Human antibodies binding to RSV G proteins

• US 10,035,842 B2
• Filed: 04/14/2014
• Issued: 07/31/2018
• Est. Priority Date: 04/15/2013
• Status: Active Grant

• Current Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Original Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Inventors: Wadia, Jehangir, Williamson, Robert Anthony, Langedijk, Johannes P. M., Pascual, Gabriel, Van 't Wout, Angelique
• Primary Examiner(s): Foley, Shanon A.
• Assistant Examiner(s): Hill, Myron G
• Application Number:
  US14/784,938
• Publication Number:
  US 20160145322A1
• Time in Patent Office: 1,569 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/155 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: A61K 47/6841 the antibody targeting a RNA virus
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 14/115 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: C07K 16/1027 Paramyxoviridae, e.g. respiratory syncytial virus
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/50 characterized by immunoglobulin fragments
• 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 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/135 Respiratory syncytial virus
• CPC Class Codes: G01N 2469/10 Detection of antigens from microorganism in sample from host
• CPC Class Codes: G01N 33/56983 Viruses

Abstract

The disclosure provides isolated antibodies and antigen-binding fragments that bind to the G protein of RSV and which are capable of neutralizing RSV.

Claims

1. An antibody able to specifically bind to attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A2 and B strains, wherein the antibody binds to an epitope within the central conserved domain of the RSV G protein, wherein the antibody is selected from the group consisting of:

a) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

1, a heavy chain CDR2 region of SEQ ID NO;

2, and a heavy chain CDR3 region of SEQ ID NO;

3, a light chain CDR1 region of SEQ ID NO;

4, a light chain CDR2 region of SEQ ID NO;

5, and a light chain CDR3 region of SEQ ID NO;

6;

b) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

7, a heavy chain CDR2 region of SEQ ID NO;

8, and a heavy chain CDR3 region of SEQ ID NO;

9, a light chain CDR1 region of SEQ ID NO;

10, a heavy chain CDR2 region of SEQ ID NO;

1, and a light chain CDR3 region of SEQ ID NO;

12,

c) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

13, a heavy chain CDR2 region of SEQ ID NO;

14, and a heavy chain CDR3 region of SEQ ID NO;

15, a light chain CDR1 region of SEQ ID NO;

16 a light chain CDR2 region of SEQ ID NO;

17, and a light chain CDR3 region of SEQ ID NO;

18;

d) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

19, a heavy chain CDR2 region of SEQ ID NO;

20, and a heavy chain CDR3 region of SEQ ID NO;

21, a light chain CDR1 region of SEQ ID NO;

22, a light chain CDR2 region of SEQ ID NO;

23, and a light chain CDR3 region of SEQ ID NO;

24;

e) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

25, a heavy chain CDR2 region of SEQ ID NO;

26, and a heavy chain CDR3 region of SEQ ID NO;

27, a light chain CDR1 region of SEQ ID NO;

28, a light chain CDR2 region of SEQ ID NO;

29, and a light chain CDR3 region of SEQ ID NO;

30;

f) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

31, a heavy chain CDR2 region of SEQ ID NO;

32, and a heavy chain CDR3 region of SEQ ID NO;

33, a light chain CDR1 region of SEQ ID NO;

34, a light chain CDR2 region of SEQ ID NO;

35, and a light chain CDR3 region of SEQ ID NO;

36;

g) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

37, a heavy chain CDR2 region of SEQ ID NO;

38, and a heavy chain CDR3 region of SEQ ID NO;

39, a light chain CDR1 region of SEQ ID NO;

40, a light chain CDR2 region of SEQ ID NO;

41, and a light chain CDR3 region of SEQ ID NO;

42;

h) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

43, a heavy chain CDR2 region of SEQ ID NO;

44, and a heavy chain CDR3 region of SEQ ID NO;

45, a light chain CDR1 region of SEQ ID NO;

46, a light chain CDR2 region of SEQ ID NO;

47, and a light chain CDR3 region of SEQ ID NO;

48;

i) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

49, a heavy chain CDR2 region of SEQ ID NO;

