Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: The present invention relates to a compound of the formula These modified streptavidin compounds have are useful as part of a delivery system to deliver a molecule to a target site for use in diagnosis or therapy.

Abstract: This invention provides protease-activatable Pseudomonas exotoxin A-like (“PE-like”) proproteins. The proproteins comprise (1) a cell recognition domain of between 10 and 1500 amino acids that binds to a cell surface receptor; (2) a modified PE translocation domain comprising an amino acid sequence sufficiently homologous to domain II of PE to effect translocation to a cell cytosol upon proteolytic cleavage, wherein the translocation domain comprises a cysteine-cysteine loop that comprises a protease activatable sequence cleavable by a protease and wherein the cysteine-cysteine loop is substantially un-activatable by furin; (3) optionally, a PE Ib-like domain comprising an amino acid sequence up to 1500 amino acids; (4) a cytotoxicity domain comprising an amino acid sequence substantially homologous to domain III of PE, the cytotoxicity domain having ADP-ribosylating activity; and (5) an endoplasmic reticulum (“ER”) retention sequence.

Abstract: This invention provides protease-activatable Pseudomonas exotoxin A-like (“PE-like”) proproteins. The proproteins comprise (1) a cell recognition domain of between 10 and 1500 amino acids that binds to a cell surface receptor; (2) a modified PE translocation domain comprising an amino acid sequence sufficiently homologous to domain II of PE to effect translocation to a cell cytosol upon proteolytic cleavage, wherein the translocation domain comprises a cysteine-cysteine loop that comprises a protease activatable sequence cleavable by a protease and wherein the cysteine-cysteine loop is substantially un-activatable by furin; (3) optionally, a PE Ib-like domain comprising an amino acid sequence up to 1500 amino acids; (4) a cytotoxicity domain comprising an amino acid sequence substantially homologous to domain m of PE, the cytotoxicity domain having ADP-ribosylating activity; and (5) an endoplasmic reticulum (“ER”) retention sequence.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: A composition comprising at least one antigenic medium and at least one adjuvant, wherein the at least one antigenic medium and the at least one adjuvant each comprise one or more phases which are distinct from each other when the composition is in a solid state, and the composition is in the liquid state when its temperature is greater than or equal to 4° C.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions.

Abstract: Pharmaceutical compositions useful in the treatment of autoimmune conditions include as an active ingredient a soluble lectin having a molecular weight of about 14 kilodaltons or a fragment thereof. The lectin or fragment binds &bgr;-galactoside-containing moieties independent of the presence or absence of Ca+2, stimulates hemagglutination of trypsinized rabbit erythrocytes in standard lectin assays wherein the stimulation is inhibited by lactose or thiogalactoside, has an amino acid sequence containing at least one N-glycosylation site and is at least 90% homologous to the amino acid sequence shown in positions 2-135 of FIG. 1 or the relevant portions thereof. The composition is used for treatment of autoimmune conditions such as rheumatoid arthritis, myasthenia gravis, and multiple sclerosis, as well as modulating the immune response in an allergic reactions or to organ or tissue transplant rejection. The inventive composition can be combined with general immunosuppressants.

Abstract: Activation of &agr;2-macroglobulin (&agr;2M) with a nucleophilic compound followed by incubation of the activated &agr;2M at elevated temperature with a biomolecule results in covalent incorporation of the intact biomolecule into the &agr;2M molecule, without the use of proteinases. The thus-formed structurally defined and stable complex may be used as an antigen for stimulating the immune response, for example, in the form of a vaccine. Enhanced antigen presentation of a particular biomolecule is provided, especially for those that are poorly immunogenic; reduction of the immunodominance of particular epitopes is also provided.

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. Methods of using said reagents and diagnostic kits are also provided.

Abstract: DNA encoding a therapeutically suitable glutaminase has been molecularly cloned. This allows one to obtain a polypeptide which is a therapeutically suitable glutaminase free of contaminating endotoxin. It has been found that this polypeptide is a potent anti-viral agent and when coupled to an anti-tumor monoclonal antibody is a potent anticancer agent. The glutaminase of the present invention is particularly useful for treating lung, breast and colon cancer cells and in the treatment of HIV-infected cells.

Abstract: The present invention relates to immunotoxins, that effectively kill malignant cells having a given surface marker and nucleic acid constructs encoding them. These reagents comprise a toxic moiety that is derived from a Rana pipiens protein having ribonucleolytic activity linked to an antibody capable of specific binding with a chosen tumor cell.

