Ion Exchange Patents (Class 530/416)
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Patent number: 7223561Abstract: A process is provided for the preparation of albumin which has extremely low levels of or is essentially free of colorants, metal ions, human proteins, host proteins, fragments of albumin, polymers or aggregates of albumin and viruses, and which is essentially non-glycated, relatively high in free thiol and with an intact C-terminus. The process comprises passing albumin (preferably expressed and secreted by transformed yeast) through positive mode cation exchange and then positive mode anion exchange chromatography. Other steps may also be employed, ultrafiltration, gel permeation chromatography, affinity chromatography binding the albumin by using blue dyes) and affinity chromatography binding contaminants by using an aminophenylboronic acid resin. Elution of albumin, with a compound having affinity for albumin, from a material having no specific affinity for albumin is also disclosed, as is removal of ammonium ions with a counter-ion.Type: GrantFiled: June 22, 2004Date of Patent: May 29, 2007Assignee: Novozymes Delta, LimitedInventors: Andrew Robert Goodey, Darell Sleep, Hendrik Van Urk, Stephen Berezenko, John Rodney Woodrow, Richard Alan Johnson, Patricia Carol Wood, Stephen James Burton, Alan Victor Quirk
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Patent number: 7223848Abstract: The present invention provides a process for dissociating Fc-containing molecules from complexes of Protein A/Fc-containing molecules or mixtures containing Fc-containing molecules and Protein A. The association, e.g., by hydrophobic interactions, between the Fc-containing molecules and Protein A can be reduced or inhibited by raising the pH of dissociation. The pH of dissociation can be raised by addition of agents capable of inhibiting hydrophobic interactions, including buffers containing arginine and/or ethylene glycol, to the mixture, either prior to adding the mixture to the column chromatography substrate, after adding the mixture to the column chromatography substrate, or both prior to and after adding the mixture to the column chromatography substrate.Type: GrantFiled: June 5, 2002Date of Patent: May 29, 2007Assignee: Genetics Institute, LLCInventors: Jonathan L. Coffman, William B. Foster, Shujun Sun
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Patent number: 7202211Abstract: The present invention relates to use of Narp inhibitor in order to promote or enhance recovery from ischemic events, particularly focal ischemia of the central nervous system, as well as for preventing or diminishing chronic degenerative changes.Type: GrantFiled: February 20, 2003Date of Patent: April 10, 2007Assignees: Astellas Pharma Inc., Quark Biotech, Inc.Inventors: Alexander Faerman, Sylvia G. Kachalsky, Gregory Hirsch Idelson
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Patent number: 7195923Abstract: The present invention provides methods for determining a ratio of an amount of a glycated form of a protein to a total amount of the protein in a sample containing the glycated protein, the glycosylated protein, or the glycoprotein. The method incorporates lateral flow test strip or vertical flow test strip devices having negatively charged carboxyl or carboxylate groups and hydroxyboryl groups immobilized and interspersed on a solid support matrix. The solid support matrix may include derivatives of cellulose (e.g., carboxy cellulose) derivatized with carboxylic acid (e.g., carboxylate, carboxyl) groups and hydroxyboryl compounds including phenylboronic acid (e.g., phenylborate), aminophenylboronic acid, boric acid (e.g., borate), or other boronic acid (e.g., boronate) compounds. The present invention is usefi.il for monitoring glycation or glycosylation of hemoglobin or albumin for monitoring glycemic control (e.g., glycemia in diabetes).Type: GrantFiled: January 31, 2002Date of Patent: March 27, 2007Assignee: Scripps Laboratories, Inc.Inventors: Ralph P. McCroskey, Cameron E. Melton
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Patent number: 7193066Abstract: Toxin derivatives are prepared by proteolytic treatment of holotoxin, and their toxicity is reduced by contacting the preparation with a ligand, which can be a metal or an antibody or another ligand. This ligand selectively binds to the toxin but not to the toxin derivative. Removing the ligand and toxin bound to the ligand further reduces toxicity. A second ligand is used to remove conjugates of the toxin and the first ligand. Compositions contain the purified derivative, optionally plus the toxin and the ligand.Type: GrantFiled: September 13, 2000Date of Patent: March 20, 2007Assignee: The Health Protection AgencyInventors: John Andrew Chaddock, Frances Celine Gail Alexander, Keith Alan Foster
