Abstract: The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular MAb H33, to soluble JAM-C and JAM-B and to small molecules.

Abstract: Disclosed are nucleic acids encoding BAFF-R polypeptides, as well as antibodies to BAFF-R polypeptides and pharmaceutical compositions including the same. Methods of treating tumorigenic and autoimmune conditions using the nucleic acids, polypeptides, antibodies and pharmaceutical compositions of this invention are also provided.

Abstract: This invention relates to a method for assessing risk of prostate cancer. Specifically, it relates to utilizing both Pro108 and Prostate Specific Antigen (PSA) in combination to determine the risk of prostate cancer. In addition, it is directed to a method for assessing risk of ovarian, colon, breast or stomach cancer utilizing Pro108 or specific antibodies to Pro108. The invention provides isolated anti-prostate, ovarian, colon, breast or stomach cancer antigen (Pro108) antibodies that bind to Pro108 on a mammalian cell in vivo. The invention also encompasses compositions comprising an anti-Pro108 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-Pro108 antibody, as well as an expression vector comprising the isolated nucleic acid. Also provided are cells that produce the anti-Pro108 antibodies. The invention encompasses a method of producing the anti-Pro108 antibodies.

Abstract: The vascular endothelial growth factor (VEGF) activity in a patient's bloodstream or other biological sample can serve as a diagnostic and prognostic index for cancer, diabetes, heart conditions, and other pathologies. Antibody-sandwich ELISA method and kits for VEGF as an antigen were developed to detect VEGF levels in biological samples from animal models and human patients and are used as a diagnostic/prognostic index.

Abstract: The monoclonal antibodies of this invention are antibodies that specifically recognize human Integrin Associated Protein, and the antigens that induce apoptosis of nucleated blood cells having human Integrin Associated Protein. Accordingly, they are useful as antibodies that recognize human Integrin Associated Protein for its distinction and identification, while also having an action of inducing apoptosis of nucleated blood cells; these properties can be utilized to prepare useful therapeutic agents in the field of treatment for myeloid leukemia and lymphoid leukemia.

Abstract: The present invention relates to a rabbit monoclonal antibody that binds to human Id1 protein and/or mouse Id1 protein with high specificity and high affinity. The antibody has a binding constant, measured with respect to human Id1 protein and/or mouse Id1 protein, equal to or greater than 1×108/molar. The antibody has no substantial cross-reactivity with other family Id proteins such as Id2, Id3, or Id4, or other endogenous proteins present in the cells that express Id1 protein. The high specificity and high affinity of the rabbit monoclonal antibodies of the present invention allows sensitive and specific detection and/or quantitation of Id1 protein in biological samples. The antibodies are useful in immunochemical-based assays such as ELISA, western blot, and immunohistochemical staining.

Abstract: Novels immuno-interactive fragments of the (alpha)C portion of a mammalian inhibin alpha subunit are disclosed, together with their variants and derivatives for producing antigen-binding molecules that are interactive with said (alpha)C portion, which are chemically well defined and which can be produced in commercially significant quantities. The antigen-binding molecules of the invention can be used for the detection of a mammalian inhibin and for the treatment and/or prevention of conditions associated with aberrant levels of a mammalian inhibin.

Abstract: The invention provides in vitro and in vivo methods of killing cancer cells, including therapeutic methods in humans, and also provides antibodies specific for the cancer specific antigen C35, and polynucleotides encoding such antibodies, as well as therapeutic and diagnostic methods of using such antibodies.

Abstract: An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of DR5 and DR4 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

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 present invention relates to a method for the early diagnosis of cancer in a subject, which is based on determination of the relative fraction of microorganisms derived from the feces of the subject, as compared to the total count of microorganisms in the same of corresponding sample. This relation has been found to be indicative of the presence or absence of cancer in said subject. After isolating at least one of the microorganisms from the fecal sample to form a so-called diagnostic sample, and incubating, for a sufficient time, the diagnostic sample with cancer cells. The microorganism being in an amount corresponding to its relative fraction in the original fecal sample, the cancerolytic activity of the microorganism/s is indicative to the presence or absence of cancer cells in the subject. The cancerolytic activity is expressed by terms of a tumor cell necrosis index (TCNI).

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 immunologically active antibodies directed against the CD20 antigen, as well as host cells comprising nucleic acid sequences encoding the light chains and heavy chains of immunologically active antibodies wherein the cell is capable of expressing and secreting an immunologically active chimeric anti-CD20 antibody and methods of using such host cells to make purified antibodies. The antibodies are useful for treating and diagnosing B cell disorders.

