Separation, Purification Or Synthesis Patents (Class 530/364)
  • Patent number: 6001974
    Abstract: A method of separating albumin from serum by ion exchange chromatography with membrane adsorbers characterized by high productivity and yields of high purity albumin. The separation of the albumin is carried out on highly basic anion exchange membranes and on highly acidic cation exchange membranes. The albumin fraction can be eluted from the anion exchange membrane such that it can be fed directly to the cation exchange membrane without any special conditioning and the albumin can be extracted therefrom as an end product.
    Type: Grant
    Filed: March 10, 1998
    Date of Patent: December 14, 1999
    Assignee: Sartorius AG
    Inventors: Wolfgang Demmer, Heinrich Klaus Gebauer, Maria-Regina Kula, Dietmar Nussbaumer, Jorg Thoemmes
  • Patent number: 5994507
    Abstract: A method for binding albumin by contacting an aqueous liquid containing an albumin with an albumin-binding compound is selected from albumin-binding compounds containing the scaffold --CO--NH--C(.dbd.C--)--CO--, and conjugates that are capable of binding albumin and exhibiting the scaffold --CO--NH--C(.dbd.C--)--CO--.
    Type: Grant
    Filed: December 31, 1997
    Date of Patent: November 30, 1999
    Assignee: Amersham Pharmacia Biotech AB
    Inventors: .ANG.ke Pilotti, Tor Regberg, Christel Ellstrom, Charlotta Lindqvist, Ann Eckersten, Lars Fagerstam
  • Patent number: 5986062
    Abstract: Human serum albumin obtained by gene manipulation techniques can be purified by a combination of specified steps in which a culture supernatant obtained from a human serum albumin-producing host is subjected to ultrafiltration, heat treatment, acid treatment and another ultrafiltration, followed by subsequent treatments with a cation exchanger, a hydrophobic chromatography carrier and an anion exchanger, and by salting-out to thereby obtain a pure form of human serum albumin which contains substantially no proteinous and polysaccharide contaminants, which is formulated into a pharmaceutical preparation. The thus obtained human serum albumin can further be purified by treating recombinant human serum albumin with a hydrophobic chromatography carrier at pH of 2 to 5 and a salt concentration of 0.4 to 1 and exposing the carrier to a pH of 6 to 8 and a salt concentration of 0.01 to 0.
    Type: Grant
    Filed: October 3, 1995
    Date of Patent: November 16, 1999
    Assignee: The Green Cross Corporation
    Inventors: Takao Ohmura, Akinori Sumi, Wataru Ohtani, Naoto Furuhata, Kazuya Takeshima, Kaeko Kamide, Munehiro Noda, Masahide Kondo, Syoichi Ishikawa, Kazuhiro Oohara, Kazumasa Yokoyama, Nagatoshi Fujiwara
  • Patent number: 5962649
    Abstract: The invention provides a process for purifying recombinant human serum albumin (rHSA) by heating a culture medium containing rHSA and the rHSA-producing host cello, feeding said heated solution upwardly into a fluidized bed in which adsorbent particles are suspended to effect contacting with the adsorbent particles and then recovering the adsorbed fraction containing the rHSA, and a composition comprising rHSA which shows a A35D/A280 ratio of below 0.015, when formulated into a 25% solution of said albumin.
    Type: Grant
    Filed: August 31, 1995
    Date of Patent: October 5, 1999
    Assignee: Yoshitomo Pharmaceutical Industries, Ltd.
    Inventors: Munehiro Noda, Akinori Sumi, Takao Ohmura, Kazumasa Yokoyama
  • Patent number: 5919907
    Abstract: A method of preparing a novel, sterile, receptor rich-albumin molecule which utilizes the disinfecting properties of iodine by reacting an iodine donating material or solution with a pure preparation of albumin, and preferably subsequently removing the iodine. The resulting iodine has improved binding properties because the production method strips bacterial endotoxin and other previously bound substances from the albumin. The improved binding site capacity of the albumin product is advantageously used as an adjunct in removing toxins by means of exchange transfusions. Because iodine disinfects the albumin typical pasteurization and related additives are unnecessary.
    Type: Grant
    Filed: December 22, 1997
    Date of Patent: July 6, 1999
    Assignee: Shanbrom Technologies LLC
    Inventor: Edward Shanbrom
  • Patent number: 5912328
    Abstract: In order to separate viruses from protein solutions, particles of a solid phase are suspended in said protein solution. The solid phase is an adsorbent chosen from the group kieselguhr, silicic acid, clay minerals, metal hydroxide or oxihydrate, cellulose, perlite, and water insoluble synthetic polymers. Subsequently the solid phase together with the viruses that have adsorbed to it is separated from the fluid phase. The protein solution is brought into contact at least once with the solid phase for at least 10 minutes during which time a suspension is formed; subsequently the solid phase is separated from the liquid phase.
