Human binding molecules capable of binding to and neutralizing hepatitis B viruses and uses thereof

Patent metadata

Field	Value
Publication number	US-9512201-B2
Application number	US-201314428904-A
Country	US
Kind code	B2
Filing date	Sep 24, 2013
Priority date	Sep 27, 2012
Publication date	Dec 6, 2016
Grant date	Dec 6, 2016

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Crucell Holland Bv
• Janssen Vaccines & Prevention Bv

Inventors

• Van Den Nieuwenhof Ingrid
• Van Der Neut Kolfschoten Marijn
• Apetri Constantin Adrian
• Friesen Robert H E

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/56

  variable (Fv) region, i.e. VH and/or VL · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• C07K16/082 Primary

  Hepadnaviridae (F), e.g. hepatitis B virus · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title