Solvent Extraction Patents (Class 530/422)
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Patent number: 6136959Abstract: A process for isolating edible protein from animal muscle by solubilizing the protein in an alkaline aqueous solution is disclosed.Type: GrantFiled: June 22, 1998Date of Patent: October 24, 2000Assignee: University of MassachusettsInventors: Herbert O. Hultin, Stephen D. Kelleher
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Patent number: 6117984Abstract: Divalent cation crystals of human growth factor (hGH) or derivatives thereof, and pharmaceutical preparations comprising divalent cation crystals of hGH. In specific embodiments, the divalent cation is Zn++ and the molar ration Zn++ and hGH is about 0.2 to about 10.Type: GrantFiled: April 21, 1998Date of Patent: September 12, 2000Assignee: Novo Nordisk A/SInventors: Flemming Junker, Claus Friis Theisen
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Patent number: 6110469Abstract: The invention concerns a hybrid plasmid for the expression of unfused 38 kDa antigen of M. tuberculosis in E. coli, E. coli with the plasmid, an 38 kDa antigen and a protein of about 33 kDa useful for diagnoses.Type: GrantFiled: August 5, 1993Date of Patent: August 29, 2000Assignee: Gesellschaft fuer Biotechnologische Forschung mbH (GBF)Inventors: Mahavir Singh, Kenneth Nigel Timmis
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Patent number: 6107468Abstract: Disclosed is a method of obtaining a highly soluble protein which method generally includes at least the step of contacting the protein with an amount of antioxidant suitable to raise the solubility of the protein, which method may also be utilized to raise the protein yield of the process. Antioxidants suitable for use in the present invention include substituted and unsubstituted quinones, anisoles, toluenes and tocopherols. Also disclosed is a highly soluble protein which includes a protein and added antioxidant. Further disclosed are food products made from a highly soluble protein. Finally, a method of processing food products is disclosed which at least includes the step of incorporating a highly soluble protein into the food product.Type: GrantFiled: July 6, 1998Date of Patent: August 22, 2000Assignee: Board of Trustees of the University of ArkansasInventor: William L. Boatright
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Patent number: 6107467Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.Type: GrantFiled: September 5, 1997Date of Patent: August 22, 2000Assignee: Pharmacia & Upjohn ABInventors: Hans Ageland, Lena Nystrom, Josefine Persson, Folke Tjerneld
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Patent number: 6080844Abstract: The present invention involves a process of purifying and recovering a recombinant protein from a suspension of cells. The process of the present invention involves extracting a recombinant protein from a concentrated suspension of cells using a water-miscible organic solvent, isolating the recombinant protein from the suspension of cells, concentrating the recombinant protein to remove the water-miscible organic solvent, precipitating the recombinant protein using an acid, washing the recombinant protein with the salt or free form of a suitable organic acid and recovering the recombinant protein.Type: GrantFiled: April 23, 1998Date of Patent: June 27, 2000Assignee: Abbott LaboratoriesInventors: Ronald E. Carney, Joseph Arndt, Julie R. List, Ellen Marie Schwartz
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Patent number: 6051234Abstract: A health diet for preventing life-habit diseases (adult diseases) is provided.The health diet is prepared by directly encapsulating or tableting an organic solvent extract of soy sauce cakes or an aqueous alkali extract of a soy sauce oil, or blending the extracts with a diet.Type: GrantFiled: February 4, 1998Date of Patent: April 18, 2000Assignee: Kikkoman CorporationInventors: Shigehiro Kataoka, Akio Obata, Jun Yamakoshi, Yukihiko Iwai, Tatuo Manaka, Toru Izumi, Koichiro Tobe, Nobuyuki Yamaji
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Patent number: 6019999Abstract: Described is a process for making a liposomal, ion-exchange whey protein and products thereof, which result in the sustained release of amino acids into the body's circulation to generally promote skeletal muscle protein synthesis, decrease body fat in association with diet modification and improve exercise performance. The whey protein is preferably encapsulated in a liposome using a cold, or non-heated, process. After the liposomal, ion-exchange whey protein has been prepared, it is then preferably lyophilized to deliver macronutrients for use as a sports nutrition supplement and for use in medical or clinical catabolic applications.Type: GrantFiled: December 2, 1998Date of Patent: February 1, 2000Inventors: David F. Miller, Ian Hicks, Charles B. Quick, Joey Antonio, Ian J. Reynolds, David Rush, S. Keith Klein, IV
