Polymeric, E.g., Polyethylene Glycol, Etc. Patents (Class 530/421)
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Patent number: 7407932Abstract: Methods for use of an exendin, an exendin agonist, or a modified exendin or exendin agonist having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, for lowering glucagon levels and/or suppressing glucagon secretion in a subject are provided. These methods are useful in treating hyperglucagonemia and other conditions that would be benefited by lowering plasma glucgon or suppressing glucagon secretion.Type: GrantFiled: October 19, 2006Date of Patent: August 5, 2008Assignee: Amylin Pharmaceuticals, Inc.Inventors: Andrew A. Young, Bronislava Gedulin
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Publication number: 20080139465Abstract: A process suitable for processing scaled-up amounts of source material in the range of tens of kilograms for the purification of alpha-1 proteinase inhibitor (API) from a mixture of unpurified proteins is provided. More particularly, a process for the purification of API from blood plasma or from plasma fractions to obtain pharmaceutical grade API on a commercial scale is provided. The API produced by the process is highly pure (at least 90% API out of the total protein) and highly active (at least 90% active API). Pharmaceutical compositions comprising the purified API and methods of using same are also described.Type: ApplicationFiled: June 23, 2005Publication date: June 12, 2008Applicant: KAMADA LTD.Inventor: Shabtai Bauer
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Patent number: 7211650Abstract: The present invention provides a method for the part purification of fibrinogen from milk, the method comprising the transfer of protease enzyme which is present in the milk, into the whey phase with the removal or partition if fibrinogen into another phase of the milk. The present invention also provides a method for obtaining fibrinogen from a fluid, the method comprising: a) contacting the fluid with a hydrophobic interaction chromatography resin under conditions where the fibrinogen binds to the resin; and b) removing the bound protein by means of elution.Type: GrantFiled: March 22, 2001Date of Patent: May 1, 2007Assignee: Pharming Intellectual Property BVInventors: Graham McCreath, Udell Michael
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Patent number: 7193056Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.Type: GrantFiled: June 8, 2004Date of Patent: March 20, 2007Assignee: Pharmacia & UpJohn ABInventors: Hans Ageland, Lena Nyström, Josefine Persson, Folke Tjerneld
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Patent number: 7087719Abstract: The present invention relates to the purification and production of human albumin from various sources through crystallization and repeated crystallization. Basic features of the invented process include providing specific reaction conditions and precipitating reagents to maximize albumin crystallization. Solubility diagrams are utilized as the basis for process control of the invented method. The current invention specifically controls phosphate concentration, pH and temperature to precisely guide crystallization kinetics and crystal yield.Type: GrantFiled: November 19, 2002Date of Patent: August 8, 2006Assignee: GTC Biotherapeutics, Inc.Inventors: Kalevi Visuri, Sinikka Uotila, Scott P. Fulton, Daniel E. Couto
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Patent number: 7060299Abstract: Disclosed herein are biodegradable microparticle compositions, and methods for the generation of biodegradable and biocompatible microparticles that stabilize proteins and also control the kinetics of release of proteins over a period of several weeks to several months under physiological conditions.Type: GrantFiled: December 31, 2003Date of Patent: June 13, 2006Assignee: Battelle Memorial InstituteInventors: Sreedhara Alavattam, Richard S. Brody
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Patent number: 7038016Abstract: The present invention employs a dissolved activated polyethylene glycol (aPEG) or related molecule that has been passed through a filtration means for the substantial reduction of bioburden or endotoxin levels in the aPEG solution. The resulting filtered aPEG solution can be used for the preparation of a PEGylated hemoglobin solution containing substantially reduced levels of bioburden or endotoxin.Type: GrantFiled: August 21, 2001Date of Patent: May 2, 2006Assignee: Apex Bioscience, Inc.Inventors: Todd Lewis Talarico, Cyrus John Stacey
