Antibodies that neutralize hepatitis B virus and uses thereof
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Publication Number
US-12304946-B2
Publication Date
2025-05-20
Expiration Date
Abstract
The present disclosure relates to antibodies, and antigen binding fragments thereof, that can bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and can neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The present disclosure also relates to epitopes to which the antibodies and antigen binding fragments bind, as well as to fusion proteins that comprise the antigen binding fragments, and to nucleic acids that encode and cells that produce such antibodies and antibody fragments. In addition, the present disclosure relates to the use of the antibodies and antibody fragments of the present disclosure in the diagnosis, prophylaxis and treatment of hepatitis B and hepatitis D.
Core Innovation
The invention relates to HBV/HDV-neutralizing antibodies and antibody fragments that bind hepatitis B surface antigen (HBsAg). The antibody comprises a heavy chain with the amino acid sequence according to SEQ ID NO: 91 and a light chain with the amino acid sequence according to SEQ ID NO: 93, and targets an antigenic loop region of the HBsAg S domain. The disclosed antibodies bind antigenic-loop sequences and loop-region variants, with reference to HBsAg antigenic loop sequences such as SEQ ID NO: 3 and loop variants SEQ ID NOs: 5-33.
The invention includes VH/VL variable regions and CDRs, as well as antibody fragments such as scFv, Fab, F(ab')2, and Fv. The invention further includes nucleic acids encoding the antibodies, including codon-optimized nucleotide sequences and sequence-identity variants, and vectors and host cells for production and expression of the antibodies.
Fc moiety engineering is also included, including GAALIE (G236A/A330L/I332E), with optional Fc modifications such as MLNS (M428L/N434S) and related FcRn half-life variants. The described antibody formats extend through specific heavy chain and light chain sequence combinations, together with IgG subclass/isotype switching and chimeric Fc/hinge designs.
Claims Coverage
The independent claims cover three inventive features: a sequence-defined isolated anti-HBsAg antibody, a polynucleotide encoding that antibody with specified VH and VL sequences, and a method of attenuating hepatitis B and/or hepatitis D infection by administering the defined antibody.
Sequence-defined anti-HBsAg antibody
An isolated antibody that binds HBsAg comprising a heavy chain comprising the amino acid sequence according to SEQ ID NO: 91 and a light chain comprising the amino acid sequence according to SEQ ID NO: 93.
Sequence-defined antibody encoding polynucleotide
A polynucleotide that encodes an antibody, comprising a VH-encoding nucleotide sequence according to SEQ ID NO: 103 and a VL-encoding nucleotide sequence according to SEQ ID NO: 105.
Administered sequence-defined antibody for attenuation of HBV/HDV infection
A method of attenuating a hepatitis B infection and/or hepatitis D infection in a subject, comprising administering to the subject an effective amount of an antibody comprising a heavy chain comprising the amino acid sequence according to SEQ ID NO: 91 and a light chain comprising the amino acid sequence according to SEQ ID NO: 93.
Overall claim coverage centers on antibodies that bind HBsAg via specified heavy- and light-chain sequences, polynucleotides encoding specified VH/VL sequences, and attenuation of hepatitis B and/or hepatitis D infection by administering an effective amount of the sequence-defined antibody.
Stated Advantages
Neutralization potency against HBsAg, including across HBsAg genotypes (A-J) and infectious loop-region mutants.
Fc moiety engineering is associated with FcγR binding modulation and complement binding (C1q), including engagement relevant to ADCC/NK activation and reduced complement via C1q.
Attenuation of a hepatitis B infection and/or hepatitis D infection in a subject.
In vitro diagnosis of hepatitis B infection by contacting a subject sample with an antibody and detecting an antigen-antibody complex.
Documented Applications
In vitro diagnosing hepatitis B infection by contacting a subject sample with an antibody and detecting an antigen-antibody complex.
Attenuating hepatitis B infection and/or hepatitis D infection in a subject by administering an effective amount of an antibody with the specified heavy- and light-chain sequences.
Vectors and host cells for production of the antibodies.
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