Abstract: The present invention relates to a method for stabilizing chimeric immunoglobulins or immunoglobulin fragments. Furthermore, the invention also provides a stabilized anti-EGP-2 scFv fragment.

Abstract: Myc protein is an unevenly distributed intermediate agent for cell proliferation, and activates a gene expression via E.box. Mina53 gene encodes a protein of 53 kDa molecular weight and is present in the nucleoplasm and nucleolus. Mina53 mRNA and protein expression are induced by artificial introduction of c-Myc activity. E.box site is present in the vicinity of the transcription initiation site of mina53 gene, and the expression from mina53 promoter is activated by c-Myc through the medium of E.box. Specific inhibition of mina53 expression in HeLa cells and rat fibroblast cells 3Y1 having high expression c.myc strikingly inhibits cell proliferation. The combination of these results show that mina53 is a Myc target gene and is associated with cell proliferation in mammals.

Abstract: Methods, compositions and kits comprising dimeric antibodies for the treatment of neoplastic, autoimmune or other disorders are provided. The dimeric antibodies of the instant invention may comprise two antibody molecules (H4L4) having the same antigen binding specificity (homodimers) or, alternatively, may comprise two different antibody molecules having binding specificity for two distinct antigens (heterodimers). In preferred embodiments the antibody molecules comprising the dimers are non-covalently associated.

Abstract: This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.

Abstract: Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.

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: 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. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

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: The present invention encompasses monoclonal antibodies that bind to lipoteichoic acid (LTA) of Gram positive bacteria. The antibodies also bind to whole bacteria and enhance phagocytosis and killing of the bacteria in vitro. The invention also provides antibodies having human sequences (chimeric, humanized and human antibodies). The invention also sets forth the variable regions of three antibodies within the invention and presents the striking homology between them.

Abstract: This invention relates to monovalent and multivalent, monospecific binding proteins and to multivalent, multispecific binding proteins. One embodiment of these binding proteins has one or more binding sites where each binding site binds with a target antigen or an epitope on a target antigen. Another embodiment of these binding proteins has two or more binding sites where each binding site has affinity towards different epitopes on a target antigen or has affinity towards either a target antigen or a hapten. The present invention further relates to recombinant vectors useful for the expression of these functional binding proteins in a host. More specifically, the present invention relates to the tumor-associated antigen binding protein designated RS7, and other EGP-1 binding-proteins. The invention further relates to humanized, human and chimeric RS7 antigen binding proteins, and the use of such binding proteins in diagnosis and therapy.

Abstract: The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MART-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.

Abstract: The invention is a method of identifying the presence of a disease state in a mammal which is associated with degradation of connective tissue in the mammal which contains the protein known as YKL-40. The method is a competitive immunoassay for YKL-40. It can be used, for example, to identify the presence of inflammatory or degenerative joint disease and tumor metastasis (to the extent it can be correlated to serum YKL-40 levels). 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.

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 provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G?CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.

Abstract: A method for detecting DNA damage in a tissue sample involves contacting an immobilized biological sample with a labeled ligand which binds to human 53Bp1, and examining the immobilized sample for the presence of a label generated-detectable signal concentrated in foci in said sample. The presence of concentrated foci is indicative of DNA damage and the presence of diffuse signal is indicative of a normal sample. Diagnostic reagents contain a ligand that binds to human 53Bp1 associated with a detectable label. Diagnostic kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. Compositions that inhibit or antagonize the biological activity of 53Bp1 are identified by suitable assays, and are employed in methods of retarding the growth of a cancer cell.

Abstract: A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble A? peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13–28 of the amyloid beta peptide A?.

Abstract: This invention relates to the diagnosis and treatment of cancerous diseases, particularly to the mediation of cytotoxicity of tumor cells; and most particularly to the use of cancerous disease modifying antibodies (CDMAB), optionally in combination with one or more chemotherapeutic agents, as a means for initiating the cytotoxic response. The invention further relates to binding assays which utilize the CDMABs of the instant invention.

Abstract: A monoclonal antibody which recognizes an antigen of a molecular weight of 40 kD or 80 kD on the surface of tumor vessel endothelial cells, hybridomas producing the monoclonal antibody, pharmaceutical agents comprising the monoclonal antibody, as well as pharmaceutical or diagnostic agents comprising a conjugate of the monoclonal antibody and another conjugating molecule.