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Patent number: 7189324Abstract: A method for separating one or more components of a biomolecule mixture by means of an ion exchange chromatographic system operated in the displacement mode includes sequentially perfusing the system with a first solution including the biomolecule mixture, and a second solution including a displacer having a structure selected from formula I and formula II:Type: GrantFiled: June 8, 2005Date of Patent: March 13, 2007Assignee: Rensselaer Polytechnic InstituteInventors: Steven M. Cramer, James A. Moore, Sun Kyu Park, Nihal Tugcu
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Patent number: 7148048Abstract: A process for purification of recombinant porphobilinogen deaminase (rhPBGD) on an industrial scale by starting from a rhPBGD containing extract obtained from a fermentation of a recombinant cell capable of expressing the rhPBGD and the use of the purified product for the preparation of a medicament.Type: GrantFiled: December 13, 2002Date of Patent: December 12, 2006Assignee: Zymenex A/SInventors: Jens Fogh, Claes Andersson
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Patent number: 7144855Abstract: The present invention relates to the use of alpha-lactalbumin in the preparation of preparations to be used in therapeutic or prophylactic treatment and/or for diagnostic use for infections, preferably of the respiratory tract, caused by bacteria, in particular S. pneumoniae and/or H. influenzae. The present invention further relates to essentially pure protein complexes comprising alpha-lactalbumin and the use of these protein complexes for therapeutically or prophylactically treating a bacterial infection, especially infections of the respiratory tract caused by S. pneumoniae and/or H. influenzae.Type: GrantFiled: July 11, 2003Date of Patent: December 5, 2006Assignee: Hamlet Pharma ABInventors: Catharina Svanborg, H. Sabharwal
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Patent number: 7138120Abstract: 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: July 10, 2001Date of Patent: November 21, 2006Assignee: Statens Serum InstitutInventors: Inga Laursen, Børge Teisner
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Patent number: 7122344Abstract: The present invention relates generally to the production of recombinant human uteroglobin (rhUG) for use as a therapeutic in the treatment of inflammation and fibrotic diseases. More particularly, the invention provides processes, including broadly the steps of bacterial expression and protein purification, for the scaled-up production of rhUG according to current Good Manufacturing Practices (cGMP). The invention further provides analytical assays for evaluating the relative strength of in vivo biological activity of rhUG produced via the scaled-up cGMP processes.Type: GrantFiled: July 2, 2001Date of Patent: October 17, 2006Assignee: Claragen, Inc.Inventors: Aprile L. Pilon, Richard W. Welch
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Patent number: 7112453Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.Type: GrantFiled: August 5, 2002Date of Patent: September 26, 2006Assignee: Ciphergen Biosystems, Inc.Inventors: T. William Hutchens, Tai-Tung Yip
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Patent number: 7098026Abstract: Disclosed are a novel hedgehog protein, i.e., a Desert hedgehog protein of human origin including mature and precursor forms, a DNA encoding the protein, a monoclonal antibody recognizing the protein, a process for producing the protein, and a method for detecting the protein. The hedgehog protein is useful in establishment of hybridomas which produce antibodies recognizing the protein, and the monoclonal antibody is useful in detection and purification of the protein. The hedgehog protein, DNA, and monoclonal antibody of this invention have efficacy in elucidation of hereditary morphological abnormalities in humans to establish their treatments and diagnoses.Type: GrantFiled: July 14, 2000Date of Patent: August 29, 2006Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku KenkyujoInventors: Toshio Ariyasu, Shuji Nakamura, Kunzo Orita
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Patent number: 7084262Abstract: Methods for improving purification and quantification of platelet derived growth factor (PDGF) proteins having structural heterogeneity are provided. Preparation of substantially pure isoforms of these proteins is achieved using TSK sulfopropyl cation exchange chromatography and reverse phase high performance liquid chromatography. A reverse charged capillary zone electrophoresis method enables quantification of substantially pure isoforms of these proteins resulting from endoproteolytic post-translational modifications. Compositions of the invention are substantially purified isoforms of secreted PDGF proteins having structural heterogeneity, more particularly purified intact, single-clipped, and double-clipped isoforms of recombinant PDGF-BB. Pharmaceutical compositions comprising at least one of these substantially purified recombinant PDGF isoforms and methods for their use in promoting wound healing are also provided.Type: GrantFiled: July 26, 2002Date of Patent: August 1, 2006Assignee: Chiron CorporationInventors: Michael Kunitani, An D. Tran, Hugh Parker