Abstract: The invention provides for the production of several humanized murine antibodies specific for the antigen FB5, which is recognized by the murine antibody FB5. The FB5 antigen is expressed on the luminal surface of vascular endothelial cells of a wide range of malignant tumours. The invention also provides for numerous polynucleotide encoding humanized FB5 specific antibodies, expression vectors for producing humanized FB5 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 FB5 specific antibodies. Additionally, the invention provides methods of treating cancer using FB5 specific antibodies.

Abstract: The present invention relates to methods and pharmaceutical formulations for orally delivering an antigen to induce tolerance. The antigen is combined with derivatized amino acids or salts thereof. The induction of oral tolerance may be applied clinically for the prevention or treatment of auto-immune diseases and clinical allergic hypersensitivities, and for the prevention of allograft rejection.

Abstract: Novel monoclonal antibodies to the CD25 antigen are characterized by the amino acid sequence of their hypervariable regions. Initially produced in murine form, they may be converted to chimeric or humanized forms, immunoconjugates or antibody fragments (generally described as binding molecules). The products are useful for the prophylaxis or treatment of transplant rejection, paticularly in combination with other antibodies to activated T-cells, for example CD7 antibodies.

Abstract: Recombinant antibody proteins are provided that specifically bind fibroblast activation protein alpha (FAP&agr;) and comprise framework modifications resulting in the improved producibility in host cells. The invention also relates to the use of said antibodies for diagnostic and therapeutic purposes and methods of producing said antibodies.

Abstract: Bioactive materials, e.g. therapeutic agents for treating a condition that afflicts a patient, are delivered to the afflicted organ in a site-specific manner by coupling the bioactive agent to an antibody or fragment or derivative thereof that recognizes a substance unique to that organ. For example, therapeutic agents for treating conditions of the prostate gland such as adenocarcinoma of the prostate, benign prostatic hypertrophy and prostatitis can be delivered to the prostate by coupling the thereapeutic agent to an antibody against a substance secreted by the prostate, e.g. prostatic specific antigen or prostatic acid phosphatase.

Abstract: The present invention is directed to compositions and methods for modulating cellular activity. The invention is particularly suited for delivering an agent which modulates cellular activity to a neuronal cell. In a typical embodiment, a composition of the invention includes an agent associated with a neuronal tracer which associates with a neuron to facilitate uptake of the agent by the neuron cell body.

Abstract: The present invention provides a novel biotherapeutic agent comprising a monoclonal antibody TXU-7, which is specific to the CD7 antigen, conjugated to the pokeweed antiviral protein (PAP). This immunoconjugate was designated TXU-7-PAP. The CD7 antigen is present on the surface of the majority of T-lymphocytes, including those that are the cellular target of the human immunodeficiency virus (HIV). The pokeweed antiviral protein displays broad spectrum antiviral activity toward various plant, animal, and human viruses, including HIV. Prior attempts to generate PAP immunoconjugates with anti-HIV activity have been unsuccessful due to the poor stability of the immunoconjugate in vivo. However, the TXU-7-PAP immunoconjugate described herein displayed potent antiviral activity against HIV-1 and low toxicity in various animal models. Preliminary clinical studies in HIV-1-infected patients demonstrated that the immunoconjugate was well-tolerated and reduced the HIV-1 viral load.

Abstract: The present invention relates particularly to neoplastic cells targeted chimeric toxins comprising of cell targeting moieties and cell killing moieties for recognizing and for destroying the neoplastic cells, wherein the cell targeting moieties consist of gonadotropin releasing hormone homologues and the cell killing moieties consist of Pseudomonas Exotoxin A. The present invention further relates to pharmaceutical compositions containing as an active ingredient these neoplastic cells targeted chimeric toxins and to a method for the production of these chimeric toxins. The said invention also relates to a method for cancer therapy, treating malignant carcinoma cells and benign hyperplasia including uterine lyomyoma cells, extra uterian endometrial island cells, benign hyperplasia of prostate and breast and pituitary tumor adenoma cells, by the use of the above-mentioned chimeric toxins.

Abstract: The present invention concerns isolated nucleic acid molecules encoding the novel TIE ligands NL1, NL5 and NL8, the proteins encoded by such nucleic acid molecules, as well as methods and means for making and using such nucleic acid and protein molecules.

