Abstract: The present invention provides diagnostic and prognostic methods for predicting the effectiveness of treatment of a cancer patient with an IGF-1R kinase inhibitor. Methods are provided for predicting the sensitivity of tumor cell growth to inhibition by an IGF-1R kinase inhibitor, comprising assessing whether the tumor cell has undergone an epithelial to mesenchymal transition (EMT), by determining the expression level of epithelial and/or mesenchymal biomarkers, wherein tumor cells that have undergone an EMT are substantially less sensitive to inhibition by IGF-1R kinase inhibitors. Improved methods for treating cancer patients with IGF-1R kinase inhibitors that incorporate the above methodology are also provided.

Abstract: This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of primary and metastatic human tumor cells; and most particularly to the use of an isolated monoclonal antibody or cancerous disease modifying antibodies (CDMAB) thereof, optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response in such human tumors, e.g. any primary or metastatic tumor sites which arise from hepatocytes. The invention further relates to binding assays which utilize the CDMAB of the instant invention.

Abstract: The present invention provides the amino acid and nucleic acid sequences of heavy chain and light chain complementarity determining regions of a tumor specific antibody. In addition, the invention provides tumor-specific antibodies and immunoconjugates comprising the tumor-specific antibody attached to a toxin or label, and methods and uses thereof. The invention also relates to diagnostic methods and kits using the tumor-specific antibodies of the invention.

Abstract: The invention provides anti-SPARC antibody-based techniques for predicting a response to chemotherapy.

Abstract: The use of monoclonal antibodies to the angiotensin-II type-I receptor is provided for the treatment of cancer and vascular smooth muscle cell proliferation. Specifically, use is provided of a monoclonal antibody or a fragment thereof to a peptide comprising the N-terminal portion of the angiotensin-II type-1 receptor defined by the sequence MILNSSTEDG IKRIQDDCPK AGHRHNYIFVM IPTLYSIIFV VGIFG in the preparation of a medicament for the treatment of cancer or in the preparation of a medicament for the treatment of vascular smooth muscle (VSM) cell proliferation.

Abstract: The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

Abstract: The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

Abstract: Compositions and methods for inducing cell membrane wounding, cell permeabilization and cell killing are provided. The composition comprises a polyvalent agent that binds to a highly expressed cell surface antigen present on the surface of a cell. Preferably, the cell surface antigen is associated with the cytoskeleton of the cell. A preferred polyvalent agent is an IgM, and enhanced cell wounding and killing can be provided by the addition of a crosslinking agent. At sublethal concentrations in vivo, the cell wounding antibodies permeabilize cells and dramatically enhance response to chemotherapeutic agents, even in patients refractory to the chemotherapeutic agents.

Abstract: The present invention is directed to antibodies binding to the MUC1 cytoplasmic domain and methods of using such antibodies to treat, diagnose, detect and monitor cancers that express the MUC1 antigen.

Abstract: The present invention is directed to therapeutic methods and compositions, especially subcutaneous and intravenous composition using antibodies and fragments thereof having binding specificity for IL-6 to prevent or treat cachexia, fever, weakness and/or fatigue in a patient in need thereof. In preferred embodiments, the anti-IL-6 antibodies will be humanized and/or will be aglycosylated. Also, in preferred embodiments these patients will comprise those exhibiting (or at risk of developing) an elevated serum C-reactive protein level. In another preferred embodiment, the patient's survivability or quality of life will preferably be improved.

Abstract: The present invention provides monoclonal IgE antibodies comprising Fc epsilon (?) constant regions and variable regions comprising at least one antigen binding region specific for binding a single epitope of a circulating, tumor-associated antigen (TAA) that is not a cell surface antigen wherein the epitope of the targeted antigen is not highly repetitive or is a non-repetitive epitope. The IgE antibodies of the invention are useful in the treatment of cancer associated with the tumor antigen. In one embodiment the TAA is prostate-specific antigen (PSA).

Abstract: The current disclosure provides for specific peptides from the Epidermal Growth Factor Receptor (EGFR) protein and the derived ionization characteristics of those peptides that are advantageous for quantifying the EGFR directly in formalin fixed biological samples by the method of Selected Reaction Monitoring (SRM) mass spectrometry. Such fixed biological samples include: formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and formalin fixed and paraffin embedded tissue culture cells. EGFR protein is quantitated in biological samples by the method of SRM/MRM mass spectrometry by quantitating one or more of the peptides described herein. The peptides can be quantitated if they reside in a modified or an unmodified form. Examples of potentially modified forms of an EGFR peptides include those bearing phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

Abstract: Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKK?/? and I?B?, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

Abstract: The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to ErbB2, preferably human ErbB2. In another embodiment, the antibodies or antigen-binding portions thereof inhibit ErbB2. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins or portions thereof derived from human anti-ErbB2 antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-ErbB2 antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.

