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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 1456. Отображено 100.
17-05-2012 дата публикации

Media For Membrane Ion Exchange Chromatography Based On Polymeric Primary Amines, Sorption Device Containing That Media, And Chromatography Scheme And Purification Method Using The Same

Номер: US20120121819A1
Принадлежит: Millipore Corp

Media and devices, such as anion exchangers including such media, wherein the media is a membrane having a surface coated with a polymer such as a polyallylamine. The resulting membrane offers stronger binding of protein impurities and superior removal of host cell proteins from biological samples than conventional ligands based on quaternary ammonium salts, including trimethylammonium ligands. Also described is a chromatography scheme and method for purifying monoclonal antibodies, wherein the anion exchange sorber is placed downstream of an affinity column (e.g., Protein A or Protein G) and optionally one or more polishing devices such as cationic exchange columns. Little or no dilution of the cation exchanger pool (or affinity column exchange pool where no cation exchanger is used) is necessary to lower the conductivity of the sample. The sorber functions well to strongly bind host cell proteins and other impurities in biological samples even at high conductivities and pH.

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21-06-2012 дата публикации

Rhenium recovery

Номер: US20120152063A1
Автор: Neil Nebeker
Принадлежит: ASARCO LLC

Method for rhenium recovery from copper solvent extraction solution. It is determined whether the copper solvent extraction solution contains trace amounts of rhenium. If so, a feedstock from the copper solvent extraction solution is provided, which is then filtered, producing filtered feedstock. Trace amounts of rhenium are absorbed from the filtered feedstock using a supply of ion exchange resin selective for rhenium. The ion exchange resin is washed. Trace amounts of rhenium are eluted from the ion exchange resin using a first amount of eluent, a second amount of eluent and a third amount of eluent. The first amount and the third amount of eluent produce supplemental feedstock and the second amount of eluent produces rhenium eluate. The rhenium eluate is collected and the ion exchange resin is protonated.

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28-02-2013 дата публикации

Cation and anion exchange chromatography method

Номер: US20130053551A1
Принадлежит: Hoffmann La Roche Inc

Herein is reported a method for purifying a polypeptide comprising the steps of i) applying a solution comprising the polypeptide to an ion exchange chromatography material, and ii) recovering the polypeptide with a solution comprising a denaturant and thereby purifying the polypeptide, whereby the ion exchange chromatography material comprises a matrix of cross-linked poly (styrene-divinylbenzene) to which ionic ligands have been attached, and wherein the solution comprising the polypeptide applied to the ion exchange chromatography material is free of the denaturant and the polypeptide adsorbed to the ion exchange chromatography material is recovered with a solution comprising a denaturant at a constant conductivity.

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18-07-2013 дата публикации

CAPILLARY ION CHROMATOGRAPHY

Номер: US20130180922A1
Принадлежит:

An apparatus for capillary ion chromatography comprising a suppressor comprising flow-through ion exchange packing in a housing and capillary tubing formed of a permselective ion exchange membrane, and at least partially disposed in said ion exchange packing. Also, a recycle conduit for aqueous liquid from the detector to the packing. Further, the capillary tubing may have weakly acidic or weakly basic functional groups. Also, a method for using the apparatus. 1. An electrolytically-regenerated suppressor for capillary ion chromatography comprising: (i) an ion exchange packing; and', '(ii) a capillary tubing having an inlet and an outlet and formed of a permselective ion exchange membrane, the capillary tubing being at least partially disposed in the ion exchange packing;, '(a) a central chamber including (i) a first electrode:', '(ii) a first permselective barrier that separates the first electrode chamber from the ion exchange packing; and, '(b) a first electrode chamber having an inlet and an outlet, the first electrode chamber including (i) a second electrode;', '(ii) a second permselective barrier that separates the second electrode chamber from the ion exchange packing;, '(c) a second electrode chamber having an inlet and an outlet, the second electrode chamber including2. The suppressor of further comprising: (d) a source of flowing an aqueous regenerant liquid in fluid communication with an inlet of the central chamber.3. The suppressor of claim 1 , in which an outlet of the central chamber is in fluid communication with the first electrode chamber inlet.4. The suppressor of claim 1 , in which the first electrode chamber outlet is in fluid communication with the second electrode chamber inlet5. The suppressor of claim 1 , in which the ion exchange packing includes substrates with exchangeable ions comprising weakly acidic or weakly basic functional groups.6. The suppressor of claim 1 , in which an outer wall of the capillary tubing comprises exchangeable ...

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08-08-2013 дата публикации

ION EXCHANGE EXOSKELETON AND FILTER ASSEMBLY

Номер: US20130199986A1
Автор: Miller Stuart
Принадлежит: MANN+HUMMEL GMBH

An ion exchange filter for a coolant may include a porous ion exchange filter exoskeleton and ion exchange resin beads. The exoskeleton may be adapted for receiving a coolant flow and may define a first set of channels. The ion exchange resin beads may be located within the first set of channels. 1. An ion exchange filter for a coolant comprising:a porous ion exchange filter exoskeleton adapted for receiving a coolant flow and defining a first set of channels; andion exchange resin beads located within the first set of channels.2. The ion exchange filter of claim 1 , wherein the ion exchange filter exoskeleton has a total porosity of at least 50 percent.3. The ion exchange filter of claim 1 , wherein the first set of channels extend generally parallel to a longitudinal axis of the ion exchange filter along a coolant flow direction from an inlet of the ion exchange filter to an outlet of the ion exchange filter.4. The ion exchange filter of claim 3 , wherein the porous ion exchange filter exoskeleton includes a first porous sheet defining the first set of channels and a second porous sheet adjacent to the first porous sheet claim 3 , the first and second porous sheets being wound to define the exoskeleton.5. The ion exchange filter of claim 4 , wherein the second porous sheet defines a second set of channels oriented generally transverse relative to the first set of channels.6. The ion exchange filter of claim 5 , wherein the first porous sheet includes pleats defining the first set of channels and the second porous sheet includes pleats defining the second set channels.7. The ion exchange filter of claim 1 , wherein the ion exchange resin beads include anode resin beads and cathode resin beads with a diameter of the anode resin beads being within 10 percent of a diameter of the cathode resin beads.8. The ion exchange filter of claim 1 , wherein a ratio between a height of the first set of channels and a diameter of the ion exchange resin beads is at least 4-to-1 and ...

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21-11-2013 дата публикации

PROCESS FOR REMOVING IRON IONS FROM AN ORGANIC STREAM

Номер: US20130310582A1
Принадлежит: Dow Global Technologies LLC

Embodiments of the present disclosure include a process for removing iron ions from an organic stream by contacting the organic stream with an ion exchange resin prior to contacting the organic stream with a peroxide solution including a stabilizer. 1. A system for producing an oxirane , comprising:a first pipe for transporting an organic stream including allyl chloride and iron ions;an exchange vessel holding a solid support with active sites that remove iron ions from the organic stream to provide the organic stream with an iron ion concentration of less than one weight percent based on the total weight of the organic stream, wherein the exchange vessel is connected to the first pipe;a second pipe connected to an outlet of the exchange vessel for transporting the organic stream with the iron ion concentration of less than one weight percent from the exchange vessel;a third pipe for transporting a peroxide solution including a stabilizer; anda reaction vessel for reacting the organic stream having the iron ion concentration of less than one weight percent and the peroxide compound to form the oxirane, wherein the second pipe and the third pipe are connected to the reaction vessel.2. The system of claim 1 , wherein the solid support is a strong acid3. The system of claim 1 , wherein the second pipe is of a non-ferrous metal material.4. The system of claim 1 , wherein the exchange vessel is arranged in a fixed-bed configuration holding the solid support.5. The system of claim 1 , wherein the exchange vessel is of a non-ferrous metal material.6. A process for removing iron ions from an organic stream claim 1 , the process comprising:providing an organic stream having iron ions;providing an ion exchange resin;removing the iron ions from the organic stream by contacting the organic stream with the ion exchange resin to provide the organic stream with an iron ion concentration of less than one weight percent based on the total weight of the organic stream; andcontacting ...

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12-12-2013 дата публикации

Enrichment and concentration of select product isoforms by overloaded bind and elute chromatography

Номер: US20130331554A1
Принадлежит: Biogen Idec Inc

Disclosed is a method for enhancing or increasing the concentration of biological product in a final mixture, wherein said biological product has one or more selected characteristics, wherein said method comprises: (a) allowing an initial mixture of biological products with and without said selected characteristics to contact a chromatography medium wherein the quantity of biological products in said initial mixture exceeds the binding capacity or the dynamic binding capacity of said chromatography medium; (b) allowing biological product not having said one or more selected characteristics to be separated by said chromatography medium; and (c) recovering a final mixture of biological products from said chromatography medium wherein said final mixture comprises an enhanced or increased concentration of biological product with one or more selected characteristics, compared to the concentration of biological product in said initial mixture.

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06-02-2014 дата публикации

FUEL FILTER FOR THE REMOVAL OF A SOAP CONTAMINANT FROM DIESEL FUEL

Номер: US20140034577A1
Принадлежит: CUMMINS FILTRATION IP, INC.

This disclosure describes a filtration system and method for removing soap from diesel fuel. The removal involves passing fuel through the filtration system. By removing soap, injector sticking and plugging can be reduced and for fuel already contaminated with soap, lubricity and/or corrosion inhibition functionality resulting from the conversion of carboxylic acid additives can be restored to metal carboxylates 1. A filter element , comprisinga filtration media; andan ion exchange media.2. The filter element of claim 1 , wherein the filtration media surrounds at least a portion of a central cavity.3. The filter element of claim 1 , wherein the ion exchange media surrounds at least a portion of a central cavity.4. The filter element of claim 1 , wherein the ion exchange media is configured to remove a metal ion from the fluid.5. The filter element of claim 4 , wherein the metal ion is at least one selected from the group consisting of Na claim 4 , K claim 4 , Mg claim 4 , Ca claim 4 , Zn claim 4 , Fe claim 4 , Cu claim 4 , Al and Pb claim 4 , and wherein Na and K have a valency of one claim 4 , Mg claim 4 , Ca claim 4 , Zn claim 4 , Cu claim 4 , and Pb have a valency two claim 4 , and Al and Fe have a valency of three.6. The filter element of claim 1 , wherein the ion exchange media includes a cation exchange resin.7. The filter element of claim 1 , wherein the ion exchange media is wetted with a polar liquid.8. The filter element of claim 7 , wherein the polar liquid is at least one selected from the group consisting of water claim 7 , methanol claim 7 , ethanol and biodiesel.9. The filter element of claim 1 , further comprising an ion exchange media retainer.10. The filter element of claim 1 , wherein the filter media is configured to remove soap that is present in the fluid.11. The filter element of claim 10 , wherein the soap is a metal carboxylate.12. The filter element of claim 1 , wherein the filter media has a mean flow pore size of less than 5 microns.13. ...

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13-03-2014 дата публикации

Zirconium Phosphate Particles Having Improved Adsorption Capacity And Method Of Synthesizing The Same

Номер: US20140069858A1
Автор: Wong Raymond June-Hin
Принадлежит:

Zirconium phosphate particles are synthesized by providing a solution of zirconium oxychloride in an aqueous solvent, adding at least one low molecular weight, oxygen containing, monofunctional, organic additive to the solution, and combining this solution with heated phosphoric acid or a phosphoric acid salt to obtain zirconium phosphate particles by sol gel precipitation. 128-. (canceled)29. Zirconium phosphate (ZrP) particles having the following characteristics:an average particle size of about 45-90 microns,{'sup': '2', 'a BET surface area of at least 2 m/g ZrP, and'}{'sub': 4', '4, 'an ammonia capacity in dialysate of at least about 15 mg NH—N/g ZrP, at 20 mg/dL NH—N.'}30. The particles of having a BET surface area of at least 10 m/g ZrP.31. The particles of further having a pore volume of at least 0.0071 mL/g claim 29 , a monolayer volume of at least 0.5 mL/g (STP) claim 29 , and a 20-80 nm pore size content of at least 30%.32. A dialysis cartridge comprising a cartridge that contains the zirconium phosphate particles of .33. Zirconium phosphate (ZrP) particles having the following characteristics:a pore volume of at least 0.0071 mL/g,a monolayer volume of at least 0.5 mL/g (STP), anda 20-80 nm pore size content of at least 30%.34. A dialysis cartridge comprising a cartridge that contains the zirconium phosphate particles of . This application claims the benefit under 35 U.S.C. §119(e) of prior U.S. Provisional Patent Application No. 61/102,466, filed Oct. 3, 2008, which is incorporated in its entirety by reference herein.The present invention relates to zirconium phosphate particles, and to methods of making zirconium phosphate particles, such as by sol gel synthesis, that have improved porosity, BET surface area, and/or ammonium ion adsorption properties.Zirconium phosphate (ZrP) particles are used as ion exchange materials and are particularly useful as a sorbent material for regenerative dialysis. Zirconium phosphate (ZrP) particles can be synthesized by ...

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13-03-2014 дата публикации

GLYCIDOL FUNCTIONALIZED ANION EXCHANGE STATIONARY PHASES

Номер: US20140069870A1
Автор: Pohl Christopher A.
Принадлежит:

Treatment of anion exchange materials containing hydroxyl containing moieties in the beta position relative to the quaternary center in the hydroxide form with glycidol substantially alters the selectivity of the anion exchange material. Furthermore, sequential treatments of first a hydroxide containing solution to put the anion exchange material in the hydroxide form followed by treatment with glycidol in an alternating sequence progressively changes selectivity in a predictable manner allowing facile manipulation of selectivity. Unique to the selectivities achievable with this chemistry is the ability to reverse the elution order of sulfate and carbonate. With all other known systems, carbonate elutes ahead of sulfate and sometimes compromises the ability to quantitate sulfate. With glycidol treatment, carbonate can be moved after sulfate which eliminates interference issues for samples containing significantly more carbonate than sulfate. This modification is useful for columns operated with a hydroxide or carbonate eluent system. 6. The anion exchange chromatographic medium according to claim 1 , wherein said support comprises a polymerized synthetic organic polymer.7. The anion exchange chromatographic medium according to claim 6 , wherein said solid support is a resin.8. The anion exchange chromatographic medium according to claim 1 , wherein said glycidol-derived ether is attached to said solid support by a bond which is a member selected from an ionic bond and a covalent bond.9. The anion exchange chromatographic medium according to claim 1 , wherein at least one member selected from R claim 1 , Rand Ris or comprises a covalent bond to said solid support.12. The anion exchange chromatographic medium according to claim 1 , wherein said solid support is a product of condensation polymerization.13. The anion exchange chromatographic medium according to claim 12 , wherein said condensation polymerization is between an amine and a diepoxide.14. The anion exchange ...

