Abstract: The present invention relates to novel metalloproteinase-like proteins. In particular, isolated nucleic acid molecules are provided encoding the human TACE-like and matrilysin-like proteins. TACE-like and matrilysin-like 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 TACE-like and matrilysin-like activity. Also provided are diagnostic methods for detecting cancer and therapeutic methods for cancer and other disorders characterized by an over or under production of these metalloproteinases.

Abstract: MAT II &bgr; subunit proteins and cDNAs encoding the same. Recombinant host cells, recombinant nucleic acids and recombinant proteins are also disclosed, along with methods of producing each. Isolated and purified antibodies to MAT II &bgr; subunit homologs, and methods of producing the same, are also disclosed. MAT II &bgr; subunit gene products are characterized as having activity in modulating the biological activity of MAT II. Thus, therapeutic methods involving these activities are also disclosed.

Abstract: The present invention relates to polynucleotide and polypeptide molecules, and variants thereof, for MAPP, a novel member of the Disintegrin Proteases. The polypeptides, and polynucleotides encoding them, are cell-cell interaction modulating and may be used for delivery and therapeutics. The present invention also includes antibodies to the MAPP polypeptides.

Abstract: Compositions and methods involving agents that specifically bind to methylthioadenosine phosphorylase (MTAP) protein are disclosed. Illustrative compositions comprise binding agents that bind to human MTAP protein in biological samples, including embedded samples. The binding agents are useful, for example, in the detection, prognosis, and/or treatment of MTAP deficient cancers. Also disclosed are kits containing the reagents necessary for the detection of human MTAP protein in an embedded sample.

Abstract: The invention relates to an isolated nucleic acid molecule encoding a caspase-14 polypeptide or functional fragment thereof, a vector that contains the nucleic acid molecule and a host cell that contains the vector. The invention also relates to an isolated gene encoding caspase-14, as well as functional fragments thereof. The gene or nucleic acid molecule can include single or double stranded nucleic acids corresponding to coding or non-coding strands of the caspase-14 nucleotide sequence. Isolated caspase-14 polypeptides or functional fragments thereof are also provided, as are antibodies that specifically bind thereto. In addition, the invention relates to methods of identifying compounds that modulate caspase-14 activity.

Abstract: The present invention provides a monoclonal antibody which can specifically and efficiently recognize hTERT protein; which is the catalytic subunit of telomerase, and provides a human chimeric antibody, a CDR grafted antibody, a single chain antibody, and a disulfide stabilized antibody each containing the monoclonal antibody. In addition, the present invention provides a method for detecting/quantitating hTERT protein using these antibodies, and provides diagnosis method, diagnosis agent, and therapeutic agent, for diseases, such as cancer, in which telomerase is involved using these antibodies.

Abstract: Chimeric, humanized and other RANK-L mAbs, derived from high affinity neutralizing mAbs, pharmaceutical compositions containing same, methods of treatment and diagnostics are provided.

Abstract: A monoclonal antibody having high affinity for NT-proBNP is described. The monoclonal antibody is prepared against a synthetic peptide having the Sequence ID No. 1 The monoclonal antibody can be used as a reagent in an immunoassay system to identify blood, serum or plasma levels of NT-proBNP. Such an immunoassay system can be used for diagnosing and quantifying congestive heart failure.

Abstract: The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

Abstract: The present invention relates to a novel member of the plasminogen activator inhibitor protein family. In particular, isolated nucleic acid molecules are provided encoding the pancreas-derived plasminogen activator inhibitor protein. Pancreas-derived plasminogen activator inhibitor polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to methods for treating physiologic and pathologic disease conditions and diagnostic methods for detecting pathologic disorders.

Abstract: Invention relates to antibodies with a specificity to an abnormally truncated form of tau protein which is conformationally different from normal tau and does not bind to normal tau protein, conformationally different tau proteins (“tauons”) and diagnostic and therapeutical aspects in relation to Alzheimer's disease and related tauopathies.

Abstract: The invention concerns human trkB and trkC receptors and their functional derivatives. The invention further concerns immunoadhesins comprising trk receptor sequences fused to immunoglobulin sequences.

Abstract: Human Inositol Monophosphatase H1 polynucleotide and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptide by recombinant techniques and utilizing such polypeptide for therapeutic purposes, for example, screening and designing compounds capable of inhibiting hIMP-H1 and mapping genetic diseases are disclosed. Further disclosed are antibodies against hIMP-H1 polypeptides and methods for producing such antibodies and utilizing such antibodies for therapeutic or diagnostic purposes. Also disclosed is antagonists against such polypeptide along with procedures for using such antagonists for therapeutic purposes, for example, for treating psychotic and depressive disorders. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

Abstract: The present invention relates to phosphatase polypeptides, nucleotide sequences encoding the phosphatase polypeptides, as well as various products and methods useful for the diagnosis and treatment of various phosphatase-related diseases and conditions. Through the use of a bioinformatics strategy, mammalian members of the MAP kinase hosphatase PTP's and STP's have been identified and their protein structure predicted.