Abstract: A cancer cell separating apparatus includes: a flow channel including an antibody fixation area having antibodies which bind specifically to cancer cells fixed thereon, wherein the cancer cells and non-cancer cells are separated using a difference in velocity of movement between the cancer cells and the non-cancer cells in cell slurry introduced into the flow channel.

Abstract: The present invention provides humanized, chimeric and human anti-CD19 antibodies, anti-CD19 antibody fusion proteins, and fragments thereof that bind to a human B cell marker. Such antibodies, fusion proteins and fragments thereof are useful for the treatment and diagnosis of various B-cell disorders, including B-cell malignancies and autoimmune diseases. In more particular embodiments, the humanized anti-CD19 antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels. In a particularly preferred embodiment, the substitutions comprise a Ser91Phe substitution in the hA19 VH sequence.

Abstract: A method of treating an autoimmune disease comprising administering to a patient a therapeutically effective amount of a CD20-binding polypeptide composition comprising a combination of a modified heavy chain variable region polypeptide and a modified light chain variable region polypeptide. The combination can be (a) a modified 2B8 antibody heavy chain variable region polypeptide of SEQ ID NO: 48; and a modified 2B8 antibody light chain variable region polypeptide of SEQ ID NO: 49; or (b) a modified Leu16 antibody heavy chain variable region polypeptide of SEQ ID NO: 50; and a modified Leu16 antibody light chain variable region polypeptide of SEQ ID NO: 51.

Abstract: Methods for identifying subjects having a cancer or pre-malignant condition that will benefit from anti-CD40 therapeutic agents that modulate CD40L-mediated CD40 signaling are provided. The methods comprise the use of biomarkers of cellular apoptosis, cell proliferation and survival, and CD40 signaling pathways to monitor ex vivo response to one or more anti-CD40 therapeutic agents of interest that modulate CD40 signaling on CD40-expressing neoplastic cells. The ex vivo prognostic assays can be used alone or in conjunction with other prognostic assays to identify candidate subjects who will benefit from treatment with anti-CD40 therapeutic agents. Methods of the invention also comprise the use of these biomarkers to monitor in vivo efficacy of treatment with an anti-CD40 therapeutic agent.

Abstract: The present invention relates to novel Death Domain Containing Receptor-4 (DR4) proteins which are members of the tumor necrosis factor (TNF) receptor family. In particular, isolated nucleic acid molecules are provided encoding the human DR4 proteins. DR4 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of DR4 activity and methods for using DR4 polynucleotides and polypeptides. The invention also relates to the treatment of diseases associated with reduced or increased levels of apoptosis using antibodies specific for DR4, which may be agonists and/or antagonists of DR4 activity.

Abstract: The present invention provides methods for treating a B-cell lymphoma in a human subject. The methods of the invention comprise administering to a subject in need thereof an antibody or antigen-binding fragment thereof that specifically binds human CD20. In certain embodiments, the methods of the invention are useful for treating non-Hodgkin's B-cell lymphoma.

Abstract: New combined therapeutic regimens for treatment of B-cell lymphomas are disclosed which comprise in particular administration of anti-CD20 antibodies to patients having low-, intermediate- or high-grade non-Hodgkins lymphomas.

Abstract: A therapeutic composition for treatment of cancer in a mammal is disclosed. The composition comprises an effective amount of a yeast beta-glucan composition which is suitable for oral administration and for absorption through the gastrointestinal tract of the mammal. The above therapeutic composition may further comprise antitumor antibodies or cancer vaccine composition, wherein the antitumor activities of the antitumor antibodies or the cancer vaccine composition are enhanced by the yeast glucan.

Abstract: The present invention provides chimeric and humanized versions of anti-CD19 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD19 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of B cell diseases and disorders, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft-versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.

Abstract: The present disclosure relates to anti-high molecular weight melanoma associated antigen (HMW-MAA) antibodies which bind to human HMW-MAA. Such antibodies may be used to treat diseases or disorders characterized by expression of HMW-MAA including cancer, for example, melanoma, basal cell carcinoma, ALL or AML.

Abstract: The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline, e.g. doxorubicin or epirubicin. The invention further provides a method of treating cancer in a human patient comprising administering effective amounts of an anti-ErbB2 antibody and a cardioprotectant to the patient.