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Patent number: 7022673Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.Type: GrantFiled: April 11, 2002Date of Patent: April 4, 2006Assignee: Chiron CorporationInventors: Robert J. Drummond, Steve Rosenberg
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Patent number: 6989373Abstract: The present invention relates to a method for treating damaged or degenerated fat pads in a foot of a host in need thereof. The method comprises the step of injecting into the fat pad of the host a biocompatiable solution having physico-chemical and mechanical properties substantially similar to a fatty acid mixture normally present in a healthy fat pad.Type: GrantFiled: October 29, 2001Date of Patent: January 24, 2006Assignee: Bio Syntech Canada Inc.Inventor: Eric André DesRosiers
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Patent number: 6989436Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual and complexed subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the specific subunit complexes in their native conformation in liquid medium.Type: GrantFiled: February 4, 2003Date of Patent: January 24, 2006Assignee: Medical Analysis Systems, Inc.Inventors: Kirti I. Davé, Brian Robert Fernández
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Patent number: 6875848Abstract: The gammaglobulin is extracted from a fraction isolated by fractionation with ethanol in the presence of a carbohydrate, and after reducing the content of contaminants with PEG, it is applied to an anionic resin exchange column, an effluent being obtained in which the PEG content is subsequently reduced by ultrafiltration and which is concentrated in order to carry out sequentially an optional treatment at an acid pH and at least one of the following steps of viral inactivation, consisting of pasteurisation and a treatment with solvent/detergent, the product afterwards being precipitated and washed with PEG in order to eliminate any chemical viral inactivation reagents and then, by solubilisation and change of pH, the protein contaminants, and finally purified by ultrafiltration to reduce the volume and the PEG content, then carrying out an optional virus filtration and subsequent concentration.Type: GrantFiled: January 17, 2002Date of Patent: April 5, 2005Assignee: Probitas Pharma, S.A.Inventors: Pere Ristol Debart, Francisco Rabaneda Gimenez, Ma Teresa Lopez Hernandez
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Patent number: 6872700Abstract: Methods for use of an exendin, an exendin agonist, or a modified exendin or exendin agonist having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, for lowering glucagon levels and/or suppressing glucagon secretion in a subject are provide. These methods are useful in treating hyperglucagonemia and other conditions that would be benefited by lowering plasma glucagon or suppressing glucagon secretion.Type: GrantFiled: January 14, 2000Date of Patent: March 29, 2005Assignee: Amylin Pharmaceuticals, Inc.Inventors: Andrew A. Young, Bronislava Gedulin
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Patent number: 6767994Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.Type: GrantFiled: May 16, 2000Date of Patent: July 27, 2004Assignee: Pharmacia ABInventors: Hans Ageland, Lena Nyström, Josefine Persson, Folke Tjerneld
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Patent number: 6709655Abstract: The present invention is directed to a pharmaceutical composition comprising F(ab′)2 antibody fragments that are preferably free from albumin and of whole antibodies and also substantially free of pyrogens, and an effective amount of a pharmaceutically acceptable carrier. It is also directed to a method for the production of a pharmaceutical composition comprising F(ab′)2 antibody fragments using serum or blood plasma of a mammal that has been previously immunized, as a source of antibodies. The serum or blood plasma is digested with pepsin, followed by separation and purification until the pharmaceutical composition of F(ab′)2 fragments is free of albumin and complete antibodies, and substantially free of pyrogens.Type: GrantFiled: March 5, 2001Date of Patent: March 23, 2004Assignee: Instituto Bioclon, S.A. de C.V.Inventors: Juan López de Silanes, Rita Mancilla Nava, Jorge F. Paniagua Solis