    Type: Grant
    Filed: October 7, 1997
    Date of Patent: June 15, 1999
    Assignee: Rotkreuzstiftung Zentrallaboratorium Blutspendedienst
    Inventors: Adames Omar, Jean-Jacques Morgenthaler
  • Patent number: 5905143
    Abstract: When proteins are purified using a protein-binding dye immobilized on a chromatographic matrix, the dye or a portion/derivative may leak into the eluant. An ion-exchange resin (e.g. Dowex-1) and a disrupting material (e.g. salt and a fatty acid such as sodium octanoate) are used to separate the dye from the protein to overcome the protein of the leaking dye.
    Type: Grant
    Filed: February 28, 1997
    Date of Patent: May 18, 1999
    Assignee: Delta Biotechnology Limited
    Inventors: Richard A. Johnson, Alan V. Quirk, John R. Woodrow
  • Patent number: 5849874
    Abstract: Recombinantly produced serum albumin is purified in a series of steps, optionally by incubation with an anion-exchange adsorbent, followed by affinity chromatography employing a hydrophobic solid phase and using a water-soluble lipid anion as desorbens in the aqueous phase. This immobile phase comprises a carrier coupled to a 2-mercapto or 2-hydroxy alkanoic acid.
    Type: Grant
    Filed: December 8, 1994
    Date of Patent: December 15, 1998
    Assignee: Gist-Brocades, N.V.
    Inventors: Cornelis Jacobus van der Laken, Marcellinus Petrus Johannes Piet
  • Patent number: 5846930
    Abstract: There is described a therapeutic human albumin having a very low capacity for the absorption of aluminium, during storage in a glass receptacle, wherein the final composition of the albumin solution adjusted to be stable and isotonic at a concentration of 5, 20 or 25% of protein in an aqueous medium, preferably, or to any other therapeutic concentration acceptable for intravenous administration, has a citrate content in the final albumin composition equal to or less than 0.5 mM (millimolar) and, preferably, less than 0.037 mM (millimolar).
    Type: Grant
    Filed: January 24, 1997
    Date of Patent: December 8, 1998
    Assignee: Grupo Grifols, S.A.
    Inventors: Pere Ristol Debart, David Camarero Torrecillas
  • Patent number: 5834592
    Abstract: Compositions and methods for preventing, treating and detecting leishmaniasis and stimulating immune responses in patients are disclosed. The compounds provided include polypeptides that contain at least an immunogenic portion of one or more Leishmania antigens, or a variant thereof. Vaccines and pharmaceutical compositions comprising such polypeptides are also provided and may be used, for example, for the prevention and therapy of leishmaniasis, as well as for the detection of Leishmania infection.
    Type: Grant
    Filed: September 22, 1995
    Date of Patent: November 10, 1998
    Assignee: Corixa Corporation
    Inventors: Steven G. Reed, Antonio Campos-Neto, John R. Webb, Davin C. Dillon, Yasir A. W. Skeiky
  • Patent number: 5817765
    Abstract: Virus inactivating chemicals and/or detergents in an aqueous composition containing a water-soluble plasma protein are reduced by selecting a suitable combination of temperature and concentration above 0.5M of salt with a high salting out effect according to the Hofmeister series, thereby forming vesicles containing the virus inactivating chemical and/or detergent. These vesicles are removed from the aqueous phase, e.g. by phase separation or filtration, and the protein thereafter isolated from the aqueous phase. The water-soluble plasma protein can be e.g. antithrombin III, transferrin or albumin. When the aqueous phase comprises e.g. a salt of citrate or sulphate in a concentration above 1M at room temperature, the reduction of virus inactivating chemical or detergent can be as high as 2000 times or more, giving a final concentration below 5 ppm.
    Type: Grant
    Filed: October 30, 1995
    Date of Patent: October 6, 1998
    Assignee: Pharmacia & Upjohn Aktiebolag
    Inventors: Sven Isaksson, Stefan Winge
  • Patent number: 5783423
    Abstract: Reduction (preferably elimination) of the HSP150 protein in a yeast used to produce desired foreign proteins, especially human albumin, facilitates purification of the protein.
