Chromatography Or By Septum Selective As To Material, E.g., Gel Filtration, Molecular Sieve Dialysis, Etc. Patents (Class 530/417)
  • Patent number: 7136759
    Abstract: A method for predicting the elution time of a peptide in chromatographic and electrophoretic separations by first providing a data set of known elution times of known peptides, then creating a plurality of vectors, each vector having a plurality of dimensions, and each dimension representing the elution time of amino acids present in each of these known peptides from the data set. The elution time of any protein is then be predicted by first creating a vector by assigning dimensional values for the elution time of amino acids of at least one hypothetical peptide and then calculating a predicted elution time for the vector by performing a multivariate regression of the dimensional values of the hypothetical peptide using the dimensional values of the known peptides. Preferably, the multivariate regression is accomplished by the use of an artificial neural network and the elution times are first normalized using a transfer function.
    Type: Grant
    Filed: December 18, 2002
    Date of Patent: November 14, 2006
    Assignee: Battelle Memorial Institute
    Inventors: Lars J. Kangas, Kenneth J. Auberry, Gordon A. Anderson, Richard D. Smith
  • Patent number: 7122344
    Abstract: 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: Grant
    Filed: July 2, 2001
    Date of Patent: October 17, 2006
    Assignee: Claragen, Inc.
    Inventors: Aprile L. Pilon, Richard W. Welch
  • Patent number: 7119166
    Abstract: A universal folding method that has been demonstrated to be effective in refolding a variety of very different proteins expressed in bacteria as inclusion bodies has been developed. Representative proteins that can be dissolved and refolded in biologically active form, with the native structure, are shown in Table I. The method has two key steps to unfold and then refold the proteins expressed in the inclusion bodies. The first step is to raise the pH of the protein solution in the presence of denaturing agents to pH greater than 9, preferably 10. The protein solution may be maintained at the elevated pH for a period of up to about 24 hours, or the pH immediately decreased slowly, in increments of about 0.2 pH units/24 hours, until the solution reaches a pH of about 8.0, or both steps used. In the preferred embodiment, purified inclusion bodies are dissolved in 8 M urea, 0.1 M Tris, 1 mM glycine, 1 mM EDTA, 10 mM beta-mercaptoethanol, 10 mM dithiothreitol (DTT), 1 mM reduced glutathione (GSH), 0.
    Type: Grant
    Filed: April 17, 2003
    Date of Patent: October 10, 2006
    Assignee: Oklahoma Medical Research Foundation
    Inventor: Xinli Lin
  • Patent number: 7098026
    Abstract: 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: Grant
    Filed: July 14, 2000
    Date of Patent: August 29, 2006
    Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo
    Inventors: Toshio Ariyasu, Shuji Nakamura, Kunzo Orita
  • Patent number: 7087719
    Abstract: 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: Grant
    Filed: November 19, 2002
    Date of Patent: August 8, 2006
    Assignee: GTC Biotherapeutics, Inc.
    Inventors: Kalevi Visuri, Sinikka Uotila, Scott P. Fulton, Daniel E. Couto
  • Patent number: 7071313
    Abstract: 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: Grant
    Filed: May 2, 2000
    Date of Patent: July 4, 2006
    Assignees: Cephalon, Inc., Chiron Corporation
    Inventors: 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
  • Patent number: 7060460
    Abstract: In a method for reconstituting a recombinant protein from a denatured state to its active form, a feed solution containing the recombinant protein in its denatured and/or in biologically inactive intermediate forms is subjected to a chromatographic separation process, in which the protein is reconstituted under conditions that promote refolding of the protein and the intermediate forms are separated from the refolded protein. The denatured form and/or the inactive intermediate forms of the protein are separated from the refolded protein in a continuous or quasi-continuous manner and optionally recycled to the feed solution.
    Type: Grant
    Filed: October 2, 2002
    Date of Patent: June 13, 2006
    Assignee: Boehringer Ingelheim Austria GmbH
    Inventors: Roman Necina, Robert Schlegl, Alois Jungbauer, Christine Machold
  • Patent number: 7034128
    Abstract: A method for extracting proteins from the intercellular space of plants is provided. The method is applicable to the large scale isolation of many active proteins of interest synthesized by plant cells. The method may be used commercially to recover recombinantly produced proteins from plant hosts thereby making the large scale use of plants as sources for recombinant protein production feasible.