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03-01-2019 дата публикации

Continuous Sample Purification Systems and Methods

Номер: US20190001237A1
Принадлежит:

Sample purification systems include a particle extraction assembly having a mixing compartment and a settling compartment. A biological sample is mixed with two liquid phases formulated to effectuate transfer of a biological molecule into a first phase and particulate contaminants into a second phase. The first phase includes a solubilizing salt, the second phase includes an organic molecule, and the mixture can have little or no monoatomic salt or dextran. The molecule-containing first phase can be optionally concentrated without also concentrating the particulate contaminants and introduced into a multi-stage liquid-liquid extractor, by which the biological molecule or molecular contaminants are extracted from the first phase into a third phase, thereby purifying the molecule away from contaminants. The extracted sample can be further purified through a series of processing steps. The system can be run in continuously mode to maintain sterility of the sample. 1. A method of purifying a biological molecule , comprising:mixing a biological sample with a first fluid phase and a second fluid phase to form a first mixture, the first fluid phase having a first density and the second fluid phase having a second density, the second density being different than the first density, the first fluid phase being immiscible with the second fluid phase, the biological sample comprising an amount of a biological molecule and an amount of a particulate contaminant; andallowing the first mixture to settle into a first phase body comprising the first fluid phase and a second phase body comprising the second fluid phase, the first phase body being separable from the second phase body, at least a portion of the amount of the biological molecule being disposed in the first phase body, and at least a portion of the amount of the particulate contaminant being disposed in the second phase body.2. The method of claim 1 , wherein:(i) greater than about 75% of the amount of the biological ...

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07-01-2016 дата публикации

CHROMATOGRAPHIC PURIFICATION OF VIRUS PREPARATIONS WITH NEGATIVELY CHARGED PARTICLES

Номер: US20160002605A1
Автор: GAGNON Peter Stanley

A method of purifying a sample that includes a desired virus includes the steps of (i) providing a packed chromatographic column having negatively charged porous particles, (ii) equilibrating the column to the conditions to which the desired virus in the sample is to elute, (iii) contacting the sample with the packed chromatographic column such that the sample volume applied to the packed chromatographic column is less than or equal to the interparticle space of the negatively charged porous particles within the packed chromatographic column, (iv) eluting the desired virus from the packed chromatographic column, where the desired virus is in a purer state and in the conditions to which the packed chromatographic column was equilibrated. 133.-. (canceled)34. A method of purifying a sample comprising a desired virus , the method comprising the steps of (i) providing a packed chromatographic column comprising negatively charged porous particles , (ii) equilibrating the packed chromatographic column to a condition to which the desired virus in the sample is to elute , (iii) contacting the sample with the packed chromatographic column such that a sample volume applied is less than or equal to an interparticle space of the negatively charged porous particles within the packed chromatographic column , (iv) eluting the desired virus from the packed chromatographic column , wherein the desired virus is in a purer state and in the condition to which the packed chromatographic column was equilibrated.35. The method of claim 34 , wherein the desired virus is a lipid-enveloped virus claim 34 , a non-lipid-enveloped virus claim 34 , a bacteriophage claim 34 , a pseudovirus claim 34 , or a virus-like particle.36. The method of claim 34 , wherein the sample is unpurified claim 34 , at an intermediate level of purity claim 34 , highly purified claim 34 , or concentrated.37. The method of claim 34 , wherein the desired virus has been concentrated prior to its application to the ...

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04-01-2018 дата публикации

SEPARATION OF OLIGOSACCHARIDES FROM FERMENTATION BROTH

Номер: US20180002363A1
Принадлежит:

The present invention relates to the isolation and purification of sialylated oligosaccharides from an aqueous medium in which they are produced. 1. A method for separating a sialylated oligosaccharide from an aqueous medium , the method comprising treating an aqueous medium containing said sialylated oligosaccharide with a strong anion exchange resin in Cl-form and a strong cation exchange resin.2. The method of claim 1 , wherein said aqueous medium is a fermentation broth or an enzymatic reaction mixture containing said sialylated oligosaccharide.3. The method of claim 1 , wherein the separated sialylated oligosaccharide is obtained in the form of its alkali metal salt.4. The method of claim 1 , wherein the strong cation exchange resin is in an alkali metal cation form or H-form.5. The method of claim 1 , further comprising neutralizing an eluate of the strong cation resin in H-form with an alkali metal containing basic solution.6. The method of claim 1 , wherein said treating of said aqueous medium with said strong cation exchange resin follows treating said aqueous medium with said strong anion exchange resin.7. The method of claim 2 , wherein said fermentation broth is obtained by culturing a genetically modified cell claim 2 , wherein said cell is capable of producing said sialylated oligosaccharide from an internalized carbohydrate precursor.8. The method of claim 1 , wherein said sialylated oligosaccharide is a sialylated lactose.9. The method of claim 8 , wherein said sialylated lactose is 3′-SL or 6′-SL.1012-. (canceled)13. The method of claim 6 , wherein said treating of said aqueous medium with said strong cation exchange resin immediately follows treating said aqueous medium with said strong anion resin.14. The method of claim 7 , wherein said genetically modified cell is from a genetically modified microorganism.15E. coli,E. coli. The method of claim 14 , wherein said genetically modified microorganism is an wherein the contains one or more ...

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03-01-2019 дата публикации

METHODS OF PURIFICATION AND/OR VIRAL INACTIVATION

Номер: US20190002518A1
Принадлежит: FERRING B.V.

Methods of purification and/or viral deactivation of a protein (e.g. glycoprotein) comprising a step of treating the protein (e.g. glycoprotein) with a combination of caprylic acid and ethanol. 1. A method of purification of a protein , the method comprising a step of treating the protein with a combination of caprylic acid and ethanol.2. A method of viral inactivation in a protein , the method comprising a step of treating the protein with a combination of caprylic acid and ethanol.3. A method according to claim 1 , which comprises treating a solution of the protein with a combination of caprylic acid and ethanol.4. A method according to claim 1 , wherein the protein is a glycoprotein.5. A method according to claim 1 , wherein the protein is FSH claim 1 , hCG or LH.6. A method according to claim 1 , wherein the protein is a recombinant glycoprotein.7. A method according to claim 1 , wherein the protein is a recombinant protein produced in a cell by a method comprising culturing the cell in a suitable medium and harvesting the recombinant protein from said cell and/or said medium.8. A method according to claim 7 , wherein the cell is a mammalian cell.9. A method according to claim 1 , wherein treating the protein with a combination of caprylic acid and ethanol takes place at pH 2 to pH 6.5.10. A method according to claim 1 , wherein the caprylic acid concentration is from 10 mM to 30 mM caprylic acid.11. A method according to which comprises:(a) treating the protein with ethanol and caprylic acid for an incubation time of from 1 minute to 6 hours at a temperature of 23±2° C. with stirring;(b) treating the protein with ethanol and caprylic acid at a temperature of 4°-8° C. for an incubation time of from 1 minute to 32 hours, without stirring;(c) treating the protein with ethanol and caprylic acid for an incubation time of from 0.5 hours to 1 hour at a temperature of 23±2° C. with stirring, followed by reducing the temperature to a temperature of 4°-8° C. and ...

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10-01-2019 дата публикации

Application of Zea Mays Cob as a Heavy Metal Ion Exchange Filter for Water purification

Номер: US20190009191A1
Автор: Kohli Simar
Принадлежит:

The present invention pertains to the use of cob of as an ion exchange filter to remove heavy metal impurities from water, for human consumption. The present invention also relates to the chemical methods and processes that enable cob of to act as an ion exchange filter. In preferred embodiments, the organometallic cellulose is derived from any plant material that comprises of cellulose. 1{'i': 'Zeya Mays', 'activated cellulose of the cob of is used as ion exchange heavy metal filter'}activated cellulose from other plant based organic materials may also be used for the claimed purposes.{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'i': 'Zeya Mays', 'Method of where the cob of has been previously treated with alkaline metal compound and tri-chloro-acetic acid.'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'i': 'Zeya Mays', 'Method of where the chemically treated cob of is neutral on pH scale (pH=7)'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'i': 'Zeya Mays', 'Method of where the pH neutral, chemically treated cob of has least one alkaline ion which is bonded to the at least one terminal or non-terminal atom of the cellulose or hemi-cellulose of the cob.'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'Method of where when the chemical treated cob as in [14-30] comes in contact with water containing heavy impurities; an ion exchange occurs between at least one atom of alkaline material of the cob and heavy metal ions like copper dissolved in water.'}As a result of this ion exchange, the water now has lower concentration of heavy metal ions than prior to filtration.{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'Method of , wherein after the filtration is completed, the heavy metal ions are now immobile and bonded to the cellulose or hemi-cellulose of the cob.'}{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'Method of , wherein the heavy metal filtration can be repeated using the same cob for at least one time.'}. A method of filtration of ...

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10-01-2019 дата публикации

ISOTOPE PREPARATION METHOD

Номер: US20190009265A1
Принадлежит:

The present invention comprises a method for the generation of Th of pharmaceutically tolerable purity comprising i) preparing a generator mixture comprising Ac, Th and Ra; ii) loading said generator mixture onto a strong base anion exchange resin; iii) eluting a mixture of said Ra and Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution; iv) eluting Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first Th solution containing contaminant Ra and Ac; v) loading the first Th solution onto a strong acid cation exchange resin; vi) eluting at least a part of the contaminant Ra and Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and vii) eluting the Th from said strong acid cation exchange resin using a first aqueous buffer solution to provide a second Th solution. Purified thorium-227 of pharmaceutical purity and a pharmaceutical composition comprising the same are also provided. 1) A method for the generation of Th of pharmaceutically tolerable purity comprising the steps of:{'sup': 227', '227', '223, 'i) preparing a generator mixture comprising Ac, Th and Ra;'}ii) loading said generator mixture onto a strong base anion exchange resin;{'sup': 223', '227, 'iii) eluting a mixture of said Ra and Ac from said strong base anion exchange resin using a first mineral acid in an aqueous solution;'}{'sup': 227', '227', '223', '227, 'iv) eluting Th from said strong base anion exchange resin using a second mineral acid in an aqueous solution whereby to generate a first Th solution containing contaminant Ra and Ac;'}{'sup': '227', 'v) loading the first Th solution onto a strong acid cation exchange resin;'}{'sup': 223', '227, 'vi) eluting at least a part of the contaminant Ra and Ac from said strong acid cation exchange resin using a third mineral acid in aqueous solution; and'}{'sup': 227', '227, 'vii) eluting the Th from ...

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09-01-2020 дата публикации

METHOD OF ISOLATING BOTULINUM TOXIN FROM BOTULINUM TOXIN-CONTAINING SOLUTION

Номер: US20200009473A1
Принадлежит:

Provided is a method of isolating a toxin type A macro complex from a toxin-containing solution, the method including performing anion exchange chromatography and cation exchange chromatography. 1botulinumbotulinum. A method of isolating a toxin type A macro complex from a toxin-containing solution , the method comprising:{'i': botulinum', 'botulinum, 'contacting the toxin-containing solution with an anion exchange chromatography medium at a pH lower than an isoelectric point (PI) of toxin;'}{'i': 'botulinum', 'contacting the solution, which is not bound to the anion exchange chromatography medium, with a cation exchange chromatography medium at a pH lower than the PI of toxin; and'}{'i': 'botulinum', 'separating the toxin type A macro complex from the cation exchange chromatography medium; or'}{'i': botulinum', 'botulinum, 'contacting the toxin-containing solution with the cation exchange chromatography medium at a pH lower than the PI of toxin;'}{'i': 'botulinum', 'separating toxin from the cation exchange chromatography medium;'}contacting the solution containing the toxin separated from the cation exchange chromatography medium, with the anion exchange chromatography medium at a pH lower than the PI; and{'i': 'botulinum', 'separating the toxin type A macro complex from the solution which is not bound to the anion exchange chromatography medium.'}2botulinum. The method of claim 1 , wherein the pH lower than the PI of toxin is pH 3.5 to 6.0.3botulinumbotulinumbotulinum. The method of claim 1 , further comprising adjusting the pH of the toxin or the toxin-containing solution to a pH lower than the PI of toxin claim 1 , before the contacting of the solution with the anion exchange chromatography medium claim 1 , before the contacting of the solution with the cation exchange chromatography medium claim 1 , or before each of these two processes.4botulinumbotulinumbotulinum. The method of claim 3 , wherein the adjusting comprises mixing the toxin or the toxin- ...

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11-01-2018 дата публикации

MODULATION OF CHARGE VARIANTS IN A MONOCLONAL ANTIBODY COMPOSITION

Номер: US20180009876A1
Принадлежит:

Combinations of different chromatography modalities with particularly refined conditions significantly reduce acid charge variants in a preparation of monoclonal antibodies. The process for reducing acid charge variants utilizes a combination of anion exchange and hydrophobic interaction chromatography, followed by cation exchange chromatography polishing, whereby the levels of acidic or basic charge species of the monoclonal antibodies may be modulated to a desired level. 1. A process for removing acid charge variants from a monoclonal antibody , comprising(a) loading a mammalian cell-expressed monoclonal antibody preparation onto a Protein A support, and eluting the monoclonal antibody from the Protein A support, thereby producing a first eluate comprising the monoclonal antibody;(b) loading the first eluate from step (a) onto an anion exchange and hydrophobic interaction (AEX/HIC) chromatography support, and allowing the first eluate to flow through the support, thereby producing a flow-through pool comprising the monoclonal antibody;(c) loading the flow-through pool comprising the monoclonal antibody onto a cation exchange (CEX) chromatography support having an antibody binding capacity of from about 25 g/L to about 65 g/L, determining when the absorbance units measured at UV A280 decrease from about 7% to about 14% from the peak absorbance units measured at UV A280, and then washing the CEX chromatography support with a wash buffer having a pH of from about 5.8 to about 6.6 and a conductivity target of from about 6.6 mS/cm to about 7.6 mS/cm; and(d) eluting the monoclonal antibody from the CEX chromatography support in step with an elution buffer having a pH of from about 6.0 to about 6.4 and a conductivity target of from about 10 mS/cm to about 14 mS/cm, thereby producing a second eluate comprising the monoclonal antibody and from about 10% to about 20% by weight of acid charge variants of the monoclonal antibody.2. The method of claim 1 , wherein the ...