50 and a heavy chain CDR3 region of SEQ ID NO;

51, a light chain CDR1 region of SEQ ID NO;

52, a light chain CDR2 region of SEQ ID NO;

53, and a light chain CDR3 region of SEQ ID NO;

54;

j) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

55, a heavy chain CDR2 region of SEQ ID NO;

56, and a heavy chain CDR3 region of SEQ ID NO;

57 a light chain CDR1 region of SEQ ID NO;

58, a light chain CDR2 region of SEQ ID NO;

59, and a light chain CDR3 region of SEQ ID NO;

60;

k) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

61, a heavy chain CDR2 region of SEQ ID NO;

62, and a heavy chain CDR3 region of SEQ ID NO;

63, a light chain CDR1 region of SEQ ID NO;

64, a light chain CDR2 region of SEQ ID NO;

65, and a light chain CDR3 region of SEQ ID NO;

66; and

l) an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

67, a heavy chain CDR2 region of SEQ ID NO;

68, and a heavy chain CDR3 region of SEQ ID NO;

69 a light chain CDR1 region of SEQ ID NO;

70, a light chain CDR2 region of SEQ ID NO;

71, and a light chain CDR3 region of SEQ ID NO;

72.

4. An immunoconjugate comprising:

the antibody of claim 1, and

at least one therapeutic agent and/or detectable agent.

9. A pharmaceutical composition comprising:

the antibody of claim 1, and

at least one pharmaceutically acceptable excipient.

13. A method of detecting RSV infection, the method comprising:

assaying a level of RSV antigen in a sample with the antibody of claim 1; and

comparing the assayed level of RSV antigen with a control level,

wherein an increase in the assayed level of RSV antigen compared to the control level is indicative of RSV infection.

16. A method of prophylaxing against and/or treating a subject diagnosed with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the antibody of claim 1 in the prophylaxis and/or treatment of the RSV infection.

18. The antibody of claim 1, wherein the antibody comprises a heavy chain CDR1 region of SEQ ID NO:

7, a heavy chain CDR2 region of SEQ ID NO;

8, and a heavy chain CDR3 region of SEQ ID NO;

9, a light chain CDR1 region of SEQ ID NO;

10, a heavy chain CDR2 region of SEQ ID NO;

11, and a light chain CDR3 region of SEQ ID NO;

12.

2. An antigen-binding fragment that specifically binds to the G protein of a respiratory syncytial virus (RSV) and neutralizes RSV A2 and B strains, wherein the antigen-biding fragment is selected from the group consisting of:

a) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

1, a heavy chain CDR2 region of SEQ ID NO;

2, and a heavy chain CDR3 region of SEQ ID NO;

3, a light chain CDR1 region of SEQ ID NO;

4, a light chain CDR2 region of SEQ ID NO;

5, and a light chain CDR3 region of SEQ ID NO;

6;

b) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

7, a heavy chain CDR2 region of SEQ ID NO;

8, and a heavy chain CDR3 region of SEQ ID NO;

9, a light chain CDR1 region of SEQ ID NO;

10, a heavy chain CDR2 region of SEQ ID NO;

11, and a light chain CDR3 region of SEQ ID NO;

12,

c) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

13, a heavy chain CDR2 region of SEQ ID NO;

14, and a heavy chain CDR3 region of SEQ ID NO;

15, a light chain CDR1 region of SEQ ID NO;

16 a light chain CDR2 region of SEQ ID NO;

17, and a light chain CDR3 region of SEQ ID NO;

18;

d) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

19, a heavy chain CDR2 region of SEQ ID NO;

20, and a heavy chain CDR3 region of SEQ ID NO;

21, a light chain CDR1 region of SEQ ID NO;

22, a light chain CDR2 region of SEQ ID NO;

23, and a light chain CDR3 region of SEQ ID NO;

24;

e) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

25, a heavy chain CDR2 region of SEQ ID NO;

26, and a heavy chain CDR3 region of SEQ ID NO;