    Type: Grant
    Filed: February 20, 1997
    Date of Patent: July 21, 1998
    Assignee: Delta Biotechnology Ltd.
    Inventors: Patricia Carolyn Wood, Alan Victor Quirk
  • Patent number: 5763748
    Abstract: This invention provides for a method to produce excreted and correctly processed heterologous protein-material in a plant host. The method comprises the step of transforming a plant host using a recombinant polynucleotide, which comprises the DNA sequences encoding the fully processed heterologous protein material, directly preceded by a DNA sequence coding for a plant signal peptide, and regulatory sequences necessary for the plant host to express the heterologous gene construct, resulting in excretion of the heterologous protein from the cell and correct cleavage of the N-terminal signal peptide, so that the mature heterologous protein produced by the plant host is identical to the corresponding protein produced in its authentic host.
    Type: Grant
    Filed: March 31, 1997
    Date of Patent: June 9, 1998
    Assignee: Mogen International N.V.
    Inventors: Peter Christiaan Sijmons, Andreas Hoekema, Bernardus Martinus M. Dekker, Barbara Schrammeijer, Teunis Cornelius Verwoerd, Peturs Josephus M. Van Den Elzen
  • Patent number: 5756468
    Abstract: Lyophilized pharmaceutical compositions containing botulinum toxin or botulinum neurotoxin and effective amounts of trehalose and methionine have a shelf life of up to 4 months or more at room temperature and above.
    Type: Grant
    Filed: March 27, 1996
    Date of Patent: May 26, 1998
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Eric A. Johnson, Michael C. Goodnough
  • Patent number: 5756680
    Abstract: A method is disclosed for the sequential separation of whey proteins using radial-flow chromatography. Different buffer systems adjusted to suitable pH and ionic strength are utilized in the separation process. The method separates at least five different proteins from whey. Infant feeding formulas, and other food formulations are also disclosed incorporating therein in different proportions various proteins separated from the whey.
    Type: Grant
    Filed: July 16, 1996
    Date of Patent: May 26, 1998
    Assignee: Sepragen Corporation
    Inventors: Salah H. Ahmed, Vinit Saxena, Zahid Mozaffar, Quirinus R. Miranda
  • Patent number: 5733885
    Abstract: In a method of producing a virus-safe biological preparation by heating while preserving a least 50% of its biologic activity, a biologially compatible tenside is added to the preparation before heating and heating is carried out in the presence of the same, whereupon the tenside, preferably, is eliminated.
    Type: Grant
    Filed: July 15, 1996
    Date of Patent: March 31, 1998
    Assignee: Immuno Aktiengesellschaft
    Inventors: Johann Eibl, Gabriela Hummel, Gerda Redl, Thomas Seelich, Peter Turecek, Gunter Wober
  • Patent number: 5728553
    Abstract: A process for the preparation of albumin which has extremely low levels of or is essentially free of colorants, metal ions, human proteins, fragments of albumin, polymers or aggregates of albumin, and viruses, and which is relatively 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 two chromatography purifications, ultrafiltering the product, passing through two further chromatography steps and again ultrafiltering the product.
    Type: Grant
    Filed: May 25, 1995
    Date of Patent: March 17, 1998
    Assignee: Delta Biotechnology Limited
    Inventors: Andrew R. Goodey, Darrell Sleep, Hendrik van Urk, Stephen Berezenko, John R. Woodrow, Richard A. Johnson, Patricia C. Wood, Steven J. Burton, Alan V. Quirk, David St. J. Coghlan, Mark J. Wilson
  • Patent number: 5710253
    Abstract: A method for decoloring a recombinant human serum albumin by treating the albumin with a reducing agent is disclosed. Also, a method for decoloring a recombinant human serum albumin by treating the albumin with a method removing free polysaccharides with a cation exchanger followed by heat treatment is disclosed. The present invention provides a recombinant human serum albumin, coloring of which is fully suppressed by preventing binding of certain coloring components, which are contained in the raw materials or contaminants secreted by a microorganism, to human serum albumin so as not to cause coloring of the human serum albumin.
    Type: Grant
    Filed: December 19, 1994
    Date of Patent: January 20, 1998
    Assignee: The Green Cross Corporation
    Inventors: Wataru Ohtani, Naoto Furuhata, Akinori Sumi, Munehiro Noda, Takao Ohmura
  • Patent number: 5696236
    Abstract: In order to separate viruses from protein solutions, particles of a solid phase are suspended in said protein solution. The solid phase is an adsorbent chosen from the group kieselguhr, silicic acid, clay minerals, metal hydroxide or oxihydrate, cellulose, perlite, and water insoluble synthetic polymers. Subsequently the solid phase together with the viruses that have adsorbed to it is separated from the fluid phase. The protein solution is brought into contact at least once with the solid phase for at least 10 minutes during which time a suspension is formed; subsequently the solid phase is separated from the liquid phase.
