This application relates to methods of quantifying AKT1 and AKT2 and determining AKT1 and AKT2 phosphorylation status. The disclosed methods allow for selection of cancer therapy.

An immunoassay kit including a monoclonal antibody coupled to a labeling agent (labeled mAb) for detecting tumor pyruvate kinase M2 (tM2-PK) in a biological sample. The monoclonal antibody includes a heavy chain variable region (HCVR) including heavy chain complementarity-determining regions (CDRs) (SEQ ID NOs: 3, 4, and 5) and a light chain variable region (LCVR) including light CDRs (SEQ ID NOs: 7, 8, and 9).

The present disclosure provides methods of treating diseases or disorders using allosteric inhibitors of SHP2 and to methods and diagnostic tests for identifying subjects likely to respond to such allosteric inhibitors of SHP2. In particular, the present disclosure provides diagnostic and therapeutic uses related to certain Receptor Tyrosine Kinase (RTK) mutations that are indicative of sensitivity to allosteric SHP2 inhibitors.

Novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have been identified herein in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides.

The present invention provides a highly sensitive in vitro method for diagnosing injury to the central nervous system (CNS), such as a traumatic brain injury (TBI) or stroke. The method involves contacting a sample of blood from a subject suspected of suffering a CNS injury event with at least one antibody capable of detecting a proteolytic fragment of the biomarker Protein Kinase C, gamma isoform (PKCg or PKCγ), which fragment corresponds to a proteolytic fragment of PKCg formed in the excitotoxic environment resulting from neuronal damage. Also disclosed are novel anti-PKCg antibodies useful in the diagnostic methods of the invention to provide diagnosis of CNS injury with essentially 100% accuracy.

AXL-specific antibodies and uses therefor are described, including monoclonal and single domain antibodies. Such antibodies bind to cell surface expressed human AXL at an epitope in an immunoglobulin-like (IgL) domain of the AXL ectodomain. The antibody may be used in an antibody-drug conjugate (ADC), for example in the treatment, detection or staging of cancer. The antibody may be biparatopic.

The present invention provides methods for predicting the response of a patient in need of an immune checkpoint inhibitor (ICI), to treatment with a programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) ICI, comprising the steps of: (a) measuring the kinase activity of at least two kinases independently selected from within at least two families of kinases selected from the group consisting of: the VEGFR or PDGFR family of kinases; the SRC family of kinases; the SYK family of kinases; the TAM family of kinases; the JakA family of kinases; and the ALK family of kinases, in a blood sample obtained from said patient, thereby providing a kinase activity profile of said blood sample; and (b) predicting from said kinase activity profile the response of said patient to treatment with said PD-1 or PD-L1 ICI, and kits for predicting the response of a patient in need of an ICI to treatment with a PD-1 or PD-L1 ICI.

Aspects of the present disclosure are directed to methods and compositions for facilitating β-cell regeneration by inhibition of the HIF1α-PFKFB3 pathway. Certain aspects describe methods for treatment and prevention of prediabetes and diabetes, including type 2 diabetes. Also disclosed are methods and compositions for enhancing β-cell regeneration.

Provided herein are antibody molecules that bind specifically to C-MET and related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

A peptide ligand specific for EphA2 comprising a polypeptide comprising three residues selected from cysteine, L-2,3-diaminopropionic acid (Dap), N-beta-alkyl-L-2,3-diaminopropionic acid (N-AlkDap) and N-beta-haloalkyl-L-2,3-diaminopropionic acid (N-HAlkDap), with the proviso that at least one of said three residues is selected from Dap, N-AlkDap or N-HAlkDap, the said three residues being separated by at least two loop sequences, and a molecular scaffold, the peptide being linked to the scaffold by covalent alkylamino linkages with the Dap or N-AlkDap or N-HAlkDap residues of the polypeptide and by thioether linkages with the cysteine residues of the polypeptide when the said three residues include cysteine, such that two polypeptide loops are formed on the molecular scaffold.