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19-01-2017 дата публикации

PROCESS FOR THE MANUFACTURE OF A PRODUCT FROM A PLANT MATERIAL

Номер: US20170013859A1
Принадлежит: KOBENHAVNS UNIVERSITET

A process for the manufacture of a product from a plant material comprising the steps of providing a disrupted plant material comprising <10% (w/w) starch and <10% (w/w) oil/lipids; adjusting the pH of the disrupted plant material to a value of pH 3.5 or below to provide an acidic suspension; heating the acidic suspension to a temperature in the range of about 50° C. to about 80° C.; isolating the product from the heated, acidic suspension. The product may be a protein product or a non-protein product. In particular, the process of the invention provides a protein product with reduced contents of non-protein components of negative nutritional value. 1. A process for the manufacture of a phytate depleted product from a plant material comprising the steps of:providing a plant material comprising ≧10% (w/w) starch and <10% (w/w) oil/lipids;disrupting the plant material;lowering the content of starch in the plant material to <10% (w/w) to provide a starch depleted plant material;suspending the disrupted, starch depleted plant material in acid at value of pH 3.0 or below preheated to an increased temperature in the range of 60° C. to 80° C. to provide a heated, acidic suspension;isolating the phytate depleted product from the heated, acidic suspension.2. The process for the manufacture of a phytate depleted product according to claim 1 , wherein the pH is in the range of 1.0 to 2.5.3. The process for the manufacture of a phytate depleted product according to claim 1 , wherein the pH is adjusted with an acid capable of serving as a chelating agent.4. The process for the manufacture of a phytate depleted product according to claim 1 , wherein the acid comprises and acid selected from the group consisting of citric acid claim 1 , oxalic acid claim 1 , lactic acid claim 1 , malic acid claim 1 , maleonic acid claim 1 , tartaric acid claim 1 , succinic acid or a combination thereof.5. The process for the manufacture of a phytate depleted product according to claim 1 , wherein ...

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03-02-2022 дата публикации

PROCESS AND SYSTEM FOR OBTAINING BOTULINUM NEUROTOXIN

Номер: US20220033796A1
Принадлежит:

Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use. 1. A substantially animal product free (APF) process utilizing chromatography for obtaining a biologically active botulinum neurotoxin , the process comprising the following steps:(a) providing a substantially APF fermentation medium;{'i': 'Clostridium botulinum', '(b) fermenting bacteria in the fermentation medium, and;'}(c) recovering the biologically active botulinum neurotoxin from the fermentation medium by contacting the fermentation medium with an anion exchange chromatography media followed by contacting an eluent from the anion exchange chromatography medium with a cation exchange chromatography, thereby obtaining the biologically active botulinum neurotoxin from the substantially APF chromatography process.2. The process of claim 1 , wherein the botulinum neurotoxin obtained comprises one part or less residual nucleic acid per million of the botulinum neurotoxin obtained.3. The process of claim 1 , wherein the process is carried out in one week or less.4. A biologically active botulinum neurotoxin obtained by the process of .5. A substantially APF chromatographic process for obtaining a biologically active botulinum neurotoxin type A complex claim 1 , the process comprising the following sequential steps:{'i': 'Clostridium botulinum', '(a) culturing bacteria in a substantially APF culture medium;'}{'i': 'Clostridium botulinum', '(b) fermenting bacteria from the culture medium in about 2 L to about 75 L of a substantially APF fermentation medium, wherein at least one of the culture medium and the fermentation medium includes a vegetable protein;'}(c) harvesting the fermentation medium by removing cellular debris present in the fermentation medium;(d) concentrating the harvested fermentation medium by filtration;(e) diluting the concentrated fermentation medium by adding a buffer;(f) a first ...

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17-01-2019 дата публикации

ISOTOPE PREPARATION METHOD

Номер: US20190015530A1
Принадлежит: BAYER AS

The present invention provides a method for the purification of Th from a mixture comprising Th and Ra, said method comprising: i) preparing a first solution comprising a mixture of Th and Ra ions dissolved in an aqueous solution of first mineral acid; ii) loading said first solution onto a strong base anion exchange resin; iii) eluting Ra from said strong base anion exchange resin using a second mineral acid in an aqueous solution; iv) optionally rinsing said strong base anion exchange resin using a first aqueous medium; v) eluting Th from said strong base anion exchange resin using a third mineral acid in an aqueous solution whereby to generate a second solution comprising Th. The invention further provides a purified Th solution, a corresponding pharmaceutical formulation and methods of treatment of neoplastic disease. 1) A method for the purification of Th from a mixture comprising Th and Ra , said method comprising:{'sup': 227', '223, 'i) preparing a first solution comprising a mixture of Th and Ra ions dissolved in an aqueous solution of first mineral acid;'}ii) loading said first solution onto a strong base anion exchange resin;{'sup': '223', 'iii) eluting Ra from said strong base anion exchange resin using a second mineral acid in an aqueous solution;'}iv) optionally rinsing said strong base anion exchange resin using a first aqueous medium;{'sup': 227', '227, 'v) eluting Th from said strong base anion exchange resin using a third mineral acid in an aqueous solution whereby to generate a second solution comprising Th.'}2) The method of additionally comprising at least one of the steps of:{'sup': '227', 'vi) assaying for the Th content of said second solution;'}vii) evaporating the liquid from said second solution;{'sup': '227', 'viii) forming at least one radiopharmaceutical from at least a portion of the Th contained in said second solution;'}ix) sterile filtering said radiopharmaceutical.3) The method as claimed in claim 1 , wherein at least 70% of the Th ...

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18-01-2018 дата публикации

METHOD FOR TREATING LIGNOCELLULOSIC MATERIALS

Номер: US20180016649A1
Принадлежит:

A method of generating a refined sugar stream that comprises xylose from a biomass hydrolysis solution, including contacting a biomass hydrolysis solution that includes a population of mixed sugars comprising xylose, an acid, and impurities, with a thermally-phase separable solvent such as a glycol solvent to form an extraction mixture; and separating from said extraction mixture a first stream including the thermally-phase separable solvent, acid, and impurities and a second, refined sugar stream that comprises xylose. The thermally-phase separable solvent is an ethylene glycol or a propylene glycol ether, such as 2-butoxyethanol or 1-propoxy-propanol or any combination thereof. 1. A method of generating a refined a sugar stream that comprises xylose from a biomass hydrolysis solution , comprising:(i) contacting a biomass hydrolysis solution that comprises a population of mixed sugars comprising xylose, an acid, and impurities, with a thermally-phase separable solvent to form an extraction mixture; and(ii) separating from said extraction mixture a first stream comprising the thermally-phase separable solvent, acid, and impurities and a second, refined sugar stream that comprises xylose.2. The method of claim 1 , further comprising claim 1 , contacting a stream from said biomass hydrolysis solution claim 1 , which comprises said population of mixed sugars comprising xylose with a strong acid cation exchange resin prior to step (i).3. The method of claim 2 , further comprising claim 2 , contacting a stream from said biomass hydrolysis solution claim 2 , which comprises said population of mixed sugars comprising xylose with a weak base anion exchange resin after said stream is contacted with said strong acid cation exchange resin and prior to step (i).4. The method of claim 1 , further comprising heating said extraction mixture to a temperature of 30-100° C.5. The method of claim 1 , further comprising separating said second claim 1 , refined sugar stream that ...

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26-01-2017 дата публикации

ION EXCHANGE EXOSKELETON AND FILTER ASSEMBLY

Номер: US20170021285A1
Автор: Miller Stuart
Принадлежит:

An ion exchange filter for a coolant may include a porous ion exchange filter exoskeleton and ion exchange resin beads. The exoskeleton may be adapted for receiving a coolant flow and may define a first set of channels. The ion exchange resin beads may be located within the first set of channels. 1. An ion exchange exoskeleton for an ion exchange filter for a coolant comprising:a porous sheet comprising a plurality of pleats;a non-porous sheet overlaid and contacting the porous sheet, wherein the non-porous sheet is not pleated;wherein the non-porous sheet overlaid onto the porous sheet forms a multi-layer exoskeleton sheet;wherein the ion exchange exoskeleton is a spiral wrapping of the exoskeleton sheet about a central axis, the exoskeleton sheet encircling the central axis multiple times forming a plurality of spirally wrapped radially stacked layers of the exoskeleton sheet radially overlaid directly onto each other around the central axis, wherein axial herein is a direction parallel to the central axis; an inlet face for receiving coolant flow;', 'an outlet face for discharging coolant;', 'wherein the inlet and outlet faces are arranged on opposite axial end faces of the ion exchange exoskeleton;, 'wherein the ion exchange skeleton includeswherein the porous sheet has a plurality of axial pleats, each pleat extending axially from the inlet face to the outlet face of the of the ion exchange exoskeleton, the pleats forming a first set of flow channels extending axially from the inlet face to the outlet, each flow channel opening at the inlet face to receive flow into the ion exchange exoskeleton and opening at the outlet face to discharge flow from the ion exchange exoskeleton;a first set of flow channels formed by the plurality of axial pleats, the first set of flow channels extending axially completely through an interior of the ion exchange exoskeleton, each having a channel cross section that is fully open to an exterior at the inlet face and the outlet face ...

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26-01-2017 дата публикации

METHODS FOR PURIFYING ADENOVIRUS VECTORS

Номер: US20170022479A1
Автор: Fitchmun Mark Irwin
Принадлежит:

Methods of purifying an adenovirus from an impure preparation are provided. In some embodiments, a combination of mixed mode chromatography and anion exchange chromatography is used to purify the adenovirus. 1. A method of purifying an adenovirus from an impure preparation , the method comprising:(a) contacting an impure preparation comprising the adenovirus to a mixed mode chromatography support, wherein the mixed mode chromatography support is a hydrophobic cation exchange chromatography support, under conditions that allow the adenovirus to bind to the mixed mode chromatography support;(b) eluting the adenovirus from the mixed mode chromatography support, thereby forming a mixed mode eluate;(c) contacting the mixed mode eluate to an anion exchange chromatography support under conditions that allow the adenovirus to bind to the anion exchange support; and(d) eluting the adenovirus from the anion exchange chromatography support.2. The method of claim 1 , wherein the adenovirus is a recombinant adenovirus.3. The method of claim 1 , wherein the adenovirus is a serotype 5 adenovirus.4. The method of claim 1 , wherein the impure preparation comprises one or more contaminants selected from proteins claim 1 , nucleic acids claim 1 , incomplete virus particles claim 1 , and adventitious viruses.5. The method of claim 4 , wherein the impure preparation is a cell culture harvest and the contaminants comprise host cell proteins and host cell DNA.6. The method of claim 1 , wherein prior to step (a) claim 1 , the impure preparation comprising the adenovirus is treated with a nuclease.7. The method of claim 1 , wherein in step (a) claim 1 , the impure preparation that is contacted to the mixed mode chromatography support is a cell culture harvest diluted in a buffer.8. The method of claim 1 , wherein the impure preparation has a pH of about 5.5 to about 7.0 when contacted to the mixed mode chromatography support.9. The method of claim 1 , further comprising claim 1 , after step ...

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10-02-2022 дата публикации

SEPARATION OF VWF AND VWF PROPEPTIDE BY CHROMATOGRAPHIC METHODS

Номер: US20220041693A1
Принадлежит:

The present invention relates to a method for separating a mature von Willebrand Factor (mat-VWF) from von Willebrand Factor pro-peptide (VWF-PP) by incubating a composition comprising inducing dissociation of mat-VWF and VWF-PP by disruption of the non-covalently associated mat-VWF and VWF-PP, wherein said dissociation is induced by: (i) addition of at least one chelating agent, or (ii) increasing the pH to a pH of at least 7, and then collecting said mat-VWF to obtain a high purity, propeptide depleted mature VWF (mat-VWF). 178.-. (canceled)79. A pharmaceutical composition comprising a high purity mat-rVWF and a pharmaceutically acceptable buffer , wherein the high purity mat-rVWF is produced by a method comprising:a) loading a solution comprising mat-rVWF/rVWF-PP complex, mat-rVWF, and rVWF propeptide (rVWF-PP) onto a size exclusion column;b) washing said size exclusion column with a buffer, thereby dissociating said mat-rVWF/rVWF-PP complex in said solution in step (a) into mat-rVWF and rVWF-PP, wherein said dissociation occurs by disruption of the non-covalently associated mat-rVWF and rVWF-PP, wherein said buffer comprises at least one chelating agent and exhibits a pH of at least 7; andc) collecting said mat-rVWF to obtain a high purity, mat-rVWF, wherein said high purity, mat-rVWF composition comprises at least 95% mature rVWF and less than 5% rVWF-PP.80. The pharmaceutical composition of claim 79 , wherein the composition comprises 50 mM Glycine claim 79 , 10 mM Taurine claim 79 , 5% (w/w) Sucrose claim 79 , 5% (w/w) D-Mannitol claim 79 , 0.1% Polysorbate 80 claim 79 , 2 mM CaCl) claim 79 , 150 mM NaCl claim 79 , wherein said composition has a pH of about pH 7.4.81. The pharmaceutical composition of claim 79 , wherein said high purity claim 79 , mat-rVWF composition comprises at least 96% mat-rVWF and less than 4% rVWF-PP claim 79 , at least 97% mat-rVWF and less than 3% rVWF-PP claim 79 , at least 98% mat-rVWF and less than 2% rVWF-PP claim 79 , at least ...

