Ultra Filtration Or Osmosis Patents (Class 530/414)
  • Patent number: 5004806
    Abstract: The present invention encompasses a method for removing proteins from a solution containing polynucleotides and proteins comprising filtering the solution through a nitrocellulose membrane at neutral or basic pH.
    Type: Grant
    Filed: October 17, 1988
    Date of Patent: April 2, 1991
    Assignee: Molecular Devices Corporation
    Inventor: Viola T. Kung
  • Patent number: 4992531
    Abstract: A method for the recovery of proteins in a solubilized form from host cells including providing a source of host cells incorporating a synthesized or expressed protein; providing a source of at least one cationic surfactant; and treating the host cells with at least one cationic surfactant, in an amount sufficient to effect solubilization of the proteins.
    Type: Grant
    Filed: June 13, 1988
    Date of Patent: February 12, 1991
    Assignee: Bunge (Australia) Pty. Ltd.
    Inventors: Joseph J. Patroni, Malcolm R. Brandon
  • Patent number: 4985544
    Abstract: Reactivation of cysteine-containing protein in a process, in which a reduced and denatured cysteine-containing protein such as salmon growth hormone I or eel growth hormone I can be efficiently reactivated.
    Type: Grant
    Filed: August 2, 1988
    Date of Patent: January 15, 1991
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Yoshiharu Yokoo, Seiji Sugimoto
  • Patent number: 4965344
    Abstract: A process for the preparation of a spatial form, which has biological activity, of a protein from a biologically inactive spatial form is described and comprises the protein being dissolved with the addition of a denaturing agent and thus converted into the random coil form, and the solution being allowed to pass through a material which has molecular sieve properties and contains a liquid medium in which the protein can assume a spatial form which has biological activity, and this material having molecular sieve properties being selected so that the molecules of the denaturing agent can penetrate, but the protein molecules canot. It is possible by centrifugation, blowing or sucking out to remove the medium in the "external volume" of the molecular sieve and to increase the rate of passage of the solution through the molecular sieve.
    Type: Grant
    Filed: June 2, 1987
    Date of Patent: October 23, 1990
    Assignee: Behringwerke Aktiengesellschaft
    Inventor: Reinhard Hermann
  • Patent number: 4963356
    Abstract: A storage-stable, high potency allergenic extract is prepared by ultrafiltration, retaining fractions having molecular weights of from 1000 to 100,000, and drying the retained fraction to a moisture content of less than one weight percent. The extract can also be pretreated with amylase before ultrafiltration, treated with affinity chromatography before drying, and/or treated with gamma radiation after drying.
    Type: Grant
    Filed: April 20, 1987
    Date of Patent: October 16, 1990
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: Emanuel Calenoff, Myron A. Beigler, Gerald L. Friesen, James L. Nichols
  • Patent number: 4956278
    Abstract: Anaplasma marginale antigen, antigen compositions, vaccine and process for the production of said antigen, antigen composition and vaccine are disclosed. The Anaplasma marginale is free of the erythrocyte antigens that cause neonatal isoerythrolysis, and effective as a vaccinate which will not only protect the vaccinate against bovine anaplasmosis, but does not induce neonatal isoerythrolysis in offspring of vaccinates.
    Type: Grant
    Filed: February 23, 1988
    Date of Patent: September 11, 1990
    Assignee: Louisiana State University
    Inventors: Lewis T. Hart, Donald G. Luther, William J. Todd
  • Patent number: 4929700
    Abstract: A process for recovering dimeric, biologically active CSF-1 from bacterially expressed recombinant CSF1 genes is described. The process comprises recovery of the solubilized monomeric form, followed by dimerization under refolding conditions and further purification of the dimer. Heterodimers may also be produced by this process.
    Type: Grant
    Filed: April 8, 1988
    Date of Patent: May 29, 1990
    Assignee: Cetus Corporation
    Inventors: Robert Halenbeck, Kriston Koths, Cynthia Cowgill, Walter J. Laird
  • Patent number: 4919952
    Abstract: Food grade protein and dietary fibre concentrates are prepared from wheat millfeed. The process utilizes an efficient alkali extraction to obtain in excess of 75% w/w of the protein present in the millfeed in a solution which is further treated to separate the suspended starch and fat. The clarified liquid containing the protein is passed over a semipermeable membrane during which it is further purified and concentrated. Hydrogen peroxide and heat are introduced to the liquid thereby reducing its color prior to spray drying. The resulting residue from the extraction is dried or further treated with hydrogen peroxide and heat to produce a light colored dietary fibre concentrate.
