Abstract: The present invention includes compositions and methods for inhibiting an oncogenic protein or its down-stream effector protein to suppress expression of a cell-surface protein involved in inhibiting immune response against malignant cells thereby enhancing immunogenicity of a cell. The invention includes inhibitors of expression of CD274 and/or its functional cell-membrane bound immunosuppressive analog. The invention includes inhibitors of function or expression of oncogenic ALK tyrosine kinase and/or other oncogenic proteins responsible for induction of expression of CD274 or its functional immunosuppressive equivalent. The invention includes inhibitors of function or expression of STAT3 and/or other cell signal transmitters and/or transcription factors activated by ALK or its functional analog involved in induction of expression of CD274 or its functional analog.

Abstract: The present invention relates to methods of inhibiting receptor tyrosine kinases by utilizing a combination of both an extracellular and an intracellular RTK antagonist. The extracellular RTK antagonist is a biological molecule or a small molecule that inhibits activation of the receptor tyrosine kinase by interacting with the extracellular binding region of the receptor. The intracellular RTK antagonist is a biological molecule or small molecule that inhibits tyrosine kinase activity of the receptor tyrosine kinase by interacting with the receptor's intracellular region bearing a kinase domain or by interacting with an intracellular protein involved in the signaling pathway of the receptor tyrosine kinase. The present invention also provides methods of treating tyrosine kinase-dependent diseases, and compositions for use in such methods thereof, by administering a combination of both an extracellular and an intracellular RTK antagonist.

Abstract: Antibodies and molecules derived therefrom that bind to 161P2F10B protein and variants thereof, are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 161P2F10B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 161P2F10B gene or fragment thereof, or its encoded protein, or variants thereof, or a fragment thereof, can be used to elicit a humoral or cellular immune response; antibodies or T cells reactive with 161P2F10B can be used in active or passive immunization.

Abstract: EGFR biomarkers useful in a method for predicting the likelihood that a mammal that will respond therapeutically to a method of treating cancer comprising administering an EGFR modulator, wherein the method comprises (a) measuring in the mammal the level of at least one biomarker selected from epiregulin and amphiregulin, (b) exposing a biological sample from the mammal to the EGFR modulator, and (c) following the exposing of step (b), measuring in the biological sample the level of the at least one biomarker, wherein an increase in the level of the at least one biomarker measured in step (c) compared to the level of the at least one biomarker measured in step (a) indicates an increased likelihood that the mammal will respond therapeutically to the method of treating cancer.

Abstract: Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-mediated disorder or disease and methods of diagnosing a KIT-mediated disorder or disease using the antibodies described herein.

Abstract: Disclosed are specific binding agents, such as fully human antibodies, that bind to angiopoietin 1 and/or angiopoietin-2. Also disclosed are heavy chain fragments, light chain fragments, and CDRs of the antibodies, as well as methods of making and using the antibodies.

Abstract: A general method is provided for the production of purified antibodies by separation of an antibody molecule from an antibody variant by chromatographic methods, e.g. to enhance therapeutic efficacy, by for example choosing a specific harvesting time point and/or a specific purification scheme. The current invention thus reports a method for producing an antibody composition comprising an antibody molecule and a variant thereof, comprising the following steps: providing a sample comprising the antibody molecule and a variant thereof, determining the presence of the antibody molecule and/or a variant thereof and/or the ratio of the amount of the antibody molecule or variant thereof to the sum of the amounts of the antibody molecule and the variant thereof, in an aliquot of said sample, determining a subsequent harvesting time point and/or antibody purification scheme on basis of the data obtained before, thereby producing an antibody composition comprising the antibody molecule and a variant thereof.

Abstract: Novel sulfatases and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including various diagnostic and therapeutic agent screening applications. Also provided are methods of inhibiting tumor-induced angiogenesis and methods of treating disease conditions associated therewith, particularly by administering an inhibitor of a subject sulfatase.

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: The invention provides methods and compositions for modulating the HGF/c-met signaling pathway, in particular by regulating c-met dimerization and/or binding of ligand to c-met using a c-met antagonist that disrupts c-met multimerization.