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Patent number: 5990284Abstract: Methods are herein provided for the isolation and purification of zeamatin, an antifungal protein from corn. The subject methods use capture chromatography and reverse phase chromatography. The methods herein described is superior to prior art techniques as it the eliminates ammonium sulfate precipitation and centrifugation steps.Type: GrantFiled: September 4, 1998Date of Patent: November 23, 1999Assignee: Univera Pharmaceuticals, Inc.Inventors: Belaid Mahiou, Robert Rieger
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Patent number: 5981715Abstract: The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.Type: GrantFiled: March 31, 1997Date of Patent: November 9, 1999Assignee: Alpha Therapeutic CorporationInventors: Duk Sung Hwang, Evelyn Nario, Mark Lepe, Lyndon Luz, Hirokazu Ito, Kazuo Takechi
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Patent number: 5919909Abstract: A process for the preparation of factor IX from a biological source by chromatography involves prior treatment with ammonium sulfate as a protein precipitant at a concentration of from 1.5-2.3 mol/l.Type: GrantFiled: November 26, 1997Date of Patent: July 6, 1999Assignee: Octapharma AGInventors: Djuro Josic, Lutz Hoffer, Frank Morfeld
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Patent number: 5914390Abstract: Methods are disclosed for increasing the yields of recombinant proteins. Addition of one or more protective agents, such as a sulfated compound (including heparin, heparin sulfate, sodium dodecyl sulfate, and the like), hyaluronic acid or deoxycholate, to recombinant protein production processes is disclosed. Addition of protective agents to the recombinant production process results in increased yields of recombinant proteins.Type: GrantFiled: May 12, 1997Date of Patent: June 22, 1999Assignee: Celtrix Pharmaceuticals, Inc.Inventors: Ranga Nathan, Henryk Cudny
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Patent number: 5907032Abstract: A process for preparing thrombin which comprises treating a mixture comprising prothrombin, factor Xa, factor Va, and phospholipids with calcium ions, at a pH of 6.0-7.0 is provided. In particular the pH of 6.0-7.0 may be generated by the addition of the calcium ions or by buffering the preparation to a pH of 6.0-7.0. Thrombin preparations so produced may be subjected to further purification and are particularly stable even when substantially free of exogenous stabilizing agents such as proteins, sugars, polyol and mixtures thereof, and may be subject to freeze-drying and a virus inactivation by heat treatment.Type: GrantFiled: November 20, 1997Date of Patent: May 25, 1999Assignee: Common Services AgencyInventors: Ian Randle MacGregor, John Charles Hardy, Olive Drummond
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Patent number: 5886157Abstract: The invention provides a nucleic acid encoding a human cytochrome P450 2E1 comprising a 5' terminal deletion of 63 nucleotides, thereby encoding methionine at the first codon position of the 5' terminus, the codon ATG in the second codon position of the 5' terminus, and silent adenine and thymine nucleotide substitutions in the 5' region. The invention also provides a nucleic acid encoding a human cytochrome P450 2C10 comprising a 5' terminal deletion of nucleotides 7 through 60, thereby encoding methionine at the first codon position and alanine at the second position of the 5' terminus, and silent adenine and thymine nucleotide substitutions in the 5' region. The present invention also provides a method of purifying a recombinant cytochrome P450 protein from a host cell culture comprising the steps of: a. fractionating the host cells to prepare their membranes; b. adding a non-ionic detergent in a concentration of between 0.Type: GrantFiled: February 10, 1994Date of Patent: March 23, 1999Assignee: Vanderbilt UniversityInventors: F. Peter Guengerich, Zuyu Guo, Punam Sandhu, Elizabeth M. J. Gillam