    Type: Grant
    Filed: February 8, 1989
    Date of Patent: April 24, 1990
    Assignee: Robin Hood Multifoods Inc.
    Inventors: Gobind T. Sadaranganey, Wendy Zellen, John Michaelides
  • Patent number: 4908434
    Abstract: Interleukin 2 (IL 2; T-cell growth factor), produced with and without costimulation by Burkitt's lymphoma line Daudi, is highly purified approximately over 37,000-fold to apparent homogeneity from lymphocyte-conditioned medium derived from normal humaThis invention was made with support in part under Grants CA 08748, CA 22507, CA 25608, CA 20194, CA 21525, CA 31525, P01-CA-20194, AI 18 321-01, CA 23766 and CA 33050 awarded by the National Cancer Institute, National Institute of Health, DHEW. The government has certain rights in this invention.
    Type: Grant
    Filed: June 10, 1988
    Date of Patent: March 13, 1990
    Assignee: Sloan-Kettering institute for Cancer Research
    Inventors: Roland Mertelsmann, Karl Welte, Salvatore Venuta
  • Patent number: 4902673
    Abstract: A bidifobacteria growth promoter contained in soybeans is extracted from defatted soybeans with an aqueous solution of alcohol.
    Type: Grant
    Filed: November 9, 1988
    Date of Patent: February 20, 1990
    Assignee: The Calpis Food Industry Co., Ltd.
    Inventors: Kunihiko Hayakawa, Teruhisa Masai, Yasuyuki Yoshida, Takanobu Shibuta, Hiroshi Miyazaki
  • Patent number: 4897465
    Abstract: Disclosed are ultrafiltration processes for the enrichment and concentration of selected proteins from protein conaining fluids. Illustratively, IgG is concentrated from whey by means of multiple ultrafiltration "passes", using a metallic oxide ultrafiltration membrane, which are characterized by differing pH's.
    Type: Grant
    Filed: October 12, 1988
    Date of Patent: January 30, 1990
    Assignee: Abbott Laboratories
    Inventors: Christopher T. Cordle, Larry G. Criswell, Ronald L. Thomas
  • Patent number: 4894440
    Abstract: A megakarytocyte stimulatory factor (MSF), purified to homogeneity, is an acidic protein (pI=5.1) with an Mr=15,000 which stimulates PF4-like protein synthesis in rat promegakaryoblast cells by as much as 7-fold, and exhibits half-maximal activity at a concentration of 0.8 pM. MSF exhibits no biologic activity corresponding to other known hemopoietic growth factors, and appears to be specific for the megakaryocyte lineage.In the given examples, MSF was purified to homogeneity (as judged by SDS-PAGE and isoelectric focusing in the presence of 9.2 M urea) from serum-free conditioned medium obtained from cultured human embryonic kidney (HEK) cells, and to near homogeneity from thrombocytopenic plasma.
    Type: Grant
    Filed: September 17, 1986
    Date of Patent: January 16, 1990
    Assignee: Massachusetts Institute of Technology
    Inventor: Robert D. Rosenberg
  • Patent number: 4894444
    Abstract: Immunologically intact protein or peptide immunogens are recovered from vaccines consisting of immunogen-aluminum hydroxide (alum) complexes. Recovery consists of dissolution of the complexes with an alkali metal salt of a carboxylic acid at a basic pH, reduction of the pH to physiological levels, removal of excess dissolvent and isolation of the protein or peptide immunogen.
    Type: Grant
    Filed: July 16, 1987
    Date of Patent: January 16, 1990
    Assignee: Merck & Co., Inc.
    Inventors: Edgar M. Scattergood, Roy W. Grabner
  • Patent number: 4883865
    Abstract: A liquid phase containing preS2+S antigen is separated into two phases after which the desired antigen is concentrated, washed and adsorbed and desorbed from a fumed silica to produce a product that is purified and concentrated in antigen:protein ratio and that is suitable for final purification.
    Type: Grant
    Filed: September 30, 1987
    Date of Patent: November 28, 1989
    Assignee: Merck & Co. Inc.
