Separation, Purification Or Synthesis Patents (Class 530/364)
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Patent number: 5250663Abstract: A composition is disclosed which comprises a solution of human serum albumin essentially free of chemicals used in processing. The preparation is also essentially free of metals such as aluminum. The composition is 100% pure by cellulose acetate electrophoresis and is essentially monomeric when tested by high pressure liquid chromatography. The turbidity is less than 5 N.T.U. (National Turbidity Units). This preparation has a substantially longer shelf life and remains biologically active longer than products currently available. The novelty of this product is also such that it does not leach metallic substances such as aluminum from its closure. Novel applications of process methodology are taught in the preparation of this composition and a novel preparation results from essentially non hemoglobin containing albumin sources such as Source Plasma (Human).Type: GrantFiled: March 9, 1992Date of Patent: October 5, 1993Assignee: Miles Inc.Inventor: Robert A. Tenold
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Patent number: 5250662Abstract: There is provided in accordance with the practice of this invention a process for separating albumin from an impure protein fraction containing albumin. Contaminants, in an aqueous solution of the impure protein fraction containing albumin, are precipitated from the solution at a pH of from about 4.5 to about 4.7. Additional contaminants that remain soluble are bound to an anion-exchange resin. After the precipitated and anion-exchange-bound contaminants are removed from the albumin-containing solution, the pH of the solution is adjusted to from about 4.7 to about 6.1, and additional contaminants are precipitated. Further contaminants are then bound to an anion-exchange resin, and these precipitated and anion-exchange-bound contaminants are removed from the albumin-containing solution.Type: GrantFiled: February 27, 1992Date of Patent: October 5, 1993Assignee: Alpha Therapeutic CorporationInventor: Chong E. Chang
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Patent number: 5234991Abstract: A porous mineral support such as a porous mineral oxide coated with an aminated polysaccharide polymer has cationic characteristics and is capable of reversibly fixing thereto biological macromolecules. This material is employed in the separation and purification of said biologic macromolecules.Type: GrantFiled: March 17, 1987Date of Patent: August 10, 1993Assignee: Pasteur Merieux Serums and VaccinesInventors: Jean-Louis Tayot, Michel Tardy
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Patent number: 5229498Abstract: A method is provided for cleansing a protein from multivalent metal ions bound thereto, these ions being released from the protein by exchanging the ions with monovalent metal ions, whereafter the multivalent metal ions are removed. The release and removal of these ions is effected, in particular, by diafiltration or gel filtration processes.Type: GrantFiled: December 24, 1991Date of Patent: July 20, 1993Assignee: Kabi Pharmacia ABInventor: Rainer Eketorp
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Patent number: 5187261Abstract: Mature human serum albumin is produced from a human serum albumin produced by a microbiological route in the form of fused protein ("pseudo-pro-HSA") containing an N-terminal peptide elongation.Type: GrantFiled: February 8, 1991Date of Patent: February 16, 1993Assignee: GeneticaInventors: Martine Latta, Jean-Francois Mayaux, Paolo Sarmientos
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Patent number: 5145706Abstract: The present invention relates to a method for preparation of plasma powder characterized by catalytic treatment of plasma with colloidal silica and subsequent powdering of the plasma. The plasma powder thus obtained by the present invention is substantially free of malodorous substances.Type: GrantFiled: March 28, 1991Date of Patent: September 8, 1992Assignee: Taiyo Kagaku Co., Ltd.Inventors: Takashi Hagi, Kouichi Misawa, Shuji Saito, Yuji Sakamoto, Noriaki Kadota, Yoshiro Toda, Nagataka Yamazaki
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Patent number: 5138034Abstract: A method of fractionating plasma protein which comprises treating a plasma protein-containing material in the following sequence of steps, provided that steps (ii) through (v) may be performed in an optional order: (i) freeze-thaw treatment, (ii) treatment at 5 to 10% ethanol concentration, (iii) treatment with an anion exchanger, (iv) affinity chromatography with immobilized lysine, (v) affinity chromatography with immobilized heparin, (vi) treatment at 18 to 30% ethanol concentration, (vii) treatment at 35 to 45% ethanol concentration.Type: GrantFiled: June 14, 1990Date of Patent: August 11, 1992Assignee: The Green Cross CorporationInventors: Yahiro Uemura, Kazuo Takechi, Kenji Tanaka