Abstract: The invention provides isolated anti-ovarian, pancreatic, lung or breast cancer antigen (Ovr115) antibodies that bind to Ovr115 on a mammalian cell in vivo. The invention also encompasses compositions comprising an anti-Ovr115 antibody and a carrier. These compositions can be provided in an article of manufacture or a kit. Another aspect of the invention is an isolated nucleic acid encoding an anti-Ovr115 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Ovr115 antibodies. The invention encompasses a method of producing the anti-Ovr115 antibodies. Other aspects of the invention are a method of killing an Ovr115-expressing cancer cell, comprising contacting the cancer cell with an anti-Ovr115 antibody and a method of alleviating or treating an Ovr115-expressing cancer in a mammal, comprising administering a therapeutically effective amount of the anti-Ovr115 antibody to the mammal.

Abstract: Chronic Lymphocytic Leukemia (CLL) may be treated with antibodies directed against the CD20 antigen.

Abstract: Proliferation of colorectal, gastric and esophageal cancer cells is inhibited by administering ST receptor ligand. The number of ST receptor molecules on the surface of a colorectal cell or metastasized colorectal cancer cell are increased by administering an ST receptor ligand such that ligand comes into contact with an ST receptor on the surface of the colorectal cell. Pharmaceutical compositions comprise sterile, pyrogen free ST receptor ligand and a pharmaceutically acceptable carrier or diluent. Metastasized colorectal cancer is treated or imaged by increasing the number of ST receptor molecules on the surface of a metastasized colorectal cancer cell and then administering a pharmaceutical composition containing components that target the ST receptor for delivery of a therapeutic agent or imaging agent. Methods of detecting metastasized colorectal cancer are disclosed. Methods of delivering active compounds to a colorectal cell in an individual are disclosed.

Abstract: This disclosure provides tyrosine kinase protein and nucleic acid variants, particularly PDGFRA variants, which are activating forms of these molecules and are linked to neoplasms and/or the development or progression of cancer. The disclosure further provides methods of diagnosis and prognosis, and development of new therapeutic agents using these molecules and fragments thereof, and kits for employing these methods and compositions.

Abstract: The present invention relates to new antibodies capable of binding specifically to the human CD151 protein, especially monoclonal antibodies of murine origin, which are chimeric and humanised, and also to the amino acid and nucleic sequences coding for those antibodies. The invention also includes use of those antibodies as medicaments for the prophylactic and/or therapeutic treatment of cancers and in diagnostic methods or kits for diseases associated with overexpression of the CD151 protein. Finally, the invention includes products and/or compositions comprising such antibodies in association with antibodies and/or anti-cancer agents or conjugated with toxins and/or radioelements and their use in the prevention and/or treatment of certain cancers.

Abstract: Cripto, a developmental oncoprotein, antagonizes activin and TGF-b signaling by forming a complex with activin and TGF-b and their type II receptors. This complex precludes the formation of a functional activin/TGF-b•type II•type I complex, thereby blocking the signaling of activin and TGF-b. Cripto may be generally capable of blocking antiproliferative Smad2/3 signals and provides a novel mechanism of oncogenic action with multiple therapeutic implications. Inhibiting the formation of Cripto and activin/TGF-b complex may enhance antiproliferative effects of activin and TGF-b.

Abstract: The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds Fc?RIIIA and/or Fc?RIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc?R is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.

Abstract: An object of the present invention is to provide novel pharmaceutical compositions using anti-GRP78 antibodies. More particularly, the present invention provides a novel method of cancer treatment using anti-GRP78 antibodies, novel cell growth inhibitors and anticancer agents that contain anti-GRP78 antibodies, as well as novel anti-GRP78 antibodies. The present inventor prepared antitumor antibodies to target GRP78, the localization of which in cancer cells changed to the cell membrane. The inventor successfully obtained an anti-GRP78 antibody that would bind specifically to the cell surface of cancer cells, leading to the accomplishment of the above-mentioned objects.

Abstract: Use of a monoclonal antibody directed against the extracellular domain of hepatocyte growth factor is disclosed for the preparation of a medicament for the treatment of tumors and/or metastases and of a diagnostic tool for detecting neoplastic cells as well as vectors comprising at least a portion of the nucleotide sequence encoding the anti-Met monoclonal antibody, products containing the anti-Met monoclonal antibody and/or at least one fragment thereof and at least one kinase inhibitor.

Abstract: The invention provides a method of predicting the response of a patient affected with cancer to a treatment with an EGFR inhibitor, wherein the said method comprises detecting the level of expression of the phosphoprotein pP70S6k in sample from said subject. The invention also provides methods of treatment of cancer and or predicting the outcome of cancer.

