Conjugate Or Complex Includes Hormone Or Other Secreted Growth Regulatory Factor, Differentiation Factor, Intercellular Mediator, Or Fragment Thereof Patents (Class 424/195.11)
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Patent number: 6719974Abstract: The present invention relates to methods and compositions for inducing an immune response in a subject, wherein the subject is administered an effective amount of a heat shock protein complexed to a hybrid antigen comprising an antigenic domain and a heat shock protein-binding domain. These methods and compositions may be used in the treatment of infectious diseases and cancers.Type: GrantFiled: October 5, 2000Date of Patent: April 13, 2004Assignee: Sloan-Kettering Institute for Cancer ResearchInventors: James E. Rothman, Franz Ulrich Hartl, Mee H. Hoe, Alan Houghton, Yoshizumi Takeuchi, Mark Mayhew
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Patent number: 6709658Abstract: This invention pertains to vaccine compositions comprising a mixture of antigen, such as a pneumococcal or meningococcal antigen, and interleukin IL-12, which may be adsorbed onto a mineral in suspension. The pneumococcal or meningococcal antigen may be conjugated to a carrier molecule. These vaccine compositions modulate the protective immune response to the antigen.Type: GrantFiled: February 10, 1999Date of Patent: March 23, 2004Assignee: Wyeth Holdings CorporationInventors: Vincent J. LaPosta, John H. Eldridge
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Patent number: 6703238Abstract: Methods for expanding antigen-specific T cells in vitro are provided. The methods involve contacting hematopoietic precursor or progenitor cells with a heteroconjugate containing an inhibitor of dipeptidyl peptidase (DPIV) attached to an antigenic peptide, optionally with a culture step to expand T cells with a DPIV inhibitor. The culture may be performed in the absence of exogenously provided cytokines.Type: GrantFiled: March 20, 2001Date of Patent: March 9, 2004Assignee: Point Therapeutics, Inc.Inventors: William Bachovchin, Barbara Wallner
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Patent number: 6699656Abstract: The present invention relates to &bgr;-hCG, particularly &bgr;-hCG proteins having a sequence of amino acids 41-54, 45-54, 47-53, 45-57 and 45-58 and analogs and derivatives thereof. The invention further relates to methods of treatment and prevention of HIV infection by administration of a therapeutic compound of the invention. Such therapeutic compounds include hCG, &bgr;-hCG and &bgr;-hCG peptides, analogs and derivatives of hCG, &bgr;-hCG and &bgr;-hCG peptides, and nucleic acids encoding hCG, &bgr;-hCG and &bgr;-hCG peptides. In a preferred embodiment, &bgr;-hCG peptides, particularly &bgr;-hCG peptides of amino acids 47-53, 45-57 or 45-58 are administered to a subject for treatment or prevention of HIV infection in that subject. The invention also provides methods for screening hCG preparations for activity in treating or preventing HIV infection. Pharmaceutical compositions and methods of administration of Therapeutics are also provided.Type: GrantFiled: November 20, 2001Date of Patent: March 2, 2004Assignee: University of Maryland Biotechnology InstituteInventors: Robert C. Gallo, Joseph Bryant, Yanto Lunardi-Iskandar
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Patent number: 6680058Abstract: Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to induce sterility or long-term contraception in mammals. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in mammals in vivo. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) The two components—the ligand and the lytic peptide—may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide.Type: GrantFiled: February 22, 2000Date of Patent: January 20, 2004Assignee: Board of Supervisors of Louisiana State University and Agricultural and Mechanical CollegeInventors: Frederick M. Enright, Jesse M. Jaynes, William Hansel, Patricia A. Melrose, Philip H. Elzer
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Patent number: 6676941Abstract: 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: November 30, 2001Date of Patent: January 13, 2004Assignee: Board of Regents, The University of Texas SystemInventors: Philip E. Thorpe, Rolf A. Brekken
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Publication number: 20040005334Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.Type: ApplicationFiled: February 2, 1999Publication date: January 8, 2004Inventors: BRIAN SEED, CHARLES ROMEO, WALDEMAR KOLANUS