    Type: Grant
    Filed: October 29, 2004
    Date of Patent: April 25, 2006
    Assignee: Large Scale Biology Corporation
    Inventors: Thomas H. Turpen, Stephen J. Garger, Michael J. McCulloch, Terri I. Cameron, Michelle L. Samonek-Potter, R. Barry Holtz
  • Patent number: 7022822
    Abstract: 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: Grant
    Filed: April 14, 2000
    Date of Patent: April 4, 2006
    Assignee: Instituto Massone S.A.
    Inventors: Claudio Fernando Wolfenson Band, Liliana Ester Balanian, Jose-Felipe Groisman, Erundina Marta Fasanella
  • Patent number: 6998470
    Abstract: The present invention relates to a method of isolating and/or purifying hypothalamic inhibitory factor (HIF) from a sample (e.g., tissue fluid) containing HIF. The present invention provides for isolation of large amounts of HIF using diafiltration, solid phase extraction and immunoaffinity techniques. In one embodiment, the invention relates to a method of purifying hypothalamic inhibitory factor from a sample containing hypothalamic inhibitory factor comprising subjecting the sample to diafiltration, solid phase extraction and immunoaffintiy chromatography.
    Type: Grant
    Filed: February 17, 2000
    Date of Patent: February 14, 2006
    Assignees: Bion, Inc., The General Hospital Corp.
    Inventors: Rex T. Gallagher, Garner T. Haupert, Jr.
  • Patent number: 6967239
    Abstract: 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: Grant
    Filed: December 14, 1998
    Date of Patent: November 22, 2005
    Assignee: Laboratoire Francias du Franctionnement et des Biotechnologies
    Inventors: Abdessatar Chtourou, Michel Nogre, Pierre Porte
  • Patent number: 6953844
    Abstract: 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: Grant
    Filed: February 18, 2004
    Date of Patent: October 11, 2005
    Assignee: Genentech, Inc.
    Inventors: Louis E. Burton, Charles H. Schmelzer, Joanne T. Beck
  • Patent number: 6951734
    Abstract: A method for producing a protein suitable for X-ray crystallographic analysis, in a cell-free protein synthesis system comprising a cell-free extract, a nucleic acid coding for said protein, and amino acids for the substrate of said protein, wherein said amino acids comprises at least one amino acid comprising a heavy atom, and wherein the introduced rate of said amino acid comprising the heavy atom into the synthesized protein is at least 80%.
    Type: Grant
    Filed: November 20, 2001
    Date of Patent: October 4, 2005
    Assignee: Riken
    Inventors: Emi Nunokawa, Takanori Kigawa, Takashi Yabuki, Shigeyuki Yokoyama
  • Patent number: 6946075
    Abstract: A process and apparatus for purifying one or more target substances from a source liquid, employing one or more cross-flow filter elements, and one or more types of chromatography resins, in combination, to provide purification with advantageous yield, product purity, and cost- and time-efficiency.
    Type: Grant
    Filed: May 23, 2003
    Date of Patent: September 20, 2005
    Assignee: NCSRT, Inc.
    Inventor: Henry B. Kopf
  • Patent number: 6929747
    Abstract: 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: Grant
    Filed: February 28, 2003
    Date of Patent: August 16, 2005
    Assignee: Renesselaer Polytechnic Institute
    Inventors: Steven M. Cramer, James A. Moore, Sun Kyu Park, Nihal Tugcu
  • Patent number: 6924267
    Abstract: 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: Grant
    Filed: September 18, 2001
    Date of Patent: August 2, 2005
    Assignee: Suomen Punainen Risti Veripalvelu
    Inventors: 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
  • Patent number: 6919436
    Abstract: The present invention relates to a novel method for the isolation or purification of immunoglobulins (a special class of proteins) from a solution containing immunoglobulins, e.g. hybridoma cell culture supernatants, animal plasma or sera, or colostrum. The method includes the use of a minimum of salts, such as lyotropic salts, in the binding process and preferably also the use of small amounts of organic solvents in the elution process. The solid phase matrices, preferably epichlorohydrin activiated agarose matricees, are functionalised with mono- or bicyclic aromatic or heteroaromatic ligands (molecular weight: at the most 500 Dalton) which, preferably, comprises an acidic substituent, e.g. a carboxylic acid. The matrices utilised show excellent properties in a “Standard Immunoglobulin Binding Test” and in a “Monoclonal Antibody Array Binding Test” with respect to binding efficiency and purity, and are stable in 1M NaOH.
