Human binding molecules capable of binding to and neutralizing hepatitis B viruses and uses thereof
The disclosure relates to binding molecules, such as human monoclonal antibodies, that bind to Hepatitis B viruses, and have a broad neutralizing activity against such Hepatitis B viruses. The disclosure further provides nucleic acid molecules encoding the binding molecules, and compositions comprising the binding molecules. The binding molecules can be used in the diagnosis, prophylaxis and/or treatment of Hepatitis B.
1. A binding molecule comprising:
a heavy chain CDR1 comprising the peptide of SEQ ID NO:1,
a heavy chain CDR2 comprising the peptide of SEQ ID NO:2,
a heavy chain CDR3 comprising the peptide of SEQ ID NO:3,
a light chain CDR1 comprising the peptide of SEQ ID NO:4,
a light chain CDR2 comprising the peptide of SEQ ID NO:5, and
a light chain CDR3 comprising the peptide of SEQ ID NO:6,
which binds to an epitope on a Hepatitis B virus protein.
2. The binding molecule according to claim 1 , wherein the binding molecule comprises a heavy chain variable region comprising the peptide of SEQ ID NO:7 and a light chain variable region comprising the peptide of SEQ ID NO:8.
3. The binding molecule according to claim 1 , wherein the binding molecule comprises a heavy chain comprising the peptide of SEQ ID NO:9 and a light chain comprising the peptide of SEQ ID NO:10.
4. The binding molecule of claim 1 , wherein the binding molecule neutralizes a Hepatitis B virus in an in vitro assay.
5. The binding molecule of claim 1 , wherein the binding molecule is a human monoclonal antibody, or an antigen-binding fragment thereof.
6. An immunoconjugate, comprising:
at least one binding molecule of claim 1 , and at least one tag.
7. A nucleic acid molecule encoding a binding molecule comprising:
a heavy chain CDR1 comprising the peptide of SEQ ID NO:1,
a heavy chain CDR2 comprising the peptide of SEQ ID NO:2,
a heavy chain CDR3 comprising the peptide of SEQ ID NO:3,
a light chain CDR1 comprising the peptide of SEQ ID NO:4,
a light chain CDR2 comprising the peptide of SEQ ID NO:5, and
a light chain CDR3 comprising the peptide of SEQ ID NO:6.
8. A method of treating a subject for hepatitis B virus infection, the method comprising: administering to a subject the binding molecule of claim 1 in the treatment of a Hepatitis B infection caused by a Hepatitis B virus.
9. A pharmaceutical composition comprising:
the binding molecule of claim 1 , and
a pharmaceutically acceptable carrier or excipient.
10. The pharmaceutical composition according to claim 9 , further comprising:
a Hepatitis B neutralizing binding molecule.
11. A method of detecting a Hepatitis B virus infection, the method comprising: (a) assaying the level of Hepatitis B virus antigen in a biological sample utilizing the binding molecule of claim 1 ; and (b) comparing the assayed level of Hepatitis B virus antigen with a control level whereby an increase in the assayed level of Hepatitis B virus antigen compared to the control level of the Hepatitis B virus antigen is indicative of a Hepatitis B virus infection.
12. A humanized, chimeric, or human monoclonal antibody or antibody fragment that binds to hepatitis B virus (HBV) surface antigen and neutralizes at least one HBV genotype, the antibody comprising:
a heavy chain CDR1 comprising the peptide of SEQ ID NO:1,
a heavy chain CDR2 comprising the peptide of SEQ ID NO:2,
a heavy chain CDR3 comprising the peptide of SEQ ID NO:3,
a light chain CDR1 comprising the peptide of SEQ ID NO:4,
a light chain CDR2 comprising the peptide of SEQ ID NO:5, and
a light chain CDR3 comprising the peptide of SEQ ID NO:6.
13. The antibody or antibody fragment of claim 12 , wherein a heavy chain variable region comprises the peptide of SEQ ID NO:7 and a light chain variable region comprises the peptide of SEQ ID NO:8.
14. The antibody or antibody fragment of claim 12 , wherein a heavy chain comprises the peptide of SEQ ID NO:9 and the light chain comprises the peptide of SEQ ID NO:10.