Abstract: Immuno-adjuvant photodynamic therapy to treat and prevent metastatic cancer is effected using photosensitizers in combination with immuno-adjuvants to destroy metastatic tumor cells.

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: The invention provides for the production of several humanized murine antibodies specific for the antigen LK26, which is recognized by the murine antibody LK26. This antigen is expressed on all choriocarcinoma, teratocarcinoma and renal cancer cell lines whereas it is not expressed on cell lines of leukaemias, lymphomas, neuroectodermally-derived and epithelial tumor cell lines (excepting a small subset of epithelial cell lines). Furthermore, whereas renal cancer cell lines express the LK26 antigen, normal renal epithelial cells do not. Similarly, with the exception of the trophoblast, all normal adult and fetal tissues tested are negative for the LK26 phenotype. The invention also provides for numerous polynucleotide encoding humanized LK26 specific antibodies, expression vectors for producing humanized LK26 specific antibodies, and host cells for the recombinant production of the humanized antibodies.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: The invention is directed to methods of reducing the effects of cancer in a subject by administering to said subject a pharmaceutically effective amount of an anti-cancer agent conjugated to an inmmunoglobulin product which comprises one or more novel complementarity determining region and framework regions.

Abstract: A method for treating autoimmune diseases comprising administering to a patient in need of such treatment a therapeutically effective amount of an immunotoxin comprising an anti-human CD86 monoclonal antibody IG10H6D10 as deposited in the ECACC collection under No. 95060210 or a humanized antibody, a single-chain antibody or fragments and specificity of said monoclonal antibody, coupled to a toxin or active fragments thereof wherein the binding of the immunotoxin to CD86 results in the killing of the CD86 expressing cell.

Abstract: A method for increasing weight gain and feed efficiency in a subject animal, whether that subject animal is healthy or suffering from a disease resulting in weight loss, such as cachexia. The method consists of the administration of an effective amount of hyperimmunized egg product.

Abstract: Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.

Abstract: Disclosed is a method of inhibiting the growth of tumors bearing IL13-specific receptors. Included among this class of tumors is glioblastoma multiform (GBM), a rapidly progressing brain tumor for which there is currently no effective treatment available. In the disclosed method, a chimeric cytotoxin comprising an IL13 receptor-binding moiety and a cytotoxic moiety is delivered into a mammalian subject having a tumor bearing IL13-specific receptors. All studied human GBM specimens abundantly express the IL13-specific tumor.

Abstract: Novel calcium phosphate core particles, methods of making them, and methods of using them as vaccine adjuvants, as cores, as carriers of biologically active material, and as controlled release matrices for biologically active material are disclosed. The core particles may have a surface modifying agent and/or biologically active material, such as antigenic material or natural immunoenhancing factor, polynucleotide material, or therapeutic proteins or peptides, partially coating the particle or impregnated therein.

Abstract: The present invention provides recombinant peptides that specifically and selectively bind to the human milk fat globule (HMFG) antigen, BA46. In particular, the present invention provides recombinant variants of the Mc3 antibody, including humanized versions of Mc3. The variant Mc3 peptides are particularly useful for diagnostic, prognostic, and therapeutic applications in the field of breast cancer. The present invention also provides methods for the humanization of antibodies such as murine monoclonal antibodies. The novel humanization methods are applied to the production of humanized Mc3 antibodies and it is shown that these humanized antibodies retain the ability to engage in high affinity binding to their cognate antigen. Such humanization enables the use of these antibodies for immunodiagnostic and immunotherapeutic applications in humans.

Abstract: B-cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 or CD19 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 and/or anti-CD19 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.

Abstract: The present invention provides an anti-IgM antibody conjugate comprising: a monoclonal antibody which binds selectively to IgM antibody, does not bind to IgG1 or IgG2 antibody, and has a G isotype; and a cytotoxic moiety conjugated to said monoclonal antibody. The present invention also provides a method for collecting hybridoma producing IgG isotype monoclonal antibodies comprising: treating a hybrid cell population with a monoclonal antibody which has a G isotype and binds selectively to IgM antibody but does not bind to IgG1 or IgG2 antibody; subjecting said resulting immuncomplexed cells to sorting; and collecting the cells which have not complexed with said antibodies.

Abstract: The present invention provides a complex comprising a biologically active substance and a ligand that recognizes CD16.