    Type: Grant
    Filed: April 21, 1995
    Date of Patent: December 9, 1997
    Assignee: Rotkreuzstiftung Zentrallaboratorium Blutspendedienst SKR
    Inventors: Adames Omar, Jean-Jacques Morgenthaler
  • Patent number: 5691451
    Abstract: A recombinant human serum albumin (rHSA) pharmaceutical preparation is sterilized by subjecting a pharmaceutical preparation of rHSA obtained by gene manipulation techniques packed in a container in an administration unit to heat treatment at 50.degree. to 80.degree. C. for 30 minutes or more. By the disclosed method, rHSA having high safety can be provided since microorganisms contaminated in rHSA pharmaceutical preparations die as a result of the sterilization method of the present invention.
    Type: Grant
    Filed: October 26, 1994
    Date of Patent: November 25, 1997
    Assignee: The Green Cross Corporation
    Inventors: Tomoshi Ohya, Toyoo Ohda, Shinobu Kuwae, Kenji Tomomitsu, Kaoru Kobayashi, Takao Ohmura
  • Patent number: 5677424
    Abstract: Method for purifying an aqueous solution of raw albumin wherein contaminant proteins are bound by chromatography to a stationary solid phase, preferably a particulate phase, the purified albumin solution being collected as an effluent, in which a neutral phase charged with at least one compound chosen from the group formed by compounds containing C.sub.3 to C.sub.8 alkyl radicals and compounds containing sulfate groups is used as the stationary phase.
    Type: Grant
    Filed: October 24, 1994
    Date of Patent: October 14, 1997
    Inventors: Marcel Rucheton, Elie Stefas, Hubert Graafland
  • Patent number: 5658725
    Abstract: Subject matter of the invention are protein-containing interference-reducing agents for immunoassays consisting of protein aggregates that are acylated with --CO--R groups, wherein R is a branched or non-branched C1-C4 alkyl residue which can be substituted with hydroxy, carboxy, SO.sub.3 H or PO.sub.3 H.sub.2 groups. These interference-reducing substances can be used together with a buffer as an interference-reducing agent or together with an immunological binding partner as a binding reagent to reduce non-specific interactions in immunoassays. Another subject matter of the invention is an immunological testing method wherein said interference-reducing substances are used.
    Type: Grant
    Filed: August 21, 1995
    Date of Patent: August 19, 1997
    Assignee: Boehringer Mannheim GmbH
    Inventors: Dittmar Schlieper, Franz Schmid, Martin Kaufmann
  • Patent number: 5656729
    Abstract: A method for highly purifying human serum albumin (HSA), which comprises bringing a fraction containing HSA produced by genetic engineering into contact with a chelating chromatography carrier bound with copper ions, and eluting the HSA adsorbed by the carrier with a buffer containing ammonium chloride as an atagonist and having a pH of about 5-7.According to the method of the present invention, a component derived from yeast, which cannot be sufficiently removed by conventional purification methods for HSA produced by genetic engineering, can be removed from HSA produced by genetic engineering, and a highly purified HSA can be provided.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: August 12, 1997
    Assignee: The Green Cross Corporation
    Inventors: Naoto Fuluhata, Akinori Sumi, Takao Ohmura
  • Patent number: 5639730
    Abstract: In a method of producing a virus-safe biological preparation by heating while preserving a least 50% of its biologic activity, a biologially compatible tenside is added to the preparation before heating and heating is carried out in the presence of the same, whereupon the tenside, preferably, is eliminated.
    Type: Grant
    Filed: December 14, 1993
    Date of Patent: June 17, 1997
    Assignee: Immuno Aktiengesellschaft
    Inventors: Johann Eibl, Gabriela Hummel, Gerda Redl, Thomas Seelich, Peter Turecek, Gunter Wober
  • Patent number: 5633349
    Abstract: A method for the inactivation of prions, viruses and other infectious agents, which might be present in a biological raw material (e.g. plasma for the preparation of albumin), leaving the desired biological product (e.g. BSA, HSA) intact. To achieve this, the biological raw material is treated with a chaotropic agent, e.g. urea or siodium thiocyanate for approx. 18 hours. Before this, a detergent, e.g. sodium dodecyl sulfate, as well as ethanol or methanol can be added, and the solution can be heated to 70.degree. C. and kept at this temperature for 30 minutes. After cooling and acidification, denatured globulins can be removed. By modifications of this process (e.g. different concentrations, pH-values, temperatures etc.) a wide range of biological products (serum, plasma, proteins, peptides, gangliosides etc.) can be treated and rendered free of viruses, prions and all other infectivity.