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Patent number: 6676840Abstract: The precipitation and removal of suspended fat and protein components and other suspended solids from a given solution can be accomplished by the addition of an aluminate to complex with the fat and protein components and the addition of a flocculating agent to flocculate the aluminate/fat and protein component complexes into insoluble particles capable of removal by conventional technology, which insoluble particles can be rendered to produce tallow.Type: GrantFiled: March 22, 2002Date of Patent: January 13, 2004Assignee: Power Engineering CompanyInventors: Bryon J. Tarbet, Robert D. Hancock, Jeffrey W. Zidek
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Patent number: 6635746Abstract: Immunogenic compositions including vaccines are described that comprise an outer membrane antigen extract of a strain of Chlamydia and are effective in protection against disease caused by Chlamydia infection The immunogenic compositions may comprise the major outer membrane protein (MOMP) of Chlamydia which may be in a homooligomeric form or complexed with at least one other antigen of Chlamydia. The immunogenic composition may include an immunostimulating complex (ISCOM) and the outer membrane antigen may be incorporated therein. The immunogenic compositions have utility as chlamydial vaccines and in diagnostic applications.Type: GrantFiled: May 28, 1999Date of Patent: October 21, 2003Assignee: Aventis Pasteur LimitedInventors: Andrew D. Murdin, Brian J. Underdown
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Patent number: 6605273Abstract: Methods for treating treatment-naive as well as treatment-experienced patients having RCC to achieve at least a partial tumor response involving administering a therapeutically effective amount of pegylated interferon-alpha, e.g., pegylated interferon alpha-2b as monotherapy or in association with a therapeutically effective amount of IL-2 are disclosed.Type: GrantFiled: July 9, 2001Date of Patent: August 12, 2003Assignee: Schering CorporationInventors: Mary Ellen Ryback, Esther Helen Rose
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Patent number: 6559284Abstract: The present invention relates to a composition for use in purification of apolipoprotein A (ApoA) or apolipoprotein E (ApoE), said composition comprising a first and a second polymeric material, wherein the first and second polymeric material are immiscible in the primary aqueous solution, and wherein the second polymeric material is amphiphilic and water soluble. The invention further relates to a process for purifying ApoA or ApoE, or variants or mixtures thereof, by first mixing ApoA or ApoE, the composition containing a first and second polymeric material and water. The resulting primary aqueous solution is maintained for a period of time sufficient for essentially separating the phases formed, and removing the phase containing the second polymeric material and the main portion of ApoA or ApoE. Subsequently, the second polymeric material is separated from ApoA or ApoE.Type: GrantFiled: September 5, 1997Date of Patent: May 6, 2003Assignee: Esperion Therapeutics, Inc.Inventors: Hans Ageland, Lena Nyström, Josefine Persson, Folke Tjerneld
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Patent number: 6491923Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the individual subunit in its native conformation in liquid medium, which in turn acts to stabilize its biological activity.Type: GrantFiled: May 2, 2000Date of Patent: December 10, 2002Inventors: Kirti I. Davé, Janos Botyanszki, Eva Sintar
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Patent number: 6485725Abstract: A method for producing an immunoglobulin preparation for intravenous injection, which comprises the steps of: fractionating an immunoglobulin-containing solution with 4 to 10 w/v% of polyethylene glycol having a molecular weight of from 1,000 to 10,000, at a pH value of from 4.5 to 6.5, an ionic strength of from 0.0001 to 0.1 M and a temperature of from 0 to 4° C. to recover a supernatant fraction; and concentrating the supernatant fraction at a pH of from 3.5 to 5.0.Type: GrantFiled: May 3, 2000Date of Patent: November 26, 2002Assignee: Welfide CorporationInventors: Yutaka Hirao, Motonori Hashimoto, Tae Kitamura, Yahiro Uemura