Abstract: A compound comprises a target cell-specific portion, such as an antibody specific to tumor cell antigens, and an inactivating portion, such as an enzyme, capable of converting a substance which in its native state is able to inhibit the effect of a cytotoxic agent into a substance which has less effect against said cytotoxic agent. The prolonged action of a cytotoxic agent at tumor sites is therefore possible while protecting normal tissues from the effects of the cytotoxic agent.

Abstract: The subject invention relates a method for the production of monoclonal antibodies. The method utilizes an immunized germfree animal. The invention also provides methods for the use of such monoclonal antibodies, and polyclonal antibodies derived from an immunized germfree animal, for in vitro and in vivo clinical diagnostics and therapeutics. Also, the subject invention provides a fibrin-specific monoclonal antibody.

Abstract: The invention provides methods for inhibiting the growth of a cell bearing a LewisY antigen. The methods involve contacting the cell with a composition comprising an Fv region of a light chain of a monoclonal antibody selected from B1, B3, and B5, and the Fv region of a humanized heavy chain of a monoclonal antibody independently selected from B1, B3, and B5, provided that if the heavy and the light chains are from the same antibody, the residue at position 95 of the heavy chain is a serine, and, if the antibody chain is from B3, the residue at position 4 of the light chain can be a leucine and the residue at position 82b of the heavy chain can be an arginine. The Fv regions are joined to an effector molecule selected from a chemotherapeutic agent, a toxin, a radioisotope, and a liposome loaded with a chemotherapeutic agent. In preferred embodiments, the heavy chain and the light chain are recombinantly fused, and the Fv regions are recombinantly fused to a toxin.

Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: Targeting molecules for use in delivering biological agents to non-polarized epithelial cells are disclosed. Upon delivery, the biological agent(s) are lethal to the epithelial cell. The targeting molecules may be used, for example, for the eradication of metastatic epithelial cells.

Abstract: The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis.

Abstract: The present invention provides a non-viral vector, comprising a cell binding component having a biotin-binding element conjugated to a biotinylated moiety. Also, provided is a method of introducing genetic material inside a specific cell comprising the administration of the non-viral vector to a human, wherein said non-viral vector comprises a cell binding component having a biotin-binding element conjugated to a biotinylated moiety. In addition, there is provided a method of delivering a cytotoxic moiety to a cell comprising the administration of the non-viral vector to a human.

Abstract: We have modified PE40 toxin by removing at least two of its four cysteine amino acid residues and have formed hybrid molecules containing modified PE40 linked to a cell recognition protein that can be an antibody, a growth factor, a hormone, a lymphokine, or another polypeptide cell recognition protein for which a specific cellular receptor exists whereby the modified PE40 toxin is directed to cell types having receptors for the cell recognition protein linked to the modified PE40.

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

Abstract: A soluble antibody conjugate comprising an antibody linked to a structure which is recognized by T-cells and has the ability to direct T-cells to lyse the target cell, which is recognized by the antibody. The conjugate is characterized by the structure being a superantigen. One important mode is a method for the lysis of target cells, wherein the target cells are contacted with a target cell lysis effective amount of the conjugate. The method of lysis is part of a potent treatment regime for cancer, autoimmunity, parasitic infestations and fungal, viral and bacterial infections. The specification also describes modes such as the synthesis of the conjugate and pharmaceutical compositions and their manufacture.

Abstract: The subject invention relates a method for the production of monoclonal antibodies. The method utilizes an immunized germfree animal. The invention also provides methods for the use of such monoclonal antibodies, and polyclonal antibodies derived from an immunized germfree animal, for in vitro and in vivo clinical diagnostics and therapeutics. Also, the subject invention provides a fibrin-specific monoclonal antibody.

Abstract: B-Cell malignancies, such as the B-cell subtype of non-Hodgkin's lymphoma and chronic lymphocytic leukemia, are significant contributors to cancer mortality. The response of B-cell malignancies to various forms of treatment is mixed. Traditional methods of treating B-cell malignancies, including chemotherapy and radiotherapy, have limited utility due to toxic side effects. Immunotherapy with anti-CD20 antibodies have also provided limited success. The use of antibodies that bind with the CD22 antigen, however, provides an effective means to treat B-cell malignancies such as indolent and aggressive forms of B-cell lymphomas, and acute and chronic forms of lymphatic leukemias. Moreover, immunotherapy with anti-CD22 antibodies requires comparatively low doses of antibody protein, and can be used effectively in multimodal therapies.