Heterodimerizing domains with orthogonal mutations that drive heterodimerization, in particular heterodimerizing antibody CH3 domains, heterodimeric polypeptides comprising such heterodimerizing domains, and antibody constructs comprising such heterodimeric polypeptides, are provided.

The present invention is directed to novel bispecific heterodimeric Fc fusion proteins comprising an IL-15/IL-15Rα Fc-fusion protein and a PD-1 antibody fragment-Fc fusion protein.

Isolated antibodies and immunoconjugates that specifically bind Frizzled receptor (FZD) 4 cysteine rich domain (CRD) comprising a light chain variable region and a heavy chain variable region, the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, the light chain variable region comprising complementarity determining region CDR-L1, CDR-L2 and CDR-L3, and with the amino acid sequences of said CDRs comprising or consisting of sequences selected from sequences in Table 1a or 3a. Methods of using the antibodies and immunoconjugates are also provided.

The present disclosure provides a novel type of drug for treating a subject suffering from an inflammatory and/or autoimmune disease, and specifically rheumatoid arthritis. Specifically, the disclosure provides polypeptides comprising at least three immunoglobulin single variable domains (ISVDs), characterized in that at least one ISVD binds to TNF-α and at least two ISVDs bind to IL-6. The present disclosure also provides nucleic acids, vectors and compositions.

Methods for diagnosing or treating immune disorders in a subject are provided. The methods are based on the detection or modulation of Refractory state Inducing Factor (RIF).

The invention relates to new bispecific antigen binding molecules, comprising at least one antigen binding domain capable of specific binding to 4-1BB, at least one moiety capable of specific binding to a target cell antigen, and a Fc domain composed of a first and a second subunit capable of stable association, and to methods of producing these molecules and to methods of using the same.

The application pertains to a trispecific antibody molecule which may comprise a diabody-unit integrated into a polypeptide chain having at least six variable domains linked one after another. In certain instances two single-chain Fv (scFv) fragments are distally connected to the diabody-unit providing two further antigen binding sites (FIGS. 1 and 2).

The present invention is directed to binding molecules that possess one or more epitope-binding sites specific for an epitope of CD137, including antibodies, and molecules comprising epitope-binding fragments thereof The invention is further directed to multispecific binding molecules comprising one or more epitope-binding sites specific for an epitope of CD137 and one or more epitope-binding sites specific for an epitope of a tumor antigen (“TA”) (e.g, a “CD137×TA Binding Molecule”).

The present disclosure relates to novel PD-1 binding domains that have a higher binding affinity for human PD-1 than a reference PD-1 binding domain. The PD-1 binding domains of the present disclosure further provide a comparable, or equal or higher, potency in blocking ligand binding to human PD-1 than a reference PD-1 antibody. The present disclosure further relates to binding moieties comprising such PD-1 binding domains. Also provided is a method for treating a disease, in particular a disease associated with a suppressed immune system, such as cancer, with a PD-1 binding domain or binding moiety of the present disclosure. The present disclosure further relates to nucleic acids encoding the heavy chain variable region of the PD-1 binding domains, and a vector and cell comprising such nucleic acid.

The present invention generally relates to T cell activating bispecific antigen binding molecules, PD-1 axis binding antagonists, and in particular to combination therapies employing such T cell activating bispecific antigen binding molecules and PD-1 axis binding antagonists, and their use of these combination therapies for the treatment of cancer.