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Patent number: 6479300Abstract: Methods, compositions and devices for purifying polypeptides and/or proteins using metal loaded ligand bound membranes by metal ion affinity chromatography are described.Type: GrantFiled: September 22, 1999Date of Patent: November 12, 2002Assignees: Millipore Corporation, IBC Advanced Technologies, Inc.Inventors: Tongbo Jiang, Anthony J. DiLeo, Ronald L. Bruening
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Patent number: 6444211Abstract: Pertactin (formerly 69 kDa protein) is recovered in stable biologically pure form having no detectable adenylate cyclase activity from fermentation broth from the fermentation of Bordetella pertussis as well as from the cells. The broth is processed to selectively remove pertussis toxin (PT) and filamentous haemagglutinin (FHA), the pertactin is precipitated by ammonium sulphate and the precipitate is dissolved in buffer at pH 6.0 to 8.5, the solution then is passed through hydroxyapatite and ion-exchange chromatograph columns before final ultrafiltration. Cells are extracted with urea and the extract ultrafiltered and diafiltered. The pertactin is precipitated from the extract and the precipitate processed as above. In a variation, the broth is contacted with ammonium sulphate to precipitate pertactin, PT and FHA, the precipitate is dissolved and the PT and FHA selectively removed, before the solution is passed to the chromatograph columns.Type: GrantFiled: June 8, 1999Date of Patent: September 3, 2002Assignee: Connaught Laboratories, Inc.Inventors: Gail Jackson, Raafat Fahim, Larry Tan, Pele Chong, John Vose, Michel Klein
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Patent number: 6437101Abstract: Methods are provided in this invention for the isolation of human growth hormone, growth hormone antagonist, or a homologue of either, from a biological source. The methods of the invention use multi-phase extraction.Type: GrantFiled: May 7, 1999Date of Patent: August 20, 2002Assignee: Akzo Nobel N.V.Inventors: Kirk James Hayenga, Pascal P. Valex
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Patent number: 6423685Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.Type: GrantFiled: March 5, 1999Date of Patent: July 23, 2002Assignee: Chiron CorporationInventors: Robert J. Drummond, Steve Rosenberg
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Publication number: 20020086819Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.Type: ApplicationFiled: March 5, 1999Publication date: July 4, 2002Inventors: ROBERT DRUMMOND, STEVE ROSENBERG
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Patent number: 6372145Abstract: The precipitation and removal of suspended fat and protein components and other suspended solids from a given solution can be accomplished by the addition of an aluminate to complex with the fat and protein components and the addition of a flocculating agent to flocculate the aluminate/fat and protein component complexes into insoluble particles capable of removal by conventional technology, which insoluble particles can be rendered to produce tallow.Type: GrantFiled: June 5, 2000Date of Patent: April 16, 2002Assignee: Power Engineering CompanyInventors: Bryon J. Tarbet, Robert D. Hancock, Jeffrey W. Zidek
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Patent number: 6350730Abstract: The present invention relates generally to the control of body weight of animals including mammals and humans, and more particularly to materials identified herein as modulators of body weight, and to diagnostic and therapeutic uses of such modulators. In one of its broadest aspects, the present invention relates to nucleotide sequences corresponding to the murine and human OB gene, and two isoforms thereof, and proteins expressed by such nucleotides or degenerate variations thereof, that demonstrate the ability to participate in the control of mammalian body weight and that have been postulated to play a critical role in the regulation of body weight and adiposity. The present invention further provides nucleic acid molecules for use as molecular probes or as primers for polymerase chain reaction (PCR) amplification. In further aspects, the present invention provides cloning vectors and mammalian expression vectors comprising the nucleic acid molecules of the invention.Type: GrantFiled: June 7, 1995Date of Patent: February 26, 2002Assignee: The Rockefeller UniversityInventors: Jeffrey M. Friedman, Yiying Zhang, Ricardo Proenca