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Patent number: 7071313Abstract: Methods for purifying authentic, properly folded IGF polypeptides from yeast transformants are disclosed. The methods include a refolding step and provide for high yields of authentic IGF from a variety of yeast strains.Type: GrantFiled: May 2, 2000Date of Patent: July 4, 2006Assignees: Cephalon, Inc., Chiron CorporationInventors: Cynthia Cowgill, Luis Juarbe-Osorio, Patricio Riquelme, Glenn Dorin, Christopher M. Bussineau, Robert D Kudrna, Asuman G. Ozturk, Carl Scandella, Russell A. Brierley, Joan N. Abrams, John M. Hanson, Francis C. Maslanka
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Patent number: 7053185Abstract: A method for producing an oligomeric form of ?-lactalbumin which is in the molten globule-like state is described. The method suitably comprises exposing a source of ?-lactalbumin in which the ?-lactalbumin is preferably in the molten globule-like state, to an ion exchange medium which has been pre-treated with casein or an active component thereof, such as oleic acid, and recovering ?-lactalbumin in an oligomeric form therefrom. Pre-treatment of the ion exchange medium, particularly with casein derived from human milk, has been found to significantly improve yields of the oligomeric form of ?-lactalbumin and means that it can be readily isolated from readily available sources such as bovine ?-lactalbumin. This form of ?-lactalbumin is useful therapeutically, in particular as an antibacterial agent and also as an anti-cancer therapeutic.Type: GrantFiled: November 23, 1998Date of Patent: May 30, 2006Assignee: HAMLET Pharma ABInventors: Catharina Svanborg, Per Anders Hakansson, Malin Wilhelmina Svensson
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Patent number: 7033610Abstract: The invention relates to pharmaceutical or veterinary compositions for the treatment of surface wounds; pharmaceutical or veterinary compositions for the treatment of gastrointestinal injuries, diseases or ulcers; methods of treating surface wounds in animals, including humans; and methods for the treatment of gastrointestinal injuries, diseases or ulcers which compositions and methods include compositions of milk product extracts including growth factors with basic to approximately neutral isoelectric points.Type: GrantFiled: July 9, 2002Date of Patent: April 25, 2006Assignee: Gropep PTY, Ltd.Inventors: Francis John Ballard, Geoffrey Leonard Francis, Geoffrey Owen Regester, Leanna Christine Read, David Andrew Belford
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Patent number: 7022822Abstract: Purification process of humanPurification process of human urinary gonadotropins of high biological activity and chemical purity absolutely free of foreign contaminating materials derived from the use of biological reagents or chromatography dyes, from crude of gonadotropins. The high biological activity and chemically pure composition of human gonadotropins obtained by this process, are used for the treatment of infertility and are selected from the group of follitropin or menotropins, having a bioactivity greater than 2500 IU/mg protein as tested by biological assay in rats, for both FSH and LH hormones for menotropins and greater than 5000 IU/mg protein for follitropin having an FSH:LH ratio about 75:1. Pharmaceutical preparations of said gonadotropins free of these contaminating materials are also comprised within the present invention.Type: GrantFiled: April 14, 2000Date of Patent: April 4, 2006Assignee: Instituto Massone S.A.Inventors: Claudio Fernando Wolfenson Band, Liliana Ester Balanian, Jose-Felipe Groisman, Erundina Marta Fasanella
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Patent number: 7022744Abstract: A composition useful for separating lipoproteins, such as high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and modified lipoproteins with a high degree of accuracy by ion-exchange based procedures. The composition comprises an organic particle having a hydrophilic surface onto which ion-exchange groups are introduced and which is formulated so as to provide a high enough degree of hydrophilicity to prevent irreversible absorption of lipoproteins, but which is not so high as to block the pores of the ion exchange particles and prevent adequate retention and separation of lipoproteins. A method for making a composition for separating lipoproteins comprising seed polymerization of organic particles, hydrophilic treatment of the organic particles by introducing 0.Type: GrantFiled: April 10, 2003Date of Patent: April 4, 2006Assignee: Mitsubishi Chemical CorporationInventors: Jun Haginaka, Masaru Sano, Tsunehiko Kurata
