The present invention provides fully IgG bi-specific antibodies comprising designed residues in the interface of the heavy chain-heavy chain (C.sub.H3/C.sub.H3) domains, processes for preparing said fully IgG bi-specific antibodies, and nucleic acids, vectors and host cells encoding the same.

The present invention relates to antibody molecules and peptide delivery systems for use in the treatment and management of Alzheimer's disease and related disorders. In particular, the antibody molecules preferentially bind oligomeric forms of beta-amyloid peptide, in single domain format, and the peptide delivery systems facilitate specific transport of such antibody molecules, as well as other cargo molecules, across the blood-brain barrier. The invention also relates to constructs of the antibody molecules and the delivery peptides, as well as pharmaceutical compositions comprising effective amounts of the antibody molecules, delivery peptides, and/or their constructs, including humanized versions of the antibody molecules and constructs. The invention further relates to methods of making these products and pharmaceutical compositions thereof; and methods of using the pharmaceutical compositions in treating or preventing Alzheimer's and related disorders, such as those involving accumulation of beta-amyloid peptide or other peptides that aggregate in the brain; as well as to methods and kits for diagnosing these disorders.

There is provided inter alia a polypeptide comprising an immunoglobulin chain variable domain comprising three complementarity determining regions (CDR1-CDR3) and four framework regions, wherein: (a) at least one lysine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue, and/or (b) at least one arginine residue in CDR1, CDR2 and/or CDR3 has been substituted with at least one histidine residue; wherein the polypeptide has increased intestinal stability relative to a corresponding polypeptide not having said histidine substitutions.

This invention generally relates to methods for the treatment of respiratory diseases, such as asthma, utilizing anti-IL-23A antibodies.

Provided herein are methods of treating a patient with severe insulin resistance. The methods comprise administering to a patient in need thereof a therapeutic amount of a GCG/GCGR signaling pathway inhibitor, such that blood glucose or beta-hydroxybutyrate levels are lowered or that the severe insulin resistance is mediated, or a condition or disease characterized by severe insulin resistance is mediated, or at least one symptom or complication associated with the condition or disease is alleviated or reduced in severity. The GCG/GCGR signaling pathway inhibitor can be a small molecule inhibitor of the signaling pathway, an antisense inhibitor of the signaling pathway, a GCG neutralizing monoclonal antibody, a GCGR antagonist, a peptide inhibitor of the signaling pathway, a DARPin, a Spiegelmer, an aptamer, engineered Fn type-III domains, etc. The therapeutic methods are useful for treating a human suffering from severe insulin resistance.

An antibody that specifically binds to a glucocorticoid-induced tumor necrosis factor receptor (GITR), an antibody fragment and a polymer thereof, and a conjugate and a fusion comprising the antibody or the antibody fragment are provided in the present invention. A nucleic acid encoding the antibody, the antibody fragment, the polymer, the conjugate and the fusion, a vector, and a host cell expressing the nucleic acid are also provided in the present invention. In addition, a composition comprising the antibody and the antibody fragment thereof, the polymer, the conjugate or the fusion, and use thereof in therapy and diagnosis are also provided in the present invention.

Provided herein are, inter alia, anti-CD73 antibodies and methods of using the same. The antibodies provided include amino acid substitution embodiments affecting the antibody glycosylation state. The antibodies provided herein are, inter alia, useful for the treatment of cancer and effective for inhibition of CD73 activity.

The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to IP-10 with high affinity, inhibit the binding of IP-10 to its receptor, inhibit IP-10-induced calcium flux and inhibit IP-10-induced cell migration. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting IP-10 activity using the antibodies of the invention, including methods for treating various inflammatory and autoimmune diseases.

Antigen binding molecules (ABMs) comprising Fab domains in non-native configurations, ABM conjugates comprising the ABMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the ABMs and ABM conjugates, methods of using the ABMs, ABM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the ABMs, cells engineered to express the ABMs, and methods of producing ABMs.

The present invention relates to subcutaneous formulations of anti-CD38 antibodies and their uses.