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: In one aspect, the present invention provides a method of treating lung cancer, comprising administering to a subject at least one PARP inhibitor in combination with at least one growth factor inhibitor. In another aspect, the present invention provides a method of treating non-small cell lung cancer comprising administering to a subject at least one PARP inhibitor in combination with at least one growth factor inhibitor.

Abstract: The present invention relates to pharmaceutical compositions for the treatment of an epithelial tumor in a human, said pharmaceutical composition comprising an IgG1 antibody specifically binding to human CEA, wherein the variable region of said IgG1 antibody comprises at least (i) a CDR-H1 having the amino acid sequence “SYWMH” and a CDR-H2 having the amino acid sequence “FIRNKANGGTTEYAASVKG” and a CDR-H3 having the amino acid sequence “DRGLRFYFDY” or (ii) a CDR-H1 having the amino acid sequence “TYAMH” and a CDR-H2 having the amino acid sequence “LISNDGSNKYYADSVKG” and a CDR-H3 having the amino acid sequence “DRGLRFYFDY”. Furthermore, processes for the production of said pharmaceutical compositions as well as medical/pharmaceutical uses for the IgG1 antibody molecules bearing specificities for the human CEA antigen are disclosed.

Abstract: The present invention provides methods for inhibiting mTOR using pyrazolo[1,5-a]pyrimidine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with mTOR using such compounds.

Abstract: This invention provides novel erbB2-binding internalizing antibodies. The antibodies, designated F5 and C1, specifically bind to c-erbB2 antigen and, upon binding, are readily internalized into the cell bearing the c-erbB2 marker. Chimeric molecules comprising the F5 and/or C1 antibodies attached to one or more effector molecules are also provided.

Abstract: Anti-DR5 antibody agonists, combined with apoptosis-inducing agents, synergistically induce apoptosis in cancer cells.

Abstract: The present invention provides humanized, chimeric and human anti-alpha-fetoprotein antibodies, fusion proteins, and fragments thereof. The antibodies, fusion proteins, and fragments thereof, as well as combinations with other suitable antibodies, are useful for the treatment and diagnosis of hepatocellular carcinoma, hepatoblastoma, germ cell tumors carcinoma and other AFP-producing tumors.

Abstract: The present invention relates to antibodies or fragments thereof that target a conformational epitope of a HER receptor. In particular, the invention relates to antibodies or fragments thereof that target a conformational epitope of HER3 receptor and compositions and methods of use thereof.

Abstract: The subject invention provides novel uses of cytoplasmic c-Myc for modulation of innate immune responses. The invention is based, at least in part, on the surprising discovery that cytoplasmic c-Myc, instead of nuclear c-Myc, modulates pro-inflammatory immune responses via its role as a positive feedback regulator. Specifically, the subject invention provides methods for treatment or amelioration of inflammatory diseases and/or immune disorders via inhibition c-Myc expression or its activity. Also provided are methods for the development of therapeutic agents for treating infection, inflammation, immune diseases and autoimmune diseases.

Abstract: The present invention concerns a method for treating platinum-resistant, ovarian cancer, primary peritoneal carcinoma or fallopian tube carcinoma with the combination of a HER2 antibody that effectively inhibits HER dimerization as well as gemcitabine.

Abstract: The present application is directed to the discovery that hedgehog gene products, and signal transduction pathways involving hedgehog, are involved in maturation of T lymphocytes. The invention provides a method to promote T lymphocyte development using low dose Hedgehog, and a method to inhibit T lymphocyte development using high dose Hedgehog. Certain aspects of the invention are directed to preparations of hedgehog polypeptides, agonists, antagonists, or other molecules which regulate patched or smoothened signalling, and their uses as immunomodulatory agents.

Abstract: Multivalent, multispecific molecules having at least one specificity for a pathogen and at least one specificity for the HLA class II invariant chain (Ii) are administered to induce clearance of the pathogen. In addition to pathogens, clearance of therapeutic or diagnostic agents, autoantibodies, anti-graft antibodies, and other undesirable compounds may be induced using the multivalent, multispecific molecules.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Abstract: The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

Abstract: The present invention concerns cancer biomarkers. In particular, the invention concerns c-met as biomarkers for patient selection and patient prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

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

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

Abstract: Provided are methods and compositions for using MMP-14 or MMP-9 binding proteins alone or in combination with other therapeutic agents to treat osteolytic disorders such as osteotropic cancer and osteoporosis.

Abstract: The present invention relates to the treatment of cancer. More specifically, the present invention relates to the use of c-cbl as a marker for the diagnosis and/or prognosis of cancer, and to the use of a c-cbl antagonist for the treatment of a cancer associated with resistance to apoptosis.

