HUMAN ANTIBODIES BINDING TO RSV G PROTEIN

• US 20160145321A1
• Filed: 04/14/2014
• Published: 05/26/2016
• Est. Priority Date: 04/15/2013
• Status: Active Grant

• Current Assignee: Janssen Vaccines & Prevention B.V. (Johnson & Johnson)
• Original Assignee: Crucell Holland B.V (Johnson & Johnson)
• Inventors: Williamson, Robert Anthony, Langedijk, Johannes P.M., Van 'T Wout, Angelique, Wadia, Jehangir, Pascual, Gabriel
• Granted Patent: US 10,196,438 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/145 Orthomyxoviridae, e.g. influenza virus
• 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 14/005 from 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 2317/55 Fab or Fab'
• 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 relates to isolated antibodies and antigen-binding fragments that bind to the G protein of RSV and which are capable of neutralizing RSV A and B subtypes, and the use thereof in the diagnosis, prophylaxis, and/or treatment of RSV infections.

Claims

1. An antibody able to specifically bind to the G protein of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antibody binds to an epitope within the central conserved domain of the RSV G protein and wherein said epitope comprises amino acids 162-168 of the RSV G protein RSV A2 strain.

3. The antibody of claim 1, 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;

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

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

15;

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

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

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

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

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

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

18,

c) 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;

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

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

21;

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

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

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

12, 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; and

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.

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

utilizing the antibody according to claim 1 in the prophylaxis or treatment, or combination thereof, of RSV infection.

15. A kit comprising at least one antibody according to claim 1.

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

assaying the level of RSV antigen in a sample using 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.

17. The antibody of claim 1, wherein the epitope comprises amino acids 161-169 of the RSV G protein RSV A2 strain or corresponding amino acids in another strain.

2. An antibody able to specifically bind to the G protein of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, 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,

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

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

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

6,

c) 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,

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

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

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

12,

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, and

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.

4. The antibody of claim 2, wherein the antibody is a human antibody.

5. Antigen-binding fragment able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antigen-biding fragment binds to an epitope within the central conserved domain of the RSV G protein, the epitope comprising amino acids 162-168 of RSV G protein RSV A2 strain.

8. A nucleic acid molecule encoding a peptide comprising the antigen-binding fragment according to claim 5.

9. A vector comprising at least one nucleic acid molecule according to claim 8.

10. A host cell comprising at least one vector according to claim 9.

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

culturing a host cell according to claim 10 under conditions conducive to the expression of the antibody, and optionally,

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

18. The method according to claim 11, further comprising:

recovering the expressed antibody.

19. An immunoconjugate comprising:

the antigen-binding fragment of claim 5, and

at least one therapeutic agent and/or detectable agent bonded thereto.

6. A functional variant of an antibody that is able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the functional variant binds to an epitope within the central conserved domain of the RSV G protein, the epitope comprising amino acids 162-168 of RSV G protein RSV A2 strain.

20. An immunoconjugate comprising:

the functional variant of claim 6, and

at least one therapeutic agent and/or detectable agent bonded thereto.

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

assaying the level of RSV antigen in a sample with the functional variant of claim 6, 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.

7. An immunoconjugate comprising:

an antibody able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antibody binds to an epitope within the central conserved domain of the RSV G protein, the epitope comprising amino acids 162-168 of RSV G protein RSV A2 strain, and

at least one therapeutic agent and/or detectable agent bonded thereto.

12. A pharmaceutical composition comprising:

an antibody able to specifically bind to the attachment glycoprotein (G protein) of a respiratory syncytial virus (RSV) and able to neutralize RSV A and B strains, wherein the antibody binds to an epitope within the central conserved domain of the RSV G protein, said epitope comprising amino acids 162-168 of RSV G protein RSV A2 strain, and

at least one pharmaceutically acceptable excipient.

13. (canceled)