Abstract: Provided herein are tetravalent antigen binding complexes having agonist activity for a cell surface receptor. In some embodiments, the complexes comprise binding specificities for multiple epitopes of the same cell surface receptor. Further provided herein are nucleic acids, vectors, host cells, pharmaceutical compositions, and methods of production related thereto.

Abstract: The invention provides methods of using sequence based analysis and rational strategies to improve the solubility of immunobinders, and in particular of single chain antibodies (scFvs). The invention provides methods of engineering immunobinders, and in particular scFvs, by performing one or more substitutions with hydrophilic residues identified by analysis of a database of selected, stable scFv sequences. The invention also provides immunobinders with optimized solubility prepared according to the engineering methods of the invention.

Abstract: The present inventors discovered that the half-life in blood of an IgG antibody which is a polypeptide comprising an FcRn-binding domain can be controlled by controlling the surface charge through modification of residues exposed on the surface among residues in the variable regions of the IgG antibody. Antibodies whose half-life in blood had been controlled by the methods of the present invention were confirmed to actually retain the original activity. The methods of the present invention are widely applicable to polypeptides comprising an FcRn-binding domain, such as IgG antibodies, which are recycled via the FcRn salvage pathway regardless of the type of target antigen.

Abstract: T cell recruiting polypeptides are provided that bind CD3 on a T cell. The polypeptides can be used in methods for treatment of cancers.

Abstract: Disclosed herein, in certain embodiments, are anti-transferrin receptor antibodies, anti-transferrin receptor antibody conjugates, and pharmaceutical compositions which comprise the anti-transferrin receptor antibodies or conjugates. In some embodiments, also disclosed herein are methods of delivering a payload utilizing an anti-transferrin receptor antibody described herein, and methods of treatment with use of an anti-transferrin receptor antibody described herein.

Abstract: The present invention relates to a bispecific antibody construct comprising a first human binding domain which binds to human CDH3 on the surface of a target cell and a second binding domain which binds to human CDS on the surface of a T cell. Moreover, the invention provides a polynucleotide encoding the antibody construct, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or vector. Furthermore, the invention provides a process for the production of the antibody construct of the invention, a medical use of said antibody construct and a kit comprising said antibody construct.

Abstract: The instant disclosure provides antibodies that specifically bind to T-cell immunoreceptor with Ig and ITIM domains (TIGIT) (e.g., human TIGIT) and antagonize TIGIT function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: The invention discloses immunoglobulin fusion proteins designed to bind both CD47 and a tumor cell antigen. The immunoglobulin fusion proteins include a SIRP? moiety that binds CD47 and an antigen binding site for a tumor cell antigen.

Abstract: Provided herein are antibodies that selectively bind to Tim-3 and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

Abstract: The present invention provides bispecific polypeptides, such as bispecific antibodies, comprising a first binding domain capable of specifically binding to a first T cell target, and a second binding domain capable of specifically binding to a second T cell target, wherein the first and second T cell targets are different targets. The invention further provides compositions of said bispecific polypeptides, as well as methods and uses of the same. The first and/or second T cell target may be selected from the group consisting of OX40, CTLA-4, CD137, CD27, GITR and CD28.

Abstract: The present invention concerns methods of diagnosing and treating a malignant neoplasm of the CNS by detecting mammalian tissue expressing integrin alpha 10 subunit or a fragment or variant thereof, and administering a drug specific for integrin alpha 10 subunit.

Abstract: A method of reducing glycation of an amino acid in a protein produced by a host cell in cell culture medium is disclosed.

Abstract: Antibody molecules that specifically bind to TIM-3 are disclosed. The anti-TIM-3 antibody molecules can be used to treat, prevent and/or diagnose immune, cancerous, or infectious conditions and/or disorders.

Abstract: A method of detecting cell membrane expression of an MHC molecule in a subject, a method of treating cancer in a subject with an immunotherapeutic agent, and an MHC complex are provided. The method of detecting cell membrane expression of an MHC molecule includes obtaining a tumor cell sample from a subject, and detecting cell membrane expression of the MHC molecule by contacting the tumor cell sample with an antibody targeting the MHC molecule and detecting binding between the MHC molecule and the antibody. The method of treating cancer in a subject with an immunotherapeutic agent includes detecting cell membrane expression of an MHC molecule in the subject and administering a therapeutically effective amount of the immunotherapeutic agent if the level of cell membrane expression of the MHC molecule exceeds a predetermined standard. The complex includes a tumor cell in complex with an antibody or an antigen-binding portion thereof.

Abstract: Provided herein are trispecific antigen-binding proteins comprising a domain binding to CD3, a half-life extension domain, and a domain binding to a target antigen. Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such trispecific antigen-binding proteins. Also disclosed are methods of using the disclosed trispecific antigen-binding proteins in the prevention, and/or treatment diseases, conditions and disorders.

Abstract: The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.

Abstract: The present invention relates to a bispecific binding molecule comprising three binding domains, wherein a first and/or a second binding domain are capable of binding to the extracellular 5T4 antigen and the remaining binding domain(s) is (are) capable of binding to the CD3 receptor complex on T cells. Moreover, the invention relates to a nucleic acid sequence encoding fusion protein, a vector comprising said nucleic acid sequence and a host cell transformed or transfected with said vector. Furthermore, the invention relates to a process for the production of the fusion protein of the invention, a medical use of said fusion protein and a kit comprising said fusion protein.

Abstract: The present invention provides a combination epigenetic factors and bispecific compounds targeting CD33 and CD3 in the treatment of myeloid leukemia, wherein the epigenetic factor is selected from the group consisting of histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) I inhibitors, hydroxyurea, Granulocyte-Colony Stimulating Factor (G-CSF), histone demethylase inhibitors and ATRA (All Trans-retinoic acid). Accordingly, the invention provides a pharmaceutical composition comprising a CD33 targeting compound and at least one epigenetic factor and an epigenetic factor for use in the amelioration and/or treatment of a myeloid leukemia, wherein the epigenetic factor increases the responsiveness of a patient to a CD33 targeting compound.

Abstract: Disclosed herein, in certain embodiments, are anti-transferrin receptor antibodies, anti-transferrin receptor antibody conjugates, and pharmaceutical compositions which comprise the anti-transferrin receptor antibodies or conjugates. In some embodiments, also disclosed herein are methods of delivering a payload utilizing an anti-transferrin receptor antibody described herein, and methods of treatment with use of an anti-transferrin receptor antibody described herein.

Abstract: 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.