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-vims neutralizing monoclonal antibody against JCV capsid protein VPI (JCV-VP1). In some embodiments, the antibody suppresses infectivity of the JC-vims. In some embodiments, the antibody binds the sialic acid binding pocket of JCV-VP1.
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:31, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:35, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:9; and
a light chain variable domain comprising a CDR1 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:17, a CDR2 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:3, and a CDR3 amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:4.
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:20.
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:20.
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:20.
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:15.
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:15.
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:15.
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:20 and a light chain variable domain amino acid sequence that is identical to the amino acid sequence of SEQ ID NO:15.
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.