Antibodies and compositions of matter useful for the detection, diagnosis and treatment of Hepatitis B Virus infection in mammals, and to methods of using those compositions of matter for the same.

Genetically modified mice and methods for making an using them are provided, wherein the mice comprise a replacement of all or substantially all immunoglobulin heavy chain V gene segments, D gene segments, and J gene segments with at least one light chain V gene segment and at least one light chain J gene segment. Mice that make binding proteins that comprise a light chain variable domain operably linked to a heavy chain constant region are provided. Binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Modified cells, embryos, and mice that encode sequences for making the binding proteins are provided.

Provided are an antibody or antigen-binding fragment thereof that specifically binds to hepatitis B virus surface antigen (HBsAg), a pharmaceutical composition containing the antibody or antigen-binding fragment, and use thereof. Further provided are a nucleic acid molecule encoding the antibody, a vector and a host cell containing the nucleic acid molecule, and a method for preparing the antibody.

The present invention relates to specific binding molecules that bind the HLA-A*02 restricted peptide GLSPTVWLSV (SEQ ID NO: 1) derived from HBV envelope protein. The specific binding molecules may comprise alpha and/or beta TCR variable domains and may comprise non-natural mutations within the alpha and/or beta variable domains relative to a native TCR. The specific binding molecules of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of infectious or malignant disease.

Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

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.

The present invention relates to a method of producing recombinant binding proteins with binding specificity for a peptide-MHC (pMHC) complex. The invention also relates to recombinant binding proteins comprising one, two or more designed repeat domain(s), preferably designed ankyrin repeat domain(s), with binding specificity for a pMHC complex, and to such binding proteins which further comprise a binding agent having binding specificity for a protein expressed on the surface of an immune cell, preferably a T-cell. In addition, the invention relates to nucleic acids encoding such binding proteins or repeat domains, pharmaceutical compositions comprising such binding proteins or nucleic acids, and the use of such binding proteins, nucleic acids or pharmaceutical compositions in methods for treating or diagnosing diseases, including cancer, infectious diseases and autoimmune diseases.

The present disclosure relates, in part, to antibodies, and antigen-binding fragments thereof, that can bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and, optionally, can neutralize infection hepatitis B virus (HBV), and further optionally, of hepatitis delta virus (HDV). Presently disclosed antibodies and antigen-binding fragments have advantageous production characteristics, such as reduced formation of aggregates and/or improved production titer in transformed host cells, as compared to a reference antibody or antigen-binding fragment. The present disclosure also relates to fusion proteins that comprise an antigen-binding fragment, and to nucleic acids that encode and cells that produce such antibodies, antigen-binding fragments, and fusion proteins. In addition, the present disclosure relates to the use of the antibodies, antigen-binding fragments, fusion proteins, and related polynucleotides, vectors, host cells, and compositions of the present disclosure in the diagnosis, prophylaxis and treatment of hepatitis B and hepatitis D. Also provided are combination therapies comprising (i) an antibody or antigen-binding fragment and (ii) an agent that is an inhibitor of HBV gene expression and/or that reduces HBV antigenic load.

The present invention relates to antibodies, and antigen binding fragments thereof, that bind to the antigenic loop region of hepatitis B surface antigen (HBsAg) and potently neutralize infection of both hepatitis B virus (HBV) and hepatitis delta virus (HDV). The invention also relates to epitopes to which the antibodies and antigen binding fragments bind, as well as to nucleic acids that encode and cells that produce such antibodies and antibody fragments. In addition, the invention relates to the use of the antibodies and antibody fragments of the invention in the diagnosis, prophylaxis and treatment of hepatitis B and hepatitis D.

The present invention discloses products and the methods of uses of the products for preventing and treating infectious diseases and the disorders or conditions inducible by harmful antibodies. The harmful antibodies are induced during infection, or vaccination, or use of therapeutic antibodies. The products of the present disclosure comprise immunoglobulin products, serum or plasma, specific antibodies to viral pathogens.