    Type: Grant
    Filed: October 11, 2002
    Date of Patent: July 19, 2005
    Assignee: Upfront Chromatography A/S
    Inventors: Allan Otto Fog Lihme, Marie Bendix Hansen
  • Patent number: 6908740
    Abstract: Methods and apparatus for qualitative and quantitative proteome analysis are provided. The methods and apparatus allow for the isolation of a subset of peptides out of complex mixtures of peptides. The isolation is based on a specific chemical and/or enzymatic alteration of one or more types of peptides. This alteration modifies the biophysical, chemical or any other biochemical property of the affected types of peptides (e.g., net electrical charge and/or hydrophobicity) in such way that the altered peptides can be separated from the unaltered peptides.
    Type: Grant
    Filed: March 21, 2003
    Date of Patent: June 21, 2005
    Inventors: Joel Vandekerckhove, Kris Gevaert
  • Patent number: 6908985
    Abstract: Human heat-shock protein-binding proteins (HspBP-1 and HspBP-2) and fragments thereof are disclosed with the polynucleotides which identify and encode them. Genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding heat-shock protein-binding proteins (HspBP) are also disclosed and a method for producing HspBP polypeptides.
    Type: Grant
    Filed: March 7, 2002
    Date of Patent: June 21, 2005
    Assignee: Desert Genetics, Inc.
    Inventors: Vincent Guerriero, Jr., Deborah A. Raynes
  • Patent number: 6906183
    Abstract: A process for the partial or complete separation of glycosylated and nonglycosylated proteins is described, in which: a) a triazine dye immobilized on a matrix is incubated with a mixture of glycosylated and nonglycosylated proteins, b) the matrix is then washed to remove the unbound proteins, and c) the proteins are eluted by means of a stepwise or continuous increase in the ionic strength or in the pH, nonglycosylated proteins and proteins having an increasing degree of glycosylation being collected separately from one another in the eluate fractions obtained. By means of the use of this process it is possible, for example, to prepare a human albumin which is free of glycoside bonds and is expressed in yeast cells.
    Type: Grant
    Filed: December 14, 1999
    Date of Patent: June 14, 2005
    Assignee: Delta Biotechnology Ltd.
    Inventors: Jürgen Römisch, Jörg Weisse, Harald Stauss, Annette Feussner
  • Patent number: 6903202
    Abstract: Human heat-shock protein-binding proteins (HspBP-1 and HspBP-2) are disclosed with the polynucleotides which identify and encode them. Genetically engineered expression vectors and host cells comprising nucleic acid sequences encoding heat-shock protein-binding proteins (HspBP) are also disclosed, as well as methods for producing HspBP polypeptides and for detecting polynucleotide sequences that encode HspBP polypeptides.
    Type: Grant
    Filed: March 7, 2002
    Date of Patent: June 7, 2005
    Assignee: Desert Genetics, Inc.
    Inventors: Vincent Guerriero, Jr., Deborah A. Raynes
  • Patent number: 6900034
    Abstract: The invention relates to a method for solubilising and purifying recombinant proteins which are expressed in bacterial host cells and are deposited as insoluble aggregates (inclusion bodies). The purification is based on conversion of the inclusion bodies into soluble forms using organic denaturing reagents and using chromatographic methods. Inorganic, alkaline, salt-containing eluents are selected here which, after purification is complete, enable the recombinant proteins, after neutralisation, to be made available in a form which can be employed directly for medical use and is physiologically acceptable. The method is particularly suitable for purifying allergens and allergen fragments.
    Type: Grant
    Filed: August 18, 2001
    Date of Patent: May 31, 2005
    Assignee: Merck Patent GmbH
    Inventors: Roland Suck, Oliver Cromwell, Helmug Fiebig
  • Patent number: 6869934
    Abstract: The present invention relates to a method for purifying a calcium ion-binding protein by cation exchange chromatography. The present invention provide a method for isolating and purifying a calcium ion-binding protein in a simple and efficient manner from a liquid sample containing a calcium ion-binding protein and contaminants without any pretreatment such as addition of a chelating agent. More specifically, the present invention relates to a method for purifying a calcium ion-binding protein which comprises contacting said protein with a cation exchange carrier in the presence of calcium ions to let the said protein be adsorbed to the carrier, and after washing, eluting said protein, and to a calcium ion-binding protein having substantially no contaminants obtained by the method of the present invention.
