The present invention relates to an antibody or antigen-binding fragment thereof that bind human vascular endothelial growth factor receptor 2 (VEGFR-2). The present invention also relates to a method for inhibiting VEGFR-2-mediated signaling in a subject in need, a method for treating diseases and/or disorders caused by or related to VEGFR-2 activity and/or signaling in a subject afflicted with the diseases and disorders, a method for treating tumor in a subject afflicted with the tumor, a method for inhibiting cell proliferation of endothelial cells in a subject in need, and a method for detecting human vascular endothelial growth factor receptor in a sample.

Provided are a method for screening for nanobodies and a corresponding system. The method uses polymerase chain reactions and cDNA 5′ end rapid amplification technology to screen for and obtain nanobodies. The experiment cycle requires only approximately 21 days.

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is a common human, human-like, or humanized light chain. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

Disclosed herein are single domain serum albumins binding proteins with improved thermal stability, binding affinities, and robust aggregation profiles. Also described are multispecific binding proteins comprising a single domain serum albumin binding protein according to the instant disclosure. Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of using such formulations are provided.

Methods of generating sequence diversity in a protein, such as a ligand-binding protein, are provided. The methods comprise targeted introduction of two or more recombination signal sequences (RSSs) into the protein coding sequence and introduction of the modified protein coding sequence into a recombination-competent host cell, specifically a recombination-competent host cell that is capable of expressing at least RAG-1 and RAG-2, thereby allowing for recombination of the protein coding sequence and expression of variant proteins. Also provided are polynucleotides comprising a nucleic acid sequence encoding a target protein, such as a ligand-binding protein, and comprising two or more RSSs, and compositions and host cells comprising same.

[Problem to be Solved] An object of the present invention is to provide a novel peptide that has the high ability to bind to EpCAM, which can be easily prepared by a chemical synthesis method or a genetic engineering method. [Solution] The present inventors have improved a method for screening a phage library and thereby successfully screened for a peptide that has the higher ability to bind to EpCAM compared with publicly known peptides. The present inventors have also used an already disclosed peptide having the ability to bind to EpCAM as a lead compound to prepare diverse populations of derivatives thereof, from among which a peptide strongly binding to EpCAM has been selected. The obtained peptides exhibit at least 10 times higher ability to bind to EpCAM compared with publicly known peptides and as such, are effective for the detection or diagnosis of cancer cells.

The present invention provides molecules, including proteins, more particularly, immunoglobulins whose in vivo half-lives are altered (increased or decreased) by the presence of an IgG, constant domain, or FcRn binding fragment thereof (e.g., an Fc region or hinge-Fc region) (e.g., from a human IgGI, e.g., human IgGI), that have modifications of one or more of amino acid residues in at least the CH3 domain.

The present invention relates to single domain antibodies comprising at least one modification relative to the 4D5 antibody scaffold or human germline VH3 domain, the modifications selected from the group consisting of H35D, A78V, S93V, S93G and W103R, with the position numbering being according to the Kabat numbering scheme. Disulfide-free variants further comprise at least one additional modification selected from the group consisting of C22S, A24I, A24L and C92T, and with the proviso that at least one of C22S and C92T is present. Further encompassed are the multi-modular antibody molecules and antibody conjugates comprising single domain antibodies, as well as methods for producing them. The invention in particular provides a library of the single domain antibodies or multi-modular antibody molecules and a method for selecting an antibody that binds an antigen.

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for CD38, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, hematological malignancies such as multiple myeloma. Antibodies of the invention also can be used in the diagnostics field, as well as for investigating the role of CD38 in the progression of disorders associated with malignancies. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use. The invention also provides isolated novel epitopes of CD38 and methods of use therefore.