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Patent number: 5886155Abstract: A method for purifying a plant protein comprises: (a) preparing a crude plant extract; (b) passing the crude plant extract with a first buffer solution through a guard column comprising a hydrophobic interaction chromatography medium of hydrophobicity sufficiently high to prevent tannins and polyphenols from eluting from the column in the presence of the buffer solution, but sufficiently low that a protein fraction elutes with the first buffer solution; (c) passing the protein fraction through a capture column coupled in series to the guard column, the capture column comprising a hydrophobic interaction chromatography medium of hydrophobicity sufficiently high to prevent the protein from eluting in the presence of the buffer solution; and (d) eluting the protein from the capture column as a purified fraction. Preferably the plant is miracle fruit, the protein is Miraculin, and the method comprises ion exchange chromatography and gel filtration chromatography of the purified fraction of the protein.Type: GrantFiled: June 18, 1997Date of Patent: March 23, 1999Assignees: BioResources International Inc., Pharmacia Biotech ABInventors: George Enyimah Armah, Daniel Gyingiri Achel, Robert Asare Acquaah, deceased, Makonnen Belew
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Patent number: 5883231Abstract: There is provided a bodily fluid simulant made from red blood cells in an amount between about 10 and about 60 weight percent, egg white in an amount between 20 and 50 weight percent, and plasma.Type: GrantFiled: August 21, 1997Date of Patent: March 16, 1999Assignee: Kimberly-Clark Worldwide, Inc.Inventors: Amy Michele Achter, Crystal Sutphin Leach, Jack Nelson Lindon, Heather Anne Sorebo, Mary Garvie Weber
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Patent number: 5877298Abstract: A fimbrial agglutinogen preparation is prepared from a bordetella strain, particularly a B. pertussis strain, by a multiple step procedure involving extraction of the fimbrial agglutinogens from cell paste and concentrating and purifying the extracted material. The fimbrial agglutinogen preparation may be used to prepare acellular pertussis vaccines with other pertussis antigens, including pertussis toxin or toxoid thereof, the 69 kDa protein and filamentous hemagglutinin and other Bordetella antigens.Type: GrantFiled: May 4, 1995Date of Patent: March 2, 1999Inventors: Raafat E. F. Fahim, John R. Vose, John Thipphawong, Luis Barreto, Gail E. D. Jackson, Larry U. L. Tan, Andrew Herbert, Michel H. Klein
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Patent number: 5861295Abstract: The present invention provides thermostable enzymes, such as DNA polymerases and restriction endonucleases, that are substantially free from contamination with nucleic acids. The invention also provides methods for the production of these enzymes, and kits comprising these enzymes which may be used in amplifying or sequencing nucleic acid molecules, including through use of the polymerase chain reaction (PCR).Type: GrantFiled: January 2, 1997Date of Patent: January 19, 1999Assignee: Life Technologies, Inc.Inventors: Adam S. Goldstein, A. John Hughes, Jr.
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Patent number: 5861372Abstract: The present invention comprises an aggregate endothelial inhibitor and method of use therefor. The aggregate endothelial inhibitor comprises a protein having a molecular weight of between approximately 45 kilodaltons and 65 kilodaltons as determined by reducing polyacrylamide gel electrophoresis, and having an amino acid sequence substantially similar to that of a murine plasminogen fragment beginning at amino acid number 98 of a murine plasminogen molecule.Type: GrantFiled: February 22, 1996Date of Patent: January 19, 1999Assignee: The Children's Medical Center CorporationInventors: M. Judah Folkman, Jie Lin, Michael S. O'Reilly
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Patent number: 5834418Abstract: The present invention relates to a process for the preparation of porcine platelet-extract containing matured growth factors, which comprises the steps of: a) centrifuging whole porcine blood at about 1000 g to about 5000 g to isolate the platelets from the platelet-rich-plasma; b) resuspending the isolated platelets of step a) in Plasma-Lyte A and centrifuging to concentrate the platelets; c) washing the concentrated platelets of step b); d) lyophilizing the washed platelets of step c); whereby causing lysis of the platelets and producing the platelet extract in optimal amount.Type: GrantFiled: March 20, 1996Date of Patent: November 10, 1998Assignee: Theratechnologies, Inc.Inventors: Paul Brazeau, Thierry Abribat, Michel Ibea, Michele Boushira