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Patent number: 6992061Abstract: The invention relates to a method of removing endotoxin from preparation of alpha-1-acid glycoprotein (orosomucoid) by contact with a finely divided non-toxic resin such as fumed silica. The invention also relates to a purification process for alpha-1-acid glycoprotein which includes this depyrogenation step, and to the depyrogenated product and its clinical uses.Type: GrantFiled: February 26, 2002Date of Patent: January 31, 2006Assignee: National Blood AuthorityInventors: John Edward More, Jacqueline Rott, David Roger Lewin
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Patent number: 6989438Abstract: The present invention concerns a process for the purification of EPI-HNE proteins, from the culture medium of a host strain for the expression of said proteins, comprising the steps of: (a) passing a derived part of the culture medium over an expanded bed of cationic exchange adsorbent or a mechanically and chemically inert micromembrane, in order to recover an eluate, (b) optionally conducting chromatographic separation of proteins, according to their hydrophobicity, on the resulting eluate, (c) passing the resulting eluate over a cationic exchange column, (d) optionally filtering the resulting medium such as to obtain a sterile filtrate, and optionally further comprising the step of (e) causing precipitation of EPI-HNE in a crystallised form and recovering the protein crystals.Type: GrantFiled: August 30, 2001Date of Patent: January 24, 2006Assignee: Debiopharm S.A.Inventors: Alain Poncin, François Saudubray, Anne Bokman
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Patent number: 6967241Abstract: The invention includes a process for extracting a target protein from E. coli cells that includes lowering the pH of a whole E. coli cell solution to form an acidic solution, disrupting the cells to release the protein into the acidic solution, and separating the cellular debris from the released protein to obtain a protein product enriched in the heterologous target protein. The invention also includes addition of a solubility enhancer.Type: GrantFiled: September 5, 2003Date of Patent: November 22, 2005Assignee: Genentech, Inc.Inventor: Richard L. Gehant
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Patent number: 6967239Abstract: Method for preparing a factor VIII solution that is essentially free of viruses and essentially devoid of vWF (von Willebrand factor) and factor VIII-vWF complexes by (a) obtaining a starting factor VIII solution devoid of factor VIII-vWF complexes; and (b) filtering the solution through a hydrophilic virus filter.Type: GrantFiled: December 14, 1998Date of Patent: November 22, 2005Assignee: Laboratoire Francias du Franctionnement et des BiotechnologiesInventors: Abdessatar Chtourou, Michel Nogre, Pierre Porte
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Patent number: 6953844Abstract: Methods are provided for large scale purification of neurotrophins, including mature NGF, suitable for clinical use. The methods provide means to separate neurotrophins from various less desirable misprocessed, misfolded, size, glycosylated, or charge forms. Compositions of neurotrophins, including mature NGF, substantially free of these variants are also provided.Type: GrantFiled: February 18, 2004Date of Patent: October 11, 2005Assignee: Genentech, Inc.Inventors: Louis E. Burton, Charles H. Schmelzer, Joanne T. Beck
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Patent number: 6949629Abstract: Improved methods are provided for purifying selected carcinoembryonic antigen (CEA) family member proteins. Disclosed method steps include cation-exchange chromatography below pH 4.0 and size-exclusion chromatography, and do not include use of perchloric acid or antibody affinity steps. The resulting purified proteins are of at least 90% purity, substantially free of cross-reacting antigens, substantially free of CA19-9, substantially free of endotoxins, and substantially free of antibodies. Purities of greater than 98% have been achieved. Purified CEA family member proteins used as reference standards, in pharmaceutical carriers, and formulated as vaccines are disclosed. The purification, compositions, and use of CEA family member proteins containing altered immunogenic epitopes are also disclosed.Type: GrantFiled: March 13, 2002Date of Patent: September 27, 2005Assignee: AspenBio, Inc.Inventors: Diane Newman, Cathy Landmann, Mark Colgin