    Type: Grant
    Filed: September 2, 1994
    Date of Patent: May 27, 1997
    Inventor: Herwig Reichl
  • Patent number: 5625041
    Abstract: Problem: when proteins are purified using a protein-binding dye immobilised on a chromatographic matrix, the dye or a portion/derivative may leak into the eluant. Solution: an ion-exchange resin (e.g. Dowex-1) and a disrupting material (e.g. salt and a fatty acid such as sodium octanoate) are used to separate the dye from the protein.
    Type: Grant
    Filed: November 22, 1994
    Date of Patent: April 29, 1997
    Assignee: Delta Biotechnology Limited
    Inventors: Richard A. Johnson, Alan V. Quirk, John R. Woodrow
  • Patent number: 5616691
    Abstract: The process for producing the albumin preparation of the present invention comprises treating an aqueous albumin solution with an anion exchanger and a cation exchanger and subjecting the solution to heat treatment wherein a polyacrylamide type carrier having a cation exchange group is used as a cation exchanger. By using a polyacrylamide type carrier as a cation exchanger, the polymerization caused by the contaminating proteins can be suppressed, and a highly purified albumin preparation can be obtained.
    Type: Grant
    Filed: June 1, 1995
    Date of Patent: April 1, 1997
    Assignee: The Green Cross Corporation
    Inventors: Tuyoshi Takahashi, Kazuo Ikegaya, Shinobu Mochizuki, Hideo Nishimaki
  • Patent number: 5612196
    Abstract: The present invention relates to a preparation of serum-human albumin having a colorimetry index lower than 0.2 resulting from the expression, in a eukaryotic or prokaryotic host, of an exogenous DNA sequence.
    Type: Grant
    Filed: July 27, 1994
    Date of Patent: March 18, 1997
    Assignee: Rhone-Poulenc Rorer S.A.
    Inventors: J er ome Becquart, Reinhard Fleer, G erard Jung
  • Patent number: 5612197
    Abstract: A process for producing recombinant human serum albumin is disclosed, which comprises culturing a human serum albumin-producing host, prepared by gene manipulation techniques in a medium that contains an amino acid, preferably at least one amino acid selected from the group consisting of alanine, aspartic acid, glutamic acid, histidine, serine, tryptophan, valine, isoleucine, phenylalanine, cysteine and arginine, more preferably histidine. The process can significantly increase the yield of human serum albumin over that produced by known processes.
    Type: Grant
    Filed: May 17, 1995
    Date of Patent: March 18, 1997
    Assignee: The Green Cross Corporation
    Inventors: Toyoo Ohda, Wataru Ohtani, Tomoshi Ohya, Shinobu Kuwae, Kenji Tomomitsu, Kaoru Kobayashi, Takao Ohmura
  • Patent number: 5599901
    Abstract: Compounds useful as affinity chromatography supports and as labeled reagents are disclosed. The compounds are peptides which can be constituted in families of positively charged, negatively charged or uncharged small peptides or the amidated forms thereof with varying characteristics as to charge, charge distribution, hydrophobicity, cyclization, and helical conformation propensity.
    Type: Grant
    Filed: May 24, 1994
    Date of Patent: February 4, 1997
    Assignee: Terrapin Technologies, Inc.
    Inventor: Lawrence M. Kauvar
  • Patent number: 5585466
    Abstract: Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2.sub.1, C2, P1.
    Type: Grant
    Filed: December 6, 1994
    Date of Patent: December 17, 1996
    Assignee: The United States of America as represented by the Administrator of the National Aeronautics and Space Administration
    Inventor: Daniel C. Carter
  • Patent number: 5561115
    Abstract: Highly stable plasma-derived therapeutic albumin solutions, having a turbidity level of 5 NTU or less can be made by adding sodium caprylate to Cohn fraction II+III or IV-1 effluent at relatively low temperatures. The sodium caprylate acts as a partitioning agent to separate albumin from unwanted proteins. In preferred embodiments, the albumin source solution temperature is elevated, increased in pH and reacted for approximately six hours under conditions sufficient to disrupt the initial solution colloid, and partition albumin-containing supernatant from a colloidal disperse phase, which retains unwanted globulins and manufacturing debris. Since it tends to be a scavenger molecule, albumin is selectively stabilized by diafiltration against a buffer containing sodium caprylate, thereby assuring a high albumin monomer content and low turbidity level. The amount of sodium caprylate required for selective stabilization is determined by the amount of available binding sites on the albumin molecule.