Abstract: The invention relates to a monoclonal antibody specifically recognizing lipocalin-type prostaglandin D synthase (L-PGDS), a hybridoma producing said monoclonal antibody, methods for detection of L-PGDS or diseases by said monoclonal antibody, and a kit for detection of L-PGDS by said monoclonal antibody. According to the invention, there is provided a monoclonal antibody specific to L-PGDS.

Abstract: A novel gene (designated 213P1F11) and its encoded protein, and variants thereof, are described wherein 213P1F11 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 213P1F11 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 213P1F11 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 213P1F11 can be used in active or passive immunization.

Abstract: A novel gene (designated 238P1B2) and its encoded protein, and variants thereof, are described wherein 238P1B2 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 238P1B2 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 238P1B2 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 238P1B2 can be used in active or passive immunization.

Abstract: A novel gene (designated 162P1E6) and its encoded protein, and variants thereof, are described wherein 162P1E6 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 162P1E6 provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 162P1E6 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 162P1E6 can be used in active or passive immunization.

Abstract: The present invention features a method for treatment of an organism having a disease or condition characterized by an abnormality in a signal transduction pathway, wherein the signal transduction pathway includes a PYK2 protein. The invention also features methods for diagnosing such diseases and for screening for agents that will be useful in treating such diseases. The invention also features purified and/or isolated nucleic acid encoding a PYK2 protein.

Abstract: A novel anti-human tenascin ST2146 monoclonal antibody is described endowed with high affinity for the native antigen and high tumor selectivity. The cST2146 hybridoma is stably producing the antibody in high density culture conditions and is suitable for the industrial development of ST2146-based products. ST2146 exhibits properties exploitable for both therapeutic and diagnostic applications.

Abstract: The object of the present invention is to provide a method for more accurately assaying the enzyme activities of mCK isozymes and a method for separately assaying the enzyme activities of CK isozymes by separately assaying the enzyme activities of ubiquitous mCK (umCK) and sarcomeric mCK (smCK).

Abstract: A novel gene (designated 193P1E1B) and its encoded protein, and variants thereof, are described wherein 193P1E1B exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, 193P1E1B provides a diagnostic, prognostic, prophylactic and/or therapeutic target for cancer. The 193P1E1B 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 191P1E1B can be used in active or passive immunization.

Abstract: The invention discloses two newly-discovered Flt3 phosphorylation sites, tyrosine 589 (Tyr589) and tyrosine 591 (Tyr591) in the intracellular domain, and provides antibodies, both polyclonal and monoclonal, that selectively bind to Flt3 when phosphorylated at these novel sites. Also provided are assays utilizing these reagents, including methods for determining the phosphorylation of Flt3 in a biological sample, selecting a patient suitable for Flt3 inhibitor therapy, profiling Flt3 activation in a test tissue, and identifying a compound that modulates phosphorylation of Flt3 in a test tissue, by using a detectable reagent, such as the disclosed antibodies, that binds to Flt3 when phosphorylated at Tyr589 or Tyr591. The sample or test tissue may be taken from a subject suspected of having cancer, such as acute myelogenous leukemia (AML).

Abstract: Chimeric, humanized and other RANK-L mAbs, derived from high affinity neutralizing mAbs, pharmaceutical compositions containing same, methods of treatment and diagnostics are provided.

Abstract: The identification and characterization of risk factors and their molecular implications in the pathophysiology of human diseases such as cancer is essential for designing efficient diagnostic assays and therapeutic compounds. Estrogenic steroids, under normal physiological conditions, have been shown to play a critical function in several tissues. The response of such a variety of tissues to estrogen stimulation can explain in part its active role in the development and progression of different human diseases, particularly Breast Cancer. Searching for estrogen-responding cellular factors in parental cells of primary human breast carcinomas obtained from tumor biopsies an isoenzyme of putative Leucine Aminopeptidase (LAPase; EC 3.4.11.1) was idenditifed. Results have demonstrated that this marker is found to be elevated in the sera of women with invasive ductal and metastatic carcinomas. A monoclonal antibody against this cellular marker have been produced.

Abstract: The present invention provides a novel keratinocyte-specific secreted protein identified as keptin that inhibits an inflammatory response and activity of proteinase, as well as methods for treating hyperproliferative inflammatory skin diseases using proteinase inhibitor keptin. The invention provides a therapeutic agent for treating psoriasis and squamous cell carcinomas and other inflammatory skin related diseases.