    Type: Grant
    Filed: July 18, 2001
    Date of Patent: March 22, 2005
    Assignees: Juridical Foundation The Chemo-Sero-Therapeutic Research Institute, Kowa Company, Ltd.
    Inventors: Hiroshi Mizokami, Shinichi Furukawa, Keishin Sugawara, Tatsufumi Onchi, Kazuhiro Komatsu, Satoshi Koyanagi, Hideo Yoshizaki
  • Patent number: 6855263
    Abstract: A method for rapid purification of a blood component from blood is described in which the blood plasma is first separated from the cellular blood elements by any conventional means, such as centrifugation. An affinity cartridge is then activated with a molecule, such as an amino acid, which binds with a blood component such as plasminogen. The separated blood plasma is then passed through the affinity cartridge such that the blood component is retained by the affinity cartridge. Thereafter, the blood component is eluted from the affinity cartridge by passing a buffer solution containing a releasing agent through the affinity cartridge. This releasing agent disengages the blood component from the affinity cartridge. The releasing agent is then separated from the eluted solution by passing the eluted solution through a device, such as an ion exchange, gel filter, or size exclusion device. The isolated plasminogen solution is then concentrated by a factor of from 2 to 10. The separated blood component, e.g.
    Type: Grant
    Filed: July 23, 2002
    Date of Patent: February 15, 2005
    Assignee: Nuvue Technologies, Inc.
    Inventors: Michael T. Trese, George A. Williams, Michael K. Hartzer, Wendelin A. Dailey, Craig J. Bell
  • Patent number: 6852230
    Abstract: 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: Grant
    Filed: December 19, 2001
    Date of Patent: February 8, 2005
    Assignee: Amersham Biosciences AB
    Inventors: Makonnen Belew, Bo-Lennart Johansson, Jean-Luc Maloisel
  • Publication number: 20040248803
    Abstract: Compositions of purified biologically active Wnt proteins are provided. Wnt proteins are found to be hydrophobic and post-translationally modified by addition of a lipid moiety at a conserved cysteine residue. Methods for isolation of Wnt utilize detergents that maintain the solubility of the modified protein.
    Type: Application
    Filed: April 1, 2004
    Publication date: December 9, 2004
    Inventors: Roeland Nusse, Karl H. Willert
  • Patent number: 6822081
    Abstract: The invention relates to a process for the isolation and/or purification of a proteinaceous material, wherein a solid phase comprising a mixture of hydrophobic and hydrophilic groups is used.
    Type: Grant
    Filed: January 16, 2001
    Date of Patent: November 23, 2004
    Assignee: Max-Planck Gesellschaft zur Förderung der Wissenschaften e.V.
    Inventors: Holger Rauth, Richard Reinhardt, Eckhard Nordhoff, Markus Kalkum
  • Patent number: 6811969
    Abstract: 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: Grant
    Filed: June 23, 2000
    Date of Patent: November 2, 2004
    Assignee: Ciphergen Biosystems, Inc.
    Inventors: T. William Hutchens, Tai-Tung Yip
  • Patent number: 6812330
    Abstract: 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: Grant
    Filed: February 8, 2002
    Date of Patent: November 2, 2004
    Assignee: Genentech, Inc.
    Inventors: Louis E. Burton, Charles H. Schmelzer, Joanne T. Beck
  • Patent number: 6805882
    Abstract: 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: Grant
    Filed: October 2, 2000
    Date of Patent: October 19, 2004
    Assignee: University of Maryland Biotechnology Institute
    Inventors: Robert C. Gallo, Joseph Bryant, Yanto Lunardi-Iskandar
  • Patent number: 6803209
    Abstract: A cell culture preparation and methods are provided which are suitable for production in cells of a first protein in a class of proteins where the medium is deficient in a second protein in a related class, where the second protein is normally present in the serum and capable of interfering with the purification of the first compound.
