The present invention generally relates to novel bispecific antigen binding molecules for T cell activation and re-direction to specific target cells. In addition, the present invention relates to polynucleotides encoding such bispecific antigen binding molecules, and vectors and host cells comprising such polynucleotides. The invention further relates to methods for producing the bispecific antigen binding molecules of the invention, and to methods of using these bispecific antigen binding molecules in the treatment of disease.

The invention provides for a domain-exchanged antibody comprising a light chain (LC) composed of VL-CH3, and a heavy chain (HC) comprising VH-CH3-CH2-CH3, wherein the VL-CH3 of the LC is dimerising with the VH-CH3 of the HC thereby forming a domain-exchanged LC/HC dimer comprising a CH3LC/CH3HC domain pair, and means and method for producing the same.

A trispecific inhibitor for treating cancer includes a first targeting domain having a binding specificity conferred by a VEGF binding antagonist; a second targeting domain having a binding specificity conferred by an immune checkpoint regulator binding antagonist; and a third targeting domain having a binding specificity conferred by a Tie2 tyrosine kinase receptor binding antagonist. The targeting domains may contain one or more antibody variable regions, peptide inhibitors, dominant negative proteins, small molecule drugs or combinations thereof.

Provided are novel covalent multi-specific antibodies with increased stability, and use thereof for therapy, such as for immunotherapy.

The present invention relates to a novel antibody against HERV-K envelope that targets a conserved region not affected by glycosylation or by native conformation, and its use in diagnostics and/or is therapy.

The present invention relates to novel antigen binding domains and heterodimeric antibodies that bind Fibroblast Activation Protein (FAP).

An antibody-drug conjugate (ADC) or a pharmaceutically acceptable salt thereof, is provided. The ADC includes a tetravalent monoclonal antibody conjugated to a cytotoxic drug by a chemical linker. The monoclonal antibody includes two long chains and four short chains. Each of the long chains includes a first segment and a second segment, the first segment located proximal to the N-terminus of the long chain, and the second segment located proximal to the C-terminus of the long chain. Each of the first segment and second segment pairs with one of the short chains to form an antigen-binding fragment domain, therefore forming four antigen-binding fragment domains having specificity toward the same antigen. Pharmaceutical composition including the ADC and methods of treating diseases using the compositions are also provided.

An antibody specifically binding to human BCMA, characterized in that the binding of said antibody is not reduced by APRIL and not reduced by BAFF, said antibody does not alter APRIL-dependent NF-B activation, BAFF-dependent NF-B activation, and does not alter NF-B activation without BAFF and APRIL is useful as a therapeutic agent.

The present invention provides efficient methods based on alteration of the protein A-binding ability, for producing or purifying multispecific antibodies having the activity of binding to two or more types of antigens to high purity through a protein A-based purification step alone. The methods of the present invention for producing or purifying multispecific antibodies which feature altering amino acid residues of antibody heavy chain constant region and/or variable region. Multispecific antibodies with an altered protein A-binding ability, which exhibit plasma retention comparable or longer than that of human IgG1, can be efficiently prepared in high purity by introducing amino acid alterations of the present invention into antibodies.

The present invention provides method for increasing the percentage of monomer in a composition of recombinantly expressed antibody molecules characterised in that the antibody molecule comprises at least one Fv with specificity for an antigen of interest comprising one VH and one VL wherein said VH and VL are connected directly or indirectly via one or more linkers and are stabilised by a disulfide bond therebetween, said method comprises a) a thermal conversion step of holding the composition comprising the antibody molecule at a temperature in the range 30 to 60 C. for a period of at least 1 hour, wherein step a) is performed in the presence of a reducing agent or after treatment with a reducing agent.