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Patent number: 6663868Abstract: The present invention relates to methods and compositions for inducing an immune response in a subject, wherein the subject is administered an effective amount of a heat shock protein complexed to a hybrid antigen comprising an antigenic domain and a heat shock protein-binding domain. These methods and compositions may be used in the treatment of infectious diseases and cancers.Type: GrantFiled: February 13, 1998Date of Patent: December 16, 2003Assignee: Sloan-Kettering Institute for Cancer ResearchInventors: James E. Rothman, Franz Ulrich Hartl, Mee H. Hoe, Alan Houghton, Yoshizumi Takeuchi, Mark Mayhew
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Patent number: 6660271Abstract: Disclosed are epitope-containing heat shock fusion proteins, DNA constructs encoding such fusion proteins, and methods of use. More specifically, disclosed are ubiquitin fusion proteins comprising ubiquitin fused to a plurality of identical or non-identical epitopes at specified locations.Type: GrantFiled: September 26, 2001Date of Patent: December 9, 2003Assignee: Proteinix CompanyInventors: John H. Kenten, Alfonso Tramontano, Aprile L. Pilon, Gerald L. Lohnas, Steven F. Roberts
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Patent number: 6652864Abstract: A compound for delivering a non-cytotoxic therapeutic moiety into nerve cells, the compound having the general formula: B—L—TM where: B is a binding agent capable of selectively binding to a nerve cell surface receptor and mediating absorption of the compound by the nerve cell; TM is a therapeutic moiety which has a non-cytotoxic therapeutic effect when absorbed by a nerve cell; and L is a linker coupling B to TM.Type: GrantFiled: December 21, 1998Date of Patent: November 25, 2003Assignee: Asilomar Pharmaceuticals, Inc.Inventors: Robert R. Webb, Constance A. McKee
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Patent number: 6645501Abstract: The present invention provides an anti-pathogen system comprising one or more fusion proteins that includes a transduction domain and a cytotoxic domain. The cytotoxic domain is specifically activated by a pathogen infection. The anti-pathogen system effectively kills or injures cells infected by one or a combination of different pathogens. Further provided are protein transduction domains that provide enhanced transduction efficiency.Type: GrantFiled: February 1, 2001Date of Patent: November 11, 2003Assignee: Washington UniversityInventor: Steven F. Dowdy
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Publication number: 20030202978Abstract: A process for producing a powder comprises spray freeze-drying an aqueous solution or suspension comprising a pharmaceutical agent, said solution or suspension having a solids content of 20% by weight or more. The spray freeze-dried powder may be administered to a subject via a needleless syringe.Type: ApplicationFiled: June 10, 2002Publication date: October 30, 2003Inventors: Yuh-Fun Maa, Steven J. Prestrelski, Terry L. Burkoth
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Patent number: 6627200Abstract: The invention relates to the utilization of monocytes growth factor CD137 or of a functional analogue thereof in order to produce a medicament for promoting the proliferation of peripheral monocytes of a mammal. The invention especially relates to the utilization of the growth factor for treating pathological conditions.Type: GrantFiled: November 30, 2000Date of Patent: September 30, 2003Assignee: Merckle GmbHInventors: Herbert Schwarz, Joachim Langstein
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Patent number: 6599507Abstract: A complex of alpha-fetoprotein (AFP) and N-arachidonoyl aminoethyl phosphate (N-AAP) is shown to have significant immunostimulating properties and can therefore be used as a therapeutic agent in various indications, such as immune deficiencies and in particular immune deficiencies related to cancer therapy.Type: GrantFiled: December 15, 2000Date of Patent: July 29, 2003Assignee: Ardenia Investments, Ltd.Inventor: Oleg Strelchenok
