Abstract: The present invention relates to a method for the early diagnosis of carcinomas and their preliminary stages, which comprises determining the overexpression of a cell cycle regulatory protein in a body sample. The invention also provides a kit usable for this purpose.

Abstract: The present invention relates to nucleotide sequences of Serrate genes, and amino acid sequences of their encoded proteins, as well as derivatives (e.g., fragments) and analogs thereof. In a specific embodiment, the Serrate protein is a human protein. The invention further relates to fragments (and derivatives and analogs thereof) of Serrate which comprise one or more domains of the Serrate protein, including but not limited to the intracellular domain, extracellular domain, DSL domain, cysteine rich domain, transmembrane region, membrane-associated region, or one or more EGF-like repeats of a Serrate protein, or any combination of the foregoing. Antibodies to Serrate, its derivatives and analogs, are additionally provided. Methods of production of the Serrate proteins, derivatives and analogs, e.g., by recombinant means, are also provided. Therapeutic and diagnostic methods and pharmaceutical compositions are provided.

Abstract: A method for intracellular delivery of drugs or other agents for diagnosis and therapy of malignancies or immune-mediated or inflammatory conditions. A targeting moiety of an antibody and the ligand-binding region of a selected cytokine receptor is used. The targeting moiety targets surface antigen on a specific cell population. The targeting moiety is administered to a subject, and then, after a specified interval, therapeutic or diagnostic agents linked to the cognate cytokine are given. The invention provides rapid, efficient internalization of the cytokine receptor antibody/antigen complexes. Targeting of a high-level cell surface antigen with such bispecific fusion molecules substantially increases the number of cytokine receptors over their low background level.

Abstract: A reshaped human anti-HM 1.24 antibody comprising: (A) an L chain comprising (1) the C region of a human L chain, and (2) the V region of an L chain comprising the FR of a human L chain and the CDR of the L chain of a mouse anti-HM 1.24 monoclonal antibody; and (B) an H chain comprising (1) the C region of a human H chain, and (2) the V region of an H chain comprising the FR of a human H chain and the CDR of the H chain of a mouse anti-HM 1.24 monoclonal antibody. Since most of this reshaped human antibody is derived from human antibody and the CDR has a low antigenicity, the reshaped human antibody of the present invention has a low antigenicity and, therefore, is expected to be-used for medical treatment.

Abstract: The present invention relates to novel members of the Tumor Necrosis Factor family of receptors. The invention provides isolated nucleic acid molecules encoding human TR11, TR11SV1, and TR11SV2 receptors. TR11, TR11SV1, and TR11SV2 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 TR11, TR11SV1, and TR11SV2 receptor activity. The present invention further relates to antibodies that specifically bind TR11, TR11SV1, and/or TR11SV2. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of TR11, TR11SV1, and TR11SV2 receptors. Further provided are therapeutic methods for treating disease states related to aberrant proliferation and differentiation of cells which express the TR11, TR11SV1, and TR11SV2 receptors.

Abstract: Disclosed herein are therapeutic treatment protocols designed for the treatment of B cell lymphoma. These protocols are based upon therapeutic strategies which include the use of administration of immunologically active mouse/human chimeric anti-CD20 antibodies, radiolabeled anti-CD20 antibodies, and cooperative strategies comprising the use of chimeric anti-CD20 antibodies and radiolabeled anti-CD20 antibodies.

Abstract: A humanized monoclonal antibody, comprising the complementarity-determining regions of a parental murine Class III, anti-CEA monoclonal antibody engrafted to the framework regions of a heterologous antibody, wherein the humanized monoclonal antibody retains the binding specificity of, but is less immunogenic in a heterologous host than, the parental murine monoclonal antibody A preferred murine Class III, anti-CEA monoclonal antibody is the MN-14 antibody and the preferred heterologous antibody is from a human. Also provided are DNA constructs and vectors for producing the humanized monoclonal antibodies, and diagnostic and therapeutic conjugates using same.