    Type: Grant
    Filed: August 10, 1994
    Date of Patent: October 1, 1996
    Assignee: Bayer Corporation
    Inventor: Robert A. Tenold
  • Patent number: 5521287
    Abstract: Human serum albumin obtained by gene manipulation techniques can be purified by a combination of specified steps in which a culture supernatant obtained from a human serum albumin-producing host is subjected to ultrafiltration, heat treatment, acid treatment and another ultrafiltration, followed by subsequent treatments with a cation exchanger, a hydrophobic chromatography carrier and an anion exchanger, and by salting-out to thereby obtain a pure form of human serum albumin which contains substantially no proteinous and polysaccharide contaminants, which is formulated into a pharmaceutical preparation. The thus obtained human serum albumin can further be purified by treating recombinant human serum albumin with a hydrophobic chromatography carrier at pH of 2 to 5 and a salt concentration of 0.4 to 1 and exposing the carrier to a pH of 6 to 8 and a salt concentration of 0.01 to 0.
    Type: Grant
    Filed: February 25, 1994
    Date of Patent: May 28, 1996
    Assignee: The Green Cross Corporation
    Inventors: Takao Ohmura, Akinori Sumi, Wataru Ohtani, Naoto Furuhata, Kazuya Takeshima, Kaeko Kamide, Munehiro Noda, Masahide Kondo, Syoichi Ishikawa, Kazuhiro Oohara, Kazumasa Yokoyama, Nagatoshi Fujiwara
  • Patent number: 5512547
    Abstract: Pharmaceutical compositions of botulinum neurotoxin containing higher specific toxicity and increased stability at higher temperatures than currently available preparations.
    Type: Grant
    Filed: October 13, 1994
    Date of Patent: April 30, 1996
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Eric A. Johnson, Michael C. Goodnough
  • Patent number: 5473050
    Abstract: A method of producing denatured bovine serum albumin (BSA) milk products is disclosed which provides a container for containing the milk products and a source of heating the container for a period of time and within a certain temperature range sufficient for producing the denatured BSA milk products without substantially diminishing either the flavor or the nutritional value of the milk products. It appears that the consumption of denatured BSA milk products, as opposed to consumption of non-denatured BSA milk products, will tend to reduce the likelihood of a person acquiring Insulin Dependent Diabetes Mellitus (IDDM), atherosclerotic vascular disease, myasthenia gravis, multiple sclerosis, pernicious anemia, and other human autoimmune diseases.
    Type: Grant
    Filed: October 12, 1993
    Date of Patent: December 5, 1995
    Assignee: Advanced Nutrition Concepts, Inc.
    Inventor: Frederick T. Strand
  • Patent number: 5468844
    Abstract: An improvement is provided in a process for the membrane filtration of a protein solution. The improvement consists of applying a high shear force at the surface of the membrane. In embodiments of such process, the liquid is subjected to membrane filtration utilizing a rotating membrane disc mounted in close proximity e.g., about 1/8" to about 1/4" to a stationary solid disc, or a rotating solid disc mounted in close proximity e.g., about 1/8" to about 1/4" to a stationary membrane surface with the relative rotation being between bout 1,000 and about 3,450 RPM. This results in permeation characteristics of the selected membrane which essentially represents its theoretical molecular weight cut-off.
    Type: Grant
    Filed: January 7, 1994
    Date of Patent: November 21, 1995
    Assignee: Protose Technologies Inc.
    Inventor: Paul Smith
  • Patent number: 5440018
    Abstract: Human serum albumin obtained by gene manipulation techniques can be purified by a combination of specified steps in which a culture supernatant obtained from a human serum albumin-producing host is subjected to ultrafiltration, heat treatment, acid treatment and another ultrafiltration, followed by subsequent treatments with a cation exchanger, a hydrophobic chromatography carrier and an anion exchanger, and by salting-out to thereby obtain a pure form of human serum albumin which contains substantially no proteinous and polysaccharide contaminants, which is formulated into a pharmaceutical preparation. This process makes it possible to effeciently purify recombinant human serum albumin and to provide substantially pure human serum albumin which does not contain producer host-related substances and other contaminants and is sufficiently free from coloration.