Abstract: An antibody, or a derivate or a fragment thereof, having a binding structure for a target structure is described. The antibody is displayed in, and on the cell surface of, human gastrointestinal epithelial tumour cells and in a subpopulation of normal human gastrointestinal epithelial cells. Said binding structure comprises the complementarity determining region (CDR) sequences in the light chain comprising essentially the amino acids number 23–33 (CDR1), 49–55 (CDR2), 88–98 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, and the CDR sequences in the heavy chain comprising essentially the amino acids number 158–162 (CDR1), 177–193 (CDR2, 226–238 (CDR3) of the amino acid sequence shown in SEQ ID NO:2, or other binding structures with similar unique binding properties. There is also described a target structure displayed in, or on the surface of tumour cells, vaccine compositions, pharmaceutical compositions as well as methods related to human malignant diseases.

Abstract: This invention provides novel antibodies that specifically bind to the cancer antigen MUC-1. The antibodies are useful targeting moieties for specifically directing imaging agents and various therapeutic moieties to a cancer.

Abstract: Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.

Abstract: The invention concerns a method and a reagent kit for detecting cells in a biological sample using a double-fluorescence technique and the diagnostic and therapeutic application of amino acid sequence-specific antibodies against the urokinase receptor having a high affinity for tumour cell-expressed receptors.

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 neutralising activity for TGF?1 and are useful in treating conditions associated with excess TGF?1 activity, such as fibrosis, immune responses and tumor progression.

Abstract: Disclosed is a formulation for targeting an epitope on an antigen expressed in a mammal. The formulation comprises a pharmaceutically acceptable carrier together with a dimeric biosynthetic construct for binding at least one preselected antigen. The biosynthetic construct contains two polypeptide chains, each of which define single-chain Fv (sFv) binding proteins and have C-terminal tails that facilitate the crosslinking of two sFv polypeptides. The resulting dimeric constructs have a conformation permitting binding of a said preselected antigen by the binding site of each said polypeptide chain when administered to said mammal. The formulation has particular utility in in vivo imaging and drug targeting experiments.

Abstract: An improved method for producing human antibodies in SCID mice is provided. The improvement includes the use of dendritic cells pulsed with antigen-antibody complexes and antigen-antibody complexes as immunizing agents.

Abstract: The invention provides tumor-specific human monoclonal antibodies and functional fragments. Also provided are nucleic acids encoding tumor-specific human monoclonal antibodies and functional fragments. A method for reducing neoplastic cell proliferation is also provided. The method consists of administering an effective amount of a tumor-specific human monoclonal antibody or functional fragment. Also provided is a method of detecting a neoplastic cell in a sample. The method consists of contacting a cell with a tumor-specific monoclonal antibody or functional fragment and detecting the specific binding of the human monoclonal antibody or functional fragment to the sample.

Abstract: Described are novel single-chain multifunctional polypeptides comprising at least two binding sites specific for the CD19 and CD3 antigen, respectively. Further provided are polypeptides, wherein the above-described polypeptide comprises at least one further domain, preferably of pre-determined function. Furthermore, polynucleotides encoding said polypeptides as well as to vectors comprising said polynucleotides and host cells transformed therewith and their use in the production of said polypeptides are described, In addition, compositions, preferably pharmaceutical and diagnostic compositions are provided comprising any of the afore-described polypeptides, polynucleotides or vectors. Described is also the use of the afore-mentioned polypeptides, polynucleotides and vectors for the preparation of pharmaceutical compositions for immunotherapy, preferably against B-cell malignancies such as non-Hodgkin lymphoma.

Abstract: Diagnostic method for the identification of human neoplasias based on the determination of the CTN-C isoform of TN-C, fragments antibodies and their conjugates used in said method, and their therapeutic use.

Abstract: The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.

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: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

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: 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: The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.

Abstract: The present invention relates to antibodies and related molecules that immunospecifically bind to TRAIL receptor, TR4. Such antibodies have uses, for example, in the prevention and treatment of cancers and other proliferative disorders. The invention also relates to nucleic acid molecules encoding anti-TR4 antibodies, vectors and host cells containing these nucleic acids, and methods for producing the same. The present invention relates to methods and compositions for preventing, detecting, diagnosing, treating or ameliorating a disease or disorder, especially cancer and other hyperproliferative disorders, comprising administering to an animal, preferably a human, an effective amount of one or more antibodies or fragments or variants thereof, or related molecules, that immunospecifically bind to TRAIL receptor TR4.

Abstract: Hybridomally produced monoclonal antibodies specifically immunoreactive with the glycoprotein carrying the CA 125 epitope. Monoclonal antibodies recognize both high and low molecular weight subunits of the antigen, and identify the antigen in the cytoplasm and the extracellular matrix of CA 125 producing cells. An immunoassay for the detection of CA 125 utilizing the monoclonal antibodies is described.

