Conjugated Via Claimed Linking Group, Bond, Chelating Agent, Or Coupling Agent (e.g., Conjugated To Proteinaceous Toxin Via Claimed Linking Group, Bond, Coupling Agent, Etc.) Patents (Class 424/179.1)
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Patent number: 6623926Abstract: Disclosed herein is a method for generating a 5′-nucleic acid-protein conjugate, the method involving: (a) providing a nucleic acid which carries a reactive group at its 5′ end; (b) providing a non-derivatized protein; and (c) contacting the nucleic acid and the protein under conditions which allow the reactive group to react with the N-terminus of the protein, thereby forming a 5′-nucleic acid-protein conjugate. Also disclosed herein are 5′-nucleic acid-protein conjugates and methods for their use.Type: GrantFiled: June 1, 2000Date of Patent: September 23, 2003Assignee: Phylos, Inc.Inventors: Peter Lohse, Martin C. Wright, Michael McPherson
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Patent number: 6620413Abstract: The present invention concerns long-half derivative of the obesity protein OB. The invention specifically concerns OB protein-immunoglobulin chimeras and polyethylene glycol (PEG)-OB derivatives, which have extended half-life as compared to the corresponding native OB proteins. The invention further relates to methods for treating obesity by using the long half-life derivatives of OB.Type: GrantFiled: December 27, 1996Date of Patent: September 16, 2003Assignee: Genentech, Inc.Inventors: Frederic DeSauvage, Nancy Levin, Richard Vandlen
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Patent number: 6613564Abstract: The invention relates to a complex of enzyme, protein and carrier comprising two or more molecules of an enzyme conjugated through amino group or other group to a carrier such as polylysine, and a protein (for example, antibody) with a specific binding potency to other substance(s) (for example, antigen) conjugated to at least one of said two or more molecules of the enzyme, which enables accurate assay of a trace amount of a substance at a high sensitivity.Type: GrantFiled: December 21, 2000Date of Patent: September 2, 2003Assignee: Nichirei CorporationInventors: Hirokazu Ohbayashi, Yuriko Kitano
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Patent number: 6610299Abstract: The present invention relates to glycosyl-etoposide prodrugs, a process for the preparation thereof and the use thereof in combination with functionalized tumor-specific enzyme conjugates for treating cancers.Type: GrantFiled: October 19, 1994Date of Patent: August 26, 2003Assignee: Aventis Pharma Deutschland GmbHInventors: Cenek Kolar, Jörg Czech, Klaus Bosslet, Gerhard Seemann, Hans-Harald Sedlacek, Dieter Hoffmann
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Publication number: 20030157093Abstract: Provided is a method of treating an autoimmune disease in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the autoimmune disease is treated. In a further embodiment, the invention provides a method of treating T cell leukemias or lymphomas in an animal comprising administering to the animal an antibody-DT mutant immunotoxin which routes by the anti-CD3 pathway, or derivatives thereof, under conditions such that the T cell leukemias or lymphomas are treated.Type: ApplicationFiled: September 3, 1999Publication date: August 21, 2003Inventors: DAVID M. NEVILLE, JR., JOSHUA E. SCHARFF, JERRY TODD THOMPSON, HUAIZHONG HU, SHENGLIN MA
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Patent number: 6558669Abstract: Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.Type: GrantFiled: August 28, 1997Date of Patent: May 6, 2003Assignee: Immunomedics, Inc.Inventors: Serengulam V. Govindan, Gary L. Griffiths
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Patent number: 6537519Abstract: The present invention relates to a method for the preparation of a conjugate comprising a first and a second polypeptide, said method comprising the steps of (a) incubating said first polypeptide in the presence of a heterobifunctional crosslinker comprising an N-hydroxylsuccinimide ester group and a maleimide group linked via a polyethylene oxide spacer; (b) removing excess heterobifunctional crosslinker; and (c) incubating the reaction product of step (b) with said second polypeptide, wherein said second polypeptide comprises at least one sulfhydryl group. Furthermore, the present invention relates to a conjugate obtainable by the method of the present invention. Also described is a pharmaceutical composition comprising the conjugate of the present invention and, optionally, a pharmaceutically acceptable carrier and/or diluent, and the use of the conjugate for the preparation of a pharmaceutical composition for preventing and/or treating an allergic disease or an autoimmune disease.Type: GrantFiled: January 8, 2001Date of Patent: March 25, 2003Assignee: Aventis Behring GmbHInventors: Yves Borel, Werner Schlegel, Erwin Gelfand
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Patent number: 6521773Abstract: Large cobalt and nickel complexes that may be linked to antibodies and other molecules are described. These may be useful in applications benefiting from their magnetic properties.Type: GrantFiled: July 21, 2000Date of Patent: February 18, 2003Inventor: James F. Hainfeld