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28-01-2021 дата публикации

METHOD FOR SEPARATING STEVIOL GLYCOSIDE, METHOD FOR PRODUCING REBAUDIOSIDE A, AND DEVICE FOR SEPARATING STEVIOL GLYCOSIDE

Номер: US20210024563A1
Принадлежит:

A method for separating steviol glycoside, including: a separating step of performing a continuous liquid chromatography for continuously separating at least one type of steviol glycoside by allowing a liquid to be separated containing plural types of steviol glycosides to pass through a separating agent in which polyethylene imine is immobilized to a carrier. 1. A method for separating steviol glycoside , comprising:a separating step of performing a continuous liquid chromatography for continuously separating at least one type of steviol glycoside by allowing a liquid to be separated containing a plurality of types of steviol glycosides to pass through a separating agent in which polyethylene imine is immobilized to a carrier.2. The method for separating steviol glycoside according to claim 1 ,wherein the carrier is a macromolecular carrier.3. The method for separating steviol glycoside according to claim 1 ,wherein the liquid to be separated contains rebaudioside A as the steviol glycoside, andthe rebaudioside A is separated from the liquid to be separated.4. The method for separating steviol glycoside according to claim 3 ,wherein the liquid to be separated further contains stevioside as the steviol glycoside, andeach of the rebaudioside A and the stevioside is separated from the liquid to be separated.5. The method for separating steviol glycoside according to claim 3 ,wherein the liquid to be separated contains lower alcohol having carbon atoms of lower than or equal to 4 as a solvent.6. The method for separating steviol glycoside according to claim 1 ,wherein the continuous liquid chromatography is performed by using a simulated moving bed type device.7. A method for producing rebaudioside A claim 1 , comprising:a separating step of performing a continuous liquid chromatography for continuously separating rebaudioside A by allowing a liquid to be separated containing a plurality of types of steviol glycosides containing the rebaudioside A to pass through a ...

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28-01-2021 дата публикации

CEX CHROMATOGRAPHY MEDIA AND LOW SALT ELUTION OF TARGET PROTEINS FROM BIOPHARMACEUTICAL FEEDS

Номер: US20210024573A1
Принадлежит:

A bind/elute chromatography method and compositions for low salt/low solution conductivity separation of target proteins from a mixture of aggregates and other impurities. 1. A method of separating a monomeric protein of interest from a mixture comprising aggregates of the protein of interest in a sample , the method comprising contacting the sample with a solid support , the solid support comprising a polyvinyl ether resin functionalized with a 2-acrylamido-2-methylpropane sulfonic acid (AMPS) and N ,N-dimethylacrylamide (DMMA) , wherein the molar ratio of DMMA to AMPS is greater than 2.0 , and eluting the monomeric protein of interest from the solid support with a buffer having a solution conductivity between about 10 mS/cm and 20 mS/cm.2. The method of claim 1 , wherein the monomeric protein of interest is a monoclonal antibody.3. The method of claim 1 , wherein the protein of interest is a recombinant protein.4. The method of claim 1 , wherein the mixture comprises at least 1% aggregates of the protein of interest.5. The method of claim 1 , wherein the solid support is a bead.6. The method of claim 1 , wherein the solid support is a membrane. The present application claims the benefit of priority of U.S. Patent Application No. 62/651,878, filed Apr. 3, 2018, which is incorporated by reference herein in its entirety.Described herein are methods for purifying target proteins, such as therapeutic proteins and antibody molecules antibodies, from a biopharmaceutical feed using bind/elute cation exchange chromatography.Biopharmaceutical products of interest are produced by cells grown in culture. The product of interest is harvested and purified to remove impurities using a cascade of separation technologies. Examples of impurities include aggregates, host cell protein (HCP), and nucleic acids, endotoxins, viruses, etc. (see, e.g., State-of-the-Art in Downstream Processing of Monoclonal Antibodies: Process Trends in Design and Validation Biotechnol. Prog., 2012, 899- ...

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04-02-2016 дата публикации

RECOVERY OF 3-HYDROXYPROPIONIC ACID

Номер: US20160031792A1
Принадлежит: Cargill, Incorporated

A method for recovering a composition enriched in 3-hydroxypropionic acid from a fermentation broth comprising 3-hydroxypropionic acid and/or salts thereof comprises the steps of: (a) providing the fermentation broth having a pH of from about 2 to about 8 comprising: 3-hydroxypropionic acid and/or salts thereof, (b) acidifying the fermentation broth; (c) reducing the total sulfate ion and phosphate ion (d) distilling the resulting reduced ion aqueous solution and (e) recovering the product. 1. A method for recovering a composition enriched in 3-hydroxypropionic acid from a fermentation broth comprising 3-hydroxypropionic acid and/or salts thereof , the method comprising the steps of: 3-hydroxypropionic acid and/or salts thereof, and', 'a total sulfate ion and phosphate ion concentration;, '(a) providing the fermentation broth having a pH of from about 2 to about 8 comprising(b) acidifying the fermentation broth to lower the pH to from about 1 to about 3 to form an aqueous solution comprising 3-hydroxypropionic acid;(c) reducing the total sulfate ion and phosphate ion concentration of the aqueous solution to produce a reduced ion aqueous solution comprising 3-hydroxypropionic acid;(d) distilling the reduced ion aqueous solution at a pH of from about 1 to about 3 by applying vacuum and heat to the reduced ion aqueous solution to form an aqueous distillation product comprising 3-hydroxypropionic acid; and(e) recovering the aqueous distillation product comprising 3-hydroxypropionic acid at a concentration of at least thirty percent by weight of the aqueous distillation product and wherein the aqueous distillation product comprises less than five parts by weight acrylic acid per one hundred parts by weight 3-hydroxypropionic acid present.2. (canceled)3. The method of claim 1 , wherein the fermentation broth has a pH of from about 2.5 to about 4.5 in step (a).4. The method of claim 1 , wherein the pH of the fermentation broth is lowered to a pH of from about 1.5 to about ...

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28-01-2021 дата публикации

SYSTEMS, APPARATUS AND METHODS FOR SEPARATING ACTINIUM, RADIUM, AND THORIUM

Номер: US20210027905A1
Принадлежит:

A method of separating actinium and/or radium from proton-irradiated thorium metal. The thorium metal is irradiated to produce isotopes including thorium, actinium and/or radium. The resultant product is dissolved in solution and a selective precipitant is used to precipitate a bulk portion of the thorium. The precipitated thorium can be recovered. Chromatography is carried out on the remaining solution to remove residual thorium and to separate the actinium from the radium. 1. A method of separating thorium from actinium and/or radium , the method comprising:placing the thorium and the actinium and/or radium in a weak acid solution;adding a selective precipitant to the weak acid solution and precipitating a bulk portion of the dissolved thorium under precipitation conditions while leaving the actinium and/or radium in the solution; andfiltering to separate the precipitated bulk portion of the thorium from the actinium and/or radium in the solution.2. A method of separating actinium and/or radium from thorium , the method comprising the steps of:placing the thorium and the actinium and/or radium in a weak acid to yield a first solution;adding a selective precipitant and precipitating a bulk portion of the thorium under precipitation conditions while retaining the actinium and/or radium and a residual portion of the thorium in a second solution;filtering to separate the precipitated bulk portion of the thorium from the second solution; andconducting chromatographic purification of the second solution to separate the actinium and/or radium from the residual thorium.3. A method as defined in claim 2 , wherein the thorium and the actinium and/or radium are produced by irradiating thorium metal claim 2 , and wherein the irradiated thorium metal is dissolved in the weak acid to yield the first solution.4. A method of producing thorium radioisotopes claim 2 , the method comprising:irradiating thorium metal to produce thorium radioisotopes;dissolving the irradiated thorium ...

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02-02-2017 дата публикации

Human Antibodies that Bind Human TNF-Alpha and Methods of Preparing the Same

Номер: US20170029495A1
Принадлежит:

Methylglyoxal (MGO)-modified recombinant TNF-alpha antibodies (e.g., Adalimumab) are identified. MGO modification decreases binding between Adalimumab and TNF-alpha. Methods are disclosed for reducing the presence of MGO-modified antibodies in the production of Adalimumab TNF-alpha antibodies. 1. A composition comprising a binding protein capable of binding TNF-alpha , wherein said binding protein comprises at least one methylglyoxal (MGO)-susceptible amino acid , and wherein at least a portion of said binding protein comprises one or more MGO-modified amino acids.2. The composition of claim 1 , wherein the portion of the binding protein that comprises at least one MGO-modified amino acid is less than 12%.3. The composition of claim 1 , wherein the portion of the binding protein that comprises at least one MGO-modified amino acid is less than 6%.4. The composition of claim 1 , wherein the MGO-susceptible amino acid is an arginine.5. The composition of claim 1 , wherein the binding protein is a human antibody or an antigen-binding portion thereof claim 1 , wherein the binding protein dissociates from human TNF-alpha with a Kof 1×10M or less and a Krate constant of 1×10sor less claim 1 , both as determined by surface plasmon resonance claim 1 , and wherein the binding protein neutralizes human TNF-alpha cytotoxicity in a standard in vitro L929 assay with an ICof 1×10M or less.6. A composition comprising a binding protein capable of binding TNF-alpha claim 1 , said binding protein comprising a methylglyoxal (MGO)-susceptible amino acid claim 1 , wherein said composition is prepared by substantially removing molecules of said binding protein that comprise at least one MGO-modified amino acid.7. The composition of claim 6 , wherein more than 70% of said molecules that comprise at least one MGO-modified amino acid is removed.8. The composition of claim 6 , wherein more than 90% of said molecules that comprise at least one MGO-modified amino acid is removed.9. The ...

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02-02-2017 дата публикации

METHOD OF PURIFYING NUCLEIC ACIDS, METHOD OF EXTRACTING NUCLEIC ACIDS AND KIT FOR PURIFYING NUCLEIC ACIDS

Номер: US20170029804A1
Принадлежит:

[Object] To provide a method of purifying nucleic acids where the operation is simple and the nucleic acids can be extracted in a short time with high efficiency. 1. A method of amplifying nucleic acids , the method comprising:adsorbing substances in a sample containing nucleic acids with an ion exchange resin including a positive ion exchange resin and a negative ion exchange resin thereby purifying the nucleic acids, andamplifying nucleic acids by adding a nuclear acid amplification reagent to the purified nucleic acids.2. The method of claim 1 , wherein the positive ion exchange resin includes a first positive ion exchange resin and a second positive ion exchange resin having an exclusion limit molecular weight lower than that of the first positive ion exchange resin.3. The method of claim 2 , wherein the substances are adsorbed by the first positive ion exchange resin and then are further adsorbed by the negative ion exchange resin and the second positive ion exchange resin.4. The method of claim 3 , wherein the sample is flowed into a column including the first positive ion exchange resin in an upper layer and the negative ion exchange resin and the second positive ion exchange resin in a lower layer from an upper layer side.5. The method of claim 4 , wherein the step is for adsorbing the substances included in the sample that is diluted with a buffer solution by the ion exchange resin claim 4 , and the buffer solution has a pH of 4.0 to 8.0.6. The method of claim 5 , wherein the positive ion exchange resin is a strong acidic positive ion exchange resin.7. The method of claim 6 , wherein a counter ion of the first positive ion exchange resin is Na.8. The method of claim 7 , wherein a counter ion of the second positive ion exchange resin is H.9. The method of claim 8 , wherein the negative ion exchange resin is a strong basic negative ion exchange resin.10. The method of claim 9 , wherein a counter ion of the negative ion exchange resin is OH.11. The method of ...

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31-01-2019 дата публикации

SEPARATION OF OLIGOSACCHARIDES FROM FERMENTATION BROTH

Номер: US20190031698A1
Принадлежит:

The present invention relates to a method for separating sialylated oligosaccharides from a fermentation broth in which they are produced by a genetically modified microorganism The separation comprises the steps of: i) ultrafiltration; ii) nano-filtration; iii) optionally, activated charcoal treatment; and iv) treatment with strong anion and/or cation exchange resin. 1. A method for separating a sialylated oligosaccharide from a fermentation broth obtained by culturing a genetically modified microorganism capable of producing the sialylated oligosaccharide from an internalized carbohydrate precursor , wherein the separation comprises the steps of:i) ultrafiltration,ii) nanofiltration,iii) optionally, activated charcoal treatment, andiv) treatment with strong anion and/or cation exchange resin.2. The method of claim 1 , wherein step i) is conducted before any of the steps ii) claim 1 , iii) or iv).3. The method of claim 1 , wherein step i) comprises two consecutive ultrafiltrations and the molecular weight cut-off of the first ultrafiltration membrane is higher than that of the second membrane.4. The method of any of the claims 1 , wherein step i) further comprises a washing step of the ultrafiltration retentate claims 1 , to obtain a washing filtrate.5. The method of any of the claims 1 , wherein step i) further comprises the dilution of the fermentation broth prior to ultrafiltration.6. The method of claim 4 , wherein the dilution factor of step i) is 1 to 3.5.7. The method of claim 1 , wherein the ultrafiltration step is characterized by a concentration factor of at least 1.25.8. The method of claim 1 , wherein the ultrafiltration permeate is nanofiltered in step ii).9. The method of claim 8 , wherein the molecular weight cut-off of the nanofiltration membrane in step ii) is lower than that of the ultrafiltration membrane in step i).10. The method of claim 9 , wherein the molecular weight cut-off of the nanofiltration membrane in step ii) is around 25-50% of the ...

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30-01-2020 дата публикации

ANION EXCHANGE STATIONARY PHASES BASED ON A POLYALKYLPOLYAMINE POLYMER LAYER

Номер: US20200031857A1
Принадлежит:

An anion exchange for separating a plurality of carbohydrates includes a negatively charged substrate particle. A base polymer layer includes a first plurality of quaternary amines. The polyalkylpolyamine polymer layer is covalently attached to the base condensation polymer layer. The polyalkylpolyamine polymer layer includes a polymeric branch structure that includes a second plurality of quaternary amines. A density of the second plurality of quaternary amines increases in a direction away from the base condensation polymer layer. The anion exchange stationary phase does not have a hydroxy group spaced apart from any one of the first or the second plurality of quaternary amines by an ethyl group. 1. An anion exchange stationary phase for separating a plurality of carbohydrates comprises:a) a negatively charged substrate particle;b) a base condensation polymer layer attached to the negatively charged substrate particle, the base condensation polymer layer comprises a first plurality of quaternary amines, in which the first plurality of quaternary amines are spaced apart by either a first spacer or a second spacer, in which the base condensation polymer layer does not have a hydroxy group spaced apart from one of the first plurality of quaternary amines by an ethyl group;c) a polyalkylpolyamine condensation polymer layer covalently attached to the base condensation polymer layer, the polyalkylpolyamine condensation polymer layer comprises a polymeric branch structure, the polymeric branch structure includes a second plurality of quaternary amines, in which the second plurality of quaternary amines are spaced apart by the first spacer or the second spacer, in which a density of the second plurality of quaternary amines increases in a direction away from the base condensation polymer layer, in which the polyalkylpolyamine condensation polymer layer does not have a hydroxy group spaced apart from one of the second plurality of quaternary amines by an ethyl group.2. The ...