Abstract: Methods for detecting allelic variants of the myostatin (growth and differentiation factor-8) gene are provided. Specifically provided are methods of identifying subjects having or having a predisposition for increased muscle mass as compared to subjects having wild-type myostatin. Increased muscle mass is particularly desirable for identification of animals used to produce food products, including bovine, porcine, ovine, avian and piscine species.

Abstract: An antibody that binds to a specific urogenital carcinoma tumor liberated protein (TLP) epitope, wherein the TLP comprises GlyProProGluValGlnAsnAlaAsn, is described. Also described are kits comprising the antibody, and methods of identifying TLP, and methods for diagnosing urogenital carcinoma.

Abstract: The present invention provides DNA encoding a TADG-15 protein as well as a TADG-15 protein. Also provided is a vector capable of expressing the DNA of the present invention adapted for expression in a recombinant cell and regulatory elements necessary for expression of the DNA in the cell. The present invention further provides for methods of inhibiting TADG-15 expression and/or protease activity methods of detecting TADG-15 mRNA and/or protein and methods of screening for TADG-15 inhibitors. Additionally, the present invention provides for cell-specific targeting via TADG-15 and methods of vaccinating an individual against TADG-15. The methods described are useful in the diagnosis. treatment and prevention of cancer particularly breast and ovarian cancer.

Abstract: This invention concerns a family of chimeric antibodies with high affinities to a high molecular weight, tumor-associated sialylated glycoprotein antigen (TAG-72) of human origin. These antibodies have (1) high affinity animal VH and VL sequences which mediate TAG-72 binding and (2) human CH and CL regions. They are thought to produce significantly fewer side-effects when administered to human patients by virtue of their human CH and CL antibody domains. The nucleotide and amino acid sequences of VH&agr;TAG VH, CC46 VH, CC49VH, CC83 VH, and CC92 VH, and CC49VL, CC83 VL, and CC92 VL idiotype sequences are disclosed, as well as in vivo methods of treatment and diagnostic assay using these chimeric antibodies.

Abstract: This invention provides novel methods for monitoring urine for type II collagen fragment using a combination of a capture antibody and a detection antibody, such that type II collagen is distinguished from other collagen fragments.

Abstract: Antibody variants of parent antibodies are disclosed which have one or more amino acids inserted in a hypervariable region of the parent antibody and a binding affinity for a target antigen which is at least about two fold stronger than the binding affinity of the parent antibody for the antigen.

Abstract: More than 90% of mutations found in the p53 protein produce a conformational change in p53 which results in the exposure of an epitope, which is otherwise hidden in the hydrophobic core of the molecule. A single chain antibody (scFv) which specifically recognizes this common mutant epitope in mutant p53 but not in wild type p53 is disclosed. Also described are a DNA molecule encoding the scFv, pharmaceutical compositions comprising the antibody and methods of treatment using the pharmaceutical compositions.

Abstract: A process for the production of humanized chimera antibody, wherein the chimera antibody is produced easily without changing any of the amino acids of its mouse antibody variable region, which comprises the steps of: (1) constructing a cassette vector by inserting a cDNA coding for a heavy chain constant region of human antibody into an expression vector for animal cell use and establishing a cloning site in the upstream region of the heavy chain constant region of said cassette vector for inserting a cDNA which encodes a heavy chain variable region of nonhuman animal antibody; (2) digesting a cDNA coding for the heavy chain variable region of nonhuman animal antibody with restriction enzymes; (3) inserting said cDNA coding for the heavy chain variable region of nonhuman animal antibody into the cassette vector, using a synthetic DNA which comprises a base sequence corresponding to the 5′-end side of said heavy chain constant region of human antibody and a base sequence corresponding to the 3′-end

Abstract: Methods of determining collagen degradation in vivo, by quantitating the concentration of a peptide in a body fluid, the peptide being a C-terminal type II collagen telopeptide containing a hydroxylysyl pyridinoline cross-link or a type III collagen telopeptide containing a hydroxylysyl pyridinoline cross-link. Suitable methods include immunometric assays, fluorometric assays, and electrochemical titrations for quantitation. The structures of specific peptides having cross-links and kits for quantitating these peptides in a body fluid are described.

