The present invention is directed to antibodies and fragments thereof having binding specificity for ACTH. Another embodiment of this invention relates to the antibodies binding fragments thereof described herein, comprising the sequences of the V.sub.H, V.sub.L and/or CDR polypeptides described herein, and the polynucleotides encoding them. The invention also contemplates conjugates of anti-ACTH antibodies and binding fragments thereof conjugated to one or more functional or detectable moieties. The invention further contemplates methods of making said anti-ACTH antibodies and binding fragments thereof. Embodiments of the invention also pertain to the use of anti-ACTH antibodies and binding fragments thereof for the diagnosis, assessment, prevention and treatment of diseases and disorders associated with ACTH, such as Cushing's Disease, Cushing's Syndrome, Parkinson's disease, obesity, diabetes, sleep disorders depression, anxiety disorders, cancer, muscle atrophy, hypertension, hyperinsulinemia, cognitive dysfunction, Alzheimer's disease, galactorrhea, stress related conditions, cardiac conditions, metabolic syndrome, hyperaldosteronism, Conn's syndrome and familial hyperaldosteronism.

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

Trispecific antigen-binding proteins including: a first binding domain capable of binding to a cell surface protein of a tumor cell; a second binding domain capable of binding to a cell surface immune checkpoint protein of the tumor cell; and a third binding domain capable of binding to a cell surface protein of an immune cell, are provided. Methods of making trispecific antigen-binding proteins are provided.

Provided is an isolated TrkB agonist antibody that binds to an epitope contained in one of the extracellular domains of TrkB and is capable of activating TrkB, wherein the extracellular domains comprises extracellular D1, D2, D3, D4, D5 domains and juxtamembrane domain of TrkB. Methods of using the TrkB agonist antibody in treating or reducing the risk of a TrkB associated conditions in a subject, wherein said condition is selected from cell differentiation, synaptic development, neural injury repairing and/or neurite branching.

Bispecific binding molecules binding to both VEGF and Ang2, preferably in the form of immunoglobulin single variable domains like VHHs and domain antibodies, pharmaceutical compositions containing the same and their use in the treatment of diseases that are associated with VEGF- and/or Ang2-mediated effects on angiogenesis are disclosed. Further, nucleic acids encoding bispecific binding molecules, host cells and methods for preparing same are also described.

Anti-IL2R (e.g., anti-IL2RB, anti-IL2RG, anti-IL2RB/G) antibodies are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and use of such antibodies and compositions in the treatment of diseases and disorders that are mediated by the IL2/IL2R signaling pathway.

The disclosure relates to compounds specific for IL23A and BAFF, compositions comprising the compounds, and methods of use thereof. Nucleic acids, cells, and methods of production related to the compounds and compositions are also disclosed.

The subject matter described herein is directed to methods of modifying the micro-environment of a target cell or The methods comprise systemically administering to a subject a composition comprising a vector, wherein the vector comprises a construct for the expression of a trap in the target cell, wherein the trap is expressed in the target cell thereby modifiying the micro-environment. Also described herein are methods of reducing metastasis of a cancer comprising, systemically administering to a subject suffering from the cancer, a composition comprising a vector, wherein the vector comprises a construct for the expression of a trap, wherein the trap is delivered to and then expressed in tissue susceptible to metastasis, wherein metastasis of the cancer to the tissue is reduced. Compositions for carrying out the methods are also described.

The invention relates generally to multispecific polypeptides having constrained CD3 binding. In some embodiments, the multispecific polypeptides contain cleavable linkers that, when cleaved, results in dual effector functions. Also provided are methods of making and using these multispecific polypeptides in a variety of therapeutic, diagnostic and prophylactic indications.

The present application provides activatable antibodies comprising an antibody comprising an antigen-binding domain (ABD), wherein the ABD comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the N-terminus of the VH is fused to a first polypeptide shield moiety (S1), and the N-terminus of the VL is fused to a second polypeptide shield moiety (S2), wherein S1 comprises a first disease-sensing releasable moiety (DS1) and/or S2 comprises a second disease-sensing releasable moiety (DS2), wherein association of S1 with S2 blocks binding of the ABD to its target, and wherein the ABD does not specifically bind to S1, S2, or association thereof. Composition, methods of treatment using the activatable antibodies, and methods of preparation thereof are further provided.