Abstract: The present invention relates to the field of site directed therapy. More specifically the invention relates to site directed radio therapy, and provides a method for production of radioconjugates and an apparatus for radioimmunotherapy. The method, conjugates and apparatus can be practicalized without the need for radioactive shielding and/or airtight facilities. Without these restrictions the invention provides a simple and efficient means of therapy at the bed-side of the patient.

Abstract: Methods and compositions are provided for the diagnosis and treatment of iron misregulation diseases, including HFE polypeptides, agonists, and antagonists, and transferrin receptor agonists and antagonists.

Abstract: GPR64 antibody compositions are provided. These antibodies may be used for diagnosis or treatment of cancer, especially ovarian cancer, Ewing's sarcoma, uterine cancer, and other GPR64 expressing tumor types.

Abstract: A complex including an HLA class I molecule and attaching means for selectively attaching the HLA class I molecule to a target is disclosed, and a method is provided for producing or enhancing an immunological response against a target cell, by attaching said complex to the target cell. Where the target cell is diseased, foreign, or malignant cell, this method may be used to promote lysis of the target cell by T cells in the immune system. Where the target cell is an antigen presenting cell, this method may be used to promote proliferation of specific T cell clones. Uses include prevention and treatment of diseases including cancer, leukaemia, infectious diseases, viral infections, such as HIV, bacterial infections, such as tuberculosis, and parasitic infections such as malaria.

Abstract: Human Death Receptor 4 (DR4) antibodies are provided. The human DR4 antibodies may be included in pharmaceutical compositions, articles of manufacture, or kits. Methods of treatment and diagnosis using the DR4 antibodies are also provided.

Abstract: An antibody of the invention interacts with human DR5 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Nucleic acid sequences and amino acid sequences of anti-DR5 antibodies have been elucidated and vectors and cells containing and expressing these sequences have been generated. Methods and uses for the antibodies are detailed including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Abstract: The present invention relates to novel human secreted proteins and isolated nucleic acids containing the coding regions of the genes encoding such proteins. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human secreted proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating diseases, disorders, and/or conditions related to these novel human secreted proteins.

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 invention includes novel human periostin polypeptides and DNAs encoding them. Also embraced by the invention are human periostin specific antibodies, diagnostic assays for metastasis of breast cancer to bone, and preeclempsia.

Abstract: Genetically engineered, CE7-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CE7, an intracellular signaling domain, and a transmembrane domain, and methods of use for such cells for cellular immunotherapy of CE7+ neuroblastoma are disclosed. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain FvFc:? receptor where Fv designates the VH and VL chains of a single chain monoclonal antibody to CE7 linked by peptide, Fc represents a hinge —CH2—CH3 region of a human IgG1, and ? represents the intracellular signaling domain of the zeta chain of human CD3. DNA constructs encoding a chimeric T-cell receptor and a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor are also disclosed.

Abstract: A bifunctional protein comprising: 1) a single-chain antibody directed against a suitable antigen on a tumour cell, 2) a hinge region comprising from about 40 to about 200 amino acids joined to the VL domain of the single chain antibody, and 3) a functional zeta (?) chain from the T-cell antigen receptor (TCR) joined to the hinge region, wherein the hinge region is an immunoglobin-like hinge region which is joined to the C-terminus of the VL domain of the single-chain antibody. The functional zeta (?) chain comprises the transmembrane and the cytoplasmic domain. The bifunctional protein can be expressed using a cytotoxic lymphocyte (CTL) expressing DNA encoding it.

Abstract: Immunoconjugates for treating diseases associated with neovascularization such as cancer, rheumatoid arthritis, the exudative form of macular degeneration, and atherosclerosis are described. The immunoconjugates typically consist of the Fc region of a human IgG1 immunoglobulin including the hinge, or other effector domain or domains that can elicit, when administered to a patient, a cytolytic immune response or cytotoxic effect against a targeted cell. The effector domain is conjugated to a targeting domain which comprises a factor VII mutant that binds with high affinity and specificity to tissue factor but does not initiate blood clotting such as factor VII having a substitution of alanine for lysine-341 or of alanine for serine-344.

Abstract: This invention is directed toward novel synergistic combinations of ligand-mimicking agents specific to the c-erbB-2 protein and anti-neoplastic drugs or agents, which can be used to treat a mammalian host, usually a human, suspected of having cancer or tumor cells by administering the combination in a therapeutically- or synergistically-effective amount. The drug combinations cytotoxic to tumor cells comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and induces an increase in the phosphorylation of c-erbB-2 protein when placed in contact with the tumor cells. Alternatively, the drug combination cytotoxic to tumor cells may comprise an anti-neoplastic agent and a molecule, that is not conjugated to the anti-neoplastic agent, that binds the tumor cells and causes down modulation or internalization of c-erbB-2 protein. The anti-neoplastic drug is preferably an alkylating agent, most preferably cisplatin.