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Patent number: 6307013Abstract: Protein suspensions comprising soluble and insoluble components are purified via flocculation with anionic polymers, such as polyacrylamides, potato starch, or modified cellulose. The procedure improves the efficiency of solid/liquid separations and can minimize or eliminate the requirement for centrifugation and/or filtration in large scale biotechnological processes. The method is particularly well suited for the purification and clarification of protein suspensions containing soluble somatotropin monomer using polyacrylamide and polysaccharide flocculants.Type: GrantFiled: July 16, 1999Date of Patent: October 23, 2001Assignee: Monsanto Technology LLCInventor: Mark L. Chivers
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Patent number: 6284874Abstract: The present invention is directed to a process for purifying &agr;1-proteinase inhibitor. The process comprises providing an impure protein fraction which comprises &agr;1-proteinase inhibitor. The impure protein fraction is precipitated with a precipitant comprising PEG. The supernatant from the PEG precipitation, which comprises &agr;1-proteinase inhibitor, is collected and applied to an anion-exchange medium. A fraction comprising &agr;1-proteinase inhibitor is recovered from the anion-exchange medium and applied to a metal chelate medium. A fraction comprising &agr;1-proteinase inhibitor is then recovered from the metal chelate medium. Alpha1-proteinase inhibitor purified by the process has a specific activity greater than 0.6 units/mg.Type: GrantFiled: June 17, 1994Date of Patent: September 4, 2001Assignee: Alpha Therapeutic CorporationInventors: T. (Tom) Taniguchi, John M. Rolf, Prabir Bhattacharya, Yahiro (Roy) Uemura
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Patent number: 6281336Abstract: The present invention relates to a process for purifying immunoglobulin G from a crude immunoglobulin-containing plasma protein fraction. Said process includes a number of steps of which the anion exchange chromatography and the cation exchange chromatography are preferably connected in series. An acetate buffer having a pH of about 5.0-6.0 and having a molarity of about 5-25 mM is preferably used throughout the purification process. The invention further comprises an immunoglobulin product which is obtainable by this process. The invention also relates to an immunoglobulin product which has a purity of more than 98%, has a content of IgG monomers and dimers of more than 98.5%, has a content of IgA less than 4 mg of IgA/l, and contains less than 0.5% polymers and aggregates. Said product does not comprise detergent, PEG or albumin as a stabilizer. The product is stable, virus-safe, liquid and ready for instant intravenous administration.Type: GrantFiled: June 9, 1999Date of Patent: August 28, 2001Assignee: Statens Serum InstitutInventors: Inga Laursen, Børge Teisner
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Patent number: 6261803Abstract: The present invention relates to a process for preparing functional recombinant tissue factor in a prokaryotic host organism.Type: GrantFiled: November 6, 1998Date of Patent: July 17, 2001Assignee: Dade Behring Marburg, GmbHInventors: Norbert Zander, Leszek Wieczorek
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Patent number: 6204362Abstract: In a method of purifying whey separated from lactic acid fermentation liquid by electrodialysis wherein said whey contains angiotensin-converting enzyme inhibiting peptides, the improvement which comprises using an anion exchange membrane having a permeability of diffusion coefficient in the range of 3.0 to 9.0×10−6 cm/sec. An anion exchange membrane having a permeability of diffusion coefficient in the range of 5.0 to 7.0×10−6 cm/sec. is more efficiently used. The product is particularly suited to produce granules and tablets.Type: GrantFiled: January 14, 1999Date of Patent: March 20, 2001Assignee: Calpis Co., Ltd.Inventors: Shuji Kitamura, Takashi Ueyama
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Patent number: 6166187Abstract: A sample is prepared from blood in a manner which makes it possible to further analyze proteins in the sample, e.g. to detect prions in the sample. Blood is extracted, allowed to clot and subjected to separation processing (e.g. centrifugation) to obtain serum. The serum is treated with a complexing agent which agent binds prions in the sample forming an agent/protein complex which makes it possible to concentrate the complex. Concentration of the complex results in a sample which can be successfully analyzed, e.g. assayed using a range of different types of assay methodologies for detecting prions.Type: GrantFiled: March 5, 1999Date of Patent: December 26, 2000Assignee: The Regents of the University of CaliforniaInventors: Stanley B. Prusiner, Jiri G. Safar