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Patent number: 6936423Abstract: Lethal Toxin Neutralizing Factor has been isolated in purity from opossum serum by high pressure liquid chromatography (HPLC) fractionation. The amino acid sequence from the N-terminal for the first fifteen amino acids of LTNF-n is: Leu Lys Ala Met Asp Pro Thr Pro Pro Leu Trp Ile Lys Thr Glu. Antibodies to LTNF-n and synthetic peptides consisting of fifteen, ten and five amino acids from the N-terminal of the above sequence, designated as LTNF-15, LTNF-10 and LTNF-5 were produced by immunizing Balb/C mice to produce Anti-LTNF-n, Anti-LTNF-15, Anti-LTNF-10 and Anti-LTNF-5. The anti LTNF-n, anti-LTNF-15, anti-LTNF-10 and anti-LTNF-5 react immunologically with all types of toxins derived from animal, plant and bacteria and can be assayed by immunological in vitro test such as ELISA tests. Anti-LTNFs react roughly proportional to lethal dose of biological toxins under in vitro immunological ELISA test similar to the mouse bioassay test.Type: GrantFiled: April 27, 1999Date of Patent: August 30, 2005Inventors: Binie V. Lipps, Frederick W. Lipps
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Patent number: 6929747Abstract: A method for separating one or more components of a biomolecule mixture by means of an ion exchange chromatographic system operated in the displacement mode includes sequentially perfusing the system with a first solution including the biomolecule mixture, and a second solution including a displacer having a structure selected from formula I and formula II:Type: GrantFiled: February 28, 2003Date of Patent: August 16, 2005Assignee: Renesselaer Polytechnic InstituteInventors: Steven M. Cramer, James A. Moore, Sun Kyu Park, Nihal Tugcu
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Patent number: 6924267Abstract: The present invention comprises a method of protecting organs or tissue susceptible to reperfusion-induced dysfunction after ischemia. The method comprises parenterally administering to a patient a therapeutical composition containing natural alpha-1 acid glycoprotein, natural alpha-1 antitrypsin or a mixture thereof. Alternatively, organ or tissue transplants can be contacted with natural alpha-1 acid glycoprotein, natural alpha-antitrypsin or mixtures by perfusing or flushing them with a solution containing natural alpha-1 acid glycoprotein, natural alpha-1 antitrypsin or mixtures thereof in a concentration of 0.1 to 5 g/l.Type: GrantFiled: September 18, 2001Date of Patent: August 2, 2005Assignee: Suomen Punainen Risti VeripalveluInventors: Marc A. R. C. Daemen, Vincent H. Heemskerk, Cornelis van't Veer, Geertrui Denecker, Tim G. A. M. Wolfs, Peter Vandenabeele, Wim A. Buurman, Jaakko Parkkinen
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Patent number: 6924151Abstract: There are disclosed a stable factor VIII/vWF-complex, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as a method of producing this complex.Type: GrantFiled: May 7, 2001Date of Patent: August 2, 2005Assignee: Baxter AktiengesellschaftInventors: Bernhard Fischer, Artur Mitterer, Friedrich Dorner, Johann Eibl
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Patent number: 6921808Abstract: A purification process for large-scale production of Gc-globulin is described. The source of Gc-globulin is preferably a crude plasma fraction but can be any solution, suspension or supernatant containing Gc-globulin, e.g., a milk product, colostrum or a fermentation broth. The Gc-globulin can be plasma-derived or produced by a genetic modified organism. The process includes two key elements: purification by series of ion exchange chromatography steps, and performing at least two virus-reduction steps. A diagnostic method to measure the free Gc-globulin in a patient blood sample, a use of Gc-globulin in medicine and the preparation of a Gc-globulin medicinal product is also provided. The product can be used in therapy for patients with circulatory disorders and complications, i.e., where it is contemplated that patients would benefit from the administration of Gc-globulin.Type: GrantFiled: August 18, 2004Date of Patent: July 26, 2005Assignee: Statens Serum InstitutInventors: Charlotte Svaerke Joergensen, Inga Laursen, Gunnar Houen
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Patent number: 6900060Abstract: A method for analyzing a plurality of amino acids in a fluid sample by a user is provided comprising the steps of introducing the sample into a buffer solution, passing the sample in the buffer solution through a separation column and setting a lithium ion concentration in the buffer to no more than 0.3 mols/L up to a time before ?-aminoisobutyric acid (?-AiBA) is eluted.Type: GrantFiled: June 13, 2001Date of Patent: May 31, 2005Assignee: Hitachi, Ltd.Inventors: Yoshio Fujii, Masahito Ito, Kimiyoshi Koda
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Patent number: 6893639Abstract: The method for immune serum globulin purification relates to the purification of immune globulins from blood plasma with a high degree of efficiency and a high rate of recovery. The immune globulin source is Cohn's fraction I+II+III or II+III prepared from plasma or plasma intermediates by precipitation of the paste at pH 5.7 to 5.8 in the presence of 20% ethanol and 80% purified water. A glycine extraction is followed by an anion exchange chromatography column step to achieve a significantly high yield and high purity of the concentrated protein.Type: GrantFiled: October 19, 2001Date of Patent: May 17, 2005Assignee: Hemacare CorporationInventors: Joshua Levy, Fred Rothstein, Bahman Shimiaei