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30-01-2020 дата публикации

METHOD FOR TREATING LIGNOCELLULOSIC MATERIALS

Номер: US20200032359A1
Принадлежит:

A method of generating a refined a sugar stream that comprises xylose from a biomass hydrolysis solution, including contacting a biomass hydrolysis solution that includes a population of mixed sugars comprising xylose, an acid, and impurities, with a thermally-phase separable solvent such as a glycol solvent to form an extraction mixture; and separating from said extraction mixture a first stream including the thermally-phase separable solvent, acid, and impurities and a second, refined sugar stream that comprises xylose. 1. An extraction mixture comprising:a biomass hydrolysis solution that comprises a population of mixed sugars comprising xylose, an acid, and impurities; anda thermally-phase separable solvent,wherein the extraction mixture is configured to separate into two phases with an increased temperature.2. The extraction mixture of claim 1 , wherein the thermally-phase separable solvent includes ethylene glycol claim 1 , propylene glycol claim 1 , or any combination thereof.3. The extraction mixture of claim 1 , further comprising an alkanol.4. The extraction mixture of claim 3 , wherein said alkanol is hexanol.5. The extraction mixture of claim 3 , wherein said alkanol is 2-ethylhexanol.6. The extraction mixture of claim 1 , wherein the extraction mixture comprises a 2-butoxyethanol.7. The extraction mixture of claim 1 , wherein the extraction mixture comprises a 1-propoxy-2-propanol.8. The extraction mixture of claim 1 , wherein the thermally-phase separable solvent is a glycol solvent. This application is divisional of U.S. application Ser. No. 15/548,166 filed on Aug. 2, 2017, which is a U.S. National Stage under 35 U.S.C. § 371 of International Application No. PCT/IB2016/050496, filed Feb. 1, 2016, which claims priority to Swedish Patent Application No. 1550109-1, filed Feb. 3, 2015, the entireties of which are incorporated herein by reference.Currently, sugar solutions are purified with extraction and/or chromatographic techniques or combinations ...

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30-01-2020 дата публикации

LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY METHODS FOR THE ANALYSIS OF POLAR MOLECULES

Номер: US20200033304A1
Принадлежит: WATERS TECHNOLOGIES CORPORATION

A mixed-mode chromatography method for the determination of phosphorylated sugars in a sample is provided. The mixed-mode chromatography method includes obtaining a sample comprising at least one phosphorylated sugar. The sample is introduced onto a chromatography system. The chromatography system includes a column having a stationary phase material contained inside the column. The stationary phase material has a surface comprising a hydrophobic surface group and at least one ionizable modifier. The sample with a mobile phase eluent is flowed through the column, where the at least one phosphorylated sugar is substantially resolved and retained within seven minutes. The mobile phase eluent includes water with an additive and acetonitrile with the additive. The mobile phase eluent has a pH less than 6. The at least one phosphorylated sugar is detected using a detector. 1. A mixed-mode chromatography method for the determination of phosphorylated sugars in a sample , the mixed-mode chromatography method comprising:obtaining a sample comprising at least one phosphorylated sugar;introducing the sample onto a chromatography system comprising a column having a stationary phase material contained inside the column, the stationary phase material having a surface comprising a hydrophobic surface group and at least one ionizable modifier;flowing the sample with a mobile phase eluent through the column, wherein the at least one phosphorylated sugar is substantially resolved and retained within seven minutes, the mobile phase eluent comprising water with an additive and acetonitrile with the additive, the mobile phase eluent having a pH less than 6; anddetecting the at least one phosphorylated sugar using a detector.2. The mixed-mode chromatography method of claim 1 , wherein the pH of the mobile phase eluent is less than 3.3. (canceled)4. The mixed-mode chromatography method of claim 3 , wherein the pH of the mobile phase eluent is about 2.7.5. The mixed-mode chromatography ...

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11-02-2016 дата публикации

PROTEIN FOLDING AND METHODS OF USING SAME

Номер: US20160039907A1
Принадлежит:

The instant disclosure provides a microscale method for providing correctly folded, and assembled biologically active proteins in an efficient and shorted time frame, compared to conventional protein production techniques. Proteins produced from inclusion bodies and other aggregated protein sources are provided. Microscale production of correctly folded and assembled class I MHC protein and complexes thereof are also provided for, as well as for high throughput production for use in epitope discovery protocols. Microscale production of complex proteins from protein aggregates and preparations containing protein aggregates is provided that requires less than 24 hours of processing time. 2. The method of claim 1 , wherein the protein of interest is a complex protein comprising β-microglobulin (βm) claim 1 , a class I major histocompatibility complex protein heavy chain (MHC-HC) claim 1 , and a class I MHC binding molecule.3. The method of claim 2 , wherein the unpurified third folded preparation is purified by a chromatographic method or by a buffer exchange method claim 2 , said buffer exchange method comprising dialyzing the unpurified third folded preparation for about 1 to about 3 hours at temperature of about 4° C. to about 32° C.4. The method of wherein the solubilized preparation of the protein of interest is essentially free of denaturant.5. The method of claim 1 , wherein said small volume of the diluted preparation is not more than 500 microliters.6. The method of claim 2 , wherein the source of said βm and said MHC-HC are inclusion bodies.7. The method of wherein the class I MHC binding molecule is a peptide claim 2 , lipid claim 2 , glycolipid claim 2 , metabolite or other molecule having binding affinity for a class I MHC protein.8. The method of wherein the purification reagent is Ab coated beads or Ni-NTA beads.9. The method of claim 2 , wherein said first preparation of said protein of interest is incubated with an MHC-binding molecule.10. The method ...

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08-02-2018 дата публикации

PROCESS FOR THE PURIFICATION OF RECOMBINANT PROTEINS

Номер: US20180037604A1
Принадлежит:

A process for the extraction and purification of recombinant proteins, more specifically interferons and insulin, having improved quality and yield. The process comprises extraction of proteins from bacterial inclusion bodies using an extraction solution comprising at least one detergent; at least one chaotropic agent; at least one cosmotropic agent; and a protein folding agent. 1. An extraction solution for recovery of proteins from bacterial inclusion bodies , comprising:at least one detergent;at least one chaotropic agent;at least one cosmotropic agent; anda protein folding agent;wherein said extraction solution has a pH of between about 1.5 and about 12.2. The extraction solution of claim 1 , wherein said extraction solution has a pH of between about 7.2 and about 8.5.3. The extraction solution of claim 1 , wherein said chaotropic agent is selected from the group consisting of urea claim 1 , guanidinium chloride claim 1 , thiourea claim 1 , and mixtures thereof.4. The extraction solution of claim 1 , wherein said cosmotropic agent is selected from the group consisting of chloride salts claim 1 , sulfate salts claim 1 , and mixtures thereof.5. The extraction solution of claim 1 , wherein said cosmotropic agent is selected from the group consisting of sodium chloride claim 1 , potassium chloride claim 1 , ammonium sulfate claim 1 , and mixtures thereof.6. The extraction solution of claim 1 , wherein said protein folding agent is arginine.7. A kit for recovery of proteins from bacterial inclusion bodies claim 1 , comprising:an extraction solution for dissolving said proteins, comprising at least one detergent; at least one chaotropic agent; at least one cosmotropic agent; and arginine; andan oxidizing agent for oxidizing said dissolved proteins;wherein said extraction solution has a pH of between about 7.2 and about 8.5; andwherein said oxidizing agent is a thiol, a disulfide, or a mixture thereof.8. A process for recovery of a protein from bacterial inclusion ...

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11-02-2016 дата публикации

METHOD FOR REDUCING SUPPRESSOR NOISE

Номер: US20160041133A1
Принадлежит:

An electrolytic method for suppressing liquid eluent containing previously separated sample analyte anions, counterions to the sample anions, and non-sample anions suppressible to weak acids in an electrolytic device comprising a housing defining at least a sample stream flow channel and an ion receiving flow-through channel separated by an ion exchange bather. The sample stream flow channel includes an upstream channel portion and a downstream channel portion. A first current is applied across the upstream channel portion for substantially completely suppression. A second current is applied across the downstream channel portion at a magnitude of less than 10% of the magnitude of the first current. 1. An electrolytic method for suppressing liquid eluent containing previously separated sample analyte anions , counterions to said sample anions , and non-sample anions suppressible to weak acids; using an electrolytic device comprising a housing defining at least a sample stream flow channel and an ion receiving flow-through channel , said sample stream flow channel being adjacent to said ion receiving flow channel; a first ion exchange barrier which permits ion transport and blocks bulk liquid flow disposed between said sample stream flow channel and said ion receiving flow channel , said sample stream flow channel including an upstream channel portion and a downstream channel portion; and high capacity ion exchange medium disposed in said downstream channel portion; said method comprising applying a first current across said upstream channel portion to substantially completely suppress said counterions and to convert said non-sample anions to weak acids in said upstream channel portion by transport of said counterion across said first ion exchange barrier; applying a second current across said downstream channel portion to substantially reduce the noise of said weak acids during subsequent detection , said second current being at a magnitude of less than 10% of the ...

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07-02-2019 дата публикации

RECIRCULATING DIALYSATE FLUID CIRCUIT FOR BLOOD MEASUREMENT

Номер: US20190038824A1
Принадлежит:

A blood based solute monitoring system for measuring at least one blood solute species that has a first recirculation flow path in fluid communication with a dialyzer. The first recirculation flow path is configured to allow a fluid to recirculate through a dialyzer such that the concentration of at least one solute species in the fluid becomes equilibrated to the solute species concentration of the blood in a blood compartment of the dialyzer. The blood solute monitoring system has at least one sensor to measure a fluid characteristic. 1. A system , comprising:at least a first recirculation flow path;the first recirculation flow path in fluid communication with a dialyzer;the first recirculation flow path comprising at least one pump and at least one sensor measuring at least one fluid characteristic;wherein a concentration of at least one solute in a fluid recirculating in the first recirculation flow path becomes equilibrated with a concentration of the at least one solute in a blood of a patient.2. The system of claim 1 , wherein the sensor is located upstream of the dialyzer and downstream of a dialysate regeneration unit wherein the dialysate regeneration unit is fluidly connectable to the first recirculation flow path.3. The system of claim 1 , wherein the at least one sensor comprises an ion selective sensor.4. The system of claim 1 , further comprising at least two sensors to measure the at least one fluid characteristic.5. The system of claim 4 , wherein the at least two sensors include a conductivity sensor.6. The system of claim 4 , wherein the at least two sensors include any one of a potassium sensor claim 4 , a bicarbonate sensor claim 4 , and an ammonia sensor.7. The system of claim 1 , wherein the at least one sensor comprises a pH sensor.8. The system of claim 1 , wherein the at least one sensor comprises a urea sensor.9. The system of claim 1 , wherein the at least one sensor comprises a conductivity sensor.10. The system of claim 9 , further ...

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24-02-2022 дата публикации

METHOD FOR SEPARATING AND PURIFYING RECOMBINANT HUMAN FIBRONECTIN FROM GENETICALLY ENGINEERED RICE SEED

Номер: US20220056071A1
Автор: YANG Daichang, ZHAN Quan
Принадлежит:

Disclosed is a chromatographic method for separating and purifying a recombinant human fibronectin from a genetically engineered rice seed that expresses the human fibronectin. In the method, the genetically engineered rice seed is milled, mixed with an extraction buffer, and then filtered to obtain a crude extract comprising the recombinant human fibronectin; the crude extract comprising the recombinant human fibronectin is subjected to cation exchange chromatography, so as to perform primary separation and purification, thereby obtaining a primary product comprising the recombinant human fibronectin; and the primary product is subjected to anion exchange chromatography so as to perform final separation and purification to obtain the recombinant human fibronectin as a target substance. The method is low cost and easily utilized on an industrial scale. The obtained OsrhFn target substance has a SEC-HPLC purity greater than 95% with excellent bioactivity. 1. A chromatographic method for separating and purifying a recombinant human fibronectin from genetically engineered rice seeds or grains expressing the recombinant human fibronectin , comprising the following steps in sequence:1) extracting the recombinant human fibronectin from the genetically engineered rice seeds or grains containing the recombinant human fibronectin, to obtain a crude protein extract comprising the recombinant human fibronectin;2) subjecting the crude protein extract comprising the recombinant human fibronectin to cation exchange chromatography, to obtain a primary product; and3) subjecting the primary product to anion exchange chromatography, to obtain a purified recombinant human fibronectin;wherein a resin for the cation exchange chromatography comprises a resin selected from the group consisting of Nano Gel 30/50 SP, Uni Gel 30/80 SP, SP Bestarose FF, SP Bestarose HP, Bestarose Diomond MMC, Uniphere S, MacroPrep S, POROS XS, SP-6FF, SP-6HP, and SP Sepharose™ Fast Flow; anda resin for the ...

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07-02-2019 дата публикации

SYSTEM AND METHOD FOR STORING AND SUPPLYING WATER TO AN INTERNAL COMBUSTION ENGINE OF A MOTOR VEHICLE

Номер: US20190040819A1
Принадлежит:

The invention relates to a system for storing and supplying water to an internal combustion engine of a motor vehicle with a reservoir for the water, with at least a delivery pump for the water, and with at least a pipeline system comprising at least a feed line to a consumer which is preferably designed in the form of at least a metering unit, and at least a return line into the reservoir as well as with means for demineralizing the water which are disposed inside the reservoir or in the pipeline system. 114-. (canceled)15. A system to store water and supply the water to an internal combustion engine of a motor vehicle comprising:a reservoir for the water,at least a delivery pump for the water,at least a pipeline system comprising at least a feed line to a consumer,at least a return line into the reservoir, anda water demineralizer, wherein the water demineralizer is arranged inside the reservoir or on the reservoir or in the pipeline system or communicating with the pipeline system, andwherein the water demineralizer comprises at least one filter, and the filter is arranged inside the feed line or the return line.16. The system as claimed in claim 15 , wherein the water demineralizer is connected in front of a delivery connection of the reservoir or is arranged in the feed line or in a supply line to the consumer.17. The system as claimed in claim 15 , wherein the at least one filter comprises an exchangeable filter cassette or filter pack mounted inside the reservoir.18. The system as claimed in claim 15 , wherein the at least one filter comprises an exchangeable filter cartridge arranged inside the pipeline system or attached to the pipeline system.19. The system as claimed in claim 18 , wherein the filter cartridge is arranged in the feed line.20. The system as claimed in claim 19 , wherein the filter cartridge is switched in before the delivery pump in the flow direction of the delivery.21. The system as claimed in claim 18 , wherein the filter cartridge ...