Abstract: Chimeric, humanized and other RANK-L MAbs, derived from high affinity neutralizing MAbs, pharmaceutical compositions containing same, methods of treatment and diagnostics are provided.

Abstract: A monoclonal antibody binding selectively to neurosin obtained from hybridomas, in particular, strain 2B2-6 and strain S2E5 showing stable proliferation ability. These hydridomas are obtained by fusing mouse spleen cells having a high antibody titer against neurosin with mouse-derived myeloma cells, screening fused cells being highly reactive with neurosin, and thus producing an antibody binding specifically to neurosin. By using this antibody, various diseases in which neurosin participates can be diagnosed.

Abstract: The present invention provides a monoclonal antibody which can specifically and efficiently recognize hTERT protein; which is the catalytic subunit of telomerase, and provides a human chimeric antibody, a CDR grafted antibody, a single chain antibody, and a disulfide stabilized antibody each containing the monoclonal antibody. In addition, the present invention provides a method for detecting/quantitating hTERT protein using these antibodies, and provides diagnosis method, diagnosis agent, and therapeutic agent, for diseases, such as cancer, in which telomerase is involved using these bodies.

Abstract: DNA sequences encoding a novel human intercellular adhesion molecule polypeptide (designated “ICAM-R”) and variants thereof are disclosed along with methods and materials for production of the same by recombinant procedures. Binding molecules specific for ICAM-R and variants thereof are also disclosed as useful in both the isolation of ICAM-R from natural cellular sources and the modulation of ligand/receptor binding biological activities of ICAM-R.

Abstract: A novel gene (designated 103P2D6) and its encoded protein are described. 103P2D6 is not expressed in normal adult tissue, but is highly expressed in prostate tissue xenografts, providing evidence that it is turned on in prostate cancer. 103P2D6 is also expressed in some fetal tissues, and in breast, bladder, lung, bone, colon, pancreatic, testicular, cervical and ovarian cancers. Consequently, 103P2D6 provides a diagnostic and/or therapeutic target for cancers, and the 103P2D6 gene or fragment thereof, or its encoded protein or a fragment thereof can be used to elicit an immune response.

Abstract: Anti-Fas antibodies which are cross-reactive with mouse and human Fas and are useful in the treatment of conditions attributable to abnormalities in the Fas/Fas ligand system.

Abstract: The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

Abstract: A fibronectin type III (Fn3) polypeptide monobody, a nucleic acid molecule encoding said monobody, and a variegated nucleic acid library encoding said monobody, are provided by the invention. Also provided are methods of preparing a Fn3 polypeptide monobody, and kits to perform said methods. Further provided is a method of identifying the amino acid sequence of a polypeptide molecule capable of binding to a specific binding partner (SBP) so as to form a polypeptide:SSP complex, and a method of identifying the amino acid sequence of a polypeptide molecule capable of catalyzing a chemical reaction with a catalyzed rate constant, kcat, and an uncatalyzed rate constant, kuncat, such that the ratio of kcat/kuncat is greater than 10.

Abstract: A protein obtainable from a non pathogenic microorganism, said protein having mucosa binding promoting activity and a molecular weight of 20-40 kD is disclosed. Application of such a protein or a peptide derived therefrom in a method of screening non pathogenic microorganisms for a microorganism capable of specifically binding mucosa, said method comprising detection in a manner known per se of the presence of a particular protein on or in a microorganism or in a culture of microorganisms, said particular protein being the already defined protein. Kits suitable for such a screening method are also disclosed.

Abstract: The invention provides not only a smooth muscle growth inhibitory composition and a composition for inhibiting expression of adhesion molecules in vascular endothelial cells, each comprising the adipose tissue-specific secretory factor apM1 as an active ingredient, but also a method for diagnosis of arteriosclerosis which comprises assaying apM1 in a sample, an antibody against apM1, and a diagnostic kit for arteriosclerosis which comprises the antibody as an active component, all of which contribute to the elucidation of obesity-related genes and corresponding expression products which are useful for the etiologic exploration and establishment of therapeutic modalities for various obesity-related diseases, particularly arteriosclerosis inclusive of angina pectoris and myocardial infarction. By utilizing the information thus obtained, therapeutic and diagnostic methods for various diseases can be established.

Abstract: The present invention provides compositions including polypeptides useful for regulating the cell cycle, proliferation, tumorigenesis, and genomic stability, mutants of such polypeptides useful in identifying abnormal cells and diagnosing disease, antibodies useful for identifying the polypeptides, and polynucleotides that encode the polypeptides.

