Compositions and methods related to human neutralizing antibodies to hepatitis b

By developing modified HBsAg-specific monoclonal antibodies and recombinant peptide vaccine formulations, the problem of uncontrollable HBV infection in existing technologies has been solved, achieving effective prevention and treatment, especially against viral mutation escape in the in vivo environment.

CN114728066BActive Publication Date: 2026-06-16THE ROCKEFELLER UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
THE ROCKEFELLER UNIV
Filing Date
2020-09-11
Publication Date
2026-06-16

AI Technical Summary

⚠Technical Problem

Existing methods and compositions for combating HBV infection have failed to effectively utilize the human humoral immune response with high serum neutralizing activity, resulting in chronic infection that is difficult to control and a lack of effective treatment options.

⚗Method used

A specific monoclonal antibody against HBsAg was developed. Its constant region was modified to enhance its in vivo half-life and binding capacity. Multiple antibodies were combined to target non-overlapping epitopes in HBsAg. Combined with recombinant peptide vaccine formulations and expression vectors, it was used for the prevention or treatment of hepatitis B virus infection.

🎯Benefits of technology

It showed significant protective and therapeutic effects in in vivo experiments, inhibiting viral mutation escape and improving neutralizing activity and therapeutic efficacy against HBV.

✦ Generated by Eureka AI based on patent content.

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Abstract

Broadly neutralizing antibodies (bNAbs) and antigen-binding fragments thereof that specifically bind to epitopes expressed by hepatitis B virus (HBV) are provided. The bNAbs target non-overlapping epitopes on the HBV S antigen (HBsAg). Pharmaceutical compositions comprising the bNAbs or modified bNAbs are provided. Also included are combinations of bNAbs that are useful for preventing and treating HBV infection, as well as inhibiting the development of HBV escape mutations in infected individuals. Also included are expression vectors encoding the bNAbs and antigenic fragments thereof, as well as methods of making the bNAbs and antigenic fragments thereof. HBV peptides for use as vaccines are provided that include at least two non-overlapping epitopes from HBsAg. Diagnostic reagents comprising the bNAbs or antigenic fragments thereof are provided, as well as methods of detecting HBV and diagnosing HBV infection.
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Claims

1. A combination of isolated or recombinant antibodies or antigen-binding fragments thereof, wherein the isolated or recombinant antibody or antigen-binding fragment specifically binds to hepatitis B virus surface antigen (HBsAg), wherein the isolated or recombinant antibody or antigen-binding fragment comprises a complementarity-determining region (CDR), wherein the CDR comprises the heavy chain and light chain amino acid sequences CDR1, CDR2, and CDR3 of the antibody heavy chain and light chain CDRs, the combination comprising antibody H017 and antibody H019 or antigen-binding fragments thereof, wherein The antibody H017 or its antigen-binding fragment comprises a heavy chain CDR1 with the amino acid sequence GFTFSNYW (SEQ ID NO: 13), a heavy chain CDR2 with the amino acid sequence ISTDGSST (SEQ ID NO: 14), a heavy chain CDR3 with the amino acid sequence ARGSTYYFGSGSVDY (SEQ ID NO: 15), a light chain CDR1 with the amino acid sequence SSDIGVYNY (SEQ ID NO: 16), a light chain CDR2 with the amino acid sequence DVT, and a light chain CDR3 with the amino acid sequence SSYRGSSTPYV (SEQ ID NO: 17); and The antibody H019 or its antigen-binding fragment comprises a heavy chain CDR1 with the amino acid sequence GGSITTGDYY (SEQ ID NO: 18), a heavy chain CDR2 with the amino acid sequence IYYSGST (SEQ ID NO: 19), a heavy chain CDR3 with the amino acid sequence AIYMDEAWAFEI (SEQ ID NO: 20), a light chain CDR1 with the amino acid sequence QSVGNY (SEQ ID NO: 21), a light chain CDR2 with the amino acid sequence AVS, and a light chain CDR3 with the amino acid sequence QQSYTISLFT (SEQ ID NO: 22).

2. The combination of isolated or recombinant antibodies or antigen-binding fragments thereof according to claim 1, further comprising antibody H016 or its antigen-binding fragment, wherein the antibody H016 or its antigen-binding fragment comprises a heavy chain CDR1 with the amino acid sequence GFTFPSHT (SEQ ID NO: 8), a heavy chain CDR2 with the amino acid sequence ISTTSEAI (SEQ ID NO: 9), a heavy chain CDR3 with the amino acid sequence ARVGLALTISGYWYFDL (SEQ ID NO: 10), a light chain CDR1 with the amino acid sequence QSISSN (SEQ ID NO: 11), a light chain CDR2 with the amino acid sequence RAS, and a light chain CDR3 with the amino acid sequence QQYDHWPLT (SEQ ID NO: 12).

3. The isolated or recombinant antibody or combination of antigen-binding fragments thereof according to claim 1 or 2, comprising at least one modification of its constant region, wherein the modification increases the in vivo half-life of the antibody, or alters the ability of the antibody to bind to an Fc receptor, or inhibits the aggregation of the antibody, or a combination of the modifications, or wherein the antibody is linked to a detectable marker or substrate.

4. The combination of isolated or recombinant antibodies or antigen-binding fragments thereof according to claim 3, comprising a modification that increases the in vivo half-life of the antibody.

5. The combination of isolated or recombinant antibodies or antigen-binding fragments thereof according to claim 3, comprising modifications that alter the ability of the antibody to bind to the Fc receptor.

6. A pharmaceutical composition comprising a combination of an antibody or an antigen-binding fragment thereof according to any one of claims 1-5.

7. The pharmaceutical composition according to claim 6, comprising the antibody.

8. The use of any combination of the antibody or antigen-binding fragment thereof as described in any one of claims 1-5 in the preparation of a medicament for the prevention or treatment of hepatitis B virus infection.

9. The application according to claim 8, comprising administering to an individual in need an effective amount of a combination of the antibody or antigen-binding fragment of any one of claims 1-5.

10. The application according to claim 8, wherein at least one of the antibodies comprises at least one modification of a constant region.

11. The application according to any one of claims 8 to 10, wherein administration of the combination provides a therapeutic and / or preventive effect against hepatitis B virus infection, said hepatitis B virus comprising one or more escape mutations in at least one of the HBsAg or S-protein of said hepatitis B virus.

12. One or more recombinant expression vectors encoding a combination of the heavy and light chains of an antibody or an antigen-binding fragment thereof according to any one of claims 1-5.

13. A cell comprising one or more recombinant expression vectors according to claim 12.

14. A method for preparing an antibody, comprising culturing the cells according to claim 13 and isolating the antibody from the cells.

15. A kit comprising one or more recombinant expression vectors encoded according to claim 12.

16. Use of any combination of antibodies or antigen-binding fragments thereof as described in any one of claims 1-5 in the preparation of reagents for detecting hepatitis B virus.

17. The application of claim 16, comprising contacting a biological sample from an individual with the antibody in the combination and detecting the presence of a complex comprising the antibody and hepatitis B virus protein.