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06-02-2020 дата публикации

Urease Purification And Purified Urease Products Thereof And Sorbent Cartridges, Systems And Methods Using The Same

Номер: US20200040323A1
Принадлежит:

Methods for purifying urease are described that make use of a precipitating agent such as ammonium sulfate to obtain urease as a precipitate. The method can involve use of a solubilizing agent, such as a citrate-containing solution, to dissolve the precipitate. The method can involve the use of a sugar to provide protected urease in a sugar-urease solution and immobilization of the urease. The method can involve freeze drying of the immobilized urease. A sugar-urease preparation and an immobilized urease, and a sorbent cartridge containing the urease are described as well as methods to conduct dialysis. 1. A method of purifying urease , comprising:a) mechanically separating an extract mixture to provide a separated solution, wherein the extract mixture comprises an extracting agent in solution and a comminuted source of urease;b) combining ammonium sulfate with the separated solution to precipitate urease in the separated solution to provide a precipitate-containing mixture;c) mechanically separating the precipitate-containing mixture to collect the precipitate;d) dissolving the precipitate collected to provide a urease-containing solution;e) combining the urease-containing solution with a sugar to provide a sugar-urease solution;f) combining the sugar-urease solution and a sorbent material to immobilize urease on the sorbent material to provide an immobilized urease preparation; andg) optionally freeze drying the immobilized urease preparation to provide an immobilized urease product.2. The method of claim 1 , wherein the source of urease is a botanical source of urease claim 1 , fungal source of urease claim 1 , algal source of urease claim 1 , bacterial source of urease claim 1 , invertebrate source of urease claim 1 , or any combination thereof.3. The method of claim 1 , wherein the source of urease comprises jack beans claim 1 , sword beans claim 1 , soy beans claim 1 , or any combination thereof.4. The method of claim 1 , wherein the source of urease is jack ...

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18-02-2021 дата публикации

METHODS FOR PURIFYING HETERODIMERIC MULTISPECIFIC ANTIBODIES FROM PARENTAL HOMODIMERIC ANTIBODY SPECIES

Номер: US20210047387A1
Принадлежит:

Methods for purifying multispecific antibodies on interest (MAIs) that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), from compositions comprising the MAI and parental homodimeric antibody species are provided, as well as reagents which may be used to practice such methods. 159-. (canceled)60. An ion exchange eluant comprising either:(i) CAPS, CHES, TAPS, HEPPSO, MOPSO, MES, acetic acid, formic acid, and a salt; or(ii) methylamine, 1,2-ethanediamine, 1-methylpiperazine, 1,4-dimethylpiperazine, 2-[Bis(2-hydroxyethyl)amino]-2-(hydroxymethyl)propane-1,3-diol (bis-tris), and hydroxylamine and optionally at least one salt.61. (canceled)62. The ion exchange eluant according to claim 60 , with the proviso that the eluant does not include TRIS claim 60 , piperazine claim 60 , or imidazole.63. (canceled)64. (canceled)65. The ion exchange eluant according claim 60 , wherein the salt is selected from the group consisting of NaCl claim 60 , KCl claim 60 , or NaSO.66. The ion exchange eluant according claim 60 , wherein the eluant is suitable for use in the purification of an MAI from a composition comprising the MAI and parental homodimeric antibody species.67. The ion exchange eluant according to claim 60 , wherein the eluant comprises at least one salt at a concentration range selected from the group consisting of: 0 mM to about 100 mM; 0 mM to about 60 mM; 0 mM to about 50 mM; 0 mM to about 40 mM; 0 mM to about 30 mM; 0 mM to about 20 mM; 0 mM to about 10 mM; 0 mM to about 5 mM; about 10 mM to about 200 mM; about 10 mM to about 100 mM; about 10 mM to about 50 mM; about 10 mM to about 40 mM; about 10 mM to about 30 mM; about 10 mM to about 20 mM; about 20 mM to about 200 mM; about 20 mM to about 100 mM; about 20 mM to about 50 mM; about 20 mM to about 30 mM; about 30 mM to about 200 mM; about 30 mM to about 100 mM; and about 30 mM to about 50 mM; and about 5 mM to about 15 mM.68. The ion exchange eluant ...

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18-02-2021 дата публикации

SCALABLE CHROMATOGRAPHY PROCESS FOR PURIFICATION OF HUMAN CYTOMEGALOVIRUS

Номер: US20210047626A1
Принадлежит: Merck Sharp & Dohme Corp.

The present invention relates to a scalable process for the purification of human cytomegalovirus particles from cell culture medium. In particular, the process involves a two step chromatography process starting with an anion exchange chromatography step followed by a polishing chromatography step selected from mixed mode chromatography or cation exchange chromatography. 1. A method of purifying human cytomegalovirus (HCMV) from a cell culture medium , the method comprising:a) contacting the cell culture medium comprising HCMV to an anion exchange chromatography medium under conditions that allow the HCMV to bind to the anion exchange chromatography medium;b) eluting the HCMV from the anion exchange chromatography medium to obtain an eluate;c) contacting the eluate with a polishing chromatography medium; andd) collecting the HCMV from the polishing chromatography medium to obtain purified HCMV.2. The method of claim 1 , wherein the polishing chromatography medium is selected from a mixed-mode chromatography resin and a cationic exchange chromatography medium.3. The method of claim 2 , wherein the polishing chromatography medium is a mixed-mode chromatography resin and the HCMV flows through the mixed-mode chromatography resin.4. The method of claim 2 , wherein the mixed-mode chromatography resin has size exclusion properties and the HCMV is excluded from the mixed-mode chromatography resin.5. The method of claim 4 , wherein the mixed-mode chromatography resin includes a hydrophobic anion exchange chromatography ligand and a molecular weight exclusion of about 700 kDa.6. The method of claim 2 , wherein the polishing chromatography medium is a cationic exchange chromatography medium claim 2 , the HCMV binds the cation exchange chromatography medium claim 2 , and the HCMV is eluted from the cationic exchange chromatography medium.7. The method of claim 1 , further comprising tangential flow filtration of the eluate from step b) claim 1 , the purified HCMV from step d) ...

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15-02-2018 дата публикации

ISOIDIDE MANUFACTURE AND PURIFICATION

Номер: US20180044744A1
Принадлежит: ARCHER DANIELS MIDLAND COMPANY

Methods are provided for the purification of isoidide. The methods comprise subjecting an at least partially deionized isoidide composition comprising isoidide and other isohexides to chromatographic separation of isoidide from other isohexides, removal of solvent from the isoidide, and crystallization of the isoidide. Isoidide of monomer-grade purity is obtained. 1. A method of preparing an isoidide enriched composition comprising , at least partially removing ionic species from an epimerization product comprising isoidide to obtain an at least partially deionized isoidide composition comprising isoidide and other isohexides; and ,chromatographically separating the isoidide from other isohexides to obtain a stream enriched in isoidide and a stream enriched in the other isohexides.2. The method of claim 1 , wherein the chromatographic separation is carried out by contacting the at least partially deionized isoidide composition with a resin comprising strong acid ion exchange resin in the calcium 2 form;contacting the at least partially deionized isoidide composition comprising isoidide and other isohexides and the resin with a solvent; and,eluting a stream enriched in isoidide and a second stream enriched in the other isohexides.3. The method according to claim 1 , wherein the amount of ions in the at least partially deionized isoidide composition is below detection limits as determined by inductively coupled plasma atomic emission spectroscopy.4. The method according to claim 2 , wherein the resin is contained on chromatographic beds claim 2 , columns or parts thereof arranged in a simulated moving bed chromatographic array.5. The method according to claim 1 , wherein the solvent comprises water.6. A method according to claim 1 , wherein upon removing solvent the stream enriched in isoidide claim 1 , the proportion of isoidide in the stream enriched in isoidide is greater than 40 claim 1 , 45 claim 1 , 50 claim 1 , 55 claim 1 , 60 claim 1 , 65 claim 1 , 70 claim 1 ...

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18-02-2021 дата публикации

NEW METHOD AND APPARATUS FOR THE PRODUCTION OF HIGH PURITY RADIONUCLIDES

Номер: US20210050126A1
Принадлежит:

An apparatus is for the automated production of a daughter radionuclide from a parent radionuclide using a generator comprising a solid medium onto which the parent nuclide is fixed and whereby the daughter nuclide is formed by radioactive decay of the parent nuclide. The apparatus includes a fluid circuit including a chromatography column having a head port and a tail port, at least one connection port for connecting the generator to the fluid circuit, at least one inlet port for connecting fluid sources to the fluid circuit and at least one valve controlled by an electronic control unit for selectively connecting the chromatography column, the connection port and the at least one inlet port in various configurations. The various configurations include a first elution configuration for circulating an A′ solution exiting the generator and containing the daughter radionuclide, through the chromatography column from the head port to the tail port for loading the chromatography column with the daughter radionuclide; a first washing configuration for circulating an A washing solution from a solution inlet through the chromatography column from the head port to the tail port; and a second washing configuration for circulating an A′ washing solution from a solution inlet through the chromatography column from the tail port to the head port. 1. An apparatus for the automated production of a daughter radionuclide from a parent radionuclide using a generator comprising a solid medium onto which the parent nuclide is fixed and whereby the daughter nuclide is formed by radioactive decay of the parent nuclide , the apparatus comprising a fluid circuit comprising:a chromatography column having a head port and a tail port;at least one connection port for connecting the generator to the fluid circuit;at least one inlet port for connecting fluid sources to the fluid circuit; and [{'b': '1', 'a first elution configuration for circulating an A′ solution exiting the generator and ...

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03-03-2022 дата публикации

SAMPLE SIZE CHROMATOGRAPHY DEVICE

Номер: US20220062790A1
Принадлежит:

A chromatography device having a housing formed from an upper housing ultrasonically welded to a lower housing. A compression extension and a boss located inside of the housing with the media disposed between the compression extension and the boss such that a perimeter of the media is compressed between the compression extension and the boss forming a liquid impermeable seal along the perimeter after the upper housing is ultrasonically welded to the lower housing.

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03-03-2022 дата публикации

VARIABLE-POROSITY FILTERING APPARATUS HAVING COMPRESSIBLE FILTERING MEDIUM

Номер: US20220062797A1
Автор: KIRK Todd William
Принадлежит:

A filtering apparatus has a volume-changeable filtering chamber having one or more flexible enclosing walls and receiving therein a compressible porous filtering medium, a fluid inlet coupled to the filtering chamber for introducing an input fluid stream with impurities into the filtering chamber, a fluid outlet coupled to the filtering chamber for discharging a filtered fluid stream from the filtering chamber, and a volume-changing structure coupled to or in association with the filtering chamber, adapted to permit increasing or decreasing of the volume of the filtering chamber so as to compress or decompress the compressible porous filtering medium therein so as to correspondingly adjust the pore size of the compressible porous filtering medium in said filtering chamber. A method for flushing a compressible filter media, and a method of variably adjusting the amount of filtering, is further disclosed and claimed.

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03-03-2022 дата публикации

METHODS OF PURIFYING POLYPEPTIDES

Номер: US20220064209A1
Принадлежит: Genentech, Inc.

The present invention provides methods for purifying a polypeptide from a composition comprising the polypeptide and at least one contaminant and formulations comprising the polypeptide purified by the methods. The methods for purifying include cation exchange material and/or mixed mode material.

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14-02-2019 дата публикации

LITHIUM EXTRACTION WITH COATED ION EXCHANGE PARTICLES

Номер: US20190046898A1
Автор: SNYDACKER David Henry
Принадлежит:

The present invention relates to the extraction of lithium from liquid resources such as natural and synthetic brines, leachate solutions from minerals, and recycled products. 142.-. (canceled)44. The method of claim 43 , wherein the coating material protects the ion exchange material from chemical degradation.45. The method of claim 43 , wherein the coating material protects the ion exchange material from mechanical degradation.46. The method of claim 43 , the liquid resource is a natural brine claim 43 , a dissolved salt flat claim 43 , seawater claim 43 , concentrated seawater claim 43 , a desalination effluent claim 43 , a concentrated brine claim 43 , a processed brine claim 43 , an oilfield brine claim 43 , a liquid from an ion exchange process claim 43 , a liquid from a solvent extraction process claim 43 , a synthetic brine claim 43 , a leachate from an ore or combination of ores claim 43 , a leachate from a mineral or combination of minerals claim 43 , a leachate from a clay or combination of clays claim 43 , a leachate from recycled products claim 43 , a leachate from recycled materials claim 43 , or combinations thereof.47. The method of claim 43 , wherein the acid solution comprises hydrochloric acid claim 43 , sulfuric acid claim 43 , phosphoric acid claim 43 , hydrobromic acid claim 43 , chloric acid claim 43 , perchloric acid claim 43 , nitric acid claim 43 , formic acid claim 43 , acetic acid claim 43 , or combinations thereof.48. The method of claim 43 , wherein the acid solution comprises hydrochloric acid claim 43 , sulfuric acid claim 43 , nitric acid claim 43 , or combinations thereof.49. The method of claim 43 , wherein the ion exchange material is selected from the group consisting of LiMnO claim 43 , LiTiO claim 43 , LiTiO claim 43 , LiMnO claim 43 , LiSnO claim 43 , LiMnO claim 43 , LiMnO claim 43 , LiTiO claim 43 , LiFePO claim 43 , LiMnPO claim 43 , solid solutions thereof claim 43 , and combinations thereof claim 43 , and the coating ...

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13-02-2020 дата публикации

METHOD FOR PRODUCING PURIFIED STEVIOL PRODUCT USING SIMULATED MOVING BED CHROMATOGRAPHY

Номер: US20200047083A1
Принадлежит: OROCHEM TECHNOLOGIES INC.