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Patent number: 6592872Abstract: The present invention provides a vaccine for inducing an immune response in mammal to a specific antigen, where the vaccine comprises a unit dose of a binary, cytotoxic T lymphocyte vaccine comprising an anthrax protective antigen and a full length protein antigen bound to a nontoxic anthrax protective antigen binding protein comprising at least about the first 250 amino acid residues of the lethal factor of Bacillus anthracis and less than all of the amino acid residues of the lethal factor. The present invention also provides a method of immunizing a mammal against an antigen using the vaccine, and a method of inducing antigen-presenting mammalian cells to present specific antigens via the MHC class I processing pathway.Type: GrantFiled: September 15, 1997Date of Patent: July 15, 2003Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Kurt Klimpel, Theresa J. Goletz, Naveen Arora, Stephen H. Leppla, Jay A. Berzofsky
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Patent number: 6583272Abstract: Conjugates of erythropoietin with poly(ethylene glycol) comprise an erythropoietin glycoprotein having at least one free amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; the glycoprotein being covalently linked to “n” poly(ethylene glycol) groups of the formula —CO—(CH2)x(OCH2CH2)m—OR with the carbonyl of each poly(ethylene glycol) group forming an amide bond with one of said amino groups; wherein R is lower alkyl; x is 2 or 3; m is about 450 to about 900; n is from 1 to 3; and n and m are chosen so that the molecular weight of the conjugate minus the erythropoietin glycoprotein is from 20 kilodaltons to 100 kilodaltons.Type: GrantFiled: June 27, 2000Date of Patent: June 24, 2003Assignee: Hoffmann-La Roche Inc.Inventor: Pascal Sebastian Bailon
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Patent number: 6579853Abstract: The present invention provides preparations for efficaciously administering ginsenoside Rb1 or its salt useful as cytoprotective agents. More particularly, the present invention provides pharmaceutical compositions comprising ginsenoside Rb1 or its salt for inhibiting apoptosis or apoptosis-like cell death or pharmaceutical compositions comprising ginsenoside Rb1 or its salt for promoting the expression of a cell death-inhibitory gene product Bcl-xL. Further, the present invention provides preparations for intravenous administration comprising ginsenoside Rb1 or its salt. The above pharmaceutical compositions contain ginsenoside Rb1 or its salt at low extracellular concentrations in lesion, preferably at 1 ng/ml or less and still preferably at 1 to 100 fg/ml. These compositions promote the expression of the cell death-inhibitory gene product Bcl-xL and inhibit apoptosis or apoptosis-like cell death.Type: GrantFiled: June 22, 2001Date of Patent: June 17, 2003Assignee: Japan Science and Technology CorporationInventors: Masahiro Sakanaka, Junya Tanaka, Kohji Sato
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Patent number: 6569416Abstract: Compositions for treating viral and bacterial diseases are described. The compositions contain a synthetic soil phenolic polymeric material which contains sulfur, boron, alkaline earth, or transition metals but does not contain nitrogen. The synthetic materials may be synthetic humic acids or fulvic acids. The polymeric materials in the compositions are prepared by oxidizing one or more organic phenols in the presence of inorganic salts. Polymeric materials prepared from organic phenols having at least one carboxylic acid group are especially effective. The compositions can be injected, applied topically, ingested, inhaled, or applied as a suppository.Type: GrantFiled: July 1, 1999Date of Patent: May 27, 2003Assignee: Lamb Biochemicals Corp.Inventor: Richard J. Laub
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Patent number: 6548066Abstract: The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.Type: GrantFiled: May 12, 1998Date of Patent: April 15, 2003Assignee: Aphton CorporationInventors: Dov Michaeli, Martyn Caplin, Susan A. Watson, Stephen Grimes