    Type: Grant
    Filed: February 9, 2001
    Date of Patent: October 12, 2004
    Inventor: Pratap Malik
  • Patent number: 6776911
    Abstract: The present invention refers to the use of novel molecules able to bind tenaciously to silica, borosilicate and silicate surfaces, and thus to modify their properties and characteristics. When applied to silica-based chromatography, it offers important advantages in all cases in which it is necessary to modulate the interaction of analytes with the stationary phase. In capillary zone electrophoresis (CZE), such compounds will eliminate or invert the electroendoosmostic (EEO) flow, greatly simplifying the analysis of negatively-charged compounds and permitting the analysis of bio(macro)molecules via the direct use of naked capillaries.
    Type: Grant
    Filed: July 3, 2002
    Date of Patent: August 17, 2004
    Inventors: Attilio Citterio, Roberto Sebastiano, Cecilia Gelfi, Pier Giorgio Righetti
  • Patent number: 6777538
    Abstract: A 24 kd protein capable of binding the E2 envelope protein of hepatitis C virus (HCV), and functionally equivalent variants or fragments of the 24 kd protein, are disclosed. Processes for production and purification of the 24 kd protein, and functionally equivalent variants or fragments thereof, are also disclosed.
    Type: Grant
    Filed: January 5, 2001
    Date of Patent: August 17, 2004
    Assignee: Chiron S.r.l.
    Inventor: Sergio Abrignani
  • Patent number: 6777196
    Abstract: NTNR&agr;, NTNR&agr; extracellular domain (ECD), NTNR&agr; variants, chimeric NTNR&agr; (e.g., NTNR&agr; immunoadhesion), and antibodies which bind thereto (including agonist and neutralizing antibodies) are disclosed. Various uses for these molecules are described, including methods to modulate cell activity and survival by response to NTNR&agr;-ligands, for example NTN, by providing NTNR&agr; to the cell.
    Type: Grant
    Filed: September 1, 1999
    Date of Patent: August 17, 2004
    Assignee: Genentech, Inc.
    Inventors: Robert D. Klein, Arnon Rosenthal, Mary A. Hynes
  • Patent number: 6773599
    Abstract: An affinity ligand-matrix conjugate comprises the matrix and, conjugated thereto by the group Z, a ligand having general formula (I) wherein on X is N and the other X is N, CCL or CCn; A1 and A2 are each independently O, S or N—R1 and R1 is H, C1-6alkyl, C1-6 hydroxyalkyl, benzyl or &bgr;-phenylethyl; B1 and B2 are each independently an optionally substituted hydrocarbon lingkage containing from 1 to 10 carbon atoms; D1 is H or a primary amino, secondary amino, tertiary amino, quaternary ammonium, imidazole, guanidino or amidino group; and D2 is a secondary amino, tertiary amino, quaternary ammonium, imadazole, guanidino or amidino group; of B2-D2 is —CHCOOH—(CH2)3-4—NH2; AND p is 0 or 1. Such conjugates are useful for the separation, isolation, purification, characterisation, identification or quantification of an endotoxin.
    Type: Grant
    Filed: May 13, 2002
    Date of Patent: August 10, 2004
    Assignee: Prometic Biosciences Ltd.
    Inventors: Christopher Robin Lowe, Kim Hilary Lawden
  • Publication number: 20040138432
    Abstract: The present invention provides porous monoliths with high flow permeability that can be produced by polymerising and divinylbenzene in the presence of an initiator, a carboxy-functionalized nitroxide stable free radical and polymeric porogens. The monoliths produced with these stable free radicals functionalized with carboxylic groups feature porosities very different from those produced by polymerizations involving other SFRs, characterized by very large surface areas in combination with relatively large through-pores. The invention also provides a method for producing the monoliths, a column containing the monoliths and an assay method using the column.
    Type: Application
    Filed: March 10, 2004
    Publication date: July 15, 2004
    Inventors: Camilla Viklund, Knut Irgum
  • Patent number: 6756484
    Abstract: 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: Grant
    Filed: July 12, 2000
    Date of Patent: June 29, 2004
    Assignees: Cephalon, Inc., Chiron Corporation
    Inventors: Russell A. Brierley, Joan N. Abrams, John M. Hanson, Francis C. Maslanka, Cynthia Cowgill, Luis G. Juarbe-Osorio, Patricio Riquelme, Glenn Dorin
  • Patent number: 6746607
    Abstract: The invention concerns the use of an adsorptive size exclusion chromatography gel, said gel essentially consisting of a polysaccharide matrix whereon is grafted a polymer coupled with an affinity ligand and having a cleavage threshold ranging between 2 kDa and 60 kDa for eliminating a purifying biomolecules.