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Patent number: 6881540Abstract: An effective technique for the high throughput screening of displacers is described. In this technique, potential displacers are employed to displace a biomolecule (e.g., protein) adsorbed on a chromatographic resin in small-scale batch displacement experiments. The amount of protein displaced from a specific resin by a defined concentration of displacer is determined by monitoring the supermatant for the protein. By evaluating the displaced protein rather than the displacer itself, this technique enables a single detection technique (e.g., absorbance, fluorescence, etc.) to be employed for all batch displacement experiments. By monitoring the amount of protein displaced, the effacy of a large number of potential displacers can be rapidly evaluated. The entire experimental procedure can be carried out rapidly and is thus amenable to high throughput parallel screening of molecules possessing a large range of affinities and physico-chemical properties.Type: GrantFiled: February 23, 2001Date of Patent: April 19, 2005Assignee: Rensselaer Polytechnic InstituteInventors: Steven Cramer, Kaushal Rege, Jonathan Dordick
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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: 6866782Abstract: There is disclosed a process for the purification of pharmacologically active proteins based on the use of the cationic exchange chromatography on a solid matrix carried out at a more basic pH, i.e. higher, in respect of the pH corresponding to the isoelectric point, pI, of the proteins to be purified, pH at which however said proteins still remain absorbed. Buffer solutions with values of pH and of ionic strength adjusted from time to time to the kind of pharmacologically active protein to be purified are used in order to obtain such a result. The process is mainly addressed to the purification of the interferon and albumin proteins.Type: GrantFiled: June 10, 2002Date of Patent: March 15, 2005Assignee: Alfa Wassermann S.p.A.Inventors: Lucia Scapol, Giuseppe Claudio Viscomi
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Patent number: 6866846Abstract: A process for preparing a patient-specific immunoadsorber, which comprises (i) extracting a body fluid from a patient having an immunopathological condition, the fluid containing immune complexes that are relevant to that immunopathological condition, (ii) contacting the extracted fluid with an adsorbent for the immune complexes to form adsorbed immune complexes, (iii) eluting the adsorbed complexes to form an eluate, (iv) fractionating the eluate into a plurality of immune complex component fractions, and (v) immobilizing the immune complex components on one or more biologically compatible carriers activated to bond to its surface one or more desired immune complex components.Type: GrantFiled: April 3, 1998Date of Patent: March 15, 2005Assignee: Privates Institut Bioserv GmbHInventors: Hans-Werner Heinrich, Wolfgang Ramlow, Hans-Friedrich Boeden, Hans-Georg Neumann, Udo Meyer, Joachim Teller
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Patent number: 6852230Abstract: Method for desalting an aqueous liquid containing a charged substance comprising the steps of: (i) contacting liquid (I) with an ion-exchanger (1) under conditions permitting binding between ion-exchanger and substance, said ion-exchanger comprising a base matrix carrying an ion-exchange ligand (Ligand 1) with the opposite charge compared to the substance, (ii) desorbing said substance from said ion-exchanger by the use of a liquid (liquid (II)). Wherein: (A) ion-exchanger (1) is an ion-exchanger: (a) that can bind the substance in an aqueous reference liquid at ionic strength corresponding to 0.1 M NaCl, preferably 0.25 M NaCl; and (b) permits a breakthrough capacity at the pH provided by liquid (I) which is more than 2 mg/ml of gel, at a breakthrough of 10% and linear flow velocity of 300 cm/h; and (B) in step (ii) the pH of liquid (11) is adjusted to a pH value where the charge difference between the substance, the ligand and/or the ion-exchanger is lowered.Type: GrantFiled: December 19, 2001Date of Patent: February 8, 2005Assignee: Amersham Biosciences ABInventors: Makonnen Belew, Bo-Lennart Johansson, Jean-Luc Maloisel