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Publication number: 20030049273Abstract: The present invention relates to &bgr;-hCG, particularly &bgr;-hCG proteins having a sequence of amino acids 41-54, 45-54, 47-53, 45-57 and 45-58 and analogs and derivatives thereof. The invention further relates to methods of treatment and prevention of HIV infection by administration of a therapeutic compound of the invention. Such therapeutic compounds include hCG, &bgr;-hCG and &bgr;-hCG peptides, analogs and derivatives of hCG, &bgr;-hCG and &bgr;-hCG peptides, and nucleic acids encoding hCG, &bgr;-hCG and &bgr;-hCG peptides. In a preferred embodiment, &bgr;-hCG peptides, particularly &bgr;-hCG peptides of amino acids 47-53,45-57 or 45-58 are administered to a subject for treatment or prevention of HIV infection in that subject. The invention also provides methods for screening hCG preparations for activity in treating or preventing HIV infection. Pharmaceutical compositions and methods of administration of Therapeutics are also provided.Type: ApplicationFiled: November 20, 2001Publication date: March 13, 2003Inventors: Robert C. Gallo, Joseph Bryant, Yanto Lunardi-Iskandar
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Patent number: 6524567Abstract: Phenolic polymers are prepared by oxidizing and polymerizing starting organic compounds comprising at least one hydroxyl group and at least one carbonyl group or at least two hydroxyl groups on an aromatic structure. One or more inorganic compounds or salts is added and the solution is allowed to stand at about 20° C. to 80° C. for a period of about at least 2 hours. Salt molecules as well as starting compounds and other low molecular-weight materials below about 500 to about 10,000 daltons are removed from the product solution. Purified phenolic polymers are prepared in concentrated aqueous solution or in dried powder form in a final step if necessary. The resultant phenolic polymers exhibit physicochemical properties strongly resembling those of typical commercially-available natural-product soil extracts. The materials are active hemorrhagic fever anti-viral agents, and are effective in anti-viral compositions for treating or preventing hemorrhagic fever viral diseases.Type: GrantFiled: October 11, 2001Date of Patent: February 25, 2003Assignee: Laub Biochemicals Corp.Inventor: Richard J. Laub
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Patent number: 6514500Abstract: Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.Type: GrantFiled: September 7, 2000Date of Patent: February 4, 2003Assignee: Conjuchem, Inc.Inventors: Dominique P. Bridon, Benoit L'Archeveque, Alan M. Ezrin, Darren L. Holmes, Anouk Leblanc, Serge St. Pierre
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Patent number: 6506362Abstract: Described are peptides and peptide mimetics that bind to and activate the thrombopoietin receptor. Such peptides and peptide mimetics are useful in methods for treating hematological disorders and particularly, thrombocytopenia resulting from chemotherapy, radiation therapy, or bone marrow transfusions as well as in diagnostic methods employing labeled peptides and peptide mimetics.Type: GrantFiled: April 10, 2001Date of Patent: January 14, 2003Assignee: Glaxo Group LimitedInventors: William J. Dower, Ronald W. Barrett, Steven E. Cwirla, Christian M. Gates, Peter J. Schatz, Palaniappan Balasubramanian, Christopher R. Wagstrom, Richard Wayne Hendren, Randolph B. Deprince, Surekha Podduturi, Qun Yin
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Publication number: 20020182225Abstract: The present invention relates generally to the field of prothrombin time reagents for determining dysfunction in the coagulation system and more specifically to reagents made from native thromboplastin or purified or recombinant tissue factor and phospholipids from a natural or synthetic source. The present invention relates to methods to make a diagnostic reagent that includes a membrane-bound protein incorporated into a liposome and having additional empty liposomes (liposomes without membrane-bound protein incorporated therein) added to the solution.Type: ApplicationFiled: March 22, 2001Publication date: December 5, 2002Inventors: Jianfang Wang, Kevin Bruce Johnson, Liliana Maria Tejidor, Hema Doobay
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Patent number: 6482927Abstract: The present invention relates to the discovery, identification and characterization of nucleotides that encode Ob receptor (ObR), a receptor protein that participates in mammalian body weight regulation. The invention encompasses obR nucleotides, host cell expression systems, ObR proteins, fusion proteins, polypeptides and peptides, antibodies to the receptor, transgenic animals that express an obR transgene, or recombinant knock-out animals that do not express the ObR, antagonists and agonists of the receptor, and other compounds that modulate obR gene expression or ObR activity that can be used for diagnosis, drug screening, clinical trial monitoring, and/or the treatment of body weight disorders, including but not limited to obesity, cachexia and anorexia.Type: GrantFiled: September 3, 1996Date of Patent: November 19, 2002Assignee: Millennium Pharmaceuticals, Inc.Inventors: Louis A. Tartaglia, Robert I. Tepper, Janice A. Culpepper, David W. White
