The present inventors succeeded in discovering specific amino acid mutations in the variable region, framework region, and constant region of TOCILIZUMAB, and this enables to reduce immunogenicity risk and the heterogeneity originated from disulfide bonds in the hinge region, as well as to improve antigen binding activity, pharmacokinetics, stability under acidic conditions, and stability in high concentration preparations.

A method for determining predisposition of a subject to developing renal dysfunction (AKI), and to a kit for use in making such a determination is provided. Suitably at least one marker selected from Midkine (MK) or H-FABP present in a blood or urine sample is used in the method.

The present invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in inducing cell death and/or inhibiting the growth and/or proliferation of pathological stem cells and/or progenitor cells associated with a neoplastic hematologic disorder, wherein the cells express IL1RAP. A related aspect of the invention provides agents comprising or consisting of a binding moiety with specificity for interleukin-1 receptor accessory protein (IL1RAP) for use in detecting pathological stem cells and/or progenitor cells associated with a neoplastic hematologic disorder, wherein the cells express IL1RAP. Further provided are pharmacological compositions comprising the agents of the invention and methods of using the same.

A method identifies an adhesion in a human subject by obtaining a sample of a bodily fluid derived from the subject, and assaying the sample for activity of a biomarker specific for an adhesion in internal tissue of the subject to thereby determine whether the subject has an internal adhesion. Another method identifies an adhesion in a human subject by administering an imaging agent to the subject with the imaging agent identifying a biomarker specific for an adhesion in internal tissue of the subject, and utilizing imaging equipment to locate the adhesion identified by the imaging agent.

Provided are methods for diagnosing and predicting the outcome of a breast cancer patient or related cancers. The methods include determining expression levels of a plurality of biomarkers (selected genes) related to immune function in a biological sample, such as tumor tissues or a body fluid such as blood, from the patient. The expression levels of the biomarkers are used to derive an index which can be used as an indicator predictive of cancer patient outcome. Overexpression of a plurality of biomarkers of the invention can be used to generate a score or value which has been demonstrated herein to be indicative of a good or better patient outcome. The index, generated by the methods of the invention can also be used to stratify cancer subtypes, and also can be combined with conventional clinical parameters to better inform clinical decisions.

Methods and compositions are provided for displaying a protein of interest (POI) on the surface of a eukaryotic cell by fusing the POI to a signal polypeptide, a stalk polypeptide, and a surface anchor polypeptide to generate a surface accessible fusion protein. Nucleic acids are provided that include nucleotide sequences encoding a signal polypeptide, a stalk polypeptide, and a surface anchor polypeptide. In some cases, a subject nucleic acid includes and insertion site for the insertion of a POI. In some cases, a subject nucleic acid includes a nucleotide sequence that encodes a POI. In some cases a stalk polypeptide is a synthetic stalk polypeptide and various example synthetic stalk polypeptides are disclosed. In some cases, a surface anchor polypeptide is a glycosylphosphatidylinisotol (GPI) anchor domain, which can be synthetic. Kits are also provided for practicing the subject methods.

The present invention provides a non-human animal in which a DNA comprising an hp7 sequence-encoding DNA and a poly A addition signal-encoding DNA added on the 3 side of a DNA encoding an arbitrary foreign gene is inserted in the same reading frame as that of an arbitrary target gene present on the genome of the non-human animal.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Thymic stromal lymphopoietin, Vascular endothelial growth factor receptor 1, C-C motif chemokine 1, C-C motif chemokine 17, C-C motif chemokine 21, C-C motif chemokine 27, FLT-3 Ligand, Immunoglobulin G subclass 3, Interleukin-1 receptor type I, Interleukin-20, Interleukin-29, Interleukin-7, Platelet-derived growth factor A/B dimer, Platelet-derived growth factor A/A dimer, and MMP9:TIMP2 complex as diagnostic and prognostic biomarkers in renal injuries.

The present disclosure relates generally to methods of treating human patients suffering from a liver disease or condition. The disclosure also provides diagnostic methods for determining the stage or status of the liver disease or condition and monitoring methods for assessing the effectiveness of a treatment, using serum protein, metabolites or bile acid markers.

The present invention provides an antibody or an antigen-binding fragment thereof with binding specificity for human interleukin-1 receptor accessory protein (IL1RAP) wherein the antibody or antigen-binding fragment is capable of inhibiting the binding of antibody CAN04 to human IL1RAP. The invention further provides the use of such antibodies or an antigen-binding fragments in the treatment and/or diagnosis of IL-1 associated diseases and conditions, including cancers such as acute myeloid leukemia and melanoma.