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Publication number: 20020187153Abstract: The present invention relates to immunotoxins that effectively kill malignant cells having a given marker. The immunotoxins are reagents that comprise internalizing antibodies conjugated to cytotoxic ribonucleases or fragments thereof. The internalizing antibodies are capable of binding with a chosen tumor cell, and thereby confer little non-specific toxicity to the immunotoxin in a host. The immunotoxins exhibit up to 2000-fold higher toxicity against malignant B cells than did the ribonuclease counterparts alone.Type: ApplicationFiled: November 7, 2001Publication date: December 12, 2002Applicant: Immunomedics, Inc.Inventor: David M. Goldenberg
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Patent number: 6485932Abstract: Liquid compositions for intravenous administration that comprise an aqueous solution of immunoglobulin and methods of preparing such compositions are disclosed. The solution has a pH in the range of 5.0 to 5.8 and an ionic strength is the range 0.02 to 0.25. The liquid compositions are formulated so as to be stable upon storage such that the immunoglobulin does not substantially aggregate nor degrade and maintains acceptable levels of anti-complementary activity, PKA activity and kallikrein activity during storage for an extended period at a temperature in the range of 4° C. to 25° C.Type: GrantFiled: October 25, 1999Date of Patent: November 26, 2002Assignee: Common Services AgencyInventors: Ronald Vance McIntosh, Anne Gillian Welch
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Publication number: 20020164350Abstract: The present invention provides a papillomavirus-like particle having conformational epitopes comprising a papillomavirus L1 fusion product and, optionally, a papillomavirus L2 product; and related DNA molecules, host cells, and methods.Type: ApplicationFiled: June 11, 2001Publication date: November 7, 2002Inventors: Douglas R. Lowy, John T. Schiller, Heather Greenstone
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Patent number: 6472179Abstract: The present invention provides a fusion polypeptide capable of binding a cytokine to form a nonfunctional complex. It also provides a nucleic acid sequence encoding the fusion polypeptide and methods of making and uses for the fusion polypeptide.Type: GrantFiled: May 19, 1999Date of Patent: October 29, 2002Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Neil Stahl, George D. Yancopoulos
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Patent number: 6461617Abstract: A polypeptide has first and second domains which enable the polypeptide to be translocated into a target cell or which increase the solubility of the polypeptide, or both, and further enable the polypeptide to cleave one or more vesicle or plasma-membrane associated proteins essential to exocytosis. The polypeptide thus combines useful properties of a clostridial toxin, such as a botulinum or tetanus toxin, without the toxicity associated with the natural molecule. The polypeptide can also contain a third domain that targets it to a specific cell, rendering the polypeptide useful in inhibition of exocytosis in target cells. Fusion proteins comprising the polypeptide, nucleic acids encoding the polypeptide and methods of making the polypeptide are also provided. Controlled activation of the polypeptide is possible and the polypeptide can be incorporated into vaccines and toxin assays.Type: GrantFiled: February 23, 1999Date of Patent: October 8, 2002Assignees: Microbiological Research Authority, The Speywood Laboratory LimitedInventors: Clifford Charles Shone, Conrad Padraig Quinn, Keith Alan Foster
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Publication number: 20020136731Abstract: The present invention is directed to a conjugate which includes at least one vitamin D moiet thereof and at least one targeting molecule moiety to pharmaceutical compositions of the conjugate. and to methods for using the conjugate for target- specific delivery of vitamin D or analogs thereof to tissues in need thereof. When a particularly preferred form is administered to a patient, the targeting molecule component of the conjugate of this invention seeks out and binds to a tissue of interest, such as bone or tuinor tissue, where the vitamin D has a therapeutic effect.Type: ApplicationFiled: April 26, 2000Publication date: September 26, 2002Inventors: Richard B. Mazess, Charles W. Bishop
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Patent number: 6451545Abstract: Provided are a monoclonal antibody making it possible to detect a native fibrin monomer, which is produced at the initial state of blood coagulation, and soluble fibrin; a hybridoma; and an immunoassay for detecting the initial stage of blood coagulation with high sensitivity, quickly, using the monoclonal antibody. Using a fibrinogen analog in blood as an immune source, cell fusion is carried out to prepare a monoclonal antibody which is not reactive with fibrinogen and is specifically and simultaneously reactive with a native fibrin monomer (that is, a fibrin monomer which is present in a body fluid, in particular in blood, and is not solubilized) and soluble fibrin. The fibrin monomer analog is preferably fibrinogen treated with bathroxobin, which is a snake venom.Type: GrantFiled: February 17, 1999Date of Patent: September 17, 2002Assignee: Nissui Pharmaceutical Co., Ltd.Inventors: Seiji Tanaka, Akiei Hamano, Mamoru Umeda
