Abstract: Embodiments of the present invention utilize a more efficient CDR grafting technique to generate humanized versions of the T84.66 antibody. The technique used to generate these antibodies utilizes crystallographic structural data to select an immunoglobulin framework having maximum structural overlap with a non-human donor molecule. This technique was used to develop humanized T84.66 antibodies exhibiting in vitro binding affinity and specificity for carcinoembryonic antigen (CEA) nearly identical to that of T84.66 and the ability to specifically target tumors expressing CEA in vivo.

Abstract: The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab.

Abstract: It has been found that Toll-like receptor 1 and Toll-like receptor 2 (TLR2) physically interact. Antibodies that specifically bind to TLR2 and selectively inhibit induction of cytokines are also described. The invention relates to specific antibodies that selectively bind to TLR2, and to methods of identifying compounds that selectively interfere with signaling through TLR1/TLR2 complexes.

Abstract: Novel immunotoxins and methods of treating neoplastic diseases are provided. More specifically, immunotoxins comprised conjugation of a c-erbB-2 targeting moiety and a cell growth modulator are provided. These immunotoxins specifically and selectively kill tumor cells that over-express the c-erbB-2 protein. The novel immunotoxins would be useful in treating human mammary carcinomas, human ovarian carcinomas, lung carcinomas, gastric tumors, salivary gland adenocarcinomas, and colon adenocarcinomas.

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: Provided herein is disclosure about the development and characterization of an antibody (mPA7) which binds to antigen CD46 which is present on a variety of human cancers from ovary, breast, lung, prostate, colon, kidney, and pancreas. Methods of diagnosing and treating various cancers by using antibodies such as mPA7 directed against this antigen are also disclosed.

Abstract: The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the Fc?RI receptor by a chimeric cytotoxin Fc2?-3-PE40. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE40?—a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in E. coli, specifically and efficiently kills mouse mast cell lines expressing the Fc?RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc?RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc?RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product of Pseudomonas aeruginosa.

Abstract: The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.

Abstract: The invention provides antibodies having an antigenic binding site specifically directed against an MN protein, and methods for using such antibodies in treating and diagnosing an MN-related disorder.

Abstract: The present invention relates to a combination therapy method for treating gastrin-dependent tumors. The method comprises the immunization of a patient with an anti-gastrin 17 immunogenic composition in combination with the administration of chemotherapeutic agents such as 5-fluorouracil and leucovorin.

Abstract: A process for the selection of anti c-Met antibodies capable of inhibiting both ligand-dependent and ligand-independent activation of c-Met, wherein said process is based on the inhibition of the c-Met dimerization. The present invention also concerns such antibodies and compositions comprising antibodies for the preparation of a medicament to treat cancer including diagnosis process and kits.

Abstract: The present invention relates to compositions and methods of use, wherein the composition comprises a conjugate of a bacterial superantigen and an antibody moiety. More particularly, the bacterial superantigen has been modified to decrease seroreactivity with retained superantigen activity.

Abstract: The present invention relates to novel antibodies, particularly antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to the type III deletion mutant, EGFRvIII. The invention also relates to human monoclonal antibodies directed against deletion mutants of epidermal growth factor receptor and particularly to EGFRvIII. Diagnostic and therapeutic formulations of such antibodies, and immunoconjugates thereof, are also provided.

Abstract: The subject invention pertains to antibodies that have binding specificity for an antigen that is expressed on a subset of human, hematopoietic mononuclear cells, including a hematopoietic stem cell population, but is not expressed on normal, mature myeloid cells. In one embodiment, a monoclonal antibody, MG1, is provided. This antibody is useful in methods of isolating cell suspensions from human blood and marrow that can be employed in bone marrow transplantation, genetic therapy, and in treating other diseases of the hematopoietic system. Cell suspensions containing MG1+ human hematopoietic cells are also provided, as well as therapeutic methods employing the cell suspensions. The subject invention also pertains to the novel antigen recognized by the subject antibodies.

Abstract: The present invention generally relates to a new approach for the therapy of allergic responses, based on targeted elimination of cells expressing the Fc?RI receptor by a chimeric cytotoxin FC2?-3-PE40. A sequence encoding amino acids 301-437 of the Fc region of the mouse IgE molecule was genetically fused to PE40—a truncated form of PE lacking the cell binding domain. The chimeric protein, produced in E. coli, specifically and efficiently kills mouse mast cell lines expressing the Fc?RI receptor, as well as primary mast cells derived from bone marrow. The present invention provides a chimeric protein for targeted elimination of Fc?RI expressing cells especially useful for the therapy of allergic responses. The said chimeric protein is comprised of a cell targeting moiety for Fc?RI expressing cells and a cell killing moiety. The preferred killing moiety is the bacterial toxin Pseudomonas exotoxin (PE). This Pseudomonas exotoxin is a product of Pseudomonas aeruginosa.

