JCV neutralizing antibodies

• US 9,567,391 B2
• Filed: 03/15/2013
• Issued: 02/14/2017
• Est. Priority Date: 03/20/2012
• Status: Active Grant

• Current Assignee: Biogen MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen MA Inc. (Biogen, Inc.)
• Inventors: Simon, Kenneth, Cameron, Thomas, Rushe, Mia, Caravella, Justin, Kaynor, George Campbell
• Primary Examiner(s): Zou, Nick
• Application Number:
  US14/386,228
• Publication Number:
  US 20150056188A1
• Time in Patent Office: 1,432 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/084 Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
• CPC Class Codes: C07K 2317/00 Immunoglobulins specific features
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/40 characterized by post-translational modification
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

In one aspect, the disclosure provides neutralizing antibodies against JCV and methods for the treatment of PML. In some embodiments, aspects of the invention relate to an isolated JC-virus neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-virus. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VPI. In some embodiments, the antibody binds JCV-VP 1 comprising one or more of the following mutations: S269F, S269Y, S267F, N265D, Q271 H, D66H, K60E, K60N and L55F.

Claims

1. An isolated monoclonal antibody comprising:

a heavy chain variable domain comprising a CDR1 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

48, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

49, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

63; and

a light chain variable domain comprising a CDR1 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

64, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

65, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

66).

2. The isolated monoclonal antibody of claim 1, wherein at least one framework region amino acid sequence of the heavy chain variable domain is at least 90% identical to at least one corresponding framework region amino acid sequence of a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

10.

3. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

10.

4. The isolated monoclonal antibody of claim 3, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

10.

5. The isolated monoclonal antibody of claim 1, wherein at least one framework region amino acid sequence of the light chain variable domain is at least 90% identical to at least one corresponding framework region amino acid sequence of a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

12.

6. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody comprises a light chain variable domain amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

12.

7. The isolated monoclonal antibody of claim 6, wherein the isolated monoclonal antibody comprises a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

12.

8. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

10 and a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

12.

9. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is an isolated chimeric monoclonal antibody.

10. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody comprises an IgG1 Fc-region.

11. The isolated monoclonal antibody of claim 8, wherein the isolated monoclonal antibody is an isolated chimeric monoclonal antibody.

12. The isolated monoclonal antibody of claim 8, wherein the isolated monoclonal antibody comprises an IgG1 Fc-region.

13. An isolated monoclonal antibody comprising:

a heavy chain variable domain comprising a CDR1 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

48, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

53, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

63; and

a light chain variable domain comprising a CDR1 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

64, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

65, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

68).

14. The isolated monoclonal antibody of claim 13, wherein at least one framework region amino acid sequence of the heavy chain variable domain is at least 90% identical to at least one corresponding framework region amino acid sequence of a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

23.

15. The isolated monoclonal antibody of claim 13, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

23.

16. The isolated monoclonal antibody of claim 15, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

23.

17. The isolated monoclonal antibody of claim 13, wherein at least one framework region amino acid sequence of the light chain variable domain is at least 90% identical to at least one corresponding framework region amino acid sequence of a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

43.

18. The isolated monoclonal antibody of claim 13, wherein the isolated monoclonal antibody comprises a light chain variable domain amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:

43.

19. The isolated monoclonal antibody of claim 18, wherein the isolated monoclonal antibody comprises a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

43.

20. The isolated monoclonal antibody of claim 13, wherein the isolated monoclonal antibody comprises a heavy chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:

23 and a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO;

43.

21. The isolated monoclonal antibody of claim 13, wherein the isolated monoclonal antibody is an isolated chimeric monoclonal antibody.

22. The isolated monoclonal antibody of claim 13, wherein the isolated monoclonal antibody comprises an IgG1 Fc-region.

23. The isolated monoclonal antibody of claim 20, wherein the isolated monoclonal antibody is an isolated chimeric monoclonal antibody.

24. The isolated monoclonal antibody of claim 20, wherein the isolated monoclonal antibody comprises an IgG1 Fc-region.