The presently disclosed subject matter provides antigen-binding proteins that specifically bind to Preferentially expressed antigen of melanoma (PRAME), including humanized, chimeric and fully human antibodies against PRAME, antibody fragments (e.g., scFv, Fab and F(ab).sub.2), chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen-binding proteins and antibodies bind to a PRAME peptide/HLA class I molecule complex. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of PRAME associated diseases, including for example, breast cancer, ovarian cancer, melanoma, lung cancer, gastrointestinal cancer, brain tumor, head and neck cancer, renal cancer, myeloma, neuroblastoma, mantle cell lymphoma, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML), Non-Hodgkin lymphoma (NHL), and Chronic lymphocytic leukemia (CLL). The antibodies or antigen binding proteins may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

Antigen binding proteins that bind to human CGRP receptor (CGRP R) are provided. Nucleic acids encoding the antigen binding protein, vectors, and cells encoding the same are also provided. The antigen binding proteins can inhibit binding of CGRP R to CGRP, and are useful in a number of CGRP R related disorders, including the treatment and/or prevention of migraine headaches.

Contemplated compositions and methods are directed to cancer neoepitopes and uses of such neoepitopes, especially to generate synthetic antibodies against neoepitopes that may then be employed in the manufacture of a therapeutic agent. Preferred therapeutic agents will comprise a synthetic antibody against a neoepitope, and most preferably in combination with a cellular or non-cellular component for use as a diagnostic or therapeutic agent.

The present invention provides antibodies and fragments thereof that specifically detect the complex of a specific cognate antigen-binding moiety, in particular antibodies, and its antigen. The antibodies of the present disclosure do not bind either said cognate antigen binding moiety or said antigen alone and this can be used e.g. to directly detect antigen-bound antigen-binding moieties. Further disclosed are methods for production and use of said antibodies and antibody fragments.

Provided herein are display systems for simultaneously displaying two different ligand binding polypeptides at the surface of a phage. Also provided are kits, methods of using such display systems and methods of discovering novel bispecific antibodies.

The present invention relates to a use of a macrophage inflammatory protein-1 (MIP-1) inhibitor to protect the pancreas and prevent blood sugar from rising. The present invention relates to a use of a macrophage inflammatory protein-1 (MIP-1) inhibitor to protect the pancreas, and to prevent blood sugar from rising in a diabetic subject.

The present invention relates to amino acid sequences and Nanobodies that are directed against Epidermal Growth Factor Receptor 2 (HER2), as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

The invention provides novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule and methods for producing novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule. The antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other of a Lambda constant domain. The invention provides methods for the isolation of antibodies of different specificities but sharing a common heavy chain. The invention also provides methods for the controlled co-expression of two light chains and a single heavy chain leading to the assembly of monospecific and bispecific antibodies. The invention provides a mean of producing a fully human bispecific and bivalent antibody that is unaltered in sequence and does not involve the use of linkers or other non-human sequences, as well as antibody mixtures of two monospecific antibodies and one bispecific antibody. The invention also provides the means of efficiently purifying the bispecific antibody.

A first aspect of the disclosure relates to the field of binding molecules targeted at pathogens. The disclosure further relates to proteinaceous binding molecules targeting cells displaying pathogen-associated molecular patterns, in particular targeting cell surface molecules associated with or derived from pathogens, more in particular cell surface proteins displaying peptides from intracellular (pathogen associated) proteins.

Antibodies that modulate insulin receptor signaling are provided.