Abstract: RNA interference using small interfering RNAs which are specific for the ICAM-1 gene inhibits expression of this gene. Diseases which involve ICAM-1-mediated cell adhesion, such as inflammatory and autoimmune diseases, diabetic retinopathy and other complications arising from type I diabetes, age related macular degeneration and many types of cancer, can be treated by administering the small interfering RNAs.

Abstract: An enhancer of expression, in the myeloma cell, of HM1.24 antigen, said enhancer comprising interferon-? or interferon-?, or IRF-2 protein as an active ingredient. Interferon-? or interferon-? is expected to enhance the expression of HM1.24 antigen by activating the promoter of a gene encoding HM1.24 antigen.

Abstract: The present invention provides vascular endothelial cell growth factor (VEGF) antagonists and methods of using VEGF antagonists. VEGF antagonists contemplated by the invention include VEGF antibodies and VEGF receptor fusion proteins. Methods of treating edema and stroke using VEGF antagonists are also provided.

Abstract: The invention relates to the identification of genetic products expressed in association with tumors and to coding nucleic acids for the expressed products. An embodiment of the invention also relates to the therapy and diagnosis of disease in which the genetic products are aberrantly expressed in association with tumors, proteins, polypeptides and peptides which are expressed in association with tumors, and to the nucleic acids coding for the polypeptides, peptides and proteins.

Abstract: The present invention concerns methods and compositions for forming cytokine-antibody complexes using dock-and-lock technology. In preferred embodiments, the cytokine-MAb DNL complex comprises an IgG antibody attached to two AD (anchor domain) moieties and four cytokines, each attached to a DDD (docking and dimerization domain) moiety. The DDD moieties form dimers that bind to the AD moieties, resulting in a 2:1 ratio of DDD to AD. The cytokine-MAb complex exhibits improved pharmacokinetics, with a significantly longer serum half-life than either naked cytokine or PEGylated cytokine. The cytokine-MAb complex also exhibits significantly improved in vitro and in vivo efficacy compared to cytokine alone, antibody alone, unconjugated cytokine plus antibody or cytokine-MAb DNL complexes incorporating an irrelevant antibody.

Abstract: The present invention relates to diagnostic and therapeutic methods in the field of malignant disorders. Most particularly, the invention provides methods of determining the invasivity of malignant disorders and methods for reducing the invasivity of malignant disorders including the prevention or treatment of cancer cell invasion.

Abstract: The present invention relates to a method for producing cancerous disease modifying antibodies using a novel paradigm of screening. By segregating the anti-cancer antibodies using cancer cell cytotoxicity as an end point, the process makes possible the production of anti-cancer antibodies for therapeutic and diagnostic purposes. The antibodies can be used in aid of staging and diagnosis of a cancer, and can be used to treat primary tumors and tumor metastases. The anti-cancer antibodies can be conjugated to toxins, enzymes, radioactive compounds, cytokines, interferons, target or reporter moieties and hematogenous cells.

Abstract: The invention describes the use of a pharmaceutical preparation containing a trifunctional bispecific and/or trispecific having the following properties: a) binding to a T cell; b) binding to at least an antigen on a tumor cell associated with malignant ascites and/or pleural effusion; c) binding, by its Fc portion (in the case of bispecific antibodies) or by a third specificity (in the case of trispecific antibodies), to Fc receptor-positive cells for the destruction of the tumor cells in the treatment of malignant ascites and/or pleural effusion.

Abstract: The present invention provides a novel diagnostic or therapeutic method for pancreatic cancer employing a blood marker. The present invention provides a diagnostic or therapeutic drug for pancreatic cancer containing an anti-AMIGO2 antibody.

Abstract: The invention relates to the use of a binding member which binds to LewisY and Lewisb haptens in the treatment of tumours and leukaemia. The binding member may be an antibody which binds to LewisY and Lewisb haptens and cancer cells and induces cells death.

Abstract: The present invention relates to an isolated antibody or antigen-binding fragment thereof that specifically binds with high affinity to at least a portion of a segment of human prostate-derived Ets transcription factor (PDEF). The anti-PDEF antibody of the present invention is effective in prognostic and diagnostic assays for detecting PDEF with immunohistochemistry. The present invention also relates to methods of making the anti-PDEF antibody disclosed herein. The present invention further relates to vaccines against cancers associated with positive expression of PDEF, as well as methods for treating those cancers. Vectors, diagnostic kits, and hybridomas are also disclosed.