Abstract: The invention relates to a monoclonal antibody which forms an immunological complex with an epitope of an antigen belonging to normal human tau protein as well as abnormally phosphorylated human tau protein, with said tau protein being liable to be obtained from a brain homogenate, itself isolated from human cerebral cortex. The monoclonal antibodies of the invention can be used to detect tau and abnormally phosphorylated tau in brain extracts and in unconcentrated cerebrospinal fluid.

Abstract: A peptide from 6 to 100 amino acids long, including an amino acid sequence depicted by one of a) Val-Arg-Thr-Pro-Pro (amino acid 229-233; human tau numbering, SEQ ID NO 2) wherein the peptide is able to form an immunological complex with the monoclonal antibody AT180 produced by the hybridoma deposited at the ECACC on Dec. 22, 1992 under No.92122204 and b) Pro-Lys-Thr-Pro-Pro (amino acid 179-183; human tau numbering, SEQ ID NO 3) wherein the peptide is able to form an immunological complex with the monoclonal antibody AT270 produced by the hybridoma deposited at the ECACC on Jul. 7,1993 under No.93070774, with Thr being phosphorylated. A method of detecting PHF-tau protein one of the peptides is also disclosed.

Abstract: The present invention provides methods and compositions for regulating ubiquitination in a cell. In particular, the present invention provides purified polypeptides comprising an ubiquitination-regulating domain. The invention also provides methods of using such polypeptides for screening for agents, for producing antibodies, and for treatment of diseases, e.g., proliferative diseases, neurodegenerative diseases, autoimmune diseases, metabolic disease and developmental abnormalities. The invention further provides antibodies that bind an ubiquitination-regulating domain and agents and antibodies that regulate ubiquitination in cells, e.g., by modulating the interaction between a TSG101 protein and an MDM2 protein.

Abstract: A method for determining a soluble human ST2 in a sample conveniently at a high sensitivity and an assay kit are provided. By an immunological method comprising a step for bringing a sample into contact with an immobilized antibody formed by binding to an insoluble support a first anti-human ST2 antibody which binds specifically to a non-denatured human ST2, a step for labelling a first reaction product generated in the previous step by reacting said first reaction product with a second anti-human ST2 antibody which binds specifically to a non-denatured human ST2 by recognizing a site different from the site on ST2 where said first anti-human ST2 antibody binds and which is labelled with a label, and a step for determining the amount of the label on said first reaction product which has been labelled, a soluble human ST2 in a sample is determined. In addition, a recombinant ST2 is employed as a standard to prepare a calibration curve, based on which the ST2 in a sample is quantified.

Abstract: A human inhibitor of apoptosis polypeptide and DNA (RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polypeptide for the treatment of degenerative diseases, rheumatoid arthritis, septic shock, as an antiviral defense mechanism and to prevent the death of cells during trauma and strokes. Antagonists against such polypeptides and their use as a therapeutic to promote cell development, kill viral infections, promote tissue differentiation and development and maintain tissue homeostasis are also disclosed (tumors). Diagnostic methods for detecting mutations in the nucleic acid sequence encoding hIAP-1 protein are also disclosed.

Abstract: The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing.

Abstract: Anti-Fas antibodies which are cross-reactive with mouse and human Fas and are useful in the treatment of conditions attributable to abnormalities in the Fas/Fas ligand system.

Abstract: The invention provides antibodies to a membrane protease complex, consisting of two homodimers of seprase and dipeptidyl peptidase IV (DPPIV), obtained from human cell membranes. The antibodies specifically bind the DPPIV protease of the seprase-DPPIV complex that resides on cell surface invadopodia at the leading edge of angiogenic endothelia, migratory fibroblasts, and invading cancer cells, while failing to react with resting cells in adjacent human tissues and blood vessels. These antibodies block interaction of collagen matrix with the seprase-DPPIV complex in the invasive cells during angiogenesis and cancer spreading but not that with other endothelia or tumor cells. The invention further provides methods of using DPPIV antagonists to inhibit capillary sprouting, angiogenesis and cancer invasion in tumor tissues and metastases. Also provided are therapeutic compositions comprising DPPIV antagonists.

Abstract: The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts transformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains.

Abstract: A novel monoclonal antibody against glyceraldehyde-3-phosphate dehydrogenase (GAPDH), its use and a hybridoma strain NCK-J24 which produces the antibody.

Abstract: Monoclonal antibodies have been generated that bind to human sialoadhesion factor-2.

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: Nucleic acid compositions encoding polypeptide products with diglyceride acyltransferase activity, as well as the polypeptide products encoded thereby and methods for producing the same, are provided. The subject polypeptide and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications, as well as in treatment therapies and in the production of triacylglycerols.