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Patent number: 6440386Abstract: A radiotherapeutic agent comprising a 32P or 33P radiolabeled protein selected from the group consisting of: wherein X is an targeting peptide, Y is a phosphorylation peptide, L is a flexible linker, preferably a peptide linker, and SH2 represents an SH2 domain; whereby said phosphorylation peptide is radiolabeled with 32P or 33PType: GrantFiled: July 6, 1999Date of Patent: August 27, 2002Assignee: Immunomedics, Inc.Inventor: Shui-on Leung
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Patent number: 6429297Abstract: 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.Type: GrantFiled: February 3, 2000Date of Patent: August 6, 2002Assignee: University of RochesterInventor: Scott F. Rosebrough
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Publication number: 20020102208Abstract: Antibody binding assays and radiolabeling kits are disclosed for radiolabeling and testing therapeutic antibodies in the commercial setting. In particular, the kits are designed for making and evaluating radiolabeled anti-CD20 conjugates to be used for the treatment and imaging of B cell lymphoma tumors. All kit reagents are sterile and are designed to achieve a high level of antibody radiolabeling and product stability with results which are highly reproducible.Type: ApplicationFiled: March 1, 1999Publication date: August 1, 2002Inventors: PAUL CHINN, RONALD MORENA, MICHAEL LABARRE, JOHN E. LEONARD
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Patent number: 6426400Abstract: Antibodies to cell surface ligands such as EGFRvIII can be used to therapeutically or diagnostically deliver a radiolabel to tumor cells with high selectivity. The utility of radioconjugated internalizing antibodies is limited, however, by release of the label and its reuptake into normal cells. The invention provides new technology for radioconjugation of internalizing antibodies which reduces the release of label and improves retention of radioconjugated antibodies in lysosomes, where radiation is more effectively and selectively delivered to the nucleus of tumor cells.Type: GrantFiled: April 26, 2000Date of Patent: July 30, 2002Assignee: Duke UniversityInventor: Michael R. Zalutsky
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Patent number: 6420126Abstract: 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.Type: GrantFiled: June 8, 1999Date of Patent: July 16, 2002Assignee: Ixsys, Inc.Inventors: William D. Huse, Jeffry D. Watkins
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Patent number: 6416758Abstract: 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.Type: GrantFiled: April 28, 2000Date of Patent: July 9, 2002Assignee: Board of Regents, The University of Texax SystemInventors: Philip E. Thorpe, Rolf A. Brekken
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Patent number: 6416738Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin, as well as related compounds, are described. Clearing agents and clearance mechanisms are also discussed.Type: GrantFiled: April 25, 2000Date of Patent: July 9, 2002Assignee: NeoRx CorporationInventors: Louis J. Theodore, Donald B. Axworthy, John M. Reno
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Patent number: 6416785Abstract: A new approach for targeting chemotherapeutics to focal bacterial infections is provided. Such focal infections are characterized by high densities of different bacteria and thus high concentrations of their extracellular signal molecules sensing the cell density. In gram-negative bacteria, one of such signal molecules is acyl-homoserine lactone (acyl-HSL, member of the autoinducer family AI-1), wherein species-specificity is achieved by acyl-residues, and HSLs are common for all gram-negative bacteria. In gram-positive bacteria, oligopeptides secreted by the bacteria communicate the cell density. In addition, there are cell density signal molecules (members of the autoinducer family AI-2) which communicate between gram-positive and gram-negative bacteria. The general scheme of the present invention is molecular modules that comprise both a targeting component and a chemotherapeutical component which serves for photodynamic antimicrobial chemotherapy (PACT).Type: GrantFiled: August 23, 2000Date of Patent: July 9, 2002Assignee: Biolitec AGInventors: Dieter Riesenberg, Volker Schroeckh, Burkhard Gitter, Wolfgang Neuberger
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Publication number: 20020071841Abstract: The present invention provides a recombinant toxin and monoclonal antibody which specifically binds to glial-derived or meningioma-derived tumor cells. Also provided are various methods of screening for malignant gliomas and meningiomas. Further provided are methods of treating malignant gliomas, including glioblastoma multiforme and astrocytomas.Type: ApplicationFiled: November 28, 1997Publication date: June 13, 2002Inventors: HARALD W. SONTHEIMER, NICOLE ULLRICH
