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.

A trispecific inhibitor for treating cancer includes a first targeting domain having a binding specificity conferred by a VEGF binding antagonist; a second targeting domain having a binding specificity conferred by an immune checkpoint regulator binding antagonist; and a third targeting domain having a binding specificity conferred by a Tie2 tyrosine kinase receptor binding antagonist. The targeting domains may contain one or more antibody variable regions, peptide inhibitors, dominant negative proteins, small molecule drugs or combinations thereof.

The present invention relates to bispecific molecules comprising an EGFR binding domain and a distinct IGFIR binding domain for use in diagnostic, research and therapeutic applications. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and vectors comprising the polynucleotides encoding the innovative proteins. Exemplary bispecific molecules include antibody-like protein dimers based on the tenth fibronectin type III domain.

Disintegrin variants that bind specifically to one or more of α5β1 and αv integrins, such as αvβ1, αvβ3, αv7β5, αvβ6 and αvβ8, but with reduced binding activity to αIIbβ3, are described. Also described are uses of the disintegrin variants for the treatment or prevention of a disease associated with an αv integrin or an α5β1 integrin.

Synbodies specific for Norovirus and coupled with a substrate provide Norovirus binding and detection platforms (FIG. 1). A Norovirus capturing platform, comprising one or more synbodies selected from the group consisting of synbodies 6-6, 92-92, 93-93, and 94-94 coupled to a substrate, has been found to found to bind with either GII.4 Minerva or both GII.4 Minerva and GII.4 Sydney# strains of norovirus.

Disclosed is a group of chimeric antigen receptors (CARs) having two, three or four CAR molecules, wherein each member of the group of CARs is different in its amino acid sequence from one another, and wherein each of the CAR molecules of the group include at least a transmembrane domain and an ectodomain, wherein the ectodomain has one or two antigen binding moieties and/or one or two binding sites to which other polypeptides each including at least an antigen binding moiety are able to bind; wherein the ectodomain of each CAR molecule of the group in its prevalent conformation is free of cysteine amino acid moieties which are able to form intermolecular disulphide bonds with other CAR molecules of the group, respectively, and wherein each CAR molecule of the group includes at least one heterodimerization domain.

Walk-through mutagenesis and natural-variant combinatorial fibronectin Type III (FN3) polypeptide libraries are described, along with their method of construction and use. Also disclosed are a number of high binding affinity polypeptides selected by screening the libraries against a variety of selected antigens.

Antiviral biomimetic polymers (ABPs) are disclosed that can be used to prevent and/or treat viral disease. The ABPs are discovered by a process involving high-throughput screening of polymer libraries using disease-relevant bioactive molecules as target molecules. ABPs can be nanoscale (termed nanoABPs) or larger. Methods are described for the preparation and use of ABPs as prophylactics and therapeutics (in vivo) and as preventative agents, for example, in personal protective equipment (ex vivo). ABPs can be used to prevent and treat viral diseases including those caused by Filoviridae.

The present invention relates to recombinant binding proteins comprising one or more designed ankyrin repeat domains with binding specificity for coronavirus spike proteins, nucleic acids encoding such proteins, pharmaceutical compositions comprising such proteins or nucleic acids, and the use of such proteins, nucleic acids or pharmaceutical compositions in the treatment of coronavirus diseases, particularly diseases caused by SARS-CoV-2.

Wnt signaling agonist compositions and methods for their use are provided. Wnt signaling agonists of the invention comprise a frizzled binding moiety, which is fused or conjugated to an LRP5 or LRP6 binding moiety.