host cell genetically engineered to contain or express the nucleic acid molecule of claim 3, 7, 8, 9, 10, 66, 68, 69 or 70.

76. An isolated, purified, or cultured host cell comprising the vector of claim 73.

77. The host cell of claim 75 which is a mammalian cell.

78. The host cell of claim 76 which is a mammalian cell.

79. A method of producing an antibody, said method comprising culturing the host cell of claim 75 under conditions in which the nucleic acid molecule is expressed and obtaining the antibody from the host cell culture.

80. A method of producing an antibody, said method comprising culturing the host cell of claim 76 under conditions in which the nucleic acid molecule is expressed and obtaining the antibody from the host cell culture.