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Patent number: 6395276Abstract: 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.Type: GrantFiled: May 1, 1998Date of Patent: May 28, 2002Assignee: Immunomedics, Inc.Inventors: Susanna M. Rybak, Dianne L. Newton, David M. Goldenberg
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Publication number: 20020052443Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.Type: ApplicationFiled: April 7, 2000Publication date: May 2, 2002Inventors: Richard B Greenwald, Anthony J Martinez
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Patent number: 6379699Abstract: Complexes are prepared containing two or more different effector molecules joined to each other by a joining component. One effector molecule is a binding molecule such as an antibody or Fc receptor that binds to a molecular target such as a virus or antibody at a site of infection or tumor, and another effector molecule is a therapeutic molecule such as an enzyme or drug. The joining component may be a liposome, protein or an organic polymer (including a dendrimer type polymer), and may be of sufficient length and/or flexibility to permit the therapeutic molecule to physically interact with the target at the same time as the binding molecule. Supramolecules are formed containing at least two supramolecular component molecules that contain an effector molecule and a nucleic acid chain.Type: GrantFiled: September 28, 1999Date of Patent: April 30, 2002Assignee: Burstein Technologies, Inc.Inventors: Jorma Virtanen, Sinikka Virtanen
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Patent number: 6379669Abstract: 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.Type: GrantFiled: August 2, 1996Date of Patent: April 30, 2002Inventor: Akhouri A. Sinha
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Patent number: 6376460Abstract: 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.Type: GrantFiled: August 6, 1999Date of Patent: April 23, 2002Assignee: Flinders Technologies Pty. Ltd.Inventor: Ida Jonassen Llewellyn-Smith
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Publication number: 20020042081Abstract: The present invention is a method for selectively removing objects from a surface utilizing a probe. The probe is scanned over the surface utilizing a greater and greater relative amount of force so that a certain number of the objects are removed from the surface. The force required to remove the objects from the surface can be calculated utilizing Hook's law and the spring constant of the probe. After removal of the objects that have a relatively weaker binding affinity with the surface, the remaining objects can be harvested, characterized, and subjected to further study.Type: ApplicationFiled: October 9, 2001Publication date: April 11, 2002Inventors: Eric Henderson, Curtis Mosher
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Patent number: 6368598Abstract: A drug complex for delivery of a drug or other agent to a target cell, comprising a targeting carrier molecule which is selectively distributed to a specific cell type or tissue containing the specific cell type; a linker which is acted upon by a molecule which is present at an effective concentration in the environs of the specific cell type; and a drug or an agent to be delivered to the specific cell type. In particular, a drug complex for delivering a cytotoxic drug to prostate cancer cells, comprising a targeting carrier molecule which is selectively delivered to prostate tissue, bone or both; a peptide which is a substrate for prostate specific antigen; and a cytotoxic drug which is toxic to androgen independent prostate cancer cells.Type: GrantFiled: July 6, 1998Date of Patent: April 9, 2002Assignee: JCRT Radiation Oncology Support Services, Inc.Inventors: Anthony V. D'Amico, Glenn J. Bubley, David J. Jebaratnam, James S. Weinberg
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Patent number: 6369206Abstract: Novel metal-lipid molecules have the formula M—Or—L. M represents a cluster or colloid of atoms of Au, Ag, Pt, Pd, or combinations thereof. Or is an organic group covalently attached to the metal atoms. L represents a lipid moiety. In a preferred embodiment, M represents a cluster of about 50-70 gold atoms having a diameter of about 1.4 nm in diameter and L represents dipalmitoyl phosphatidyl ethanolamine.Type: GrantFiled: July 19, 2000Date of Patent: April 9, 2002Inventors: Robert D. Leone, James F. Hainfeld
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Patent number: 6361774Abstract: A method for increasing the target-specific toxicity of a drug is effected by pretargeting an enzyme to a mammalian target site, and then administering a cytotoxic drug known to act at the target site or a prodrug form thereof which is converted to the drug in situ, which drug is also detoxified to form an intermediate of lower toxicity using said mammal's ordinary metabolic processes, whereby the detoxified intermediate is reconverted to its more toxic form by the pretargeted enzyme and thus has enhanced cytotoxicity at the target site. Further enhancement can be achieved by pretargeting an enzyme which converts the prodrug to the cytotoxic drug at the target site. Kits for use with the method also are provided. The method and kits permit lower doses of cytotoxic agents, maximize target site activity and minimize systemic side effects.Type: GrantFiled: September 17, 1999Date of Patent: March 26, 2002Assignee: Immunomedics, Inc.Inventors: Gary L. Griffiths, Hans J. Hansen