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Patent number: 6159471Abstract: A method for producing an immunoglobulin preparation for intravenous injection, which comprises the steps of: fractionating an immunoglobulin-containing solution with 4 to 10 w/v % of polyethylene glycol having a molecular weight of from 1,000 to 10,000, at a pH value of from 4.5 to 6.5, an ionic strength of from 0.0001 to 0.1 M and a temperature of from 0 to 4.degree. C. to recover a supernatant fraction; and concentrating the supernatant fraction at a pH of from 3.5 to 5.0.Type: GrantFiled: October 23, 1998Date of Patent: December 12, 2000Assignee: Yoshitomi Pharmaceutical Industries, Ltd.Inventors: Yutaka Hirao, Motonori Hashimoto, Tae Kitamura, Yahiro Uemura
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Patent number: 6124432Abstract: The present invention aims at providing a method for preparing dermonecrotic toxin, an improved toxoid of dermonecrotic toxin produced by Bordetelia and a toxoid mixture comprising said improved toxoid of dermonecrotic toxin produced by Bordetella and a toxoid of dermonecrotic toxin produced by Pasteurella. There is provided a method for partially purifying dermonecrotic toxin which comprises bringing a dermonecrotic toxin-containing solution into contact with a chromatographic gel sulfated by direct sulfation or a chromatographic gel to which a sulfated molecule is covalently bonded to thereby make the dermonecrotic toxin adsorbed on the gel, and eluting the adsorbed dermonecrotic toxin from the gel.Type: GrantFiled: December 2, 1996Date of Patent: September 26, 2000Assignee: Juridical Foundation The Chemo-Sero-Therapeutic Research InstituteInventors: Toru Kawai, Toshihiro Ushijima, Kozo Takase, Hideo Fujikawa
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Patent number: 6107467Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.Type: GrantFiled: September 5, 1997Date of Patent: August 22, 2000Assignee: Pharmacia & Upjohn ABInventors: Hans Ageland, Lena Nystrom, Josefine Persson, Folke Tjerneld
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Patent number: 6087478Abstract: The present invention provides a crystal containing the N-terminal domain of a STAT protein that is of sufficient quality to perform X-ray crystallographic studies. Methods of preparing the crystals are include in the invention. The present invention further discloses the three-dimensional structure of the crystal. The present invention also provides methods of using the structural information in drug discovery and drug development.Type: GrantFiled: January 23, 1998Date of Patent: July 11, 2000Assignee: The Rockefeller UniversityInventors: Uwe Vinkemeier, Ismail Moarefi, James E. Darnell, Jr., John Kuriyan
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Patent number: 6072040Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the individual subunit in its native conformation in liquid medium, which in turn acts to stabilize its biological activity.Type: GrantFiled: October 15, 1997Date of Patent: June 6, 2000Assignee: Medical Analysis Systems, Inc.Inventors: Kirti I. Dave, Janos Botyanszki, Eva Sintar
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Patent number: 6025146Abstract: The present invention is directed to methods for crystallizing macrophage colony stimulating factor. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.Type: GrantFiled: June 5, 1995Date of Patent: February 15, 2000Assignee: Chiron CorporationInventors: Jayvardhan Pandit, Jarmila Jancarik, Sung-Hou Kim, Kirston Koths, Robert Halenbeck, Anna Lisa Fear, Eric Taylor, Ralph Yamamoto, Andrew Bohm
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Patent number: 5990289Abstract: The instant invention relate to a new method for the purification of proteins using copper chelate-affinity chromatography, wherein the impure or pre-purified protein is adsorbed on immobilized copper(II) ions, optionally washed with buffer and deionized water, washed with a solution of a Lewis-base, and finally eluted with deionized water.Type: GrantFiled: January 2, 1998Date of Patent: November 23, 1999Assignee: Novartis AGInventors: Pierre Fran.cedilla.ois Fauquex, Catherine Georges
