Abstract: Disclosed are methods for obtaining cells that express antibodies that bind transmembrane proteins, methods for generating antibodies from such cells, antibodies to transmembrane proteins and fragments thereof, and nucleic acids encoding the antibodies. More particularly, the disclosure relates to methods for obtaining antibody-producing cells that express an antibody that binds to a transmembrane protein based on the use of lipid bilayer-membrane scaffold protein complexes to present transmembrane protein antigens to cells.

Abstract: Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Abstract: Computational systems and methods for predicting amino acid position(s) within a target peptide presented in a complex with a major histocompatibility complex (MHC) molecule (MHC-target peptide complex), the amino acid position(s) being involved in interacting with an antigen-recognition molecule that recognizes said MHC-target peptide complex, are presented herein. Computational systems and methods for estimating a number of off-target peptide(s) for an antigen-recognition molecule that recognizes a target peptide presented in a complex with a major histocompatibility complex (MHC) molecule (MHC-target peptide complex) is presented herein. Computational systems and methods for ranking potential target peptides to mitigate off-target toxicity are presented herein. Such computational systems and methods can streamline development of effective, well tolerated antigen-recognition molecules to treat diseases.

Abstract: The present invention provides, in part, protein-drug conjugates comprising an anti-fibroblast growth factor receptor 3 (FGFR3) (e.g., human FGFR3) antigen-binding protein (e.g., scFv, Fab) conjugated to a molecular cargo (e.g., polynucleotides, polypeptides, liposomes or lipid nanoparticles) for delivery of the molecular cargo to a targeted tissue (e.g., brain). Methods for treating various diseases or disorders, such as neurological diseases, with the conjugates are provided.

Abstract: A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that express just one or a few immunoglobulin light chain variable domains from a limited repertoire in their germline. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided. Bispecific antibodies capable of binding first and second antigens are provided, wherein the first and second antigens are separate epitopes of a single protein or separate epitopes on two different proteins are provided.

Abstract: The present invention provides antibodies that bind specifically to FGFR3 and methods for treating or preventing cancer, such as bladder cancer.

Abstract: Methods for making, identifying, isolating and/or making binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Exemplary binding proteins specific to small molecules are also provided.

Abstract: Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.

Abstract: Provided, in part, are an anti-human transferrin receptor antigen-binding proteins and fusion proteins comprising an anti-human transferrin receptor antigen-binding proteins (e.g., in scFv, Fab or antibody format) which may be fused to a payload for delivery of the payload to a targeted tissue (e.g., past the blood-brain barrier and to the brain). Payloads include, for example, alpha-glucosidase (GAA) polypeptide. Methods for treating various diseases with such molecules, e.g., glycogen storage diseases, such as Pompe Disease, with the fusions are provided.

Abstract: The present disclosure relates to a method for identifying cells that express antigen-specific antibodies with a high binding affinity for a monomeric antigen. Using fluorescence activated cell sorting, cells expressing high affinity antigen-specific antibodies are selected from a population of immune cells isolated from a mammal that has been immunized with or otherwise exposed to the antigen. Nucleic acids encoding the high affinity antibodies can then be cloned into other lymphoid and non-lymphoid cells where the antibody can be expressed and from which the antibodies can be secreted.

Abstract: CD38 is expressed on malignant plasma cells. 4-1BB is a costimulatory molecule required for T-cell activation and survival. Provided herein are novel multispecific antigen binding molecules (MABMs) that bind to both CD38 and 4-1BB, for example, to provide “signal 2” in order to enhance the activation of T cells in the presence of a “signal 1”, provided by a Tumor-associated antigen (TAA)×CD3 bispecific antibody or an allogeneic response provided by an antigen presenting cell. In certain embodiments, the multispecific antigen binding molecules of the present invention are capable of inhibiting the growth of tumors expressing CD38. The multispecific antigen binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced CD38-targeted immune response is desired and/or therapeutically beneficial.

Abstract: Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity.

Abstract: The present disclosure relates to a method for identifying cells that express antigen-specific antibodies with a high binding affinity for a monomeric antigen. Using fluorescence activated cell sorting, cells expressing high affinity antigen-specific antibodies are selected from a population of immune cells isolated from a mammal that has been immunized with or otherwise exposed to the antigen. Nucleic acids encoding the high affinity antibodies can then be cloned into other lymphoid and non-lymphoid cells where the antibody can be expressed and from which the antibodies can be secreted.

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Abstract: Nucleic acid constructs and compositions that allow insertion of a multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence into a target genomic locus such as an endogenous ALB locus and/or expression of the multidomain therapeutic protein (e.g., GAA fusion protein) coding sequence are also provided. The nucleic acid constructs and compositions can be used in methods of integration of a multidomain therapeutic protein (e.g., GAA fusion protein) nucleic acid into a target genomic locus, methods of expression of a multidomain therapeutic protein (e.g., GAA fusion protein) in a cell, methods of reducing glycogen accumulation, methods of treating Pompe disease or GAA deficiency in a subject, and method of preventing or reducing the onset of a sign or symptom of Pompe disease in a subject, including neonatal cells and subjects.

Abstract: Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecific antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing an expression-enhancing locus.

Abstract: The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Abstract: This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific and bispecific antibodies in eukaryotic cells, particularly Chinese hamster (Cricetulus griseus) cell lines, by employing multiple expression-enhancing locus.