    Type: Grant
    Filed: March 24, 1993
    Date of Patent: August 8, 1995
    Assignee: The Green Cross Corporation
    Inventors: Takao Ohmura, Akinori Sumi, Wataru Ohtani, Naoto Fuluhata, Kazuya Takeshima, Kaeko Kamide, Munehiro Noda, Masahide Kondo, Syoichi Ishikawa, Kazuhiro Oohara, Kazumasa Yokoyama
  • Patent number: 5380712
    Abstract: Polypeptides corresponding to mature human serum albumin residues 1 to n, where n is between 369 and 419 inclusive, are useful as substitutes for albumin in the treatment of burns and shock in humans, the clearance of undesirable compounds, (such as bilirubin) from human blood, in laboratory growth media and in HSA assays. The polypeptides may be produced by recombinant DNA techniques, especially in yeast.
    Type: Grant
    Filed: February 14, 1992
    Date of Patent: January 10, 1995
    Assignee: Delta Biotechnology Limited
    Inventors: David J. Ballance, Edward Hinchliffe, Michael J. Geisow, Peter J. Senior
  • Patent number: 5372997
    Abstract: It has been found that aluminum, which is considered as to cause various diseases such as dialysis dementia, bone diseases, hypochromic anemia and Alzheimer's disease, would be eluted into a conventional albumin preparation preserved in a hard glass container, which increases the aluminum concentration of the preparation. According to the present invention, it has been found that the substitution of the conventional hard glass container with a soft glass container dealkalized by, for example, treatment with sulfurous acid gas or ammonium sulfate solution for preserving an albumin preparation can make it possible to prevent the elution of aluminum from the container, thus giving a highly safe albumin preparation which can be maintained with an extremely low aluminum concentration over a long period of time.
    Type: Grant
    Filed: May 28, 1993
    Date of Patent: December 13, 1994
    Assignee: The Green Cross Corporation
    Inventors: Masahiro Inoue, Hirokazu Ito, Shinji Tomioka, Sadao Yabushita, Koei Ikariya, Kohichi Furuta
  • Patent number: 5369020
    Abstract: A method for suppressing coloring of human serum albumin expressed by genetic engineering, which comprises culture and/or purification in the presence of an amine compound selected from the group consisting of alkylamines, diamines, guanidines, benzamidines, basic amino acids, and aminophenylacetic acids. According to the present invention, coloring of HSA expressed by genetic engineering can be suppressed to from one-half to one-tenth of that without treatment for coloring suppression. In addition, HSA can be recovered in high yields, and the treatment of the invention does not affect the inherent properties of HSA.
    Type: Grant
    Filed: March 16, 1993
    Date of Patent: November 29, 1994
    Assignee: The Green Cross Corporation
    Inventors: Akinori Sumi, Wataru Ohtani, Naoto Furuhata, Kazuya Takeshima, Kaeko Kamide, Takao Ohmura, Kazumasa Yokoyama
  • Patent number: 5346992
    Abstract: The process for isolating albumin from supernatant IV, and in particular IV-4, or from COHN's fraction V or from a plasma supernatant or fraction of analogous composition derived from an alcoholic or nonalcoholic fractionation, comprises one step on a hydrophilic anion exchange column with binding of albumin to the column, and then elution, and one step on a hydrophobic anion exchange column. Albumin thus obtained having a purity >99% by cellulose acetate electrophoresis, being free from impurities detected by crossed immunoelectrophoresis and free from polymers.
    Type: Grant
    Filed: February 6, 1992
    Date of Patent: September 13, 1994
    Assignee: Pasteur Merieux Serums et Vaccins
    Inventors: Michel G. J. Grandgeorge, Jean-Luc B. Veron, Pierre L. J. Fournier
  • Patent number: 5324628
    Abstract: In order to avoid the risk of undesired side reactions of blood products, the latter are produced from plasma by using chymotrypsin to inactivate prekallikrein activator. These preparations are obtained by the fractionated enrichment of plasma proteins, with the proviso that a chymotrypsin solution or immobilized chymotrypsin is added to the fractions at any stage of the fractionation process. Before completion of the preparations, the chymotrypsin or the immobilized trypsin is removed from the preparations.
    Type: Grant
    Filed: October 15, 1991
    Date of Patent: June 28, 1994
    Assignee: Immuno Aktiengesellschaft Fur Chemisch-Medizinische Produkte
    Inventor: Yendra Linnau
  • Patent number: 5310877
    Abstract: The invention is directed to a method for the separation of gamma globulin from albumin contained in an aqueous solution of both having a pH of 8-10 by ultrafiltration using an altered substrate microfilter having a water permeability of no more than 20 gallons per square foot per day per pound per square inch.