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Patent number: 6482410Abstract: The present invention relates to cytotactin proteins, polypeptides, antibodies (including anti-idiotype antibodies), and other cytotacting derivatives useful in the mediation of neuronal attachment and enhancement of the outgrowth of neurites, as well as to methods of using same. Methods of making the disclosed proteins, polypeptides, antibodies, derivatives and related compositions, which have a variety of diagnostic and therapeutic applications, are also disclosed.Type: GrantFiled: May 22, 1997Date of Patent: November 19, 2002Assignee: The Scripps Research InstituteInventors: Kathryn L. Crossin, Greg Phillips, Anne L. Prieto
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Patent number: 6475490Abstract: The invention relates to methods and compositions for the promotion of tissue repair. Specifically, compositions comprising heat shock proteins, including gp96, hsp90, and hsp70, uncomplexed or complexed noncovalently with antigenic molecules, are disclosed. Therapeutic methods for administering the hsp-containing compositions are disclosed. The disclosed methods are useful for promoting repair of tissues that were disrupted by a variety of causes including trauma (e.g., surgery, injury or burns) or disease or disorder (e.g., atherosclerosis and multiple sclerosis).Type: GrantFiled: October 19, 1998Date of Patent: November 5, 2002Assignee: Fordham UniversityInventors: Pramod K. Srivastava, Rajiv Y. Chandawarkar
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Patent number: 6468540Abstract: Disclosed is a method for inhibiting the proliferation of a tumor in a mammal. The method involves the steps of (a) isolating a stress protein-peptide complex from tumor cells previously removed from the mammal and (b) administering the isolated stress protein-peptide complex back to the mammal in order to stimulate in the mammal an immune response against the tumor from which the complex was isolated. Stress protein-peptide complexes having particular utility in the practice of the instant invention include the Hsp70-peptide, Hsp90-peptide and gp96-peptide complexes.Type: GrantFiled: January 21, 2000Date of Patent: October 22, 2002Assignee: Mount Sinai School of Medicine of New York UniversityInventor: Pramod K. Srivastava
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Patent number: 6461615Abstract: The present invention relates to immunogenic complexes of heat shock proteins (hsp) noncovalently bound to exogenous antigenic molecules which when administered to an individual elicit specific immunological responses in the host. Methods of prevention and treatment of cancer and infectious disease are provided.Type: GrantFiled: April 7, 2000Date of Patent: October 8, 2002Assignee: Fordham UniversityInventor: Pramod K. Srivastava
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Patent number: 6458360Abstract: This invention is directed to a soluble recombinant fused protein which is stable in the mammalian circulatory system comprising a polypeptide which contains a recognition site for a target molecule, such as a complement receptor site, and is joined to the N-terminal end of an immunoglobulin chain. The invention is also directed to a construct comprising a plurality of peptides containing short consensus repeats having a complement binding site attached to a soluble, physiologically compatible, macromolecular carrier. The invention is particularly useful for inhibiting complement activation or complement-dependent cellular activation in mammals.Type: GrantFiled: December 28, 1992Date of Patent: October 1, 2002Assignee: The Johns Hopkins UniversityInventors: Douglas T. Fearon, Thomas Hebell