Abstract: This invention pertains to a method for treating ulcerative colitis. Specifically, the method comprises orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of an antibody which binds to a tropomyosin isoform associated with ulcerative colitis. In another embodiment, the invention pertains to a method for treating ulcerative colitis in a human which comprises the steps of (a) obtaining from a human a colon epithelial cell extract containing a tropomyosin isoform associated with ulcerative colitis; (b) purifying the tropomyosin isoform until the tropomyosin isoform is substantially homogeneous; (c) developing an antibody which binds to the tropomyosin isoform; and (d) orally or rectally administering to a human having ulcerative colitis a therapeutically effective amount of the antibody to bind to the tropomyosin isoform associated with ulcerative colitis.

Abstract: A novel anti-polyethylene glycol monoclonal antibody and its preparation are disclosed. Such an antibody can be used for determining polyethylene glycol concentration in vitro or accelerating the clearance of a polyethylene glycol containing compound from the blood circulation in the human body thereby reducing the toxicity associated with the polyethylene glycol containing conjugate. The antibody is particularly useful in cancer therapy where the therapeutic agent is selectively delivered to the tumor by increasing the tumor/blood ratio of the polyethylene glycol containing compound.

Abstract: This invention is a method of identifying the presence of, and monitoring, a disease state in a mammal which is associated with degradation of connective tissue in the mammal. The method detects and determines whether diagnostically or prognostically significant levels of YKL-40 protein and/or YKL-40 peptide are present in a biological sample. The method can be used, for example, to identify the presence of inflammatory or degenerative joint disease or degeneration of connective tissue in organs. Serum YKL-40 levels as detected and quantified by the inventive method are also suggestive of the prognosis for the length of survival in breast cancer patients following recurrence and/or metastasis of their cancers. The figure shows the elution position of substantially pure serum YKL-40 on a gel filtration column.

Abstract: Described is a gene and its encoded secreted tumor antigen, termed 36P6D5, and to diagnostic and therapeutic methods and compositions useful in the management of various cancers which express 36P6D5, particularly including cancers of the bladder, kidney, prostate, breast, colon, ovary and pancreas.

Abstract: Antibodies for specifically detecting pathogenic prions of human origin, and methods for detecting pathogenic prions, are described. In particular, a conformation-dependent immunoassay method for detecting pathogenic prion proteins in a sample of a body fluid, containing a PrP protein, which contains a first, natural, non-pathological conformation, i.e. PrPc, and a second, pathological conformation, i.e.

Abstract: Compounds are disclosed having the general formula R1-X-R2, wherein R1 and R2 are biologically active groups, at least one of which is polypeptidic. X is a non-peptidic polymeric group. R1 and R2 may be the same or different. Preferred R1 and R2 groups are TNF inhibitors.

Abstract: A method of characterizing a biological sample is provided. The method includes the steps of contacting the sample with at least two receptor molecules to generate a first pattern of reactivity and comparing that pattern to a second reactivity pattern generated by a known sample and indicative of oncogene expression.

Abstract: An isolated polypeptide having at least 80% sequence identity to the sequence SEQ ID NOS:2, 4, 6, 8, 10, 12, 14 or 16, and polynucleotides encoding the same, are useful for modulating angiogenesis.

Abstract: The invention provides a novel prostate cell-surface antigen, designated Prostate Stem Cell Antigen (PSCA), which is widely over-expressed across all stages of prostate cancer, including high grade prostatic intraepithelial neoplasia (PIN), androgen-dependent and androgen-independent prostate tumors. The invention also provides a method for detecting a Prostate Stem Cell Antigen (PSCA) protein of bone (SEQ ID NO:2), comprising obtaining a sample; contacting the sample with an antibody that recognizes and binds the PSCA protein; and, detecting binding of the antibody with the PSCA protein in the sample.

Abstract: The invention concerns an antibody composition which inhibits the binding of interleukin 2 to its high affinity receptor and contains (1) monoclonal antibodies against the &agr; chain of the interleukin 2 receptor and (2) monoclonal antibodies against the &bgr; chain of the interleukin 2 receptor, as well as a pharmaceutical agent which contains the antibody composition according to the present invention.