    Inventor: Dennis J. Kubek
  • Patent number: 4873317
    Abstract: A method for the separation or purification of biopolymers comprises adsorbing the biopolymer on the surface of liquid oil droplets; and separating the adsorbed biopolymer from the oil droplets. The adsorbed biopolymer is separated from the oil droplets by mixing the droplets in an aqueous liquid, removing the lower aqueous phase and adding a fresh aqueous phase to the droplets, cooling the mixture to solidify and coalesce the oil and to cause it to release the adsorbed biopolymer to the fresh liquid, separating the fresh liquid and the biopolymer from the coalesced oil, separating the biopolymer from the fresh liquid.
    Type: Grant
    Filed: March 5, 1987
    Date of Patent: October 10, 1989
    Inventors: Melvyn Rosenberg, Ilana Eli
  • Patent number: 4870053
    Abstract: A novel process for the preparation of water-soluble acyl glycoprotein extracted from Klebsiella Pneumoniae containing 30 to 45% by weight of proteins, 30 to 40% by weight of neutral saccharides, less than 4% of glucuronic acid, 2 to 5% by weight of osamines with a molecular weight of about 350,000 daltons and having a polysaccharide chain of n chains of one molecule of glucose and 4 molecules of galactose attached to an asparagine of a proteidic chain by a core formed of heptose and 2-keto-3-deoxy-octulosonic acid followed by an acyl portion containing .beta.-hydroxymyristic acid and then N-acetyl-glucosamine designated herein as F.sub.1 and compositions and a method of inducing antiallergic properties in warm-blooded animals.
    Type: Grant
    Filed: January 4, 1984
    Date of Patent: September 26, 1989
    Assignee: Roussel Uclaf
    Inventors: Rene Zalisz, Marie-France Salles
  • Patent number: 4843065
    Abstract: A method of preparing remedies for the treatment of bacterial and viral infections which involves introduction into the udder of an ungulate during lactation, a specific vaccine comprising bacterial and/or viral organisms in an inactive state, and the preparation of small dosages of the secretary fluid subsequently withdrawn during lactation from the ungulate thus treated.
    Type: Grant
    Filed: October 13, 1987
    Date of Patent: June 27, 1989
    Inventors: Robert A. Collins, Philip F. Weighner
  • Patent number: 4834974
    Abstract: A dry, immunologically active filtered product is produced through the controlled one or two stage ultrafiltration of liquid whey containing immunologically active immunoglobulin (Ig). When a predetermined quantity of the filtered product with an active Ig concentration of at least about seven percent of total solids is fed to newborn calves, the product functions as a substitute for natural colostrum, providing both temporary passive immunity as well as initiation of the active immune system of the animal. Disease resistance and growth rate in animals including humans is enhanced by oral administration of the filtered product. The immunological properties of the filtered product result from the presence of substantially enhanced concentrations of active Ig as well as other immunologically active whey components in comparison to the immunologically ineffective concentrations of these materials in the liquid whey ultrafiltration feedstock.
    Type: Grant
    Filed: December 24, 1986
    Date of Patent: May 30, 1989
    Assignee: Protein Technologies, Inc.
    Inventors: Gerald H. Stott, David O. Lucas
  • Patent number: 4814434
    Abstract: A biologically active composition extracted from thymus tissue, capable of inducing immature bone marrow cells to differentiate into competent suppressor T-cells.
    Type: Grant
    Filed: November 15, 1984
    Date of Patent: March 21, 1989
    Assignee: Ventres Laboratories, Inc.
    Inventor: Marcia F. Goldfarb
  • Patent number: 4806346
    Abstract: A process for preparing the purified F(ab).sub.2 fragment of equine Ig(T) from horses hyperimmunized with snake venom which comprises:(a) passing crude diluted hyperimmune equine serum contianing snake venom antigen specific Ig(T) buffered to an acidic pH through a strong base anion exchange polymer;(b) passing the resultant pass-through solution to which is added sodium chloride to a concentration of 0.05-0.124M through a strong acid cation exchange polymer;(c) adjusting the pH of the pass-through of step (b) to a pH of 3.3, and digesting said pass-through with pepsin; and(d) ultrafiltering said pepsin-digested pass-through to obtain purified F(ab).sub.2 fragment of the snake venom antigen specific equine Ig(T).
    Type: Grant
    Filed: December 16, 1986
    Date of Patent: February 21, 1989
    Assignee: American Home Products Corporation
    Inventors: Wah-tung Hum, Shaw-guang Lee
  • Patent number: 4801686
    Abstract: A process is provided for purifying recombinant IL-1 from microbial cells, comprising suspending the cells in an aqueous buffered medium having a pH from about 1 to about 5; disrupting the cells to provide an extract containing solubilized IL-1; and recovering solubilized Il-1 from the extract.