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Patent number: 6828436Abstract: A method for purifying oligonucleotides by displacement chromatography on anion-exchange media, using high affinity, low molecular weight (less than about 10000 Da) displacers, is disclosed. Several examples of high affinity, low molecular weight anionic displacers are provided, including polycyclic aromatic compounds having sulfonic acid moieties attached thereon. The efficacy of the technique for high resolution separation of oligonucleotides is demonstrated for an industrial mixture.Type: GrantFiled: May 15, 2002Date of Patent: December 7, 2004Assignees: ISIS Pharmaceuticals, Inc., Rensselaer Polytechnic InstituteInventors: Abhinav A. Shukla, Ranjit R. Deshmukh, Steven M. Cramer, James A. Moore
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Patent number: 6812330Abstract: Methods are provided for large scale purification of neurotrophins, including mature NGF, suitable for clinical use. The methods provide means to separate neurotrophins from various less desirable misprocessed, misfolded, size, glycosylated, or charge forms. Compositions of neurotrophins, including mature NGF, substantially free of these variants are also provided.Type: GrantFiled: February 8, 2002Date of Patent: November 2, 2004Assignee: Genentech, Inc.Inventors: Louis E. Burton, Charles H. Schmelzer, Joanne T. Beck
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Patent number: 6805882Abstract: The present invention relates to fractions of sources and or preparations of human chorionic gonadotropin, such as fractions of human early pregnancy urine, which fractions have anti-HIV activity. The present invention further relates to pharmaceutical compositions comprising such fractions for treating the effects of HIV infection.Type: GrantFiled: October 2, 2000Date of Patent: October 19, 2004Assignee: University of Maryland Biotechnology InstituteInventors: Robert C. Gallo, Joseph Bryant, Yanto Lunardi-Iskandar
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Patent number: 6800607Abstract: Modified BDNF having improved pharmacological activities, pharmacokinetics and physical properties can be obtained by modifying BDNF with a 1-acyl-glycerol derivative. This BDNF being modified with a 1-acyl-glycerol derivative of the present invention has more efficacious and more excellent pharmacokinetic properties with retaining the useful effects being characteristic to BDNF which are useful as remedies for neurodegenerative diseases and diabetes mellitus, and hence, it is particularly useful as a therapeutic agent for treatment of type 2 diabetes mellitus.Type: GrantFiled: August 29, 2002Date of Patent: October 5, 2004Assignee: LTT Bio-Pharma Co., Ltd.Inventors: Rie Igarashi, Yutaka Mizushima, Mutsuo Taiji, Chikao Nakayama, Hiroshi Noguchi
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Patent number: 6787158Abstract: A process is disclosed for extracting glycomacropeptide from a lactic raw material. This process includes the step of treating a lactic raw material containing glycomacropeptide in the presence of a weakly anionic resin wherein the glycomacropeptide is selectively adsorbed onto the resin and then eluted from the resin so as to obtain an improved protein product which can be used in foods, and pharmaceutical and dental compositions.Type: GrantFiled: November 29, 1999Date of Patent: September 7, 2004Assignee: Nestec S.A.Inventors: Peter Erdmann, Fred Neumann
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Patent number: 6780972Abstract: A method for producing peptide salts, including reacting an acid addition salt of a basic starting peptide in the presence of a diluent in a mixed bed ion exchanger, with a mixture of an acid and a basic ion exchanger during the formation of a free basic peptide, and then separating the ion exchanger and then the free basic peptide, with an inorganic or organic acid, and then forming the desired acid addition salt of the peptide, and removing the diluent.Type: GrantFiled: August 24, 2001Date of Patent: August 24, 2004Assignee: Zentaris GmbHInventors: Michael Damm, Waldemar Salonek, Jürgen Engel, Horst Bauer, Gabriele Stach
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Patent number: 6756484Abstract: Disclosed is an improved process for obtaining purified, monomeric, intact, correctly-folded insulin-like growth factor-I (also known as somatomedin-C). The improvements, consisting primarily of the addition of an IGF-I unfolding/refolding step and the substitution of a reverse phase chromatography step for a gel filtration chromatography step result in a three-fold increase in final yield. The process includes the following steps, in order: first cation exchange, unfolding/refolding, hydrophobic interaction chromatography, second cation exchange, and reverse phase chromatography.Type: GrantFiled: July 12, 2000Date of Patent: June 29, 2004Assignees: Cephalon, Inc., Chiron CorporationInventors: Russell A. Brierley, Joan N. Abrams, John M. Hanson, Francis C. Maslanka, Cynthia Cowgill, Luis G. Juarbe-Osorio, Patricio Riquelme, Glenn Dorin
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Patent number: 6756482Abstract: The present invention provides a process for purifying human activin by cation exchange chromatography and chaotropic ion concentration gradient elution.Type: GrantFiled: November 27, 2000Date of Patent: June 29, 2004Assignee: Ajinomoto Co., Inc.Inventors: Kunio Ono, Shigekatsu Tsuchiya, Daisuke Ejima, Yuzuru Eto