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Patent number: 5132404Abstract: A method of purifying human serum albumin which comprises subjecting human serum albumin-containing solution to heat treatment of about 50.degree.-70.degree. C. for 1-5 hours in the presence of acetyltryptophan and/or an organic carboxylic acid with 6-12 carbon atoms or a salt thereof.Type: GrantFiled: September 18, 1990Date of Patent: July 21, 1992Assignee: Green Cross CorporationInventors: Wataru Ohtani, Akinori Sumi, Takao Ohmura, Yahiro Uemura
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Patent number: 5118794Abstract: In order to stabilize solutions of human albumin for therapeutic use for the purpose of their treatment by heat in a container, in particular in the final container, there is added, in addition to the usual stabilizing formula, a surfactant agent selected from among Tween 80, Tween 20, Pluronic F68, laurate of polyethylene glycol 600 or any other equivalent agent.Type: GrantFiled: April 11, 1989Date of Patent: June 2, 1992Assignee: Institut MerieuxInventors: Michel Grangeorge, Pierre Fournier
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Use of intermediate length alcohols as virucidal agents in solutions of biologically active proteins
Patent number: 5071650Abstract: Soluble, intermediate length alcohols (C.sub.4 -C.sub.10) in aqueous solutions at low pH (4.0-7.0) can be used as virucidal agents for therapeutic biologically active protein preparations. Treatment with the alcohols is especially useful for proteins having activity not adversely affected by low pH.Type: GrantFiled: June 4, 1990Date of Patent: December 10, 1991Assignee: Miles Inc.Inventors: George B. Dove, Milton B. Dobkin, Michael A. Shearer -
Patent number: 5043427Abstract: This invention relates to a process for continuously fractionating plant, animal or human proteins by selective precipitation of the proteins resulting from placing a solution of proteins in contact with a precipitating agent constituted by a fatty acid of 6 to 14 carbon atoms, such as caprylic acid, is characterized in that respective deliveries of fatty acid and of the protein solution are continuously placed in contact in a mixing chamber of small volume with respect to the deliveries, creating a strong stirring in this mixing chamber; the individual deliveries of fatty acid and of protein solution are adjusted to controlled pH and temperature so as to maintain their ratio equal to a predetermined value; the mixture is then allowed to evolve during a phase of maturation so as to form a suspension; this suspension is separated into a liquid part from which are extracted the proteins having remained soluble, and a solid part containing proteins of different nature; and the parameters intervening in the proceType: GrantFiled: May 31, 1989Date of Patent: August 27, 1991Assignee: Foundation Nationale de Transfusion SanguineInventors: Catherine Leberre, Alain Faure, Gilles Beaudoin, Brigitte Roche, Pierre Colinart, Henri Renon
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Patent number: 5037744Abstract: Human serum albumin is made by culturing a bacterium (e.g. E. coli) capable of providing for the stable maintenance of a plasmid containing an inducible promoter (e.g. P.sub.trp), a ribosome binding site (e.g. that of the CII gene of bacteriophage lambda not containing the t.sub.R1 sequence), and the human serum albumin gene possessing an ATG initiation codon at the 5' end.Type: GrantFiled: December 13, 1989Date of Patent: August 6, 1991Assignee: GeneticaInventors: Michael Knapp, Georges Brefort, Paolo Sarmientos
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Patent number: 5004604Abstract: An immuno-suppressor is described in the form of an immuno-suppressor serum and/or an IS-IgG extracted from this serum, produced by immunisation of an animal with antibody-covered cells; also described is the process for making said immuno-suppressor and its use for suppressing the humoral and/or cellular immune response.Type: GrantFiled: March 25, 1988Date of Patent: April 2, 1991Assignee: Fresenius A. G.Inventors: Peter Terness, Gerhard Opelz
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Patent number: 4990447Abstract: Recombinantly produced serum albumin is purified in a series of steps, initially employing an alkaline precipitation, optionally followed by incubation with an anion exchange absorbent, followed by affinity chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase.Type: GrantFiled: March 1, 1989Date of Patent: February 5, 1991Assignee: Gist-Brocades NVInventors: Boudewijn W. Konig, Michiel N. Hamers, Cornelis J. van der Laken