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Patent number: 5827691Abstract: Disclosed is a novel protein which has a molecular weight of 45,000.+-.5,000 and pI 5.7.+-.0.5 and exhibits cancer metastasis-inhibitory activity. The protein can be prepared by culturing human cells, animal cells and microorganisms capable of producing the protein in a nutrient culture medium while stimulating them with an inducer such as Bacille Calmette-Guerin and lipopolysaccharide.Type: GrantFiled: April 9, 1997Date of Patent: October 27, 1998Assignee: Kabushiki Kaisha Hayashibara Seibutsu Kagaku KenkyujoInventors: Kanso Iwaki, Tsunetaka Ohta, Masashi Kurimoto
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Patent number: 5817765Abstract: 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: GrantFiled: October 30, 1995Date of Patent: October 6, 1998Assignee: Pharmacia & Upjohn AktiebolagInventors: Sven Isaksson, Stefan Winge
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Patent number: 5808006Abstract: A composition is provided comprising about 0.1 to 15 mg/ml of a polypeptide in a buffer having a pH of about 7-12 comprising about 5-40% (v/v) of an alcoholic or polar aprotic solvent, about 0.2 to 3M of an alkaline earth, alkali metal, or ammonium salt, about 0.1 to 9M of a chaotropic agent, and about 0.01 to 15 .mu.M of a copper or manganese salt. The buffer is suitably used in a method for refolding improperly folded polypeptides.Type: GrantFiled: October 11, 1994Date of Patent: September 15, 1998Assignee: Genentech, Inc.Inventors: Stuart Builder, Roger Hart, Philip Lester, David Reifsnyder
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Patent number: 5798446Abstract: In the method described, a protein-containing substance is first taken up in an alkaline solvent to give a solution. Insoluble constituents of the substance are separated off, the solution is neutralized and desalinated, and then the proteins contained in the solution are concentrated. The solubilization or disintegration of the protein-containing substance is carried out at room temperature using homogenization equipment. The heat dissipated into the protein-containing substance during homogenization is simultaneously removed. The pH of the alkaline solvent during the decomposition is over 11.5 and/or decomposition is carried out in the presence of a detergent, in particular sodium dodecylsulfate (SDS).Type: GrantFiled: October 16, 1996Date of Patent: August 25, 1998Assignee: Nupron GmbH ProteinwerkInventor: Waldemar Neumuller
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Patent number: 5780599Abstract: A method of producing chemically stable and biologically active growth hormone crystals and processes for production of pharmaceutical preparations containing these growth hormone crystals.Type: GrantFiled: December 7, 1994Date of Patent: July 14, 1998Assignee: Novo Nordisk A/SInventors: Flemming Junker, Claus Friss Theisen
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Patent number: 5777080Abstract: Disclosed is a method of obtaining a highly soluble protein which method generally includes at least the step of contacting the protein with an amount of antioxidant suitable to raise the solubility of the protein, which method may also be utilized to raise the protein yield of the process. Antioxidants suitable for use in the present invention include substituted and unsubstituted quinones, anisoles, toluenes and tocopherols. Also disclosed is a highly soluble protein which includes a protein and added antioxidant. Further disclosed are food products made from a highly soluble protein. Finally, a method of processing food products is disclosed which at least includes the step of incorporating a highly soluble protein into the food product.Type: GrantFiled: July 22, 1996Date of Patent: July 7, 1998Assignee: The Board of Trustees of The University of ArkansasInventor: William L. Boatright
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Patent number: 5760189Abstract: Provided by the present invention are novel methods of protein recovery and purification methods and more specifically novel methods for the recovery and purification thioredoxin fusion proteins, especially of IL-11.Type: GrantFiled: June 2, 1995Date of Patent: June 2, 1998Assignee: Genetics Institute, Inc.Inventors: Steven M. Vicik, Neil L. Schauer, James R. Mercer, Edward R. LaVallie, Catherine A. Briasco, Jeffrey S. Deetz, Dwight Winters, Jenifer L. Thomas