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Patent number: 5990081Abstract: A substantially endotoxin-free ApoA or ApoE is produced by recombinant DNA technique, suitably in E. coli. Medicaments and methods for treatment of atherosclerosis or cardiovascular diseases employ ApoA or ApoE purified by a process comprising contacting a first aqueous solution comprising ApoA or ApoE and endotoxins with a matrix comprising an immobilized compound with an end group comprising two or three nitrogen atoms bonded to a carbon atom for attaching the endotoxins to the matrix, and subsequently treating the matrix comprising the immobilized compound with a second aqueous solution comprising a surfactant for releasing the ApoA or ApoE while the endotoxins remain attached to the matrix.Type: GrantFiled: August 5, 1998Date of Patent: November 23, 1999Assignee: Esperion Therapeutics, Inc.Inventors: Hans Ageland, Lena Romander
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Patent number: 5981715Abstract: The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.Type: GrantFiled: March 31, 1997Date of Patent: November 9, 1999Assignee: Alpha Therapeutic CorporationInventors: Duk Sung Hwang, Evelyn Nario, Mark Lepe, Lyndon Luz, Hirokazu Ito, Kazuo Takechi
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Patent number: 5976382Abstract: There is provided water insoluble cross-linked polycarboxylic acid having at least two strands in a strand skeleton of the formula: ##STR1## wherein one carbonyl group of at least one maleoyl moiety thereof in each strand is covalently linked to a--HN.[(H).sub.p (CH).sub.2.(OH).sub.m ].NH-- moietyto provide the presence therein of at least one cross linked moiety of the formula: ##STR2## wherein R is hydrogen or lower alkylene or lower alkoxy of 1-4 carbon atoms, or phenyl, x and y are integers, z is an integer of 1-6, p is 0 or an integer up to z-1, m is 0 or an integer up to z, and w is an integer from 2-12. There is disclosed a method of making such polycarboxylic acid as well as methods of utilizing same to remove proteins from aqueous media containing same to provide a matrix. Methods are disclosed for recovering proteins from said matrix without denaturing them and methods for recovering the polycarboxylic acid from said matrix.Type: GrantFiled: July 10, 1996Date of Patent: November 2, 1999Assignee: LigoChem, Inc.Inventor: John Krupey
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Patent number: 5977324Abstract: A method of concentrating a disease-related conformation of a protein such as the PrP.sup.Sc in a sample is disclosed. The method comprises liquefying the sample and adding a complexing agent such as phosphotungstic acid (PTA) which complexes preferentially or exclusively with the PrP.sup.Sc. After the complex is formed the composition is centrifuged until the complex settles at the bottom. Thereafter, the supernatant is poured away. The remaining pellet may be resuspended in an aqueous solution containing a protease inhibitor for storage. The PTA stains the PrP.sup.Sc making the resulting concentrated PrP.sup.Sc susceptible to further analysis, making it possible to quickly and efficiently determine the presence of PrP.sup.Sc and its concentration in a sample. The method can be used to render a sample non-infectious by removing all or substantial of the infectious form of a protein from a sample.Type: GrantFiled: February 20, 1998Date of Patent: November 2, 1999Assignee: The Regents of the University of CaliforniaInventors: Stanley B. Prusiner, Jiri G. Safar
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Patent number: 5958248Abstract: A method and a system which enable simple and inexpensive removal of heavy metals from a heavy-metal-containing substance. In this method, a substance containing heavy metals and water are introduced into a mixing bath in proportions by weight of 1:3 to 1:6. A strong acid is added to the mixture, and the mixture is stirred while its pH is maintained at a pH lower than 4. As a result of stirring of the substance at a pH 4, heavy metals are extracted into the liquid as metal ions. The metal-ion-containing liquid is input to a heavy metal precipitation bath, and the pH of the liquid is increased to a pH higher than 10 by addition of alkali to the liquid. Gas bubbles of carbonic acid gas are input to the liquid from a lower portion of the heavy metal precipitation bath, and they are broken into a large quantity of small gas bubbles of carbonic acid gas by turbine blades. The large quantity of gas bubbles of carbonic acid are brought into contact with the metal-ion-containing liquid having a pH higher than 10.Type: GrantFiled: August 1, 1997Date of Patent: September 28, 1999Inventor: Yukimasa Satoh