27, a light chain CDR1 region of SEQ ID NO;

28, a light chain CDR2 region of SEQ ID NO;

29, and a light chain CDR3 region of SEQ ID NO;

30;

f) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

31, a heavy chain CDR2 region of SEQ ID NO;

32, and a heavy chain CDR3 region of SEQ ID NO;

33, a light chain CDR1 region of SEQ ID NO;

34, a light chain CDR2 region of SEQ ID NO;

35, and a light chain CDR3 region of SEQ ID NO;

36;

g) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

37, a heavy chain CDR2 region of SEQ ID NO;

38, and a heavy chain CDR3 region of SEQ ID NO;

39, a light chain CDR1 region of SEQ ID NO;

40, a light chain CDR2 region of SEQ ID NO;

41, and a light chain CDR3 region of SEQ ID NO;

42;

h) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

43, a heavy chain CDR2 region of SEQ ID NO;

44, and a heavy chain CDR3 region of SEQ ID NO;

45, a light chain CDR1 region of SEQ ID NO;

46, a light chain CDR2 region of SEQ ID NO;

47, and a light chain CDR3 region of SEQ ID NO;

48;

i) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

49, a heavy chain CDR2 region of SEQ ID NO;

50 and a heavy chain CDR3 region of SEQ ID NO;

51, a light chain CDR1 region of SEQ ID NO;

52, a light chain CDR2 region of SEQ ID NO;

53, and a light chain CDR3 region of SEQ ID NO;

54;

j) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

55, a heavy chain CDR2 region of SEQ ID NO;

56, and a heavy chain CDR3 region of SEQ ID) NO;

57 a light chain CDR1 region of SEQ ID NO;

58, a light chain CDR2 region of SEQ ID NO;

59, and a light chain CDR3 region of SEQ ID NO;

60;

k) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

61, a heavy chain CDR2 region of SEQ ID NO;

62, and a heavy chain CDR3 region of SEQ ID NO;

63, a light chain CDR1 region of SEQ ID NO;

64, a light chain CDR2 region of SEQ ID NO;

65, and a light chain CDR3 region of SEQ ID NO;

66; and

l) an antigen-binding fragment comprising a heavy chain CDR1 region of SEQ ID NO;

67, a heavy chain CDR2 region of SEQ ID NO;

68, and a heavy chain CDR3 region of SEQ ID NO;

69 a light chain CDR1 region of SEQ ID NO;

70, a light chain CDR2 region of SEQ ID NO;

71, and a light chain CDR3 region of SEQ ID NO;

72.

5. A nucleic acid molecule encoding a peptide comprising the antigen-binding fragment of claim 2.

6. A vector comprising at least one nucleic acid molecule of claim 5.

7. A host cell comprising at least one vector of claim 6.

8. A method of producing an antibody, an antigen-binding fragment, and/or a functional variant, wherein the method comprises the steps of:

a) culturing the host cell of claim 7 under conditions conducive to the expression of the antibody, and optionally,

b) recovering the expressed antibody, antigen-binding fragment and/or functional variant.

11. A method of prophylaxing against and/or treating a subject with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the antigen-binding fragment of claim 2 in prophylaxis or treatment, or combination thereof, of RSV infection.

12. A kit comprising at least the antigen-binding fragment of claim 2.

14. An immunoconjugate comprising:

the antibody antigen-binding fragment of claim 2, and

at least one therapeutic agent and/or detectable agent.

3. A functional variant of an antibody that specifically binds to the G protein of a respiratory syncytial virus (RSV) and neutralizes RSV A2 and B strains, wherein the functional variant of an antibody is selected from the group consisting of:

a) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

1, a heavy chain CDR2 region of SEQ ID NO;

2, and a heavy chain CDR3 region of SEQ ID NO;

3, a light chain CDR1 region of SEQ ID NO;

4, a light chain CDR2 region of SEQ ID NO;

5, and a light chain CDR3 region of SEQ ID NO;

6;

b) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

7, a heavy chain CDR2 region of SEQ ID NO;

