The present application is directed to compounds of Formula (I)-(VIII): ##STR00001## compositions comprising these compounds and their uses, for example as medicaments and/or diagnostics.

Provided is a novel anti-Plexin-A1 agonist antibody that promotes dendritic cell contraction. Also provided is a pharmaceutical composition comprising such an antibody and a pharmaceutically acceptable carrier.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

The invention is related to the fully effective gastro-protected universal oral delivery device of gastro-protected nanoparticles for the transport of intact biologically active polypeptides into the circulatory system. This universal oral delivery device is made of gastro-protected nanoparticles that transport intact therapeutic polypeptides through the gastrointestinal system and it successfully performs the paracellular transepithelial passage of all therapeutic polypeptides from the intestinal lumen into the circulatory system, fully preserving the integrity and biological activity of those therapeutic polypeptides.

Methods and compositions for treating cancer in a subject in need thereof. The method includes administering to the subject an effective amount of a composition comprising Tumor-Targeting Effectors (TITE) derived from a culture comprising a bispecific antibody armed activated T cell (BAT) and a cancer cell, to thereby treat cancer in the subject.

Provided are bispecific antibodies against CD3 and EGFR, the nucleic acid molecules encoding the antibodies, expression vectors and host cells used for the expression of the antibodies. The antibodies provide a potent agent for the treatment of CD3-related and/or EGFR-related diseases via modulating immune functions.

The present invention provides combinations of specific binding proteins, such as immunoglobulins, that are designed to be true combinations, essentially all components of the combination being functional and compatible with each other. The invention further provides a method for producing a composition comprising at least two different proteinaceous molecules comprising paired variable regions, the at least two proteinaceous molecules having different binding specificities, comprising paired variable regions, at least two proteinaceous molecules having different binding specificities, comprising contacting at least three different variable regions under conditions allowing for pairing of variable regions and harvesting essentially all proteinaceous molecules having binding specificities resulting from the pairing.

Disclosed herein are methods of treating cancer in a subject, and methods for inhibiting growth, migration and/or invasion of a cancer cell in the subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that downmodulales Fzd2. The antibody may specifically bind Fzd2, and may promote internalization of the Fzd2 receptor by the cancer cells and/or prevent ligand binding to Fzd2. Specific antibodies, and also specific portions of the Fzd2 molecule for antibody binding are disclosed. In one embodiment the antibody specifically binds to the epitope HGAEQICVGQNHSEDGAPAL (SEQ ID NO: 1). Specific cancers (e.g. late stage hepatocellular carcinoma), intended for treatment are provided, and include cancers that exhibit overexpression of Fzd2, and/or Wnt5a.

The invention provides methods for identifying protein modulators (e.g., antibody agonists) of eukaryotic cells. The methods typically involve expressing a combinatorial agent library (e.g., via lentiviral vectors) inside a eukaryotic cell type (e.g., a mammalian cell) and then directly selecting for agents (e.g., antibodies) that are agonist of a target molecule (e.g., a signaling receptor) that modulates a phenotype of or elicits a cellular response in the cell. Some related methods involve co-culturing a cell expressing a combinatorial agent library and a second cell, and then selecting agents that modulate a phenotype of or elicit a cellular response in the second cell. Preferably, the agents are antibodies and are introduced into and expressed in the starting cells under conditions each individual cell expresses no more than 3 different members of the antibody library. In addition, the invention provides methods for identifying protein agonists that capable of reprograming or trans-differentiating a target cell. Also provided in the invention are specific agonist antibodies of signaling receptors or biomolecules that modulate a phenotype or effectuate a cellular response in a eukaryotic cell (e.g., agonist antibodies of EpoR, TpoR or G-CSFR). Further provided in the invention are methods for selecting from combinatorial antibody libraries bispecific antibodies that can regulate cell phenotypes.

This invention relates generally to bifunctional molecules including (a) a TGFβRII or fragment thereof capable of binding TGFβ and (b) an antibody, or antigen binding fragment thereof, that binds to an immune checkpoint protein, such as Programmed Death Ligand 1 (PD-L1), uses of such molecules (e.g., for treating cancer), and methods of making such molecules.