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Patent number: 5760182Abstract: A soybean protein having both excellent color tone and heat gelling properties is disclosed. The soybean protein has a color tone of 25 or more as a z value of its 5% aqueous solution measured by a color difference meter and a heat-gelling value of 250 g.multidot.cm or more as a gel strength of its 18% aqueous solution heated at 80.degree. C. for 30 minutes measured by a rheometer with a plunger ball of 4 mm diameter. A process for producing a soybean protein comprising adding 2 to 5 parts by weight of water to one part by weight of defatted soybeans and holding the mixture at 55.degree. to 80.degree. C. for 10 minutes or more before extraction of the soybean protein from the defatted soybeans with water is also disclosed.Type: GrantFiled: September 15, 1995Date of Patent: June 2, 1998Assignee: Fuji Oil Company, LimitedInventors: Tomohiko Adachi, Yasuo Otani, Mayumi Inoshita, Motohiko Hirotsuka
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Patent number: 5756687Abstract: Methods of isolating components of interest from a milk sample are described. The methods include a step wherein the solubility of at least a portion of the total milk protein is stabilized in such a manner as to allow isolation of the component of interest without significant loss in yield. Kits for stabilizing the solubility of at least a portion of the total milk protein of the milk sample containing the component of interest also are described.Type: GrantFiled: January 23, 1995Date of Patent: May 26, 1998Assignee: Genzyme Transgenics CorporationInventors: Julie S. Denman, Edward S. Cole
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Patent number: 5756672Abstract: A composition is provided comprising about 0.1 to 15 mg/mL of a polypeptide in a buffer having a pH of about 7-12 comprising about 5-40% (v/v) of an alcoholic or polar aprotic solvent, about 0.2 to 3M of an alkaline earth, alkali metal, or ammonium salt, about 0.1 to 9M of a chaotropic agent, and about 0.01 to 15 .mu.M of a copper or manganese salt. The buffer is suitably used in a method for refolding improperly folded polypeptides.Type: GrantFiled: June 6, 1995Date of Patent: May 26, 1998Assignee: Genentech, Inc.Inventors: Stuart Builder, Roger Hart, Philip Lester, David Reifsnyder
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Patent number: 5747047Abstract: The present invention is directed to novel purified and isolated mite allergens possessing mite allergen activity with a molecular weight of about 94,000, about 40,000, about 16,000 or about 14,000 as determined by SDS-PAGE, which can be isolated from extracts of mite, and to a process for producing such mite allergens. The purified and isolated mites allergens of the present invention are useful as a pharmaceutical and a diagnostic composition for mite allergic diseases.Type: GrantFiled: August 22, 1994Date of Patent: May 5, 1998Assignees: Fumakilla Ltd., Hiroshima UniversityInventors: Satoru Oka, Kazuhisa Ono, Seiko Shigeta, Takeshi Wada
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Patent number: 5744038Abstract: A separating device for extracting cholesterol from plasma uses a spinner to disperse plasma into an extracting solvent in the form of fine droplets to improve separation efficiency, thereby making it suitable for delipidating blood plasma. Blood plasma is delipidated by providing the plasma to the spinner and dispersing the plasma into the extracting solvent in fine droplets. A de-emulsification step removes residual solvent from the plasma. Blood is removed from an animal and the blood plasma is delipidated. Delipidated plasma is de-emulsified and combined with the animal blood, which is then reintroduced into the animal.Type: GrantFiled: January 30, 1996Date of Patent: April 28, 1998Assignee: Aruba International PTY Ltd.Inventor: Bill Elliot Cham
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Patent number: 5734024Abstract: A method is provided for determination of the biological activity, purity and/or homogeneity of recombinant human growth hormone ("rhGH") using an analytical chemistry test. The method is based on distribution of the rhGH between two or more immiscible aqueous phases and the subsequent determination of the ratio of rhGH concentration in the phases. The ratio is then used as a relative measure of biological activity, homogeneity, and purity, when calibrated against a sample of rhGH that was previously characterized with respect to its activity, homogeneity and purity. Typical applications of this test include quality control, quality assurance, biological identity testing, etc.Type: GrantFiled: April 19, 1996Date of Patent: March 31, 1998Assignees: Boris Y. Zaslavsky, Arnon ChaitInventor: Boris Y. Zaslavsky