Abstract: A nucleic acid is provided which encodes a humanized antibody or fragment thereof, which encodes a protein which binds to human EGF-receptor. Monoclonal antibody 225 is the complementary determining region (CDR) donor.

Abstract: This invention provides monoclonal antibody-producing hybridomas designated 27.F7 and 27.B1. The invention also provides methods for detecting TIP-2 antigen-bearing cancer cells in a sample, detecting the presence of TIP-2 antigen, optionally on the surface of cancer cells, immunohistochemical screening of a tissue section for the presence of TIP-2 antigen bearing cancer cells, diagnosing cancer in a subject, monitoring progression of cancer wherein the cancer cells are TIP-2 antigen-bearing cells, delivering exogenous material to TIP-2 antigen-bearing cancer cells of a human subject, and treating cancer in a human subject. This invention further provides a kit for detecting the presence of TIP-2 antigen-bearing cancer cells. This invention also provides isolated peptides having the amino acid sequences Lys Leu Leu Gly Gly Gln Ile Gly Leu (SEQ ID No:3) and Ser Leu Leu Gly Cys Arg His Tyr Glu Val (SEQ ID NO:4).

Abstract: Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.

Abstract: A variety of heparanase specific antibodies which can be used for research and medical applications including diagnosis and therapy. Specific applications include the use of a heparanase specific antibodies for detection of the presence, absence or level of heparanase expression; the use of a heparanase specific antibodies for therapy of a condition associated with expression of heparanase; the use of a heparanase specific antibodies for quantification of heparanase in a body fluid; the use of a heparanase specific antibodies for targeted drug delivery; and the use of a heparanase specific antibodies as a therapeutic agent.

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: The present invention relates to nucleic acid molecules encoding cell surface receptors on immune cells and the characteristic peptides that comprise these receptors. More specifically, the present invention concerns the use of synthetic and recombinant peptides comprising natural killer (“NK”) cell surface receptors. The synthetic and recombinant peptides are used to generate monoclonal antibodies that bind a specific NK cell surface receptor called CS1. The binding of the monoclonal antibody to the NK cell surface receptor leads to NK cell activation. In a particular embodiments of the present invention, the monoclonal antibodies are utilized in a method that inhibits the growth of tumor cells.

Abstract: A process for purifying an antibody is provided. In this process, a mixture containing the antibody and a contaminant is subjected to low pH hydrophobic interaction chromatography (LPHIC) at low salt concentration. The antibody is eluted from the column in the fraction which does not bind thereto. This process can be preceded and followed by other purification steps.

Abstract: The present invention relates to antibodies and antigen-binding portions thereof that specifically bind to insulin-like growth factor I receptor (IGF-IR), which is preferably human IGF-IR. The invention also relates to human anti-IGF-IR antibodies, including chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulin molecules derived from anti-IGF-IR antibodies and nucleic acid molecules encoding such molecules. The present invention also relates to methods of making anti-IGF-IR antibodies, pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-IGF-IR antibodies.

Abstract: This invention provides a method of reducing an HIV infected subject's HIV-1 viral load which comprises administering to the subject an effective viral load reducing amount of an antibody which (a) binds to a CCR5 chemokine receptor and (b) inhibits fusion of HIV-1 to a CD4+CCR5+ cell, so as to thereby reduce the subject's HIV-1 viral load to 50% or less of the subject's HIV-1 viral load prior to administering the antibody to the subject.

Abstract: The present invention relates to a method for stabilizing chimeric immunoglobulins or immunoglobulin fragments. Furthermore, the invention also provides a stabilized anti-EGP-2 scFv fragment.

Abstract: Purified genes encoding a T cell surface antigen from a mammal, reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding this antigen are provided. Methods of using said reagents and diagnostic kits are also provided.

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 instant invention also includes a kit containing antibodies for the detection of TADG-15 protein. The methods described are useful in the diagnosis, treatment and prevention of cancer, particularly breast and ovarian cancer.

Abstract: The present invention discloses that the normal melanogenic gene, gp75 gene, encodes a gene product, a 24 amino acid peptide of ORF3, which is processed to an antigenic cancer peptide recognized by T lymphocytes. The cancer peptide of the invention derived from ORF3 is recognized by cancer antigen specific T lymphocytes as a tumor rejection antigen. The products of this gene are promising candidates for immunotherapeutic strategies for the treatment and diagnosis of patients with cancer.

Abstract: The invention relates to the time-staggered utilization of tumor cells in combination with intact, preferably heterologous antibodies for the immunization of humans and animals.