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Patent number: 6362328Abstract: Probes comprise S1 and P1 nuclease (as an enzyme label) linked to a specific binding member such as a nucleotide sequence or an antibody. Such probes are useful for sandwich assays. As compared with known probes using alkaline phosphatase as a label, advantages include relative insensitivity to phosphate and elevated temperature and reduced risk of nonspecific binding.Type: GrantFiled: September 20, 1999Date of Patent: March 26, 2002Assignee: London Biotechnology LimitedInventors: Mark Fisher, Christopher John Taylorson, Stuart Harbron
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Patent number: 6348194Abstract: 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.Type: GrantFiled: November 13, 1995Date of Patent: February 19, 2002Assignee: Ixsys IncorporatedInventors: William D. Huse, Jeffry D. Watkins
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Patent number: 6342221Abstract: 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.Type: GrantFiled: April 28, 2000Date of Patent: January 29, 2002Assignee: Board of Regents, The University of Texas SystemInventors: Philip E. Thorpe, Rolf A. Brekken
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Patent number: 6342586Abstract: This invention provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention also provides an immunoconjugate which comprises 1) a gamma radiation-emitting radionuclide of low to moderate cytotoxicity and 2) a CD4-gamma2 chimeric heavy chain homodimer linked thereto. This invention further provides an immunoconjugate which comprises 1) a non-peptidyl toxin and 2) a heterotetramer comprising two heavy chains and two light chains, both heavy chains being either 1) IgG2 heavy chains or b) chimeric CD4-IgG2 heavy chains, and both light chains being either a) kappa light chains or b) chimeric CD4-kappa light chains.Type: GrantFiled: September 29, 1999Date of Patent: January 29, 2002Assignee: Progenics Pharmaceuticals, Inc.Inventors: Graham P. Allaway, Paul J. Maddon
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Patent number: 6319500Abstract: A method of targeting a diagnostic or therapeutic agent to a focus of infection comprises injecting a patient infected with a pathogen parenterally with an antibody conjugate which specifically binds to an accessible epitope of the pathogen or of a pathogen-associated antigen accreted at the focus of infection, the antibody conjugate further comprising a bound diagnostic or therapeutic agent for detecting, imaging or treating the infection. Polyspecific composite conjugates enhance the efficacy of the method, which is especially useful for treating infections that are refractory towards systemic chemotherapy.Type: GrantFiled: December 1, 1993Date of Patent: November 20, 2001Assignee: Immunomedics, Inc.Inventor: M. David Goldenberg
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Patent number: 6287536Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.Type: GrantFiled: January 27, 1997Date of Patent: September 11, 2001Assignee: NeoRx CorporationInventors: John M. Reno, Louis J. Theodore, Linda M. Gustavson
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Patent number: 6274325Abstract: The invention concerns a homogeneous immunoassay based on agglutination using an Fab′-biotin material and agglutinatable particles which carry streptavidin or avidin. The invention also concerns the Fab′-biotin which is bound or linked via linkage groups to a label compound which can electrochemiluminescence and the particles having avidin or streptavidin on their surface are magnetic.Type: GrantFiled: September 28, 1994Date of Patent: August 14, 2001Assignee: Boehringer Mannheim GmbHInventors: Arno Deger, François Guillot, Michael Berger, Dittmar Schlieper
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Patent number: 6261535Abstract: 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.Type: GrantFiled: December 8, 1998Date of Patent: July 17, 2001Assignee: The University of Texas System Board of RegentsInventors: Philip E. Thorpe, Francis J. Burrows
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Publication number: 20010007755Abstract: The present invention relates to a method for the preparation of a conjugate comprising a first and a second polypeptide, said method comprising the steps of (a) incubating said first polypeptide in the presence of a heterobifunctional crosslinker comprising an N-hydroxylsuccinimide ester group and a maleimide group linked via a polyethylene oxide spacer; (b) removing excess heterobifunctional crosslinker; and (c) incubating the reaction product of step (b) with said second polypeptide, wherein said second polypeptide comprises at least one sulfhydryl group.Type: ApplicationFiled: January 8, 2001Publication date: July 12, 2001Inventors: Yves Borel, Werner Schlegel, Erwin Gelfand