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Patent number: 5945515Abstract: Solutions and methods are disclosed for the effective, simple isolation/extraction of DNA, RNA and proteins from a single biological material sample, such as cells, tissues and biological fluids. The preferred solutions include effective amounts of a chaotropic agent(s), buffer, reducing agent, and may or may not include an organic solvent. Genomic DNA and total RNA can be isolated utilizing the solutions and methods of the invention in as little as 20 minutes, and proteins in as little as 30 minutes.Type: GrantFiled: July 31, 1995Date of Patent: August 31, 1999Inventor: Piotr Chomczynski
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Patent number: 5919907Abstract: A method of preparing a novel, sterile, receptor rich-albumin molecule which utilizes the disinfecting properties of iodine by reacting an iodine donating material or solution with a pure preparation of albumin, and preferably subsequently removing the iodine. The resulting iodine has improved binding properties because the production method strips bacterial endotoxin and other previously bound substances from the albumin. The improved binding site capacity of the albumin product is advantageously used as an adjunct in removing toxins by means of exchange transfusions. Because iodine disinfects the albumin typical pasteurization and related additives are unnecessary.Type: GrantFiled: December 22, 1997Date of Patent: July 6, 1999Assignee: Shanbrom Technologies LLCInventor: Edward Shanbrom
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Patent number: 5877298Abstract: A fimbrial agglutinogen preparation is prepared from a bordetella strain, particularly a B. pertussis strain, by a multiple step procedure involving extraction of the fimbrial agglutinogens from cell paste and concentrating and purifying the extracted material. The fimbrial agglutinogen preparation may be used to prepare acellular pertussis vaccines with other pertussis antigens, including pertussis toxin or toxoid thereof, the 69 kDa protein and filamentous hemagglutinin and other Bordetella antigens.Type: GrantFiled: May 4, 1995Date of Patent: March 2, 1999Inventors: Raafat E. F. Fahim, John R. Vose, John Thipphawong, Luis Barreto, Gail E. D. Jackson, Larry U. L. Tan, Andrew Herbert, Michel H. Klein
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Patent number: 5866114Abstract: The present invention is directed to methods for crystallizing macrophage colony stimulating factor (M-CSF) and to a crystalline M-CSF produced thereby. The present invention is also directed to methods for designing and producing M-CSF agonists and antagonists using information derived from the crystallographic structure of M-CSF. The invention is also directed to methods for screening M-CSF agonists and antagonists. In addition, the present invention is directed to an isolated, purified, soluble and functional M-CSF receptor.Type: GrantFiled: May 25, 1995Date of Patent: February 2, 1999Assignee: Chiron CorporationInventors: Jayvardhan Pandit, Jarmila Jancarik, Sung-Hou Kim, Kirston Koths, Robert Halenbeck, Anna Lisa Fear, Eric Taylor, Ralph Yamamoto, Andrew Bohm
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Patent number: 5834254Abstract: Stabilized enzyme compositions for use in nucleic acid amplification. Compositions are provided for the stabilization of one or more enzymes in a single stabilized formulation. Additional compositions incorporate a dried, stabilized enzyme mixture together with necessary cofactors and enzyme substrates in a single container for use upon rehydration. Also disclosed are methods for making and using stabilized enzyme compositions and kits for nucleic acid amplification incorporating the disclosed compositions.Type: GrantFiled: July 22, 1997Date of Patent: November 10, 1998Assignee: Gen-Probe IncorporatedInventors: Nancy Lau Liu Shen, Daniel Louis Kacian, James Garfield Putnam, William Michael Davis