    Type: Grant
    Filed: September 4, 1986
    Date of Patent: January 31, 1989
    Assignee: Immunex Corporation
    Inventor: Shirley R. Kronheim
  • Patent number: 4784850
    Abstract: The present invention relates to a process for the manufacture of a preparation containing specific antibodies against the K-99 antigen of various strains of enterotoxigenic Escherichia coli (etec). In said process the milk obtained from postpartum cows, which had been previously vaccinated with E. coli strain 168, is clotted with a suitable enzyme. The fatty serum is then separated from the cheese obtained, the fat is then separated out, the fat-free serum is then subjected to ultrafiltration through a suitable number of appropriate membranes so that 30-50% of the water present is removed the retentate is then sterilized. Suitable membranes are those which are permeable only to molecules of less than about 22,000-30,000 daltons molecular weight. The preparation is advantageously lyophilized and the lyophilized preparation is subsequently sterilized by irridation, e.g. with Co.sup.60.
    Type: Grant
    Filed: September 4, 1985
    Date of Patent: November 15, 1988
    Assignee: Mutzarei Maabarot
    Inventor: Gilead B. Abraham
  • Patent number: 4783264
    Abstract: A process is disclosed for the recovery of a compound, for example, a peptide-containing compound, from a solution containing contaminants through combined affinity-chromatographic purification and ultrafiltration. The process comprises contacting the solution containing the compound and impurities with a first complex of ligand bound to a carrier so as to form a second complex of the compound, the ligand and the carrier, wherein the carrier is comprised of a macromolecular solid material; subsequently splitting off of the compound from the second complex to reform the compound and first complex; and separating of the compound from the first complex. An arrangement for the recovery of a compound from such a solution containing impurities is also disclosed.
    Type: Grant
    Filed: December 3, 1987
    Date of Patent: November 8, 1988
    Assignee: Gambro Lundia AB
    Inventors: Ulf T. G. Nylen, Bo G. Mattiasson
  • Patent number: 4774323
    Abstract: A method of preparing von Willebrand Factor by disassociating it from a chaotropic agent in solution therewith and preferably treating the same under controlled temperature either in liquid or lyophilized form.
    Type: Grant
    Filed: June 29, 1987
    Date of Patent: September 27, 1988
    Assignee: Rorer Pharmaceutical Corporation
    Inventors: Jack Newman, David L. Farb
  • Patent number: 4749783
    Abstract: Preparation of active therapeutic proteins comprising two essential steps. In the first step an active protein source is treated under conditions sufficient to inactivate any viruses present (e.g. via heat or chemical treatment). In the second step, the treated active protein source of moderate purity is then treated under conditions sufficient to remove impurities as well as denatured (once active) proteins resulting from the viral inactivation step. In an illustrative embodiment, a biologically active protein such as antithrombin is treated under conditions sufficient to assure viral inactivation and minimal antithrombin deactivation. After the viral inactivation, the antithrombin is contacted with immobilized heparin to complex only the active antithrombin which is then eluted by known means and processed further (e.g., to include desired excipients and then freeze dried).
    Type: Grant
    Filed: July 11, 1986
    Date of Patent: June 7, 1988
    Assignee: Miles Laboratories, Inc.
    Inventors: Robert E. Jordan, Jaleh Kilpatrick
  • Patent number: 4748234
    Abstract: A refractile material containing a heterologous protein is recovered from a host microorganism cell culture transformed to produce the protein. One recovery process involves disrupting the cell wall and membrane of the host cell, removing greater than 99% by weight of the salts from the disruptate, redisrupting the desalted disruptate, adding a material to the disruptate to create a density or viscosity gradient in the liquid within the disruptate, and separating the refractile material from the cellular debris by high-speed centrifugation. Another version of such a recovery process comprises the further steps of solubilizing the refractile material under reducing conditions, organically extracting the solubilized refractile material, and isolating said refractile material from the extractant.Preferably the protein is recombinant IL-2 or IFN-.beta. and the salt removal step is carried out by diafiltration.