    Type: Grant
    Filed: June 4, 2001
    Date of Patent: June 8, 2004
    Assignee: Centre National de la Recherche Scientifique
    Inventors: Mookambeswaran Vijayalakshmi, Olivier Pitiot, Cécile Legallais, Philippe Moriniere
  • Patent number: 6740736
    Abstract: 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: Grant
    Filed: March 22, 2001
    Date of Patent: May 25, 2004
    Assignee: PPL Therapeutics (Scotland) Limited
    Inventor: Graham McCreath
  • Patent number: 6737233
    Abstract: A 24 kd percent capable of binding the E2 envelope protein of hepatitis C virus (HCV), and functionally equivalent variants or fragments of the 24 kd protein, are disclosed. Processes for production and purication of the 24 kd protein, and functionally equivalent variants or fragments thereof, are also disclosed.
    Type: Grant
    Filed: February 17, 1998
    Date of Patent: May 18, 2004
    Assignee: Chiron S.r.l.
    Inventor: Sergio Abrignani
  • Publication number: 20040081703
    Abstract: The present invention relates to cartilage extracts and to a method of producing the same. Shark cartilage extracts having anti-angiogenic, anti-tumor, anti-inflammatory and anti-collagenolytic activities have been obtained by an improved process. The process comprises the steps of obtaining a crude cartilage extract in an aqueous solution, this crude extract being fractionated to recover molecules of a molecular weight less than about 500 kDa. Some of the biologically active components of the extract are prepared by further fractionation. The cartilage extract can be used for treating diseases or conditions having etiological components selected from the group consisting of tumor proliferation, angiogenesis, inflammation, metalloprotease activity and collagenolysis. Several cosmetic applications based on the capacity of the liquid extract to improve skin conditions are also disclosed. A simple and efficient process for the preparation of cartilage extracts is also disclosed.
    Type: Application
    Filed: October 17, 2003
    Publication date: April 29, 2004
    Applicant: Les Laboratoires Aeterna, Inc.
    Inventors: Eric Dupont, Paul Brazeau, Christina Juneau, Daniel H. Maes, Kenneth Marenus, Richard Beliveau
  • Publication number: 20040060855
    Abstract: A web contactor for the purposes of continuous separation of specific proteins from a mixture of proteins comprises an endless, inert, non-porous, flexible web is coated with an activated matrix material which is, in turn, bound to a plurality of ligand molecules. The ligand molecules are chosen to correspond to a desired biological molecule or class of molecules, typically a desired protein. The web is translated over a series of rolls such that it contacts a feed solution of a mixture of biological molecules in a countercurrent manner. During contact of the web and solution, the ligand molecules which are attached to the web matrix, selectively bind to the protein or other biological molecule which are to be separated from the feed solution mixture.
    Type: Application
    Filed: September 30, 2002
    Publication date: April 1, 2004
    Applicant: University of Alabama
    Inventors: Ramon L. Cerro, Krishnan K. Chittur, Douglas G. Hayes
  • Publication number: 20040058402
    Abstract: The invention concerns a method for purifying the Helicobacter adhesin-like protein A (AlpA) which consists in: (i) contacting an AlpA preparation and 2.5 to 3.5 M of guanidine with a hydrophobic interaction chromatography material, so that the AlpA is adsorbed on the material; and (ii) eluting the AlpA with a solution containing 3.5 to 4.5 M of guanidine. The AlpA preparation to be purified can be in particular derived from an E. coli culture capable of expressing AlpA in a high-level recombinant form, rAlpA being in the form of inclusion bodies, the latter being recovered and solubilized in the presence of guanidine, and optionally ammonium sulphate-precipitated for the purpose of preliminary purification. The hydrophobic interaction chromatography can be followed up by an anion exchange chromatography in the presence of 8 M of urea.