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Patent number: 4946944Abstract: Process for the selective extraction of metalloproteins from whey, by adsorption on a porous inorganic support in the form of particles, followed by elution of the metalloproteins thus absorbed by means of solutions, characterized in that the walls of the said particles are coated with a layer of aminated polysaccharides possessing acidic functional groups at the surface.Type: GrantFiled: August 21, 1989Date of Patent: August 7, 1990Assignees: Entremont S.A., National Elf AquitaneInventors: Jacques Frankinet, Andree Peyrouset, Francois Spring
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Patent number: 4902509Abstract: There is suggested a new process for the isolation of chicken egg white cystatin from an aqueous solution of chicken egg white by means of heating to max. 80.degree. C., chromatography on carboxymethylated papain-Sepharose 4B, chromatography on Sephadex-G-50 and purification by means of ion exchange chromatrography of the Fast Protein Liquid Chromatrography type. There are further suggested new agents and methods of treating viral infections in living organisms, especially mammalian and avian picornaviral infections, by means of chicken egg white cystatin.Type: GrantFiled: October 29, 1987Date of Patent: February 20, 1990Assignee: KRKA, tovarna zdravil, n.sol.o.Inventors: Vito Turk, Joze Brzin
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Patent number: 4841023Abstract: There is disclosed a process for rendering a labile protein-containing composition, substantially free of lipid-containing viruses without incurring substantial protein denaturation comprising contacting said composition with an effective amount of a fatty acid or a soluble ester, alcohol or a salt thereof for a sufficient period of time to inactivate virus contained therein.Type: GrantFiled: June 25, 1986Date of Patent: June 20, 1989Assignee: New York Blood Center, Inc.Inventor: Bernard Horowitz
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Patent number: 4833233Abstract: HSA crystals are provided in the form of tetragonal plates having the space groups P42.sub.1 2, the crystals being grown to sizes in excess of 0.5 mm in two dimensions and a thickness of 0.1 mm. Growth of the crystals is carried out by a hanging drop method wherein a precipitant solution containing PEG and a phosphate buffer is mixed with an HSA solution, and a droplet of mixed solution is suspended over a well of precipitant solution. Crystals grow to the desired size in 3 to 7 days. Concentration of reagents, pH and other parameters are controlled within prescribed limits. The resulting crystals exhibit a size and quality such as to allow performance of x-ray diffraction studies and enable the conduct of drug binding studies as well as genetic engineering studies.Type: GrantFiled: August 20, 1987Date of Patent: May 23, 1989Assignee: The United States of America as represented by the Administrator of the National Aeronautics and Space AdministrationInventor: Daniel C. Carter
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Patent number: 4791191Abstract: A simple method for the depyrogenation of clinical albumin is disclosed. It includes mixing the pyrogenic clinical albumin with human plasma, followed by a two-step albumin method reported previously by this inventor. The depyrogenated albumin, in the form of ethanol precipitate, can then be processed into clinical albumin according to the conventional procedures. This simple process not only results in the depyrogenation of the endotoxin--contaminated albumin, but also recovers the albumin which is present in the added plasma. The overall albumin yield is greater than 90% as calculated from the starting pyrogenic albumin and the albumin present in the added plasma.Type: GrantFiled: November 12, 1987Date of Patent: December 13, 1988Assignee: Plasmatech CorporationInventor: Yu-Lee Hao
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Patent number: 4780529Abstract: An endotoxin inactivator is isolated from human plasma by anion exchange (DEAE-Sephadex), dye-affinity (Cibracron Blue-Sepharose), and adsorption (on hydroxyapatite) chromatography. The endotoxin inactivator, isolated in essentially pure form, may be used to depyrogenate clinical blood products.Type: GrantFiled: June 16, 1987Date of Patent: October 25, 1988Assignee: Biotech Research Laboratories, Inc.Inventor: Yu-Lee Hao
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Patent number: 4754019Abstract: High purity albumin can be recovered in high yield from human plasma protein solution containing albumin by heat-treatment of the solution to denature and precipitate non-albumin proteins in a combination of specific conditions such as protein concentration of the solution, pH, heating time and temperature, the concentration of precipitant ammonium sulfate.Type: GrantFiled: June 12, 1987Date of Patent: June 28, 1988Assignee: The Green Cross CorporationInventors: Yoshihiko Gion, Yasuo Uehara, Minoru Inosaka, Sadao Yabushita