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Publication number: 20020131973Abstract: A therapeutic system for destroying a target cell within a host having a vascular compartment, the system comprising: (a) a compound comprising a target cellspecific portion and a portion which will convert a selected substantially noncytotoxic substance into a cytotoxic substance, and (b) said substantially noncytotoxic substance, wherein at least the said portion of compound (a) capable of said conversion is, following administration to the host, internalised into said target cell. Preferably, the portion which converts said substantially noncytotoxic substance into a cytotoxic substance requires a factor which is present in sufficient concentration within the target cell for the said portion to effect conversion of said substantially noncytotoxic substance into a cytotoxic substance and which factor is not present in sufficient concentration within the blood of the vascular compartment for the said portion to effect said conversion.Type: ApplicationFiled: December 10, 1998Publication date: September 19, 2002Inventors: KENNETH DAWSON BAGSHAWE, PHILIP JOHN BURKE
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Patent number: 6419930Abstract: A pharmacological composition including a component having pressure reductive activity obtained from Mycoleptodonoides aitchisonii fruit body which is safe and cheap, harvested constantly year-round by artificial cultivation, with equal quality, and useful for prevention and/or amelioration of symptom of hypertension caused by angiotensin I converting enzyme or the like. The invention also includes foods or beverages containing the pharmacological compositions, and methods of preventing or treating hypertension by administration of the composition.Type: GrantFiled: March 30, 2001Date of Patent: July 16, 2002Assignee: Kirin Beer Kabushiki KaishaInventors: Taku Sato, Nobuhito Shiragaki, Tomoe Kawatsu, Toshihiko Hori
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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: 6410028Abstract: The present invention relates to immunogenic complexes of heat shock proteins (hsp) noncovalently bound to exogenous antigenic molecules which when administered to an individual elicit specific immunological responses in the host. Methods of prevention and treatment of cancer and infectious disease are provided.Type: GrantFiled: August 9, 1999Date of Patent: June 25, 2002Assignee: Fordham UniversityInventor: Pramod K. Srivastava
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Patent number: 6406699Abstract: A cancer immunotherapy method and composition for treating cancer in a patient comprised of vaccinating a patient with a vaccine comprised of the patient's own malignancy and an immunologic adjuvant, removing primed peripheral blood T lymphocytes from the patient, stimulating the primed T lymphocytes to differentiate into effector lymphocytes in vitro, stimulating the effector T lymphocytes to proliferate in vitro, and infusing the effector T lymphocytes back into the patient.Type: GrantFiled: October 5, 1999Date of Patent: June 18, 2002Inventor: Gary W. Wood
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Patent number: 6403092Abstract: 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.Type: GrantFiled: March 31, 1999Date of Patent: June 11, 2002Assignee: Duke UniversityInventors: Salvatore Pizzo, Hanne Grøn
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Patent number: 6403096Abstract: A novel permeability enhancing peptide (PEP) is a fragment of interleukin-2. When joined to a delivery vehicle that can target a tumor site, the PEP can increase the subsequent uptake of antineoplastic or tumor imaging agents. The PEP can be chemically joined to a monoclonal antibody to form an immunoconjugate. Alternatively, an expression vector is genetically engineered to express a fusion protein. The fusion protein has an antigen-binding portion joined to the PEP. The PEP is most effective when it takes the form of a dimer, linked by a disulfide bridge. The PEP is substantially free of cytokine activity and produces minimal toxic side effects on normal tissues.Type: GrantFiled: November 18, 1999Date of Patent: June 11, 2002Assignee: University of Southern CaliforniaInventors: Alan L. Epstein, Leslie A. Khawli
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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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Methods and compositions for treating platelet-related disorders using MPL pathway inhibitory agents