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Patent number: 6740736Abstract: Fibrinogen is obtained from milk by contact with a cation exchange chromatography substrate under conditions where the fibrinogen binds to the substrate, followed by optional washing of the substrate. The bound fibrinogen is removed from the substrate by irrigation under increased ionic strength or increased pH conditions. The obtained fibrinogen may be naturally produced or transgenic.Type: GrantFiled: March 22, 2001Date of Patent: May 25, 2004Assignee: PPL Therapeutics (Scotland) LimitedInventor: Graham McCreath
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Patent number: 6737250Abstract: Expression systems are disclosed for the direct expression of peptide products into the culture media where genetically engineered host cells are grown. High yield was achieved with novel vectors, a special selection of hosts, and/or fermentation processes which include careful control of cell growth rate, and use of an inducer during growth phase. Special vectors are provided which include control regions having multiple promoters linked operably with coding regions encoding a signal peptide upstream from a coding region encoding the peptide of interest. Multiple transcription cassettes are also used to increase yield. The production of amidated peptides using the expression systems is also disclosed.Type: GrantFiled: February 9, 2001Date of Patent: May 18, 2004Assignee: Unigene Laboratories, Inc.Inventors: Nozer M. Mehta, Angelo P. Consalvo, Martha V. L. Ray, Christopher P. Meenan
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Publication number: 20040082047Abstract: A method for purifying a polypeptide by ion exchange chromatography is described in which a gradient wash is used to resolve a polypeptide of interest from one or more contaminants.Type: ApplicationFiled: September 10, 2003Publication date: April 29, 2004Inventors: Jefferson C. Emery, Paul J. McDonald, Rhona O'Leary
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Publication number: 20040063919Abstract: The present invention provides a process for the preparation of Avidin having a high purity of 98% from egg white, the said process comprising lyophilizing the homogenized egg white with buffer followed by equilibrating the lyophilized material with cation exchanger for an hour at a temperature range of 20° to 30° C.; filtering the mixture to obtain a filtrate and matrix residue; washing the matrix twice with buffer; separating the washings to obtain washed matrix; adding 0.01 M dye in buffer to the washed matrix; equilibrated for an hour at an ambient temperature; separating the supernatant; adding acetic acid to supernatant and dialysing the solution till it is decolorised to obtain pure Avidin.Type: ApplicationFiled: September 22, 2003Publication date: April 1, 2004Inventors: Mukkavilli Venkata Subba Rao, Munishwar Nath Gupta, Ipsita Roy
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Patent number: 6713611Abstract: The present invention relates to a method of removing an endotoxin from solution containing basic proteins. More specifically, the method of the present invention comprises the steps of adding the surfactant to solution containing the basic protein obtained from the recombinant microorganism and mixing the resultant, of loading the resultant solution on the cation exchange column, washing the cation exchange column with solution which does not contain surfactant, and eluting the basic protein of interest from the cation exchange column.Type: GrantFiled: September 6, 2001Date of Patent: March 30, 2004Assignee: Samyang Genex Co.Inventors: Sang-Hyun Pyo, Heung-Bok Park, Jin-Eon So, Jin-Hyun Kim, Seung-Suh Hong, Hyun-Soo Lee
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Patent number: 6703051Abstract: A method is provided for separating and recovering protein and isoflavones from a plant material. A clarified protein extract of the plant material is prepared and contacted with a polar ion exchange resin, such as an anion exchange resin allowing the isoflavones in the extract to bind with the ion exchange resin and depleting the extract of isoflavones. A protein extract which has been depleted of isoflavones is separated from the ion exchange resin, and an isoflavone depleted protein material is recovered from the isoflavone depleted extract. After removal of the isoflavone depleted extract from the resin, the isoflavones are separated and recovered from the ion exchange resin. Recovered isoflavone glycosides and isoflavone glycoside conjugates may be converted to their corresponding aglucone isoflavone form.Type: GrantFiled: October 13, 1998Date of Patent: March 9, 2004Assignee: Solae, LLCInventors: Gregory A. Bates, Barbara A. Bryan