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Patent number: 4720385Abstract: Compositions containing therapeutically or immunologically active proteins are rendered substantially free from infectious agents such as viable viruses and bacteria without substantial loss of therapeutic or immunologic activity by mixing the protein composition with a complex formed from transition metal ions, such as copper ions, and an angularly-fused, polynuclear heterocyclic arene having two nitrogen atoms in a "cis-ortho" relationship, such as phenanthroline, and a reducing agent such as a thiol or ascorbic acid or ascorbate salt or mixtures of ascorbic acid or ascorbate with a thiol in amounts and at a temperature and for a time sufficient to inactivate substantially all of the viruses and bacteria contained therein. Compositions containing therapeutically active proteins substantially free from viral and bacterial infectivity, which have heretofore been unattainable, can be prepared by the method of the invention.Type: GrantFiled: May 20, 1985Date of Patent: January 19, 1988Assignee: Miles Laboratories, Inc.Inventor: Kenneth J. Lembach
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Patent number: 4684723Abstract: There is disclosed an improved method for separating and recovering proteins, particularly therapeutically active proteins, from an aqueous system also containing a component having the ability to create two liquid phases by use of salt partitioning technology. By the addition of water soluble inorganic salts to an aqueous system containing one or more therapeutically active proteins or nucleic acids, especially an aqueous system obtained from fractionation of a blood plasma fraction or from a tissue culture fluid resulting from a biotechnology production operation such as recombinant DNA and monoclonal antibody technologies, the aqueous system may be separated into two or more liquid phases. Such separated phases may be selectively enriched in components of the original aqueous system having differing solubility in the so-separated liquid phases.Type: GrantFiled: September 11, 1985Date of Patent: August 4, 1987Assignee: Miles Laboratories, Inc.Inventors: George B. Dove, Gautam Mitra
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Patent number: 4678583Abstract: A process for forming a purified solute from an aqueous solution is provided whereby a mixture of an extractant, a hydrate former and the aqueous solution is first formed. The hydrate former forms a hydrate with water while the solute does not form a hydrate. The extractant takes up the solute from the aqueous solution. The mixture is subjected to a temperature and pressure sufficient to form the solid hydrate of the hydrate former, an aqueous solution of the solute and a portion comprising the extractant containing the solute. The solute is recovered from the portion comprising the extractant and the solute.Type: GrantFiled: June 12, 1986Date of Patent: July 7, 1987Assignee: Massachusetts Institute of TechnologyInventors: Richard C. Willson, III, Eric Bulot, Charles L. Cooney
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Patent number: 4675384Abstract: The plasma proteins contained in a plasma solution thereof are chromatographically fractioned, e.g., to obtain a high purity therapeutic grade albumin product, by successively contacting said plasma solution with at least one anion exchanger and at least one cation exchanger in fixed bed chromatography columns, the contact and exchange medium of chromatography therein also comprising a plurality of at least partially hydrophobic support particulates and a plurality of hydrophilic ion exchanger support particulates.Type: GrantFiled: April 2, 1984Date of Patent: June 23, 1987Assignees: Rhone-Poulenc Recherches, Institut MerieuxInventors: Adrien Dromard, Michel Exertier, Claude Rollin, Jean-Louis Tayot, Michel Tardy
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Patent number: 4673734Abstract: A porous mineral support such as a porous mineral oxide coated with an aminated polysaccharide polymer has cationic characteristics and is capable of reversibly fixing thereto biological macromolecules. This material is employed in the separation and purification of said biologic maromolecules.Type: GrantFiled: March 21, 1985Date of Patent: June 16, 1987Assignee: Institut MerieuxInventors: Jean-Louis Tayot, Michel Tardy
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Patent number: 4596768Abstract: Conjugates of penicilloic acid derivatives and certain poly(amino acids), which are either antigenic or enzymatic, are provided. Antibodies raised against the antigenic poly(amino acids) and the enzyme conjugates are used as reagents in immunoassays. In particular, the compounds of the present invention can be used for measuring the presence of a .beta.-lactamase in a patient serum sample by adding a known amount of penicillin to the sample and observing the production of penicilloic acid over a fixed period of time.Type: GrantFiled: November 2, 1983Date of Patent: June 24, 1986Assignee: Syntex (U.S.A.) Inc.Inventors: Prithipal Singh, Danton K. Leung, Richard Rodgers