    Type: Grant
    Filed: March 25, 1986
    Date of Patent: May 31, 1988
    Assignee: Cetus Corporation
    Inventors: Glenn Dorin, Wolfgang H. Hanisch, Leo S. Lin
  • Patent number: 4746731
    Abstract: A protein PP.sub.18 is isolated having the following characteristics:(a) an electrophoretic mobility in the region of that of .beta..sub.1 -globulins;(b) an isoelectric point between 5.6 and 6.2;(c) a sedimentation coefficient s.sub.20,w of 5.0.+-.0.2 S;(d) a molecular weight determined in an ultracentrifuge of 82,300.+-.5,600;(e) a carbohydrate fraction of 2.3.+-.1.3 g/100 g (mannose 0.15.+-.0.1, xylose 0.5.+-.0.5, galactose 0.5.+-.0.2, glucose 0.2.+-.0.1, N-acetylglucosamine 0.7.+-.0.2, and N-acetylneuraminic acid 0.25.+-.0.2, each g/100 g).Also described is the amino acid composition of the protein and a process for its isolation. Antiserum is prepared and used in an immunoassay to detect the protein.
    Type: Grant
    Filed: May 17, 1985
    Date of Patent: May 24, 1988
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hans Bohn, Wilhelm Winckler
  • Patent number: 4727137
    Abstract: A substantially pure protein having angiogenic activity is disclosed. A method for preparing proteins having angiogenic activity from cell culture media is also disclosed. Proteins produced according to the invention are useful in the diagnosis of malignancies, for promoting wound healing, and for other diagnostic and therapeutic purposes.
    Type: Grant
    Filed: September 20, 1985
    Date of Patent: February 23, 1988
    Assignee: President and Fellows of Harvard College
    Inventors: Bert L. Vallee, James W. Fett
  • Patent number: 4683294
    Abstract: The process is applicable to the supernatant of engineered yeast cells disrupted in the presence of a non-ionic detergent: it comprises the precipitation of contaminants by polyethylene glycol and the treatment cation or, after eventual ultrafiltration, with ammonium sulfate.
    Type: Grant
    Filed: April 3, 1985
    Date of Patent: July 28, 1987
    Assignee: Smith Kline RIT, S.A.
    Inventors: Frans Van Wijnendaele, Daniel Gilles, Guy Simonet
  • Patent number: 4668584
    Abstract: A method is provided for forming ordered macromolecular protein arrays by avoiding a binding pathway that leads to densely packed, disordered states during protein crystal growth, by a diffusion limited process or by allowing controlled growth to occur by removal of the initial supported protein layer to a different environment.
    Type: Grant
    Filed: December 23, 1985
    Date of Patent: May 26, 1987
    Assignee: General Electric Company
    Inventors: Egidijus E. Uzgiris, James R. Yates
  • Patent number: 4645831
    Abstract: Wheat gluten products may be processed to remove their components which cause undesirable flavors and color. The processing can include extraction with an aqueous solution of alcohol, alkali, or mixtures thereof, and can optionally also include ultrafiltration.
    Type: Grant
    Filed: December 10, 1984
    Date of Patent: February 24, 1987
    Assignee: The Texas A&M University System
    Inventor: James T. Lawhon
  • Patent number: 4644056
    Abstract: A method of preparing a solution of lactic or colostric immunoglobulins or both by processing milk or colostrum or both accompanied by precipitation of the caseins, characterized in that milk or colostrum or both are acidified to a pH of 4.0-5.5, subjected to cross-flow filtration in a filtration unit with a mean pore size of 0.1-1.2 .mu.m, and the low-molecular components removed by means of further cross-flow filtration in another filtration unit with a limit of separation of 5 000-80 000 daltons, as well as an agent for treating bacterial and viral infections that consists of a solution obtained by means of said method.
    Type: Grant
    Filed: September 3, 1985
    Date of Patent: February 17, 1987
    Assignee: Biotest Pharma GmbH
    Inventors: Norbert Kothe, Herbert Dichtelmuller, Wolfgang Stephan, Bertram Eichentopf
  • Patent number: 4639513
    Abstract: A method for producing intravenously injectable IgG comprising a particulate separation step, an ion exchange separation step and an affinity separation step, and the substantially pure, intravenously injectable IgG produced by the method.
    Type: Grant
    Filed: October 2, 1984
    Date of Patent: January 27, 1987
    Assignee: Cuno Inc.