Disclosed is a continuous process for the purification of steviol glycosides such as Rebaudioside D and/or Rebaudioside M extracted from the dried leaves or extracted from a fermentation broth using continuous simulated moving bed processes and nanofiltration without the addition of organic solvents to obtain a purified steviol product comprising sweet steviol glycosides. The sweet steviol glycosides can be used as substitutes for caloric sweeteners in beverages and in other food items. 1. A method of purifying one or more steviol glycosides from a mixture , the mixture including the one or more steviol glycosides and at least one impurity , the method comprising:passing the mixture through a first adsorbent with a first solvent, the first adsorbent comprising one or more hydrophobic interaction resins or one or more ion exchange resins to provide a first eluate stream, the first eluate stream having the first solvent and a higher purity of the one or more steviol glycosides than in the mixture as measured by weight percentage of the solid content, andoptionally removing at least a portion of the first solvent from the first eluate stream to provide a reduced first eluate stream.2. The method of claim 1 , the method further comprising:passing the first eluate stream or the reduced first eluate stream through a second adsorbent with a second solvent, the second adsorbent comprising one or more hydrophobic interaction resins or one or more ion exchange resins to provide a second eluate stream, the second eluate stream having the second solvent and a higher purity of the one or more steviol glycosides than in the first eluate stream or the reduced first eluate stream as measured by weight percentage of the solid content, andoptionally removing at least a portion of the second solvent from the second eluate stream to provide a reduced second eluate stream.3. The method of claim 1 , wherein the one or more steviol glycosides are selected from the group consisting of ...

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14-02-2019 дата публикации

HUMAN ANTIBODIES THAT BIND HUMAN TNF-ALPHA AND METHODS OF PREPARING THE SAME

Номер: US20190048069A1
Принадлежит: AbbVie Inc.

Methylglyoxal (MGO)-modified recombinant TNF-alpha antibodies (e.g., Adalimumab) are identified. MGO modification decreases binding between Adalimumab and TNF-alpha. Methods are disclosed for reducing the presence of MGO-modified antibodies in the production of Adalimumab TNF-alpha antibodies. 1. A composition comprising a binding protein capable of binding TNF-alpha , wherein said binding protein comprises at least one methylglyoxal (MGO)-susceptible amino acid , and wherein at least a portion of said binding protein comprises one or more MGO-modified amino acids.2. The composition of claim 1 , wherein the portion of the binding protein that comprises at least one MGO-modified amino acid is less than 12%.3. The composition of claim 1 , wherein the portion of the binding protein that comprises at least one MGO-modified amino acid is less than 6%.4. The composition of claim 1 , wherein the MGO-susceptible amino acid is an arginine.5. The composition of claim 1 , wherein the binding protein is a human antibody or an antigen-binding portion thereof claim 1 , wherein the binding protein dissociates from human TNF-alpha with a Kof 1×10M or less and a Krate constant of 1×10sor less claim 1 , both as determined by surface plasmon resonance claim 1 , and wherein the binding protein neutralizes human TNF-alpha cytotoxicity in a standard in vitro L929 assay with an ICof 1×10M or less.6. A composition comprising a binding protein capable of binding TNF-alpha claim 1 , said binding protein comprising a methylglyoxal (MGO)-susceptible amino acid claim 1 , wherein said composition is prepared by substantially removing molecules of said binding protein that comprise at least one MGO-modified amino acid.7. The composition of claim 6 , wherein more than 70% of said molecules that comprise at least one MGO-modified amino acid is removed.8. The composition of claim 6 , wherein more than 90% of said molecules that comprise at least one MGO-modified amino acid is removed.9. The ...

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23-02-2017 дата публикации

MULTI-SEGMENTED TUBE SHEET

Номер: US20170050125A1
Автор: III Paul F., Nehlen
Принадлежит: Neptune-Benson, LLC

A method of manufacturing a tube sheet by forming a plurality of separate thin tube sheet segments; forming multiple holes in each sheet in a predetermined pattern, each hole for accommodating a tube sheet filter tube; aligning all of the plurality of tube sheet segments so that the hole pattern of each sheet aligns with the hole pattern in all other sheets of the plurality of tube sheet segments; and securing all of the tube sheet segments together to form a unitary tube sheet. A tube sheet construction that includes a plurality of separate thin tube sheet segments, multiple holes being provided in each sheet in a predetermined pattern, each hole for accommodating a tube sheet filter tube, all of the tube sheet segments being aligning so that the hole pattern of each sheet aligns, and fasteners for securing all of the tube sheet segments together. A media layer is provided between adjacent sheet segments. 123.-. (canceled)24. A tube sheet construction comprising:a plurality of tube sheet segments, each of the tube sheet segment having multiple holes in a predetermined pattern, each of the multiple holes sized to accommodate an elongated tubular element;a passive layer disposed with the plurality of tube sheet segments, the passive layer formed of a material that is different from the material of the planar tube sheet segments that imparts a predetermined characteristic to the passive layer; anda plurality of fasteners securing the planar tube sheet segments and the passive layer together.25. The tube sheet construction of claim 24 , wherein the passive layer comprises a planer layer with a medical substance.26. The tube sheet construction of claim 25 , wherein the medical substance is releasable over time or when exposed to elevated temperature.27. The tube sheet construction of claim 24 , wherein the passive layer has magnetic characteristics.28. The tube sheet construction of claim 24 , wherein the passive layer comprises a flow control layer.29. The tube sheet ...

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25-02-2021 дата публикации

METHODS TO PRODUCE A HUMAN PLASMA-DERIVED IGG PREPARATION ENRICHED IN BRAIN DISEASE-RELATED NATURAL IGGS

Номер: US20210054058A1
Принадлежит:

The present invention provides, among other aspects, methods for the manufacture of plasma-derived immunoglobulin G compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-Aβ, anti-RAGE, and anti-α-synuclein antibodies). Advantageously, the methods provided do not affect the manufacturing processes or capabilities for producing plasma-derived IgG therapeutics. Plasma-derived IgG compositions that are highly enriched for anti-brain disease related protein antibodies (e.g., anti-Aβ, anti-RAGE, and anti-α-synuclein antibodies), as also provided here. Methods for the treatment of brain diseases and disorders by administration of plasma-derived IgG compositions highly enriched for anti-brain disease related protein antibodies (e.g., anti-Aβ, anti-RAGE, and anti-α-synuclein antibodies), are also provided. 152-. (canceled)53. An aqueous plasma-derived immunoglobulin G composition enriched in anti-infectious disease immunoglobulins , comprising:{'i': 'Clostridium tetani', 'an enriched content of anti-infectious disease immunoglobulin G in a relative amount of anti-infectious disease immunoglobulin G compared to the total content of immunoglobulin G that is at least 3-fold greater than the relative amount of the anti-infectious disease immunoglobulin G in a total content of immunoglobulin G in an average pool of plasma from more than 1000 random plasma donors, wherein the anti-infectious disease immunoglobulin G is selected from the group consisting of anti-cytomegalovirus (CMV) immunoglobulin G, anti immunoglobulin G, and anti-parvo B19 immunoglobulin G, and'}a pharmaceutically acceptable stabilizing agent.54. The aqueous plasma-derived immunoglobulin G composition of claim 53 , comprising the enriched content of anti-infectious disease immunoglobulin G in a relative amount of anti-infectious disease immunoglobulin G compared to the total content of immunoglobulin G that is at least 5-fold greater than the relative amount of the anti- ...

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25-02-2021 дата публикации

METHOD FOR PREPARING NATURAL L-CYSTEINE CRYSTALS BY CONTINUOUS CHROMATOGRAPHY

Номер: US20210054424A1
Принадлежит: CJ CHEILJEDANG CORPORATION

The present disclosure relates to a method for preparing L-cysteine crystals, and L-cysteine crystals prepared by the method. Through the method for preparing L-cysteine crystals of the present disclosure, L-cysteine crystals can be obtained from a natural L-cysteine fermentation broth with a high recovery rate and/or purity without a chemical reaction or the use of an artificial synthetic compound. 1: A method for preparing L-cysteine crystals , comprising:(a) obtaining a separated liquid after introducing a fermentation broth in a pH range of 3.0 to 9.0 containing L-cysteine into a continuous chromatography apparatus having a strongly acidic cation-exchange resin as a stationary phase;(b) concentrating the separated liquid; and(c) recovering L-cysteine crystals from the concentrate.2: The method of claim 1 , further comprising adjusting the fermentation broth containing L-cysteine to a pH of 3.5 to 7.5 prior to step (a).3: The method of claim 1 , further comprising concentrating the fermentation broth in a pH range of 3.0 to 9.0 containing L-cysteine prior to step (a).4: The method of claim 1 , wherein the strongly acidic cation-exchange resin in step (a) has a sulfuric acid functional group.5: The method of claim 1 , wherein the strongly acidic cation-exchange resin in step (a) is a styrene-divinylbenzene copolymer having a sulfuric acid functional group.6: The method of claim 1 , wherein the continuous chromatography apparatus in step (a) is a simulated moving bed (SMB) chromatography apparatus.7: The method of claim 1 , wherein the separated liquid in step (a) has a solid content of L-cysteine excluding moisture of 85% (w/w) or more.8: The method of claim 1 , wherein the yield of continuous chromatography in step (a) claim 1 , as a ratio of L-cysteine in the separated liquid obtained relative to the fermentation broth introduced claim 1 , is 50% (w/w).9: The method of claim 1 , wherein step (b) is carried out such that the concentration of L-cysteine in the ...

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25-02-2021 дата публикации

METHOD AND ASSOCIATED DEVICE FOR RAPID DETECTION OF TARGET BIOMOLECULES WITH ENHANCED SENSITIVITY

Номер: US20210055297A1
Принадлежит:

A rapid detection method of a target biomolecule comprising an antigenic moiety is provided. The method includes providing a source biological sample comprising the target biomolecule; contacting the source biological sample to an ion-exchange medium; eluting the captured-target biomolecule from the ion-exchange medium as an eluate, and loading the eluate to a rapid diagnostic testing device comprising an antibody. The eluate comprises a concentrated form of the biomolecule in a solution having a salt concentration greater than 150 mM. A concentration of the target biomolecule in the eluate is in a range from about 2× to 25× compared to a concentration of the biomolecule in the source biological sample. The target biomolecule binds to the antibody under the salt concentration of greater than 150 mM. A device for rapid detection of target biomolecule is also provided. 1. A method for rapid diagnostic testing of a source biological sample comprising tuberculosis-lipoarabinomannan (TB-LAM) , comprising: diluting the source biological sample by at least 2× compared to the source urine sample to form a diluted biological sample;', 'contacting the diluted biological sample to an anion-exchange medium to capture the TB-LAM of the diluted biological sample;', 'capturing the TB-LAM of the diluted biological sample by the anion-exchange medium; and', 'eluting the captured-TB-LAM from the anion-exchange medium as a concentrated form of TB-LAM in an eluate under a salt concentration of at least 1M, wherein a concentration of the TB-LAM in the eluate is in a range from about 2× to 25× compared to a concentration of the TB-LAM in the diluted biological sample; and, 'concentrating the TB-LAM byloading the eluate comprising the concentrated form of the TB-LAM to a rapid diagnostic testing device comprising a TB-LAM-specific antibody for binding the concentrated form of the TB-LAM,wherein the eluate is loaded without any dilution, and wherein the TB-LAM binds to the TB-LAM-specific ...

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10-03-2022 дата публикации

METHOD FOR PREPARING HYDRONIUM ION-DISSOLVELD WATER

Номер: US20220073346A1
Автор: LEE In Sang
Принадлежит:

The present disclosure provides a method for preparing hydronium ion-dissolved water including: (a) purifying distilled water to prepare deionized water; (b) electrolyzing the water to produce a brown gas stream; (c) mixing air with the brown gas stream to form a mixed gas stream; (d) injecting the mixed gas stream into the deionized water and dissolving the mixed gas to prepare gas-dissolved water; and (e) injecting the gas-dissolved water into thin-layer chromatography, filtering the gas-dissolved water through a stationary phase provided inside the thin-layer chromatography, and then fractionating to adjust the concentration of dissolved gas. Accordingly, functional water in which hydronium ions are dissolved can be effectively prepared. 1. A method for preparing hydronium ion-dissolved water comprising:(a) purifying distilled water to prepare deionized water;(b) electrolyzing the water to produce a brown gas stream;(c) mixing air with the brown gas stream to form a mixed gas stream;(d) injecting the mixed gas stream into the deionized water and dissolving the mixed gas to prepare gas-dissolved water; and(e) injecting the gas-dissolved water into thin-layer chromatography, filtering the gas-dissolved water through a stationary phase provided inside the thin-layer chromatography, and then fractionating to adjust the concentration of dissolved gas.2. The method of claim 1 , wherein said step (a) is characterized in that the distilled water is passed through an ion exchange resin such that the specific resistance is adjusted to 15 to 18 MΩ·cm.3. The method of claim 1 , wherein said step (b) is characterized in that sodium hydroxide is added to the water at 0.01 to 0.05% (w/w) claim 1 , and a voltage of 100 to 110 V and a current of 10 to 20 mA are applied to generate the brown gas stream.4. The method according to claim 1 , wherein said step (b) is characterized in that the brown gas stream is passed through a filter to be filtered.5. The method according to claim 1 ...

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10-03-2022 дата публикации

METHOD FOR TRANSFERRING A BATCH PRODUCTION PROCESS TO A CONTINUOUS PRODUCTION PROCESS

Номер: US20220073560A1
Принадлежит: Bayer Aktiengesellschaft

Described herein is a method for transferring of batch production process for a monoclonal antibody to a continuous production process for the same monoclonal antibody. 1. A method for transferring of batch production process for a monoclonal antibody to a continuous production process for the same monoclonal antibody comprising the stepsa) providing a particle-free fluid (product stream) from a heterogeneous cell culture-fluid mixture containing the monoclonal antibody, in the form of a product stream,b) at least one continuous Protein A chromatography, characterized in that the aseptic processing is ensured in the continuous mode via sanitization of the Protein A resin with a caustic substance,c) at least one anion exchange chromatography (AEX) in flow through mode, characterized in that the flow of the product stream in the batch production process is 1-20 membrane volumes per minute and the flow of the product stream in the continuous production process for the monoclonal antibody is 0.1-0.99 membrane volumes per minute ORd) at least one anion exchange chromatography characterized in that the batch production process for the monoclonal antibody comprises a membrane absorber for AEX and that in the continuous production process for the same monoclonal antibody said AEX is carried out in a pulsatile manner.2. The method according to claim 1 , wherein at least one filtration providing a filtrate is carried out during the production process.3. The method according to claim 1 , wherein the at least one continuous Protein A chromatography is further characterized in that the flow in continuous mode is 0-8 claim 1 , preferably 0.2-3.8 times less than in batch mode and/or wherein the cycles per column in continuous mode is 10-20 times higher than in batch mode.4. The method according to claim 1 , further comprising at least one cation exchange (CEX) chromatography step in parallel batch mode claim 1 , wherein the number of chromatography columns used in the CEX step to ...

