The present invention describes novel immunoglobulin compositions that co-engage at least two antigens, e.g. a first and second antigen, or, as outlined herein, three or four antigens can be bound, in some of the scaffold formats described herein. First and second antigens of the invention are herein referred to as antigen-1 and antigen-2 respectively (or antigen-3 and antigen-4, if applicable. As outlined herein, a number of different formats can be used, with some scaffolds relying combinations of monovalent and bivalent bindings.

The present invention provides compositions comprising molecules having multispecificity and method of their use.

The present invention relates to multispecific antibodies, methods for their production, pharmaceutical compositions containing said antibodies and uses thereof.

The present invention relates to antagonist antibodies of the human calcitonin gene-related peptide (CGRP) receptor as well as bispecific antigen binding proteins derived from the anti-CGRP antibodies that bind to and inhibit both the human CGRP receptor and another target, such as the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) receptor. Pharmaceutical compositions comprising the anti-CGRP receptor antibodies and bispecific antigen binding proteins as well as methods for producing them are also disclosed. Methods of using the anti-CGRP receptor antibodies and bispecific antigen binding proteins to ameliorate, treat, or prevent conditions associated with the CGRP and PAC1 receptors, such as chronic pain, migraine, and cluster headache, are also described.

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.

Bispecific antibodies (bsAbs) have emerged as a class of promising anti-cancer and anti-infection biological drugs. They are capable of killing target cells, either cancer cells or microbe-infected cells, at levels of nanograms per milliliter serum in vivo, about 1e+5 folds more powerful than regular antibodies. To bypass the problems of high cost in production and inconvenience in administration, a logical solution is to use gene therapy vectors to produce them in vivo. In a series of preclinical studies, we have demonstrated that DNA MiniCircle was able to express far above therapeutic levels of bsAB persistently both in the presence as well as the absence of transfection co-factors. As a specific and intended improvement of the claimed invention, an enhanced form of bispecific antibodies incorporating a target cell-effector cell bridging device (BTEC) is additionally disclosed.

The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

The invention provides a bispecific antibody construct comprising a first human binding domain capable of binding to human CDH19 on the surface of a target cell and a second domain capable of binding to human CD3 on the surface of a T cell. Moreover, the invention provides a nucleic acid encoding the antibody construct, a vector comprising the nucleic acid and a host cell transformed or transfected with the vector. Furthermore, the invention provides a process for the production of the bispecific antibody construct, a medical use of the antibody construct and a kit comprising the antibody construct. The bispecific antibody construct may be useful in the treatment of melanoma.

The present invention provides a method for production of stable and highly specific heterodimeric immunoglobulin constructs, e.g., bispecific antibodies, retaining desirable properties of native IgG and lacking undesirable heavy chain-light chain mispairing, that can simultaneously bind two target molecules and are more potent in the treatment of complex diseases.

The invention relates to antibody conjugates (e.g., a bispecific antibody), drug and nanoparticle compositions and methods and compositions for generating them. This invention further relates to methods of using these compositions for imaging, diagnosing or treating a disease.