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Patent number: 5734026Abstract: A process for manufacturing crystals of growth hormone (GH) comprising the steps of:i) mixing GH with an aqueous solution comprising a buffer and a chemical compound with the general formula (1):Ar--?--CR.sub.1 R.sub.2 --!n--?--C R.sub.3 R.sub.4 --!m--C R.sub.5 R.sub.6 --OH (1)in which Ar is phenyl, alkyl-substituted phenyl, naphthyl, or alkyl-substituted naphthyl, R.sub.1 to R.sub.6 is H, OH or alkyl and n and m is 0 or 1;ii) incubating; andiii) isolating the crystals is provided. The crystals are in the form of needles, trigonal forms, cubes or parallelepipeds with a length of at least 20 microns.Type: GrantFiled: May 24, 1995Date of Patent: March 31, 1998Assignee: Pharmacia & Upjohn AktiebolagInventors: Ebba Florin-Robertsson, Elvy Hokby, Ronny Lundin, Sirkka Thome, Gertrud Westin-Sjodahl
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Patent number: 5723310Abstract: A method is described for isolating an exogenous polypeptide in a non-native conformation from cells, such as an aqueous fermentation broth, in which it is prepared comprising contacting the polypeptide with a chaotropic agent and preferably a reducing agent and with phase-forming species to form multiple aqueous phases, with one of the phases being enriched in the polypeptide and depleted in the biomass solids and nucleic acids originating from the cells. Preferably, the method results in two aqueous phases, with the upper phase being enriched in the polypeptide.Type: GrantFiled: February 7, 1995Date of Patent: March 3, 1998Assignee: Genentech, Inc.Inventors: Stuart Builder, Roger Hart, Philip Lester, John Ogez, David Reifsnyder
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Patent number: 5714582Abstract: This invention relates to a method and process for the production of collagen preparations from marine invertebrates and compositions for these preparations. The collagen preparation includes telopeptide and atelopeptide fibrillar collagen of essentially invertebrate type V collagen. The collagen preparations may be used in a variety of medical, dental, cell culture, and food applications.Type: GrantFiled: March 17, 1995Date of Patent: February 3, 1998Assignee: Bioscience ConsultantsInventor: Lloyd Wolfinbarger
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Patent number: 5708144Abstract: A process for purifying natural pulmonary surfactant by dispersing animal lung tissue on an inert carrier and extracting with a supercritical fluid.Type: GrantFiled: May 22, 1995Date of Patent: January 13, 1998Assignee: Chiesi Farmaceutici S.p.A.Inventors: Paolo Chiesi, Paolo Ventura, Roberto Pighi, Vittorino Servadio, Walter Recchia
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Patent number: 5695958Abstract: A method is described for isolating an exogenous polypeptide in a non-native conformation from cells, such as an aqueous fermentation broth, in which it is prepared comprising contacting the polypeptide with a chaotropic agent and preferably a reducing agent and with phase-forming species to form multiple aqueous phases, with one of the phases being enriched in the polypeptide and depleted in the biomass solids and nucleic acids originating from the cells. Preferably, the method results in two aqueous phases, with the upper phase being enriched in the polypeptide.Type: GrantFiled: May 17, 1995Date of Patent: December 9, 1997Assignee: Genentech, Inc.Inventors: Stuart Builder, Roger Hart, Philip Lester, John Ogez, David Reifsnyder
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Patent number: 5693516Abstract: The present invention relates to a method for producing a protein composition soluble in organic solvents, comprising mixing a protein of interest with a surfactant and a water immiscible organic solvent in amounts and under conditions conducive to the formation of a reverse micelle solution, and evaporating the resulting reverse micelle solution to dryness.Type: GrantFiled: November 27, 1995Date of Patent: December 2, 1997Assignee: Novo Nordisk Biotech, Inc.Inventor: Alexander Blinkovsky