    Type: Grant
    Filed: April 8, 1993
    Date of Patent: May 10, 1994
    Assignee: E. I. Du Pont de Nemours and Company
    Inventor: Harold G. Spencer
  • Patent number: 5304638
    Abstract: A separation medium for use in protein separation comprising a water-insoluble matrix carrying a plurality of polyamine groupings, the polyamine groupings having at least three basic nitrogen atoms, the basic nitrogen atoms being separated from each other by a chain of at least two intervening carbon atoms, there being a total of 5 such intervening carbon atoms when there is a total of three nitrogen atoms in each polyamine group, which may be used for at least partially purifying factor VIII.
    Type: Grant
    Filed: December 4, 1991
    Date of Patent: April 19, 1994
    Assignee: Central Blood Laboratories Authority
    Inventors: Philip J. Marshall, Christopher R. Lowe
  • Patent number: 5294699
    Abstract: A method of inhibiting the coloration of human serum albumin expressed by using the gene manipulation technology which method comprises separating coloring contaminants from said human serum albumin before said coloring contaminants bind to the human serum albumin.
    Type: Grant
    Filed: June 24, 1991
    Date of Patent: March 15, 1994
    Assignee: The Green Cross Corporation
    Inventors: Takao Ohmura, Akinori Sumi, Wataru Ohtani, Naoto Fuluhata, Kaoru Kobayashi, Shinobu Kuwae, Hirotoshi Fukutsuka, Tomoshi Ohya, Hiroshi Morise
  • Patent number: 5281582
    Abstract: A novel glycosylated form of albumin designated EGA and isolated from biological fluids is further characterized by its cell growth promoting activity. A process of isolation of human or bovine glycosylated albumin is described. The EGA fractions have been identified by serological histochemical and biological assays as well as lectin reactivity. The growth-promoting effect of EGA is directed to various transformed cell lines and primary cells of mammalian origin. Hepatoma cells have been found to produce EGA, in vitro. Novel compositions of EGA containing media are provided for cell, tissue or organ culture.
    Type: Grant
    Filed: February 27, 1992
    Date of Patent: January 25, 1994
    Assignee: Alliance Pharmaceuticals, Corp.
    Inventor: Philip Dehazya
  • Patent number: 5277818
    Abstract: An albumin preparation having a polymer content of not more than 3% by weight based on the serum albumin content and an .alpha..sub.1 -AGP content of not more than a detectable limit based on the serum albumin content, which is prepared by removing a polymer-forming factor from an albumin aqueous solution by, for example, ion exchange separation or affinity chromatography, and subjecting the solution to a heat treatment.
    Type: Grant
    Filed: April 22, 1993
    Date of Patent: January 11, 1994
    Assignee: The Green Cross Corporation
    Inventors: Yasushi Matsuoka, Shinichiro Hase, Kazuo Takechi, Shinji Tomioka, Kazumasa Yokoyama
  • Patent number: 5274081
    Abstract: There is disclosed a complex comprised of an insoluble polymer carrier to which monomeric human albumin is covalently bound and of a pre-S hepatitis B surface antigen bound in an elutable form to the monomeric human albumin by its pre-S(2)- and/or pre-S(1)-region. This complex may be used for therapeutic and diagnostic purposes and enables the rapid and efficient purification of pre-S-HBsAg by affinity chromatography.
    Type: Grant
    Filed: November 8, 1991
    Date of Patent: December 28, 1993
    Assignee: Immuno A.G.
    Inventors: Johann Eibl, Friedrich Dorner, Artur Mitterer
  • Patent number: 5256769
    Abstract: A protein of interest or a Met-protein, e.g. the N-Met analog of the protein of the interest can be efficiently separated from a mixture thereof by subjecting the mixture to a separation procedure utilizing the difference in the isoelectric points between the protein and the Met-protein.
    Type: Grant
    Filed: September 11, 1985
    Date of Patent: October 26, 1993
    Assignee: Takeda Chemical Industries, Ltd.
    Inventors: Koichi Kato, Takao Yamada, Kenji Kawahara
  • Patent number: RE36259
    Abstract: 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: Grant
    Filed: July 18, 1994
    Date of Patent: July 27, 1999
    Assignee: Bayer Corporation
    Inventor: Robert A. Tenold