Abstract: Compositions and methods for modulating the growth, proliferation, and/or differentiation of B-cells in the germinal center are disclosed, and include use of IL-15 inhibitors, antagonists, and agonists. The compositions and methods find use in treating B-cell-related disorders, including neoplasms of the B-cell lineage.

Abstract: The present invention is directed to cell surface antigens found on myeloma cells and on ovarian cancer cells that are recognized by monoclonal antibodies, and antibody binding fragments thereof, as described. The monoclonal antibodies of the invention are capable of being used for therapeutic, screening, diagnostic and cell purification purposes. A representative and exemplified monoclonal antibody of the present invention recognizes and binds to an epitope common to a surface antigen that is expressed on multiple myeloma cells and to a surface antigen that is expressed on ovarian cancer cells. The function of this monoclonal antibody both in vivo and in vitro is demonstrated.

Abstract: A composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen is disclosed.

Abstract: The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.

Abstract: The present invention is directed to the use of antibodies or binding portions thereof, probes, ligands, or other biological agents which either recognize an extracellular domain of prostate specific membrane antigen or bind to and are internalized with prostate specific membrane antigen. These biological agents can be labeled and used for detection of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof. They also can be used alone or bound to a substance effective to ablate or kill such cells as a therapy for prostate cancer. Also disclosed are four hybridoma cell lines, each of which produces a monoclonal antibody recognizing extracellular domains of prostate specific membrane antigens of normal, benign hyperplastic, and cancerous prostate epithelial cells or portions thereof.

Abstract: The present invention relates to TR21 polypeptides. In particular, isolated nucleic acid molecules are provided encoding human TR21 protein. TR21 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 TR21 activity.

Abstract: The use of an ScFv Ab (ScFv Ab) capable of recognising a disease associated molecule (DAM) in the manufacture of a medicament for the prevention and/or treatment of a disease condition associated with a DAM is described. The ScFv Ab has therapeutic, diagnostic and prognostic applications.

Abstract: Antibodies which bind to activated members of the erbB, TNF, and IgSF family of receptors and pharmaceutical compositions comprising the same are disclosed. Peptides and mimetics of erbB, TNF, and IgSF receptors and pharmaceutical compositions comprising the same are also described. Methods of using such antibodies, peptides, and mimetics in tumor therapeutic, prophylactic, imaging and diagnostic applications are disclosed.

Abstract: Methods to detect, screen, and quantitate biological samples after administration of antibody conjugates, antibody-drug conjugates of Formula I, antibodies, and fragments and metabolites thereof, by affinity separation, chromatography, and mass spectrometry are disclosed. Ab-(L-D)p??I wherein Ab is an antibody; D is a drug moiety; L is a linker covalently attached to Ab, and covalently attached to D; and p is 1, 2, 3, 4, 5, 6, 7, or 8.

Abstract: The present invention relates to the use of a compound that specifically binds to JAM-C or JAM-B for the treatment of gliomas. More specifically the invention relates to the use of an antagonist of JAM-B or JAM-C for the treatment of glioma, in particular astrocytoma.

Abstract: The invention provides methods and compositions for modulating the HGF/c-met signaling pathway, in particular by inhibiting a hyperstabilized c-met protein.

Abstract: A gene (designated 161P2F10B) and its encoded protein are described wherein 161P2F10B exhibits tissue specific expression in normal adult tissue, it 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 a fragment thereof, can be used to elicit a humoral or cellular immune response.

Abstract: Primitive or progenitor hematologic cancer cells have been implicated in the early stages and development of leukemia and malignant lymphoproliferative disorders, including acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and chronic lymphoid leukemia (CLL). Interleukin-3 receptor alpha chain (IL-3R? or CD123) is strongly expressed on progenitor hematologic cancer cells, but is virtually undetectable on normal bone marrow cells. The present invention provides methods of impairing progenitor hematologic cancer (e.g., leukemia and lymphomic) cells by selectively targeting cells expressing CD123. These methods are useful in the detection and treatment of leukemias and malignant lymphoproliferative disorders. Also provided are compounds useful for selectively binding to CD123 and impairing progenitor hematologic cancer cells. These compounds may include cytotoxic moieites such as, for example, radioisotopes or chemotherapeutics.

Abstract: Modulators of phosphatidic acid phosphatase type 2C and other polypeptides, highly expressed in cancers as compared to normal tissues, are provided for treatment of proliferative disorders such as cancer. A method is provided for detecting polypeptides that are overexpressed in cancer, whereby antibodies or binding proteins that specifically recognize these molecules are contacted with a patient's bodily fluid. The method provides an early diagnosis of cancer, and can detect recurrence and metastasis following an initial diagnosis. The invention further provides methods of treating cancer with therapeutic agents directed toward these protein and peptide biomarkers.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Abstract: The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.