8, and a heavy chain CDR3 region of SEQ ID NO;

9, a light chain CDR1 region of SEQ ID NO;

10, a heavy chain CDR2 region of SEQ ID NO;

11, and a light chain CDR3 region of SEQ ID NO;

12,

c) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

13, a heavy chain CDR2 region of SEQ ID NO;

14, and a heavy chain CDR3 region of SEQ ID NO;

15, a light chain CDR1 region of SEQ ID NO;

16 a light chain CDR2 region of SEQ ID NO;

17, and a light chain CDR3 region of SEQ ID NO;

18;

d) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

19, a heavy chain CDR2 region of SEQ ID NO;

20, and a heavy chain CDR3 region of SEQ ID NO;

21, a light chain CDR1 region of SEQ ID NO;

22, a light chain CDR2 region of SEQ ID NO;

23, and a light chain CDR3 region of SEQ ID NO;

24;

e) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

25, a heavy chain CDR2 region of SEQ ID NO;

26, and a heavy chain CDR3 region of SEQ ID NO;

27, a light chain CDR1 region of SEQ ID NO;

28, a light chain CDR2 region of SEQ ID NO;

29, and a light chain CDR3 region of SEQ ID NO;

30;

f) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID) NO;

31, a heavy chain CDR2 region of SEQ ID NO;

32, and a heavy chain CDR3 region of SEQ ID NO;

33, a light chain CDR1 region of SEQ ID NO;

34, a light chain CDR2 region of SEQ ID NO;

35, and a light chain CDR3 region of SEQ ID NO;

36;

g) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

37, a heavy chain CDR2 region of SEQ ID NO;

38, and a heavy chain CDR3 region of SEQ ID NO;

39, a light chain CDR1 region of SEQ ID NO;

40, a light chain CDR2 region of SEQ ID NO;

41, and a light chain CDR3 region of SEQ ID NO;

42;

h) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

43, a heavy chain CDR2 region of SEQ ID NO;

44, and a heavy chain CDR3 region of SEQ ID NO;

45, a light chain CDR1 region of SEQ ID NO;

46, a light chain CDR2 region of SEQ ID NO;

47, and a light chain CDR3 region of SEQ ID NO;

48;

i) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

49, a heavy chain CDR2 region of SEQ ID NO;

50 and a heavy chain CDR3 region of SEQ ID NO;

51, a light chain CDR1 region of SEQ ID NO;

52, a light chain CDR2 region of SEQ ID NO;

53, and a light chain CDR3 region of SEQ ID NO;

54;

j) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

55, a heavy chain CDR2 region of SEQ ID NO;

56, and a heavy chain CDR3 region of SEQ ID NO;

57 a light chain CDR1 region of SEQ ID NO;

58, a light chain CDR2 region of SEQ ID NO;

59, and a light chain CDR3 region of SEQ ID NO;

60;

k) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

61, a heavy chain CDR2 region of SEQ ID NO;

62, and a heavy chain CDR3 region of SEQ ID NO;

63, a light chain CDR1 region of SEQ ID NO;

64, a light chain CDR2 region of SEQ ID NO;

65, and a light chain CDR3 region of SEQ ID NO;

66; and

l) a functional variant of an antibody comprising a heavy chain CDR1 region of SEQ ID NO;

67, a heavy chain CDR2 region of SEQ ID NO;

68, and a heavy chain CDR3 region of SEQ ID NO;

69 a light chain CDR1 region of SEQ ID NO;

70, a light chain CDR2 region of SEQ ID NO;

71, and a light chain CDR3 region of SEQ ID NO;

72.

10. A medicament comprising:

the functional variant of claim 3, and

at least one pharmaceutically acceptable excipient.

15. An immunoconjugate comprising:

the functional variant of claim 3, and

at least one therapeutic agent and/or detectable agent.

17. A method of prophylaxing against and/or treating a subject diagnosed with respiratory syncytial virus (RSV) infection, the method comprising:

utilizing the functional variant of claim 3 in the prophylaxis and/or treatment of the RSV infection.