Abstract: Methods and assays examining expression of one or more biomarkers in a mammalian tissue or cell sample are provided. According to the disclosed methods and assays, detection of the expression of one or more such biomarkers is predictive or indicative that the tissue or cell sample will be sensitive to apoptosis-inducing agents such as Apo2L/TRAIL and anti-DR5 agonist antibodies. Certain biomarkers which may be examined include fucosyltransferases, in particular fucosyltransferase 3 (FUT3) and/or fucosyltransferase 6 (FUT6), as well as sialyl Lewis A and/or X antigens. Kits and articles of manufacture are also provided.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of j3-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD).

Abstract: Compounds of the disclosure provide compositions, which are effective for prophylaxis and treatment of diseases or disorders, such as cell-proliferation, angiogenesis, or apoptosis mediated diseases. The disclosure encompasses compounds, analogs, prodrugs, metabolites, and pharmaceutically acceptable salts thereof, pharmaceutical compositions, and methods for prophylaxis and treatment of diseases and other maladies or conditions involving cancer, tumors, and like conditions. The disclosure also provides therapeutic methods including the administration of an effective amount of a compound of the disclosure.

Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism of acquired drug resistance. Here, we describe a mutation in the serpentine receptor, Smoothened (SMO), which results in resistance to a Hedgehog (Hh) pathway inhibitor in medulloblastoma. A single amino acid substitution in a conserved glutamic acid residue of SMO maintains Hh signaling, but results in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. The invention provides screening methods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.

Abstract: The present invention is directed to novel polypeptides having homology to certain human uncoupling proteins (“UCPs”) and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention, and methods for producing the polypeptides of the present invention.

Abstract: Novel polypeptides, designated RTD, which are capable of binding Apo-2 ligand are provided. Compositions including RTD chimeras, nucleic acid encoding RTD, and antibodies to RTD are also provided.

Abstract: In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, B, L, E, A and the subscript n are as defined herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.

Abstract: The invention provides a method for more effective treatment of patients susceptible to or diagnosed with tumors overexpressing EGFR, as determined by a gene amplification assay, with an EGFR antagonist. Such method comprises administering a cancer-treating dose of the EGFR antagonist, preferably in addition to chemotherapeutic agents, to a subject in whose tumor cells erbB1 gene has been found to be amplified e.g., by fluorescent in situ hybridization. EGFR antagonists described include an anti-EGFR antibody.

Abstract: The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula I: wherein X, Y, A, R1, R2, R3, R4, R4?, R5, R5?, R6 and R6? are as described herein.

Abstract: The present invention relates to a method for the treatment of a cartilage disorder, including cartilage damaged by injury or degenerative cartilagenous disorders. The method involves contacting the cartilage with an IGF-1 analog with altered affinity for IGF-binding proteins (IGFBPs) or an IGFBP displacer peptide that prevents the interaction of an IGF with an IGFBP and does not bind to a human IGF receptor.

Abstract: The invention provides HGF/Met modulators comprising HGF having mutations in regions that affect HGF function, and antagonists that target said regions. The invention further provides methods of identifying, making and using these modulators.

Abstract: The present invention generally relates to humanized VEGF and non-human transgenic animals expressing it. The transgenic animals are also useful to study VEGF-related therapies.

Abstract: The invention relates to anti-hedgehog antibodies, their use in the detection of hedgehog expression in tissue, and to the use of such detection in the treatment of cancer.

Abstract: The present invention relates to polypeptides that inhibit APRIL and/or BAFF binding to BCMA, nucleic acid molecules encoding the polypeptides, and compositions comprising the polypeptides. The present invention also relates to methods for treating an immune-related disease or cancer using the polypeptides and compositions of the invention. The present invention also relates to methods for identifying inhibitors of APRIL/BAFF binding to BCMA and APRIL/BAFF signaling.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The invention provides JAK kinase inhibitors of Formula Ia, enantiomers, diasteriomers or pharmaceutically acceptable salts thereof, wherein R1, R2, R7 and Z are defined herein, a pharmaceutical composition that includes a compound of Formula Ia and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of a JAK kinase activity in a patient.

Abstract: The invention provides anti-EphB4 antibodies, and compositions comprising and methods of using these antibodies.

Abstract: The invention provides inhibitors of hedgehog signaling that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula I: wherein ring A, ring B, R1, R2, R3, R4, R5, m and n are as defined herein.

Abstract: Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naive libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.