Patent classifications
C07K16/4208
Antibody chemically induced dimerizer (AbCID) as molecular switches for regulating cellular therapies
Chemically induced dimerizers (AbCIDs) have emerged as one of the most powerful tools to artificially regulate signaling pathways in cells; however, no facile method to identify or design these systems currently exists. The present invention provides a methodology to rapidly generate antibody-based chemically induced dimerizers (AbCIDs) from known small-molecule-protein complexes by selecting for synthetic antibodies that recognize the chemical epitope created by the bound small molecule. Success of this strategy is demonstrated by generating ten chemically-inducible antibodies against the BCL-xL/ABT-737 complex. Three of the antibodies are highly selective for the BCL-xL/ABT-737 complex over BCL-xL alone. Two exemplary important cellular applications of AbCIDs are demonstrated by applying them intracellularly to induce CRISPRa-mediated gene expression and extracellularly to regulate CAR T-cell activation with the small molecule, ABT-737. ABT-737 is not toxic at the concentrations used to activate AbCIDs in cells. AbCIDs provided by this invention are new and orthogonal AbCIDs, expanding the limited toolbox of available CIDs.
Modified B cells and methods of use thereof
The present invention relates to genetically modified B cells and their uses thereof, for example, for the treatment of a variety of diseases and disorders, including cancer, heart disease, inflammatory disease, muscle wasting disease, neurological disease, and the like. In certain embodiments, the invention relates to an isolated modified B cell (CAR-B cell), capable of expressing a chimeric receptor (CAR-B receptor), wherein said chimeric receptor comprises (a) an extracellular domain; (b) a transmembrane domain; and (c) a cytoplasmic domain that comprises at least one signaling domain. In various embodiments, the invention comprises an isolated modified B cell, wherein said B cell is capable of expressing and secreting a payload, wherein the payload is not naturally expressed in a B cell or is expressed at higher levels than is naturally expressed in a B cell. In various embodiments, the payload is an antibody or fragment thereof.
BROAD-SPECTRUM MONOCLONAL ANTI-FLU B ANTIBODY AND USES THEREOF
Provided are a broad-spectrum monoclonal anti-Flu B antibody, cell strains generating the antibody, and a composition comprising the antibody; also provided are uses of the antibody for diagnosing, preventing and/or treating an infection of the Flu B and/or diseases caused by the infection.
IDIOTYPIC ANTIBODIES AGAINST ANTI-PD-L1 ANTIBODIES AND USES THEREOF
The invention provides anti-idiotypic antibodies against anti-PD-L1 antibodies and methods of using the same.
ANTI-TIGIT ANTIBODIES
Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.
BINDING MEMBERS WITH ALTERED DIVERSITY SCAFFOLD DOMAINS
This invention relates to libraries of binding members that each comprise a fusion protein which contains a donor diversity scaffold domain, such as a cysteine rich protein, inserted within a recipient diversity scaffold domain, such as an antibody constant or variable domain. Libraries and methods of generating libraries are provided, along with screening methods, binding members and methods of using the binding members.
PROTEASE CLEAVABLE PRODRUGS
The application relates to prodrugs comprising a drug molecule connected by a protease-cleavable peptide linker to a binder, which reversibly inhibits a biological activity of the drug molecule, and to the inhibitory binders themselves. Also described are nucleic acids encoding the recombinant proteins described herein, and methods of making said recombinant proteins, as well as methods of treatment and medical uses of the recombinant proteins.
Anti-TIGIT antibodies
Anti-TIGIT antibodies and antigen binding fragments thereof that inhibit TIGIT-mediated signalling are provided, together with combinations comprising said antibodies or antigen binding fragments thereof and methods for their use.
ANTIGEN-BINDING MOLECULE AND COMBINATION
The present invention relates to a first antigen-binding molecule, a second antigen-binding molecule, and a combination thereof. The second antigen-binding molecule binds to an antigen/antigen-binding molecule complex containing a first antigen and the first antigen-binding molecule, and enhances the binding activity of the first antigen-binding molecule to the first antigen.
COMPOSITIONS AND METHODS FOR TREATING PEDIATRIC MYASTHENIA GRAVIS
Composition and methods for treating pediatric myasthenia gravis are provided herein using compositions comprising anti-FcRn antibodies.