JCV neutralizing antibodies
View Patent ↗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.
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.