Abstract: A reshaped human anti-HM 1.

Abstract: The invention provides for the production of several humanized murine antibodies specific for the antigen Lewis Y, which is recognized by the murine antibody Lewis Y. The Lewis Y antigen is expressed in normal tissues but the level of expression is higher in certain tumor types so that the antigen can be used as a marker for cells of some breast, colon, gastric, esophageal, pancreatic, duodenal, lung, bladder and renal carcinomas and gastric and islet cell neuroendocrine tumors. The invention also provides for numerous polynucleotide encoding humanized Lewis Y specific antibodies, expression vectors for producing humanized Lewis Y specific antibodies, and host cells for the recombinant production of the humanized antibodies. The invention also provides methods for detecting cancerous cells (in vitro and in vivo) using humanized Lewis Y specific antibodies. Additionally, the invention provides methods of treating cancer using humanized Lewis Y specific antibodies.

Abstract: This invention provides novel chimeric molecules that specifically binds a tumor cell bearing a c-erbB-2. The chimeric molecules comprise an effector molecule attached to a C6 antibody that specifically binds to c-erbB-2. The chimeric molecules can specifically target and deliver effector molecules to cells overexpressing c-erb-B2.

Abstract: Disclosed is an antibody that binds to a protein found on normal and cancerous prostate cells, but not found on nonprostate cells and a hybridoma that produces the antibody to the prostate-specific protein. Also disclosed are antibodies conjugated to labels or cytotoxic moieties.

Abstract: An immunoassay kit for the quantification of degradation products of carboxy-terminal telopeptides of type I collagen in a human serum sample, including an antibody that is characterized by binding to at least one peptide derived from the carboxy-terminal telopeptide domain of type I collagen and isolatable from a urine sample of a patient with active Patet's disease.

Abstract: This invention provides a method of inhibiting HCV infection of a cell susceptible to HCV infection which comprises contacting the cell with an amount of a compound effective to inhibit binding of an HCV envelope glycoprotein to a DC-SIGN protein present on the surface of the cell, so as to thereby inhibit HCV infection of the cell susceptible to HCV infection. This invention provides a method of inhibiting HCV infection of a cell susceptible to HCV infection which comprises contacting the cell with an amount of a compound effective to inhibit binding of an HCV envelope glycoprotein to a DC-SIGNR protein present on the surface of the cell, so as to thereby inhibit HCV infection of the cell susceptible to HCV infection.

Abstract: Novel humanized monoclonal antibodies, humanized antibody fragments, and derivatives thereof which specifically bind TAG-72 are provided as well as methods for their manufacture. These humanized antibodies are useful in the treatment of cancers which express TAG-72 as well as for diagnostic purposes, e.g., for in vivo imaging of tumors or cancer cells which express TAG-72.

Abstract: Humanized antibody molecules (HAMs) are described having specificity for human milk fat globule and having an antigen binding site wherein at least one of the complementarity determining regions (CDRs) of the variable domains is derived from the mouse monoclonal antibody CTMO1 and the remaining immunoglobulin-derived parts of the HAM are derived from a human immunoglobulin. The HAMs may be chimeric humanized antibodies or CDR-grafted humanized antibodies and are preferably produced by recombinant DNA techniques. The HAMs are useful for in vivo diagnosis and therapy.

Abstract: Humanized and chimeric monoclonal antibodies that recognize EGF-R and comprise an artificial sequence at least of the FRs of the heavy chain variable region of a human immunoglobulin. The humanized and monoclonal antibodies may comprise variable regions of non-human origin and constant regions of human origin with amino acid substitutions with the variable regions and/or framework regions. Use of the antibodies for therapeutical and diagnostic purposes is also disclosed.

Abstract: A therapeutic agent for lymphatic tumors (excluding myeloma) comprising as an active ingredient an antibody that specifically binds to a protein having the amino acid sequence as set forth in SEQ ID NO:1 and SEQ ID NO:5 and that has a cytotoxic activity.