Abstract: The present invention relates to novel Death Domain Containing Receptor-5 (DR5) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to bind TRAIL. In particular, isolated nucleic acid molecules are provided encoding the human DR5 proteins. DR5 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 antagonists and antagonists of DR5 activity.

Abstract: This invention relates to a substantially purified p100 which is a human neu related protein having a molecular weight in the range from about 97,000 daltons to about 115,000 daltons which corresponds substantially to the extracellular domain of the human neu gene product, said protein being detectable in a biological fluid. In another embodiment this invention relates to assays for detecting this protein. Finally, this invention also concerns monoclonal antibodies which are capable of binding to p100.

Abstract: The vascular endothelial growth factor (VEGF) activity in a patient's bloodstream or other biological sample can serve as a diagnostic and prognostic index for cancer, diabetes, heart conditions, and other pathologies. Antibody-sandwich ELISA method and kits for VEGF as an antigen were developed to detect VEGF levels in biological samples from animal models and human patients and are used as a diagnostic/prognostic index.

Abstract: Novel monoclonal antibodies and binding fragments thereof specific to human breast cancer, lung cancer, colon cancer and other cancers. The monoclonal antibody does not bind to the cell surface of normal human tissues. The corresponding cancer-specific antigen with an apparent molecular weight of 150 kd and polynucleotides encoding the antigen and the CDR regions of the antibody are Also disclosed are methods for diagnosis, prognosis and treatment of human breast cancer. The antibodies have tumor specificity and are useful for therapy, diagnosis, monitoring, detecting and imaging of cancers. The antibody-recognized cancer-specific surface antigens can serve as targets for detecting, diagnosing, inhibiting or killing cancer cells.

Abstract: The present invention provides a monoclonal antibody designated SM047 against cancer, specifically ovarian carcinoma. SM047 is strongly expressed in most ovarian serous adenocarcinomas and in other female genital tract adenocarcinomas. The monoclonal antibody according to the invention is useful to detect a cancer, specifically ovarian carcinoma and/or or determine the origin of cancer. The present invention also provides a hybridoma cell producing the monoclonal antibody and an antigen which binds to the monoclonal antibody according to the present invention.

Abstract: CDR-grafted antibody heavy and light chains comprise acceptor framework and donor antigen binding regions, the heavy chains comprising donor residues at at least one of positions (6, 23) and/or (24, 48) and/or (49, 71) and/or (73, 75) and/or (76) and/or (78) and (88) and/or (91). The CDR-grafted light chains comprise donor residues at at least one of positions (1) and/or (3) and (46) and/or (47) or at at least one of positons (46, 48, 58) and (71). The CDR-grafted antibodies are preferably humanised antibodies, having non human e.g. rodent, donor and human acceptor frameworks, and may be used for in vivo therapy and diagnosis. A generally applicable protocol is disclosed for obtaining CDR-grafted antibodies.

Abstract: Human antibody fragments (Fab 14.6.19 and Fab 14.6.20) including polynucleotides and amino acids (SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6) that identify them. Both Fabs are fully human, are affinity matured in vivo, are highly specific for breast cancer, and target an antigen that is immumogenic in vivo. Thus, each Fab may be a useful clinical reagent for diagnosis or therapy of breast cancer and may also lead to the discovery of a novel immunogenic and tumor specific breast cancer antigen.

Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.

Abstract: The invention relates to antibodies which specifically bind to the gc chain of cytokine receptors, as well as to cell lines which produce such antibodies, pharmaceutical compositions, and methods of treating immunological diseases by treating patients with such antibodies.

Abstract: The present invention provides monoclonal antibodies which interfere with the interactions between FDCs and B cells, thereby suppressing the proliferation and/or differentiation of B cells in lymphoid follicles. The monoclonal antibodies of the present invention are useful for treating follicular lymphomas, multiple myeloma as well as autoimmune diseases.

Abstract: The present invention provides a humanised form of the antibody 340 obtainable from the cell line deposited with the ECACC under accession number 97021428. Such antibodies have been found to have an increased ability to kill cells compared to the murine antibody 340. Also provided are nucleic acids encoding such antibodies, as well as the use of the antibodies in medicine, in particular in the treatment of cancer.