    Type: Application
    Filed: July 30, 2003
    Publication date: March 25, 2004
    Inventors: Laurence Fourrichon, Ling Lissolo, Olivier Pitiot
  • Patent number: 6706191
    Abstract: A liquid chromatographic process performed at least partly in a fluidised bed contained in a vessel and comprising particle fluidised by an upwardly directed liquid flow, said process comprising (a) a capture step in which one or more compounds of a sample are captured by the particles and (b) a wash and/or releasing step in which the particles is in form of a fluidised bed through which a liquid flow is passing. The characteristic feature is that the liquid (liquid 1) used in the wash or the releasing step (step 1) is immediately followed by a liquid (liquid 2, step 2) having a higher density than liquid 1 while maintaining the bed in a fluidised state. A liquid chromatographic process having an actual sequence of steps comprising (c) at least a capture step in which a sample deriving from an animal is bound to the particles and (d) two consecutive steps (step 1 and step 2) in which the bed is fluidised by a liquid flow passing through said vessel.
    Type: Grant
    Filed: August 23, 2001
    Date of Patent: March 16, 2004
    Assignee: Amersham Biosciences AB
    Inventor: Patrik Leijon
  • Patent number: 6706192
    Abstract: Object of the invention is a process for the chromatographic purification of cyclosporin A from a crude product containing cyclosporin complex by using a column filled with silica gel and by the application of multistep chromatography with a column filled with normal phase silica gel and by a solvent mixture containing toluene as the major component.
    Type: Grant
    Filed: May 15, 2002
    Date of Patent: March 16, 2004
    Assignee: Biogal Gyogyszergyar Rt.
    Inventors: Vilmos Kéri, Ärvai Nagyné, Lajos Deák, Györgyné Makó, Istvánné Miskolczy
  • Publication number: 20040049012
    Abstract: 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: Application
    Filed: September 5, 2003
    Publication date: March 11, 2004
    Applicant: Genentech, Inc.
    Inventor: Richard L. Gehant
  • Publication number: 20040035793
    Abstract: Methods, systems, compositions and kits for improved detection of polynucleotides. In one aspect, there is provided a method for separating polynucleotides (such as DNA or RNA) using a liquid chromatographic separation device (such as a reverse phase column or an ion exchange column), contacting eluted polynucleotides with intercalating dye, and detecting (such as by fluorescence detection) dye bound to the eluted polynucleotides. The invention preferably uses a post-column reactor, such as a mixing tee, downstream of the separation column. Sensitivity of mutation detection by denaturing high performance liquid chromatography (DHPLC) is enhanced.
    Type: Application
    Filed: November 4, 2002
    Publication date: February 26, 2004
    Applicant: Transgenomic, Inc.
    Inventors: Benjamin L. Legendre, Joseph G. Rudolph, Michael A. Marino
  • Publication number: 20040030107
    Abstract: The present invention generally relates to novel processes for protein purification in high salt solutions such as cell culture broth by increasing the dynamic binding capacity of a resin with the addition of polyethylene glycol.
    Type: Application
    Filed: November 12, 2002
    Publication date: February 12, 2004
    Inventors: Min Wan, Mark David Chavez, Jeffrey Lee Schrimsher
  • Patent number: 6689871
    Abstract: The present invention provides a method of purifying diphtheria toxin comprising (1) fermenting a microorganism strain capable of producing diphtheria toxin using glucose as a carbon source, the method comprising adding glucose to a growing culture whereby the addition of glucose maintains microorganism growth effective to support diphtheria toxin production; and (2) purifying the diphtheria toxin from the culture by contacting a toxin containing preparation derived therefrom with an ion exchange matrix, eluting a fraction containing the toxin, applying the eluate to a hydrophobic matrix, and eluting a fraction containing the toxin.
    Type: Grant
    Filed: January 25, 2002
    Date of Patent: February 10, 2004
    Assignee: Amersham Health AS
    Inventors: Henry Wolfe, Fahar Merchant, Rosemina Merchant, Christopher Black, Harry Storflor, Geir Stokke, Halldis Hellebust
  • Publication number: 20040014949
    Abstract: Packings or equivalent structures which produce radial mixing in channels can be used to enhance reagent addition devices for ion chromatography post column reactions in which band spreading at detrimental levels is effectively controlled. Application to two dimensional conductometric detection in simultaneous suppressed and nonsuppressed ion chromatography.
    Type: Application
    Filed: March 7, 2003
    Publication date: January 22, 2004
    Inventors: Purnendu K. Dasgupta, Rebecca L. Adams