Patent number: 6376242Abstract: The invention relates to the treatment of subjects for the purpose inhibiting vaso-occlusive events, including thrombosis and embolism, by administering agents which reduce the number of circulating platelets to low or below normal levels. Methods and pharmaceutical preparations comprising such agents are provided.Type: GrantFiled: September 21, 2000Date of Patent: April 23, 2002Assignee: Emory UniversityInventor: Stephen R. Hanson -
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: 6340470Abstract: A soluble isoflavone composition comprises isoflavone and a solubilizing agent consisting of anhydrous or water-containing propylene glycol and/or octenyl succinate-treated starch. The soluble isoflavone composition is prepared by, for instance, a method which comprises the step of heating isoflavone and a solubilizing agent consisting of anhydrous or water-containing propylene glycol and/or octenyl succinate-treated starch in the presence of water to thus solubilize isoflavone in water. The soluble isoflavone composition of the present invention has high solubility in water, is easily dissolved in water and is stable over a long period of time.Type: GrantFiled: December 29, 1999Date of Patent: January 22, 2002Assignee: Matsutani Chemical Industries Co., Ltd.Inventor: Koji Tsukuda
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Patent number: 6322790Abstract: The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic noeplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. “Antigenic molecule” as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual.Type: GrantFiled: August 18, 1998Date of Patent: November 27, 2001Assignee: Fordham UniversityInventor: Pramod K. Srivastava
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Patent number: 6319504Abstract: The present invention relates to &bgr;-hCG, particularly &bgr;-hCG proteins having a sequence of amino acids 41-54, 45-54, 47-53, 45-57 and 45-58 and analogs and derivatives thereof. The invention further relates to methods of treatment and prevention of HIV infection by administration of a therapeutic compound of the invention. Such therapeutic compounds include hCG, &bgr;-hCG and &bgr;-hCG peptides, analogs and derivatives of hCG, &bgr;-hCG and &bgr;-hCG peptides, and nucleic acids encoding hCG, &bgr;-hCG and &bgr;-hCG peptides. In a preferred embodiment, &bgr;-hCG peptides, particularly &bgr;-hCG peptides of amino acids 47-53, 45-57 or 45-58 are administered to a subject for treatment or prevention of HIV infection in that subject. The invention also provides methods for screening hCG preparations for activity in treating or preventing HIV infection. Pharmaceutical compositions and methods of administration of Therapeutics are also provided.Type: GrantFiled: September 9, 1996Date of Patent: November 20, 2001Assignee: University of Maryland Biotechnology InstituteInventors: Robert C. Gallo, Joseph Bryant, Yanto Lunardi-Iskandar
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Patent number: 6319503Abstract: Disclosed are epitope-containing heat shock fusion proteins, DNA constructs encoding such fusion proteins, and methods of use. More specifically, disclosed are ubiquitin fusion proteins comprising ubiquitin fused to a plurality of identical or non-identical epitopes at specified locations.Type: GrantFiled: February 19, 1998Date of Patent: November 20, 2001Assignee: Proteinix CompanyInventors: John H. Kenten, Alfonso Tramontano, Aprile L. Pilon, Gerald L. Lohnas, Steven F. Roberts
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Patent number: 6316003Abstract: This invention relates to delivery of biologically active cargo molecules, such as polypeptides and nucleic acids, into the cytoplasm and nuclei of cells in vitro and in vivo. Intracellular delivery of cargo molecules according to this invention is accomplished by the use of novel transport polypeptides which include HIV tat protein or one or more portions thereof, and which are covalently attached to cargo molecules. The transport polypeptides in preferred embodiments of this invention are characterized by the presence of the tat basic region (amino acids 49-57), the absence of the tat cysteine-rich region (amino acids 22-36) and the absence of the tat exon 2-encoded carboxy-terminal domain (amino acids 73-86) of the naturally-occurring tat protein. By virtue of the absence of the cysteine-rich region, the preferred transport polypeptides of this invention solve the potential problems of spurious trans-activation and disulfide aggregation.Type: GrantFiled: April 28, 1994Date of Patent: November 13, 2001Assignees: Whitehead Institute for Biomedical Research, Johns Hopkins Univ. School of Medicine, Biogen, Inc.Inventors: Alan Frankel, Carl Pabo, James G. Barsoum, Stephen E. Fawell, R. Blake Pepinsky