Abstract: This invention relates to the diagnosis of cancer, and in particular to the identification and detection of cancer-specific antigens. the invention provides antibody probes and methods for using the probes for detection and purification of cancer-specific antigens, and in the preparation of vaccine compositions. Antibodies against cancer-specific antigens are also disclosed and claimed.

Abstract: The invention relates to antibodies specific to AIM-I polypeptides useful in biological, diagnostic, clinical or therapeutic arts.

Abstract: Provided herein is disclosure about the discovery that the known antigen, ALCAM, is present on a variety of human cancers other than metastasizing malignant melanoma. Also disclosed herein are methods of diagnosing and treating cancers that express ALCAM by using antibodies directed against ALCAM. This invention also discloses compositions and methods for the modulation of ALCAM-mediated neovascularization.

Abstract: The present invention relates to novel antibodies, antibody fragments and antibody conjugates and single-chain immunotoxins reactive with human carcinoma cells. More particularly, the antibodies, conjugates and single-chain immunotoxins of the invention include: a murine monoclonal antibody, BR96; a human/murine chimeric antibody, ChiBR96; a F(ab′)2 fragment of BR96; ChiBR96-PE, ChiBR96-LysPE40, ChiBR96 F(ab′)2-LysPE40 and ChiBR96 Fab′-LysPE40 conjugates and recombinant BR96 sFv-PE40 immunotoxin. These molecules are reactive with a cell membrane antigen on the surface of human carcinomas. The BR96 antibody and its functional equivalents, displays a high degree of selectivity for carcinoma cells and possess the ability to mediate antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity activity.

Abstract: The present invention relates to monoclonal antibodies that bind to the extracellular domain of prostate-specific membrane antigen (PSMA), hybridoma cell lines producing the antibodies, and methods of using such antibodies for diagnosis and treatment of cancer. In. particular, thirty-five monoclonal antibodies reactive with PSMA expressed on the cell surface are exemplified. Additionally, the present invention relates to a novel protein variant (PSM′) of PSMA detected by a number of the antibodies of the invention. The hydrolase activity of PSMA and PSM′ allows the use of an immunoenzymatic assay for their detection.

Abstract: A novel gene (designated 125P5C8) and its encoded protein, and variants thereof, are described wherein 125P5C8 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 125P5C8 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 125P5C8 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 125P5C8 can be used in active or passive immunization.

Abstract: The monoclonal antibodies of this invention are antibodies that specifically recognize human Integrin Associated Protein, and the antigens that induce apoptosis of nucleated blood cells having human Integrin Associated Protein. Accordingly, they are useful as antibodies that recognize human Integrin Associated Protein for its distinction and identification, while also having an action of inducing apoptosis of nucleated blood cells; these properties can be utilized to prepare useful therapeutic agents in the field of treatment for myeloid leukemia and lymphoid leukemia.

Abstract: The invention provides monoclonal antibodies that selectively bind to ectodermally- and endodermally-derived stem cells and methods for the diagnosis of a neoplasm in a subject by contacting a tissue sample from the subject with the antibodies. Also disclosed are methods for isolating such stem cells from a heterogeneous cell population by contacting the population with antibodies which selectively bind to stem cells.

Abstract: The present invention relates to polyspecific binding molecules and particularly single-chain polyspecific binding molecules that include at least one single-chain T-cell receptor (sc-TCR) covalently linked through a peptide linker sequence to at least one single-chain antibody (sc-Ab). Further disclosed are methods and compositions for testing and using the molecules.

Abstract: The present invention provides monoclonal antibodies which interfere with the interactions between FDCs and B cells, thereby suppressing the proliferation and/or differentiation of B cells in lymphoid follicles. The monoclonal antibodies of the present invention are useful for treating follicular lymphomas, multiple myeloma as well as autoimmune diseases.

Abstract: The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C/C8, 3C/G4, and 4H84. 2C/C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C/G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

Abstract: The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.

Abstract: Monoclonal antibodies, in particular 33.28 and 31.1, and chimeric antibodies, in particular mouse/humans chimeric Chi #1 specific for glycoprotein antigens of colon carcinoma-associated antigens which are immunogenic in humans, are disclosed. Such antibodies, and fragments and derivatives thereof, are useful in immunodiagnosis and immunotherapy of human colon, breast, and ovarian cancer, and for purification of antigens which can serve as immunotherapeutic agents. Methods of detecting the colon carcinoma-associated antigen in a sample, and methods for treating subjects having colon, breast, and ovarian carcinomas are disclosed.