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Patent number: 5663304Abstract: A composition is provided comprising about 0.1 to 15 mg/mL of a polypeptide in a buffer having a pH of about 7-12 comprising about 5-40% (v/v) of an alcoholic or polar aprotic solvent, about 0.2 to 3M of an alkaline earth, alkali metal, or ammonium salt, about 0.1 to 9M of a chaotropic agent, and about 0.01 to 15 .mu.M of a copper or manganese salt. The buffer is suitably used in a method for refolding improperly folded polypeptides.Type: GrantFiled: August 20, 1993Date of Patent: September 2, 1997Assignee: Genentech, Inc.Inventors: Stuart Builder, Roger Hart, Philip Lester, David Reifsnyder
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Patent number: 5652343Abstract: The invention relates to glycoprotein ligands of selectins. The invention further relates to methods and means for preparing and to nucleic acids encoding these ligands. The invention further concerns a method of treating a symptom or condition associated with excessive binding of circulating leukocytes to endothelial cells by administering to a patient in need of such treatment a glycoprotein ligand of a selectin.Type: GrantFiled: August 23, 1994Date of Patent: July 29, 1997Assignees: Genentech, Inc., The Regents of the University of CaliforniaInventors: Laurence A. Lasky, Yasuyuki Imai, Steven D. Rosen, Mark S. Singer
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Patent number: 5618927Abstract: The invention concerns a process for the reactivation of denatured protein, in which the protein is incubated with a solution of Tris base or/and a salt of Tris at a concentration of at least 400 mmol/l and at a pH at which the protein to be treated can take up its native conformation.Type: GrantFiled: July 2, 1992Date of Patent: April 8, 1997Assignee: Boehringer Mannheim GmbHInventors: Dorothea Ambrosius, Rainer Rudolph
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Patent number: 5610284Abstract: There are disclosed (i) a purification process for obtaining a human BCDF having the intramolecular disulfide linkage and the stereostructure of natural type human BCDF which comprises subjecting to an oxidation reaction and a refolding treatment a reduced type human BCDF obtained by culturing a microorganism having a human BCDF gene integrated therein and solubilized with guanidine hydrochloride, characterized in that after the oxidation reaction, a gel filtration chromatographic treatment is conducted under the conditions of the guanidine hydrochloride concentration adjusted to 4-7M; (ii) a purification process for obtaining a natural type human BCDF monomer by removing the organic solvent from an organic solvent-containing solution of human BCDF, characterized in that the solution is passed through a gel filtration chromatographic column equilibrated with an organic solvent, followed by eluting according to a stepwise or linear gradient program; and (iii) a human BCDF purification process comprising an ionType: GrantFiled: July 15, 1994Date of Patent: March 11, 1997Assignee: Ajinomoto Co., Inc.Inventors: Daisuke Ejima, Yutaka Sato, Mayumi Watanabe, Masayo Date, Yoshiyuki Takahara
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Patent number: 5606020Abstract: A receptor (binding protein) specific for 6(R)-L-erythro-5,6,7,8-tetrahydrobiopterin which is a drug effective for neuropsychiatric disorders such as infantile autism is provided. This receptor is contained in the cytosol fraction or the membrane fraction obtained from a homogenate of an animal organ. It is solubilized from the membrane fraction in the presence of 3-{(3-cholamidopropyl)-dimethylammonio}-1-propanesulfonate (CHAPS). This receptor is characterized in that the binding ability thereof to 6R-BH4 is mostly lost by heating at 100.degree. C. for 10 minutes, the binding ability thereof to 6R-BH4 is significantly lost by incubating with trypsin at 37.degree. C. for 15 minutes, and said receptor shows a relative molecular weight of about 340 to 380 kilodaltons when specifically bound to tritium-labeled 6R-BH4 and analyzed with a molecular sieve provided with a COSMOSIL 5 Diol-300 column.Type: GrantFiled: July 15, 1993Date of Patent: February 25, 1997Assignees: Suntory Limited, Osaka Bioscience InstituteInventors: Yasuyoshi Watanabe, Yumiko Watanabe, Hiroshi Morii, Toshio Hayashi