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Patent number: 6313089Abstract: Provided herein are compositions comprising complexes of apolipoprotein E and ciliary neurotrophic factor. The apolipoprotein E can be any isoform, but is preferably apolipoprotein E3. Also preferred are covalent complexes of apolipoprotein E and ciliary neurotrophic factor, more preferably those formed by intermolecular disulfide bonds between cysteine residues. Further provided are methods of enhancing the survival of neural cells by administering a composition comprising a complex of apolipoprotein E and ciliary neurotrophic factor. The claimed methods can be carried out both in vitro and in vivo.Type: GrantFiled: August 18, 1998Date of Patent: November 6, 2001Assignee: Duke UniversityInventors: William D. Matthew, Warren J. Strittmatter, Catherine R. Gutman
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Patent number: 6309646Abstract: A method is disclosed for producing a soluble conjugate vaccine, and preferably protein/polysaccharide conjugates. In this process, the polysaccharide is reacted with a reagent so as to provide a functional group on the polysaccharide molecule. Once the functional group is in place, the polysaccharide is reacted with a homobifunctional or heterobifunctional vinylsulfone to produce a vinylsulfone derivatized polysaccharide. Thereafter, the vinylsulfone derivatized polysaccharide is reacted with a protein to produce the conjugate. If desired, the protein may be derivatized with a functional group prior to the conjugation reaction step. In an alternative embodiment, the protein may be functionalized with a reactive group and then derivatized with the vinylsulfone group to produce a vinylsulfone derivatized protein. This protein may then be reacted with a polysaccharide to produce the conjugate. Optionally, the polysaccharide may be functionalized with a reactive group prior to the conjugation reaction.Type: GrantFiled: May 7, 1997Date of Patent: October 30, 2001Assignee: The Henry M. Jackson Foundation for the Advancement of Military MedicineInventor: Andrew Lees
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Publication number: 20010024652Abstract: The invention involves isolation of nucleic acid molecules, the expression of which are upregulated by interleukin-9. The amino acid sequences of the proteins which correspond to the nucleic acid molecules show some structural features of cytokines. In addition to the nucleic acid molecules and the proteins, various uses of the molecules are disclosed. The molecules are referred to as T cell inducible factors.Type: ApplicationFiled: December 29, 2000Publication date: September 27, 2001Inventors: Laure Dumoutier, Jamila Louahed, Jean-Christophe Renauld
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Patent number: 6267964Abstract: A process for extending the half-life in vivo by a biologically active protein or peptide, characterized by covalently coupling said protein or peptide to a polypeptide fragment capable of binding to a serum protein, whereby when administering the resulting protein or peptide conjugate its binding to the serum protein results in extended biological activity, the use of the protein or peptide conjugate above for manufacturing a medicament which, when administered to a mammal including man, shows extended half-life in vivo; and a method of therapeutic or prophylactic treatment.Type: GrantFiled: December 8, 1993Date of Patent: July 31, 2001Assignee: Affibody Technology Sweden ABInventors: Per Åke Nygren, Hans Wigzell, Mathias UhlĂ©n
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Patent number: 6258361Abstract: The invention relates to a method for recovering hematopoietic function in a patient. The method includes administering orally to the patient an amount of a peanut seed coat-substance which exhibits bone marrow cell-proliferating activity and which is soluble in either water or ethanol, effective to recover hematopoietic function in the patient.Type: GrantFiled: February 2, 2000Date of Patent: July 10, 2001Assignees: Manami YahagiInventors: Akio Yoshihara, Nobuo Yahagi, Shinji Fushiya, Fumihide Takano, Hiroshi Hojo