Provided herein are immunomodulatory proteins comprising ICOSL variants and nucleic acids encoding such proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological and oncological conditions. Compositions and methods for making and using such proteins are provided.

The invention relates to monoclonal and/or monovalent antibodies that bind CD47. The invention relates to monoclonal and/or monovalent antibodies that bind CD19. The invention also relates to novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD47. The invention also relates to novel bispecific monoclonal antibodies carrying a different specificity for each binding site of the immunoglobulin molecule, where one of the binding sites is specific for CD19.

The present invention provides antibodies that specifically bind to FLT3 (Fms-Like Tyrosine Kinase 3). The invention further provides bispecific antibodies that bind to FLT3 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of FLT3-mediated pathologies, including cancer such as Acute Myeloid Leukemia (AML).

The present invention provides anti-sclerostin antibodies and methods of using the same. In some embodiments, an isolated anti-sclerostin antibody of the present invention is a multispecific antibody. The present invention also provides isolated nucleic acids encoding an anti-sclerostin antibody of the present invention. The present invention also provides host cells comprising a nucleic acid of the present invention. The present invention also provides a method of producing an antibody comprising culturing a host cell of the present invention so that the antibody is produced. The present invention also provides a pharmaceutical formulation comprising an anti-sclerostin antibody of the present invention and a pharmaceutically acceptable carrier.

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Genetically modified mice are provided that express human variable (hV) sequences, including mice that express hV sequences from an endogenous mouse light chain locus, mice that express hV sequences from an endogenous mouse light chain locus, and mice that express hV sequences from a transgene or an episome wherein the hV sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human variable sequences, including human antibodies, are provided.

Genetically modified mice are provided that express human variable (hV) sequences, including mice that express hV sequences from an endogenous mouse light chain locus, mice that express hV sequences from an endogenous mouse light chain locus, and mice that express hV sequences from a transgene or an episome wherein the hV sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human variable sequences, including human antibodies, are provided.

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate -catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Genetically modified mice are provided that express human variable (hV) sequences, including mice that express hV sequences from an endogenous mouse light chain locus, mice that express hV sequences from an endogenous mouse light chain locus, and mice that express hV sequences from a transgene or an episome wherein the hV sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human variable sequences, including human antibodies, are provided.

In this application are described chimeric, humanized, affinity matured, stability enhanced, and bispecific Anti-GD2 antibodies and fragments thereof. Also provided are methods of using individual antibodies or compositions thereof for the detection, prevention, and/or therapeutical treatment of GD2-related diseases, in particular, neuroblastoma.