Abstract: Novel humanized monoclonal antibodies, humanized antibody fragments, and derivatives thereof which specifically bind TAG-72 are provided as well as methods for their manufacture. These humanized antibodies are useful in the treatment of cancers which express TAG-72 as well as for diagnostic purposes, e.g., for in vivo imaging of tumors or cancer cells which express TAG-72.

Abstract: Humanized antibodies are described which are specific to an Fc receptor (FcR). The humanized antibodies have at least a portion of a complementarity determining region (CDR) derived from a non-human antibody, e.g., murine, with the remaining portions being human in origin. The humanized antibodies can be used therapeutically as is or formulated as bifunctional molecules or immunotoxins.

Abstract: This invention provides tumor metastasis-inhibiting monoclonal antibodies, mAb 41-2, mAb 50-6 and mAb 1A-5. The antigen recognized by mAb 50-6 and mAb 1A-5 has been identified as the PETA-3 antigen. The antigen recognized by mAb 41-2 has been identified as a novel tumor metastasis-associated antigen. Compositions and methods are provided that are useful for treating and diagnosing metastatic tumors.

Abstract: A humanized chimera antibody, a pharmaceutical composition comprising a humanized chimera antibody and a pharmaceutically acceptable carrier, and a method of treating cancer which comprises administering to a patient a pharmaceutically acceptable amount of the humanized chimera antibody, are disclosed.

Abstract: Novel composite and humanized anti-TAG-72 monoclonal antibodies, antibody fragments, and derivatives thereof using human subgroup IV kappa light chain framework regions.

Abstract: The invention provides specific binding members, for example in the form of antibody variable domains, based on the CDR3 sequences of the antibody VH regions of SL15 (SEQ ID NO:4) and JT182 (SEQ ID NO:10). The antibodies have strong neutralizing activity for TGF&bgr;1 and are useful in treating conditions associated with excess TGF&bgr;1 activity, such as fibrosis, immune responses and tumor progression.

Abstract: Novel humanized monoclonal antibodies, humanized antibody fragments, and derivatives thereof which specifically bind TAG-72 are provided as well as methods for their manufacture. These humanized antibodies are useful in the treatment of cancers which express TAG-72 as well as for diagnostic purposes, e.g., for in vivo imaging of tumors or cancer cells which express TAG-72.

Abstract: A method for diagnosing a tumor in the central nervous system of a mammal is carried out by contacting a bodily fluid from the mammal with a ligand which binds to inter-alpha trypsin inhibitor.

Abstract: A method for purifying a polypeptide by ion exchange chromatography is described which involves changing the conductivity and/or pH of buffers in order to resolve a polypeptide of interest from one or more contaminants.

Abstract: The present invention relates generally to immunointeractive molecules and their use inter alia in the detection and/or purification of T-cell antigen binding molecules (TABMs). The ability to determine the presence and levels of particular TABMs provides a useful diagnostic procedures for a variety of disease conditions.

Abstract: The present invention relates to antibody composition that are useful in preparing enriched cell preparations such as human hematopoietic progenitor cells and stem cells and non-hematopoietic tumor cells. The invention also relates to kits for carrying out the processes and to the cell preparations prepared by the processes.

Abstract: The present invention relates to screening methods for diagnosis, prognosis, or susceptibility to cancer in a subject by means of detecting the presence of serum autoantibodies to specific annexin protein antigens in sera from subjects. The present invention also provides screening methods for diagnosis and prognosis of cancer in a subject by means of detecting increased expression levels of annexin proteins in biological samples of the subject. The method of the invention can also be used to identify subjects at risk for developing cancer. The method of the invention involves the use of subject derived biological samples to determine the occurrence and level of expression of annexin proteins or expression of annexin derived peptides or antigens, and/or the occurrence and level of circulating autoantibodies to specific annexin protein antigens. The present invention further provides for kits for carrying out the above described screening methods.

Abstract: The invention relates to a therapeutic agent for cachexia comprising, as an active ingredient, a substance capab;le of inhibiting the binding between a parathyroid hormone related protein (PTHrP) and a receptor thereof.