Abstract: Methods for improving the biological and pharmaceutical properties of bispecific binding agents are described herein where the bispecific binding agent are able to target cells by a high affinity binding domain to a first cell surface marker that does not induce a significant biological effect and a low affinity binding domain that binds specifically to a second cell surface marker, causing a significant and desired biological effect. Compositions of such bispecific binding agents, uses for them, and kits containing them are also provided.

Abstract: The present invention provides antibodies, and antigen-binding fragments of antibodies, fusion polypeptides and analogs that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides. The present invention further provides methods of preventing, managing, treating or ameliorating one or more symptoms associated with a CA 125/O772P-related disorder. In particular, the present invention provides methods of preventing, managing, treating, or ameliorating one or more symptoms associated with a cell proliferative disorder, such as cancer, e.g., ovarian cancer. The present invention still further provides methods for diagnosing a CA 125/O772P-related disorder or predisposition to developing such a disorder, as well as methods for identifying antibodies, and antigen-binding fragments of antibodies, that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides.

Abstract: This invention provides a therapeutic agent for inhibiting neovascularization, a therapeutic agent for a solid cancer, a therapeutic agent for a disease pathologically caused by neovascularization, and a therapeutic agent for repairing a tissue comprising as the effective ingredient, a substance that potentiates the action of CXCR4. Based on the finding that vascularization is suppressed in CXCR4 knockout mice, it becomes possible to prepare a therapeutic agent for suppressing vascularization, a therapeutic agent for a solid cancer, a therapeutic agent for a disease pathologically caused by neovascularization, each of which comprises as the effective ingredient, a substance that inhibits the action of CXCR4, as well as to prepare a therapeutic agent for repairing a tissue comprising as the effective ingredient, a substance that potentiates the action of CXCR4. Methods for treatment are made possible that use these therapeutic agents.

Abstract: Anti-CEACAM6 antibodies and antibody fragments, nucleic acids encoding them, methods of their manufacture, and methods to treat cancer using these compounds are provided.

Abstract: The present invention relates to compositions and methods for treating inflammation-associated tissue damage, and particularly transfusion-associated, disorders, by inhibiting or reducing E-selectin mediated signal transduction pathways, such as E-selectin mediated activation of ?M?2.

Abstract: An in depth analysis of prostate cancer prostatectomy samples which over-express the ERG oncogene led to the discovery of a novel gene translocation in prostate cancer, between the NDRG1 gene (N-myc downstream regulated gene 1) on chromosome 8 and the ERG oncogene on chromosome 21, leading to the expression of a chimeric NDRG1-ERG protein. Methods and compositions useful for diagnosing and treating prostate cancer characterized by NDRG1-ERG fusion are described.

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: The present invention relates to the methods of treating endocrine-regulated cancers, including hormone resistant cancers, for example. More specifically, the present invention relates to a method of increasing the sensitivity of hormone resistant cancers to hormonal therapeutic agents. In particular embodiments, the present invention concerns delivery of a histone deacetylase inhibitor and a hormone targeted drug to an individual with cancer. In specific embodiments, the histone deacetylase inhibitor and the hormone targeted drug act synergistically to treat the cancer, including by overcoming resistance to a cancer therapy.

Abstract: Antibody for targeted induction of Apoptosis, CDC and ADCC mediated killing of Cancer cells, TBL-CLN1, is disclosed. The antibodies, TBL-CLN1, are monoclonal antibodies which can specifically target and bind to the epitope of SEQ ID NO:1 expressed on cancer cells which further leads to killing of cancer cells. TBL-CLN1 is not conjugated to toxin or cytotoxic molecules, and provides selective killing of cancer cells just by binding to cancer cell surface. Also, disclosed herein is SEQ ID NO: 2 which is an engineered epitope which comprises of polypeptide sequence of SEQ ID NO: 1 and a cysteine residue which is added at the carboxyl end of the SEQ ID NO: 1. The epitope of SEQ ID NO: 2 is used to generate monoclonal antibodies described herein.

Abstract: B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 or CD19 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 and/or anti-CD19 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.

Abstract: The present invention uses an RPN2 gene expression inhibitor as a cancer cell growth inhibitor, which further includes a drug showing an anti-cancer action if desired, and is administered in combination with atelocollagen if desired. In addition, the present invention is an anti-cancer agent including such cancer cell growth inhibitor.