The present invention relates to novel recombinant fusion proteins, such as human antibody-based molecules called Vaccibodies, which are able to trigger both a T cell- and B cell immune response. The present invention also relates to a method of treating a cancer or an infectious disease by means of these specific fusion proteins.

The present invention relates to a bispecific antibody, which is a tetravalent symmetrical bispecific antibody with a structure of F(ab).sub.2-(Fv).sub.2-Fc and comprises two identical fusion heavy chains and two identical fusion light chains.

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

The present invention provides multivalent and multispecific binding proteins that are capable of binding two or more antigens, or two or more epitopes. The present invention also provides methods of making and using such multivalent and multispecific binding proteins, including methods of using such binding proteins for prevention or treatment of various diseases, or for detecting specific antigens in vitro or in vivo.

The present disclosure provides methods of treating a subject having a proliferative disease or an autoimmune disorder with a combination of (a) a first multispecific binding molecule (MBM) that binds specifically to (i) human CD2 and (ii) a human tumor-associated antigen and/or a human tumor microenvironment antigen, and (b) a second multispecific binding molecule that binds specifically to (i) a component of a human T-cell receptor (TCR) complex or a secondary T-cell signaling molecule and (ii) a human tumor-associated antigen and/or human tumor microenvironment antigen. The disclosure further provides MBMs and combinations of MBMs that can be used in the methods of the disclosure.

The present application provides multispecific constructs that bind to Claudin-18.2 (such as various anti-Claudin-18.2×anti-PD-L1 bispecific antibodies), nucleic acids encoding the multispecific construct or a portion thereof, vectors comprising the nucleic acids, host cells containing the vectors, methods of preparing the multispecific constructs, pharmaceutical compositions comprising any of the multispecific constructs, and methods of using the multispecific constructs or compositions.

The present disclosure provides humanized antibodies that specifically bind to CD3 with an optimized affinity and induce T cell-mediated killing of tumour related target antigen high expressing cells with high potency but have limited killing activity on target antigen low expressing cells. The present disclosure also provides bispecific antibodies comprising a first antigen-binding domain that specifically binds to human CD3 with optimized affinity and a second antigen-binding molecule that specifically binds a tumor-related antigen. The disclosure further relates to methods of generating such humanized antibodies and bispecific antibodies for biological, diagnostic, pharmaceutical and other uses.

Provided herein antibodies, activatable antibodies (AAs), bispecific antibodies, and bispecific activatable antibodies (BAAs). Also provided herein are methods of making and methods of use of these antibodies, AAs, bispecific antibodies, and BAAs.

Provided herein are heterodimeric bispecific antibodies that can mediate cytolysis of a target cell by an immune effector cell, nucleic acids encoding such antibodies, methods of making such antibodies, and methods of using such antibodies. These antibodies comprise two different polypeptide chains, each comprising two immunoglobulin variable regions and, optionally, a half life-extending moiety.

The invention provides novel heterodimeric proteins including heterodimeric antibodies.