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: A composition-of-matter comprising an antibody or antibody fragment including an antigen-binding region capable of specifically binding an antigen-presenting portion of a complex composed of a human antigen-presenting molecule and an antigen derived from a pathogen is disclosed.

Abstract: This invention relates to human antibodies that bind to human insulin-like growth factor-1 receptor (IGF-IR), to derivatives of these antibodies (Fabs, single chain antibodies, bi-specific antibodes, or fusion proteins), and to uses of the antibodies and derivatives in therapeutic, and diagnostic methods. The invention relates to nucleic acids encoding the anti-IGF-IR, methods of generating the antibodies and expression. The invention further relates to combination therapies using ant-IGF-IR antibodies with anti-neoplastic drugs.

Abstract: The present invention provides an anti-human antibody or fragment thereof that is low or not immunogenic in humans. In particular, the antibodies or fragments are directed to human tumor antigens, preferably to the human tumor antigen 17-1A, also known as EpCAM, EGP or GA 733-2. Also provided are pharmaceutical compositions comprising the aforementioned antibodies or fragments thereto.

Abstract: The present invention relates to compositions and methods for inducing cell death or stasis in cancer cells or other hyperproliferative cells using anti-EphA2 or anti-EphA4 antibodies conjugated to toxins.

Abstract: There are provided peptides derived from antibodies with reactivity against a GPI linkage epitope and functionally equivalent ligands. These peptides can be used in the therapy and diagnosis of a variety of diseases, all of which are considered to be caused by the inappropriate presence in the body of autoantibodies which are reactive with GPI linkage epitopes. There is also described a mechanism of action of these autoantibodies which compromises the organism, so causing disease, and a method of prevention of disease and detection of the autoantibody.

Abstract: A chemical conjugate for treating a nerve cell related disorder is provided. This conjugate includes an active or inactive Clostridial toxin having specificity for a target nerve cell. The toxin is conjugated to a drug or other bioactive molecule without affecting the toxin's ability to enter the target nerve cell.

Abstract: The present invention relates to the use of DC-HIL and fragments and variants thereof to selectively target toxins to activated T-cells expressing a unique form of syndecan-4 that is not found on other cells. Thus, the toxin is delivered only to activated T-cells, and not to other syndecan-4 expressing cells. Such toxin-DC-HIL conjugates are useful in the treatment of T-cell inflammatory disorders such as dermatitis, autoimmune disease, and graft rejection, as well as T-cell lymphomas.

Abstract: The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

Abstract: The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

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, and hematogenous cells.

Abstract: The invention provides for methods of detecting and treating diseased tissue, particularly in skin diseases or disorders, such as psoriasis, scleroderma, eczema or atopic dermatitis tissue. The method involves administrating a composition comprising an antibody specific to the diseased tissue to a patient. After administration, the antibody in the composition binds to the exposed cell surface antigen (epitope) and allows the detection and/or disrupts the growth of the diseased tissue.

Abstract: The present invention provides compositions and methods for treating or preventing infection by Toxin A producing bacteria.

Abstract: The present invention relates to compositions and methods of use, wherein the composition comprises a conjugate of a bacterial superantigen and an antibody moiety. More particularly, the bacterial superantigen has been modified to decrease seroreactivity with retained superantigen activity.

Abstract: Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Abstract: Methods of therapy for B-cell malignancies are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity when the antibody binds a CD40 antigen on a normal human B cell, exhibits antagonist activity when the antibody binds a CD40 antigen on a malignant human B cell, and can exhibit antagonist activity when the antibody binds a CD40 antigen on a normal human B cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of malignant human B cells.

Abstract: Disclosed are surprising discoveries concerning the role of anionic phospholipids and aminophospholipids in tumor vasculature and in viral entry and spread, and compositions and methods for utilizing these findings in the treatment of cancer and viral infections. Also disclosed are advantageous antibody, immunoconjugate and duramycin-based compositions and combinations that bind and inhibit anionic phospholipids and aminophospholipids, for use in the safe and effective treatment of cancer, viral infections and related diseases.

Abstract: The present invention relates to engineered multivalent and multispecific binding proteins, methods of making, and specifically to their uses in the prevention and/or treatment of acute and chronic inflammatory and other diseases.

Abstract: A non-toxic polypeptide, for delivery of a therapeutic agent to a neuronal cell, comprises a binding domain that binds to the neuronal cell, and a translocation domain that translocates the therapeutic agent into the neuronal cell, wherein the translocation domain is not a HN domain of a clostridial toxin and is not a fragment or derivative of a HN domain of a clostridial toxin.