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Patent number: 5597572Abstract: A vaccine effective against infection caused by Group B Neisseria meningitidis microorganism is provided which comprises a purified protein antigenic complex weighing from 65 to 95 kDa, vesicles, and capsular polysaccharide. This vaccine is extracted from the cell membranes of the live microorganisms using detergent and enzyme.Type: GrantFiled: November 12, 1993Date of Patent: January 28, 1997Assignee: Centro Nacional De BiopreparadosInventors: Concepcion C. Huergo, Victoriano G. Sierra Gonzalez, Maria M. Gutierrez Vazquez, Gonzalo Bisset Jorrin, Luis G. Garcia Imia, Gisela de la Caridad Puentes Rizo, Maria del Carmen Sampedro Herrera, Franklin Sotolongo Padron, Eloisa X. Le Riverend Morales, Manuel A. Galguera Dominguez
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Patent number: 5530100Abstract: Recovery of the 52/48 kDa tryptic fragment of vWF or peptide subfragments thereof produced in the form of inclusion bodies from recombinant host cells is carried out by providing a washed recombinant host cell suspension, adding a detergent and subjecting the cells to mechanical disruption. A second detergent is added, followed by another mechanical disruption and centrifugation to a pellet. The pellet is resuspended in a buffer and subjected to another mechanical disruption. Inclusion bodies are washed, resuspended and then recovered. In addition, endotoxins and DNA are removed from inclusion bodies containing the 52/48 kDa tryptic fragment of vWF or peptide subfragments thereof by mechanically disrupting the inclusion bodies in an aqueous buffer containing a detergent. A washed pellet is formed from these mechanically disrupted inclusion bodies and dissolved in a denaturant.Type: GrantFiled: May 7, 1990Date of Patent: June 25, 1996Assignee: Rhone-Poulenc Rorer Pharmaceuticals Inc.Inventors: Thomas L. J. Darling, Lida Y. Akhnana, Jonathan J. Mitschelen, Michael E. Hrinda
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Patent number: 5525472Abstract: Applicants describe methods for purifying human ApoE or analog thereof from recombinant bacterial cells with minimal protein aggregation and degradation during the purification process. The invention involves the addition of neutralized fatty acids to the medium during cell disruption and the use of a non-ionic detergent during the purification process. Additionally applicants describe a method for increasing the production of ApoE or analog thereof in a bacterial host by adding to the culture medium neutralized fatty acids, fatty acid precursors, triglycerides, triglyceride precursors or acetate. Pharmaceutical and diagnostic uses of the ApoE analog are described.Type: GrantFiled: November 3, 1994Date of Patent: June 11, 1996Assignee: Bio-Technology General Corp.Inventors: Ruth Lifshitz, Meir Fischer, Benjamin Greenman, Daniel Bartfeld
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Patent number: 5459052Abstract: Ala-Glu-IGF-I is a novel compound which exerts IGF-I activity and is a precursor for the preparation of IGF-I. Ala-Glu-IGF-I may by converted to IGF-I by renaturation after recombinant production in E. coli under specified conditions and then cleaving Ala-Glu from the IGF-I.Type: GrantFiled: July 2, 1993Date of Patent: October 17, 1995Assignee: Novo Nordisk A/SInventors: Lars Skriver, Kim R. Hejn s, Henrik Dalboge
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Patent number: 5459042Abstract: The invention relates methods of determining Entamoeba histolytica antigenic reference patterns of proteins recognized by sera from patients having amebic liver abscesses, patients having intestinal amebiasis and patients negative for any amebic disease and methods using these antigenic reference patterns for aiding in the differential diagnosis of a patient with amebic liver abscesses or intestinal ambiasis by detecting the presence of antibodies in a sample of human serum which bind to Entamoeba histolytica proteins identified in the antigenic reference patterns.Type: GrantFiled: October 20, 1993Date of Patent: October 17, 1995Inventor: Maria D. S. Flores de Castaneda
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Patent number: 5415859Abstract: The protein doublet H110D, the individual components thereof, and the production and use thereof in a vaccine against a nematode infection. This protein doublet is a plasma membrane-associated protein material of the intestinal microvilli of Haemonchus contortus. H110D has a molecular weight of about 110 kd and reacts with antibodies raised in animals injected with a contortin-enriched fraction. Injection of preparations of the protein doublet H110D or its components induces the production of specific protective antibodies.Type: GrantFiled: August 14, 1992Date of Patent: May 16, 1995Inventor: Edward A. Munn