    Inventors: Kenneth C. Hou, Garrett Cogswell
  • Patent number: 4618670
    Abstract: A method is provided for recovering useful products from de-oiled soymeal. At least two useful products, a soluble proteic substance and a mixture of free amino acids, are recovered.
    Type: Grant
    Filed: March 19, 1985
    Date of Patent: October 21, 1986
    Assignee: Novavis Intercontinental, Ltd.
    Inventor: Giorgio Colmelet
  • Patent number: 4608199
    Abstract: A process of extracting and purifying a bone protein capable of stimulating chondrogenic expression in undifferentiated cells in culture. The purification process is monitored at various stages by bioassaying the bone protein for chondrogenic activity in embryonic limb bud mesenchymal cell cultures.
    Type: Grant
    Filed: March 20, 1984
    Date of Patent: August 26, 1986
    Inventors: Arnold Caplan, Glenn T. Syftestad
  • Patent number: 4599318
    Abstract: The protein PP.sub.19 which has(a) an electrophoretic mobility in the region between that of .alpha..sub.1 and of .beta..sub.1 globulins;(b) an isoelectric point between 4.6 and 5.4;(c) a sedimentation coefficient s.sub.20,w of 3.25.+-.0.25 S;(d) a molecular weight determined in the ultracentrifuge of 36,500.+-.4,000;(e) a carbohydrate fraction of 3.9.+-.1.5 g/100 g (mannose 0.3.+-.0.2, fucose 0.2.+-.0.1, galactose 1.0.+-.0.3, glucose 0.4.+-.0.2, N-acetylglucosamine 1.2.+-.0.3, N-acetylgalactosamine 0.1.+-.0.1, and N-acetylneuraminic acid 0.7.+-.0.3, each g/100 g); and(f) a particular amino acid composition,is described, as is a process for obtaining it.
    Type: Grant
    Filed: February 7, 1985
    Date of Patent: July 8, 1986
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hans Bohn, Wilhelm Winckler
  • Patent number: 4592863
    Abstract: The protein PP.sub.20 is described, this having the following characteristics:(a) an electrophoretic mobility which is somewhat larger than that of albumin,(b) an isoelectric point of 4.65.+-.0.1,(c) a sedimentation coefficient s.sub.20,w of 4.1.+-.0.1 S,(d) a molecular weight determined by electrophoresis in sodium dodecyl sulfate (SDS)-containing polyacrylamide gel of 50,000.+-.10,000, the molecules of PP.sub.20 being composed of apparently identical subunits which have a molecular weight of 27,000.+-.3,000 and are held together non-covalently,(e) an extinction coefficient E.sub.1cm.sup.1% (280 nm) of 9.5.+-.0.6,(f) a carbohydrate content of 3.0.+-.1.3%, including mannose 0.14.+-.0.05%, fucose 0.13.+-.0.05%, galactose 0.61.+-.0.2%, glucose 0.39.+-.0.2%, N-acetylglucosamine 0.95.+-.0.3%, N-acetylgalactosamine 0.18.+-.0.1%, and N-acetylneuraminic acid 0.6.+-.0.4%.(g) a specified aminoacid composition, and a process for obtaining it is described.
    Type: Grant
    Filed: October 19, 1984
    Date of Patent: June 3, 1986
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hans Bohn, Wilhelm Winckler
  • Patent number: 4588685
    Abstract: The invention involves isolating a food intake suppressant by subjecting blood serum to ultrafiltration transmitting up to a molecular weight of 30,000 daltons, partially evaporating the filtrate, removing the insoluble part from the concentrate obtained, adding trichloroacetic acid up to a concentration of 5 to 25 weight/volume percent to the liquid phase at a temperature of 0.degree. to 10.degree. C., removing the proteins precipitated, subjecting the obtained solution to chromatography on a gel with a void volume below a molecular weight of 4000 daltons, eluting with a solution of pH 6.0 to 7.0, concentrating the biologically active fractions, chromatographing again on a gel with a void volume below a molecular weight of 4000 daltons, fractionating by elution with water, lyophilizing the active fractions, dissolving the lyophilized fractions in a buffer of pH 8.1 to 8.2, adding trypsin and chymotrypsin to the solution in a substantially identical amount of 0.01 to 0.
    Type: Grant
    Filed: July 19, 1984
    Date of Patent: May 13, 1986
    Assignee: Richter Gedeon Vegyeszeti Gyar Rt.
    Inventors: Jozsef Knoll, Janos Nagy, Huba Kalasz, Berta Knoll