Abstract: The present invention relates to novel sequences for use in detection, diagnosis and treatment of diseases, including cancer. The invention provides novel splice products of human DKKL-1 gene. The present invention provides methods of using polynucleotides having the novel splice products of the human DKKL-1 sequences, their corresponding gene products and modulators of the DKKL-1 splice products for the detection, diagnosis, prevention and/or treatment of associated cancers.

Abstract: The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.

Abstract: Described is a novel family of cell surface serpentine transmembrane antigens. Two of the proteins in this family are exclusively or predominantly expressed in the prostate, as well as in prostate cancer, and thus members of this family have been termed “STEAP” (Six Transmembrane Epithelial Antigen of the Prostate). Four particular human STEAPs are described and characterized herein. The human STEAPs exhibit a high degree of structural conservation among them but show no significant structural homology to any known human proteins. The prototype member of the STEAP family, STEAP-1, appears to be a type IIIa membrane protein expressed predominantly in prostate cells in normal human tissues. Structurally, STEAP-1 is a 339 amino acid protein characterized by a molecular topology of six transmembrane domains and intracellular N- and C-termini, suggesting that it folds in a “serpentine” manner into three extracellular and two intracellular loops.

Abstract: The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD18, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder.

Abstract: The present invention relates to polynucleotide and polypeptide sequences which are differentially expressed in cancer cells compared to normal cells. The present invention more particularly relates to the use of these sequences in the diagnosis, prognosis or treatment of cancer and in the detection of cancer cells.

Abstract: Novel anti-NRP1 antibodies and variants thereof having unique structural and functional characteristics are disclosed. Also provided are uses of the antibodies in research, diagnostic and therapeutic applications.

Abstract: The present invention relates to a CD9-specific human antibody, more precisely a CD9-specific human antibody composed of human derived CD9-specific complementarity determining region (CDR) and framework region (FR). The human antibody of the present invention recognizes CD9 extracellular loop 2 domain (CD9-ECL2) as an epitope and thereby strongly binding thereto. The human antibody of the present invention also has CD9 antigen neutralizing effect and at the same time inhibiting effect on tumor cell lines. Therefore, it can be effectively used for the prevention and treatment of cancer overexpressing CD9.

Abstract: Methods for treating and/or preventing a TNF-mediated disease in an individual are disclosed. Also disclosed is a composition comprising methotrexate and an anti-tumor necrosis factor antibody. TNF-mediated diseases include rheumatoid arthritis, Crohn's disease, and acute and chronic immune diseases associated with transplantation.

Abstract: Genes that are up regulated in human prostate tumor tissues and the corresponding proteins are identified. These genes and the corresponding antigens are suitable targets for the treatment, diagnosis or prophylaxis of prostate cancer.

Abstract: Here we disclose the response of normal human cells to ZnO nanoparticles under different signaling environments and compare it to the response of cancerous cells. ZnO nanoparticles exhibit a strong preferential ability to kill cancerous T cells (˜28-35X) compared to normal cells. Interestingly, the activation state of the cell contributes toward nanoparticle toxicity as resting T cells display a relative resistance while cells stimulated through the T cell receptor and CD28 costimulatory pathway show greater toxicity in direct relation to the level of activation. The novel findings of cell selective toxicity towards potential disease causing cells indicate a potential utility of ZnO nanoparticle in the treatment of cancer and/or autoimmunity.

Abstract: The invention provides further characterization of the disease and cancer-associated antigen, transferrin receptor. The invention also provides a novel family of antibodies that bind to the transferrin receptor, methods of diagnosing and treating various human cancers and diseases that express transferrin receptor.

Abstract: The present invention provides a method for treating a subject having chronic lymphocytic leukemia (CLL) comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the proliferative compartment of a CLL clone of the subject to treat chronic lymphocytic leukemia in the subject. The present invention also provides a method for treating a subject having chronic lymphocytic leukemia comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the “resting re-entry compartment” to treat chronic lymphocytic leukemia in the subject.

Abstract: Described herein are compositions and methods for treating cancer, comprising administering to an individual having cancer an agent to prevent MIC shedding (initiated at the alpha-3 ectodomain of MIC) by a tumor cell. Also provided herein are screening assays for identifying, or testing the efficacy of, an agent for increasing sensitivity of a tumor to immune cell-mediated killing.

Abstract: Disclosed are methods of treating subjects having cancers including administering an effective amount of an early activation molecule agonist, antagonist or depletor, to the subject. Human monoclonal antibodies specific to the early activation molecules, and methods of use, are also disclosed.