Abstract: The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.

Abstract: The present disclosure is directed to novel FZD5-binding agents and methods and uses thereof for treating a disease or disorder associated with aberrant expression or activity of Frizzled protein.

Abstract: 53BP1 inhibitors, compositions comprising the inhibitors and methods of using same are provided. The inhibitors can be used in combination with gene editing systems.

Abstract: The present invention addresses a need for improved treatments for Filovirus infections.

Abstract: This invention provides monoclonal antibodies that recognize one or more Frizzled receptors. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: Synthetic fragment antigen-binding (Fab) antibodies are disclosed that bind to an N-terminal activation site of BCL-2-associated X-protein (BAX) and inhibit BAX activation. Also disclosed are methods of using the Fabs for measuring inactive monomeric BAX levels, screening for small molecules that bind to an N-terminal activation site of BAX, inhibiting apoptotic cell death, and predicting the ability of a cancer therapy to promote apoptotic cell death.

Abstract: The invention provides ubiquitin variants that specifically bind to SCF E3 ligases, and use of these variants to modulate the activity of SCF E3 ligases.

Abstract: The invention provides ubiquitin variants that specifically bind to HECT E3 ligases, and methods of using these variants to modulate the activity of HECT E3 ligases.

Abstract: The present invention addresses a need for improved treatments for filovirus infections. This invention provides an isolated humanized anti-filovirus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region. Also provided is a method of treating and/or inhibiting a filovirus infection in a subject comprising administering to the subject an amount of any of the antibodies described herein, or an amount of an antigen-binding fragment thereof. Also provided is composition comprising any of the antibodies described herein, or or an amount of an antigen-binding fragment thereof. In an embodiment, the composition comprises a pharmaceutically acceptably carrier.

Abstract: There is provided herein a method for identifying and/or recovering at least one genetically encoded affinity reagent specific for a target molecule by screening using molecular display in conjunction with the sequencing of positive and negative selection pools from the screen.

Abstract: The present invention addresses a need for improved treatments for Filovirus infections.

Abstract: This invention provides monoclonal antibodies that recognize one or more Frizzled receptors. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.

Abstract: The present invention addresses a need for improved treatments for filovirus infections.

Abstract: The present invention addresses a need for improved treatments for filovirus infections.

Abstract: The invention relates to modulating the SIRP?—CD47 interaction in order to treat hematological cancer and compounds therefor. In particular, there is also provided SIRP? antibodies and antibody fragments, preferably used for treating hematological cancer.

Abstract: There is provided herein a method for identifying and/or recovering at least one genetically encoded affinity reagent specific for a target molecule by screening using molecular display in conjunction with the sequencing of positive and negative selection pools from the screen.

Abstract: The present disclosure provides a method of producing enzyme-specific inhibitors or substrate binding partners comprising: identifying active site residues of the substrate in the enzyme substrate complex or in substrate binding partner-substrate complex; randomizing the active site residues to produce a combinatorial library of substrate variants; and selecting substrate variants that inhibit enzyme activity or bind substrate as substrate-specific binding partners. The present disclosure also provides ubiquitin enzyme specific inhibitors and ubiquitin variants that bind ubiquitin interaction motifs.

Abstract: The invention provides polypeptides comprising a variant heavy chain variable framework domain (VFR). In some embodiments, the amino acids defining the VFR form a loop of an antigen binding pocket. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR. The polypeptide may optionally comprise one or more complementary determining regions (CDRs) of antibody variable domains. In an embodiment, the polypeptide is a variable domain of a monobody and has a variant VFR and one or more variant CDRs. Libraries of polypeptides that include a plurality of different antibody variable domains generated by creating diversity in a VFR, and optionally, one or more CDRs are provided and may be used as a source for identifying novel antigen binding polypeptides that can be used therapeutically or as reagents. The invention also provides fusion polypeptides, compositions, and methods for generating and using the polypeptides and libraries.

Abstract: The invention provides variant CDRs comprising highly restricted amino acid sequence diversity. These polypeptides provide a flexible and simple source of sequence diversity that can be used as a source for identifying novel antigen binding polypeptides. The invention also provides these polypeptides as fusion polypeptides to heterologous polypeptides such as at least a portion of phage or viral coat proteins, tags and linkers. Libraries comprising a plurality of these polypeptides are also provided. In addition, methods of and compositions for generating and using these polypeptides and libraries are provided.

Abstract: The invention provides variant heavy chain variable domains (VH) with increased folding stability. Libraries comprising a plurality of these polypeptides are also provided. In addition, compositions and methods of generating and using these polypeptides and libraries are provided.