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Patent number: 6238667Abstract: A method of affinity cross-linking a peptide to an antibody by photo-chemically activating an azido compound in a peptide including said azido compound; adding an antibody to the photochemically activated peptide; and allowing the photochemically activated peptide and the antibody to react. The azido compound has an affinity for a hydrophobic structure in the variable domain of the antibody which binds to nucleotides or nucleosides, binding the peptide into a native binding pocket of the immunoglobulin (Ig) structure of an antibody. The site of cross-linking is located away from the antigen binding site in the Fv domain avoiding the compromise of antigen recognition. A composition of a peptide cross-linked to an antibody is also disclosed.Type: GrantFiled: May 4, 1998Date of Patent: May 29, 2001Inventor: Heinz Kohler
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Patent number: 6217869Abstract: Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed.Type: GrantFiled: September 5, 1997Date of Patent: April 17, 2001Assignee: NeoRx CorporationInventors: Damon L. Meyer, Robert W. Mallett
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Patent number: 6218166Abstract: Disclosed are compositions and methods for enhancing the antibody and T cell response to cellular antigens by incorporating an immunopotentiating agent into the cellular membrane or into an intracellular compartment. Such adjuvant-incorporated cell compositions are useful in methods to increase immune responses against antigens, including immunologically cryptic tumor cell antigens, and may be employed to generate useful diagnostic antibodies, to elicit anti-tumor effects in immunized animals, and to significantly prolong survival in animals with cancer.Type: GrantFiled: June 5, 1995Date of Patent: April 17, 2001Assignee: John Wayne Cancer InstituteInventors: Mepur H. Ravindranath, Donald L. Morton
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Patent number: 6214974Abstract: 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.Type: GrantFiled: March 27, 1995Date of Patent: April 10, 2001Assignee: Research Development FoundationInventors: Michael G. Rosenblum, Nicholas J. Donato
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Patent number: 6203794Abstract: 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.Type: GrantFiled: May 1, 1997Date of Patent: March 20, 2001Assignee: Allergan Sales, Inc.Inventors: James Oliver Dolly, Kei Roger Aoki, Larry Allen Wheeler, Michael Elwood Garst
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Patent number: 6197298Abstract: Several forms of immunoregulatory substances are derived from monoclonal antibodies (MAbs) that are specific for a T cell surface antigen, such as CD3, TCR, CD4, or CD8 on T cells. The substances include: a mixture of F(ab′)2 fragments (or other divalent binding molecules which lack Fc) which each bind noncompetitively to different monovalent antigenic epitopes on the same antigen; the F(ab′)2 fragment (or other divalent binding molecules which lack Fc) of a bispecific antibody which has each of its binding sites derived from one of the two MAbs that bind noncompetitively to monovalent antigenic epitopes on the same antigen; a conjugate including a polymeric backbone, such as polyethylene glycol (“PEG”), cellulose, dextran, agarose, or an amino acid copolymer or a liposome, that is coupled with the binding molecules, e.g., Fv, Fab, or F(ab′)2, which bind noncompetitively to monovalent antigenic epitopes on the same antigen.Type: GrantFiled: March 23, 1993Date of Patent: March 6, 2001Assignee: Tanox, Inc.Inventor: Tse Wen Chang
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Patent number: RE38008Abstract: Methods for improved targeting of antibody, antibody fragments, peptides hormones, steroid hormones and conjugates thereof are disclosed. Enhanced delivery to target cells of antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for a population of cells of a mammal comprises steps of administering to said mammal an adequate dosage of blocking antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, and administering to said mammal an effective dosage of said antibodies or fragments thereof or other receptor-mediated delivery system, such as peptide, specific for said population of cells. In the preferred embodiment, the specific antibodies are monoclonal antibodies directed toward tumor-associated antigen in man.Type: GrantFiled: November 29, 2001Date of Patent: February 25, 2003Assignee: NeoRx CorporationInventors: Paul G. Abrams, Robert W. Schroff, Alton C. Morgan, Jr.
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Patent number: RE38158Abstract: This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.Type: GrantFiled: November 4, 1998Date of Patent: June 24, 2003Assignee: Minnesota Mining and Manufacturing CompanyInventors: Thomas H. Barrows, Terry W. Lewis, Myhanh T. Truong, Matthew T. Scholz