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05-03-2015 дата публикации

Porous Adsorptive Or Chromatographic Media

Номер: US20150060342A1
Принадлежит:

A porous substrate capable of adsorptive filtration of a fluid having a porous self-supporting substrate and one or more porous, adsorptive polymeric coatings comprising from about 1 to about 80% of the void volume of the pores of the substrate. The resultant substrate has good convective and diffusive flow and capacity. The substrate may be cross-linked, have one or more capture chemistries attached to it and is useful as a chromatography media for the selective filtration of desired species including biomolecules such as proteins and DNA fragments. 1. A porous coated composite sheet for adsorption based separations comprising:a porous, self-supporting woven or non-woven fabric polyolefin base sheet, coated with one or more porous crosslinked polyallylamine coatings formed on at least a portion of all surfaces of the porous base sheet,wherein the one or more porous coatings have a void volume fraction of the porous base sheet of at least 1%, and wherein said composite sheet comprises a filter selected from a gridded filter, curricular shaped filter, disc shaped filter, pleated filter, depth filter and combinations thereof.2. The composite sheet of claim 1 , wherein the filter is incorporated into a device selected from a holder claim 1 , laboratory device claim 1 , syringe claim 1 , microtiter plate claim 1 , filter cartridge claim 1 , and cartridge.3. The composite sheet of claim 1 , wherein the porous base sheet has a mean flow pore (MFP) rating about 1 micron to 500 microns.4. The composite sheet of claim 1 , wherein the porous base sheet has a pore size about 10 microns to about 300 microns.5. The composite sheet of claim 1 , wherein the porous base sheet has a pore size about 50 microns to about 200 microns.6. The composite sheet of claim 1 , wherein the coating has a thickness about 1 micron to about 100 microns.7. The composite sheet of claim 1 , wherein the coating has a thickness about 2 microns to about 50 microns.8. The composite sheet of claim 1 , ...

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01-03-2018 дата публикации

REMOVAL OF SERINE PROTEASES BY TREATMENT WITH FINELY DIVIDED SILICON DIOXIDE

Номер: US20180057568A1
Принадлежит:

The present invention provides novel methods for reducing the serine protease and/or serine protease zymogen content of a plasma-derived protein composition. Also provided are methods for manufacturing plasma-derived protein compositions having reduced serine protease and\or serine protease zymogen content. Among yet other aspects, the present invention provides aqueous and lyophilized compositions of plasma-derived proteins having reduced serine protease and/or serine protease zymogen content. Yet other aspects include methods for treating, managing, and/or preventing a disease comprising the administration of a plasma-derived protein composition having a reduced serine protease or serine protease zymogen content. 176-. (canceled)77. A method for preparing an Immunoglobulin G (IgG) composition having a reduced amount of a serine protease or a serine protease zymogen , the method comprising the steps of:(a) precipitating a cryo-poor plasma fraction, in a first precipitation step, with from about 6% to about 10% alcohol at a pH of from about 7.0 to 7.5 to obtain a first precipitate and a first supernatant;(b) precipitating IgG from the first supernatant, in a second precipitation step, with from about 23% to about 27% alcohol at a pH of from about 6.7 to about 7.3 to form a second precipitate;(c) suspending the second precipitate to form a first suspension;(d) contacting the first suspension with from about 0.02 grams fumed silica per gram precipitate formed in step (b) to about 0.06 grams fumed silica per gram precipitate formed in step (b) under a solution condition suitable to bind a serine protease or serine protease zymogen; and (i) filtering the suspension through a filter press to form a clarified suspension;', '(ii) washing the filter press with at least 3 filter press dead volumes of a wash buffer having a pH of from about 4.6 to about 5.3, thereby forming a wash solution; and', '(iii) combining the clarified suspension formed in sub-step (i) with the wash ...

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21-02-2019 дата публикации

PURIFICATION OF CYSTATHIONINE BETA-SYNTHASE

Номер: US20190055537A1
Принадлежит:

This invention provides chromatographic methods for the purification of a cystathionine β-Synthase (CBS) protein, particularly truncated variants thereof and compositions and pharmaceutical compositions prepared therefrom. 2. The composition of claim 1 , wherein the method further comprises at least one additional step of performing chromatographic separation using a ceramic hydroxyapatite (CHAP) resin or a Hydrophobic Interaction Chromatography (HIC).3. The composition of claim 1 , wherein the metal affinity chromatography (IMAC) resin is charged with a divalent metal cation.4. The composition of claim 1 , wherein the chemically cleaved or genetically engineered truncated CBS protein has an amino acid sequence identified by SEQ ID NO: 3.5. The composition of claim 1 , wherein the ion exchange chromatography column is a weak anion exchanger.6. The composition of wherein the weak anion exchanger is selected from the group consisting of: a DEAE-Sepharose FF column claim 5 , a DEAE-Sephacel column claim 5 , a DEAE-cellulose column claim 5 , a DEAE-Sephadex column claim 5 , and a QAE-Sephadex column.7. The composition of claim 1 , wherein the metal affinity chromatography (IMAC) resin is charged with a divalent metal cation.8. The composition of claim 7 , wherein the divalent metal cation is nickel claim 7 , copper claim 7 , cobalt claim 7 , or zinc.9. The composition of claim 8 , wherein the divalent metal ion is zinc.10. The composition of claim 1 , wherein the method further comprises eluting the CBS protein from the metal affinity chromatography (IMAC) resin with an elution buffer comprising imidazole.11. The composition of claim 1 , wherein the purified CBS protein has an amino acid sequence identified by SEQ ID NO: 3.12. The composition of claim 1 , wherein the CBS protein-containing solution is a clarified CBS solution.13. The composition of claim 1 , wherein the CBS protein is produced in a recombinant cell.14. The composition of claim 13 , wherein the ...

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01-03-2018 дата публикации

ION EXCHANGER

Номер: US20180058781A1
Автор: OHIRA Junko
Принадлежит: TOYOTA BOSHOKU KABUSHIKI KAISHA

An ion exchanger includes a case having an inflow hole and an outflow hole. The case accommodates a tube. A first passage is defined between the case and the tube. A second passage is defined in the tube. A first end of the first passage and a first end of the second passage are connected to each other. The first passage includes a lower portion defining a lower accommodation portion that is filled with an anion exchange resin. The first passage includes an upper accommodation portion located above the lower accommodation portion. The upper accommodation portion is filled with a cation exchange resin. The upper accommodation portion has a smaller volume and a smaller refrigerant flow area than the lower accommodation portion. 1. An ion exchanger comprising:a case including an inflow hole into which a refrigerant flows and an outflow hole out of which the refrigerant flows; andan ion exchange resin arranged in the case to remove ions from the refrigerant, whereinthe inflow hole and the outflow hole are located in one of an upper portion and a lower portion of the case,the case accommodates a tube extending in a vertical direction,a first passage is defined between an inner wall of the case and an outer wall of the tube,a second passage is defined in the tube,the first passage and the second passage each include a first end and a second end,the first end of the first passage and the first end of the second passage are connected to each other,the second end of the first passage and the second end of the second passage are not connected to each other,one of the second end of the first passage and the second end of the second passage is connected to the inflow hole and the other one of the second end of the first passage and the second end of the second passage is connected to the outflow hole,the first passage includes a lower portion defining a lower accommodation portion that is filled with an anion exchange resin serving as the ion exchange resin,the first passage ...

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02-03-2017 дата публикации

Method for determining prognosis of renal cell carcinoma

Номер: US20170058355A1

It is intended to provide a rapid, convenient, and highly accurate method for determining the prognosis of cancer. The present invention provides a method for determining the prognosis of a renal cell carcinoma patient, comprising: (1) treating genomic DNA prepared from a renal tissue of a subject with bisulfite; (2) amplifying the bisulfite-treated DNA by PCR; (3) subjecting the obtained PCR amplification product to ion exchange chromatography; (4) obtaining the retention time of a detection signal obtained by the chromatography; and (5) determining the renal cell carcinoma of the subject as having poor prognosis when the result of the step (4) is shorter than a retention time serving as a reference.

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02-03-2017 дата публикации

SYSTEMS AND APPARATUS FOR REDUCING SIGNAL NOISE DUE TO PUMP OSCILLATIONS

Номер: US20170059534A1
Принадлежит:

A system reduces unwanted noise due to pump movement. The system includes a pump including a non-conductive piston extending into a pumping chamber for pumping the sample fluid along an analysis fluid path, a wash chamber, and a seal fluidly separating the pumping chamber from the wash chamber. The system also includes a wash path supplying a wash fluid from a wash reservoir to the wash chamber, an electrical conductor electrically connecting the analysis fluid path to the wash fluid path, and a ground conductor electrically connecting the electrical conductor to ground via a resistor. The electrical conductors and resistor combination between the chambers reduces unwanted noise in the conductivity detector due voltage potentials between the eluent and wash chambers created as the piston moves between the chambers. 1. An apparatus for reducing noise due to pump movement , the apparatus comprising:a pump for pumping a sample fluid along an analysis fluid path to a conductivity detector, the pump including a pumping chamber, a piston extending into the pumping chamber for pumping the sample fluid along the analysis fluid path, a seal wash chamber, and a seal fluidly separating the pumping chamber from the seal wash chamber, wherein the piston extends through the seal and creates a voltage potential between the pumping chamber and the seal washing chamber as the piston moves;a wash fluid path supplying a wash fluid from a wash reservoir to the seal washing chamber; andan electrical conductor for reducing noise in the conductivity detector due to pump movement, the electrical conductor electrically connecting the analysis fluid path to the wash fluid path.2. The analysis system according to claim 1 , wherein the piston is formed of sapphire.3. The analysis system according to claim 1 , wherein the electrical conductor is a platinum wire having a first end in electrical communication with the analysis fluid path and a second end in electrical communication with the wash ...

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05-03-2015 дата публикации

Methods for Inactivating Viruses During a Protein Purification Process

Номер: US20150064769A1
Автор: Alex Xenopoulos
Принадлежит: EMD Millipore Corp

The present application relates to novel and improved methods of achieving virus inactivation during a protein purification process.

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08-03-2018 дата публикации

ELECTRODIALYTIC CAPILLARY SUPPRESSOR FOR SUPPRESSED CONDUCTOMETRIC ION CHROMATOGRAPHY

Номер: US20180065089A1

An electrodialytic device for ion chromatography, including aspects functioning as an eluent suppressor device and aspects functioning as an eluent generator device. In general, the device includes a monolithic block of ionomeric polymer material having (1) a first channel with an inlet port, an outlet port, and an active length of exposed polymer material disposed therebetween, (2) a second channel having an inlet port, an outlet port, and an active length of exposed polymer material disposed therebetween, (3) a first and second at-least-partially exposed electrodes positioned in electrical communication with the second channel, with the second electrode disposed, at least in part, across the second channel from the first electrode. A current flowing between the electrodes will drive an electrodialytic migration of ions between the active lengths, from an eluent stream in the case of a suppression device or into an eluent stream in the case of a generator device. 1. An electrodialytic device for ion chromatography comprising a monolithic block of ionomeric polymer material , the block including:a first channel having an inlet port, an outlet port, and an active length of exposed polymer material disposed therebetween;a second channel having an inlet port, an outlet port, and an active length of exposed polymer material disposed therebetween;a first at-least-partially exposed electrode positioned in electrical communication with the second channel; anda second at-least-partially exposed electrode positioned in electrical communication with the second channel across from the first at-least-partially exposed electrode.2. The electodialytic device of claim 1 , wherein the active length of the first channel and the active length of the second channel are disposed so that at least 10 percent of a current applied across the first and second electrodes flows across the second channel.3. The electrodialytic device of claim 1 , wherein the ionomeric polymer material ...

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11-03-2021 дата публикации

REMOVAL OF EUROPIUM IMPURITIES FROM SAMARIUM-153 IN NITRATE MEDIA USING IONIC LIQUIDS

Номер: US20210070628A1
Принадлежит:

A process of isolating samarium from a hydrophilic composition comprises nitrate ions, europium and samarium, by reducing europium(III) to europium(II) in this hydrophilic composition, and by extracting the samarium with a water-immiscible organic phase comprising an ionic liquid comprising nitrate anions. 123.-. (canceled)24. A process of isolating samarium from a hydrophilic composition comprising nitrate ions , europium and samarium , the process comprising the steps of:a) reducing europium(III) to europium(II) in said hydrophilic composition; andb) extracting said samarium with a water-immiscible organic phase comprising an ionic liquid comprising nitrate anions.25. The process according to claim 24 , wherein said samarium is samarium-153.26. The process according to claim 24 , wherein the hydrophilic composition in step a) does not contain chloride ions.27. The process according to claim 24 , wherein the anions in the hydrophilic composition in step a) and in the water-immiscible organic phase in step b) consist of nitrate anions.28. The process according to claim 24 , further comprising the step of:c) back-extracting samarium to a hydrophilic composition wherein said concentration of nitrate ions is lower than the concentration of nitrate ions in the hydrophilic composition of step a).29. The process according to claim 24 , wherein the ionic liquid is tricaprylmethylammonium nitrate or benzyl¬trioctyl¬ammonium nitrate.30. The process according to claim 24 , wherein the hydrophilic composition is an aqueous solution.31. The process according to claim 24 , wherein the ionic liquid is impregnated on a solid support.32. The process according to claim 31 , wherein the solid support is a porous organic polymer.33. The process according to claim 32 , wherein the porous organic polymer is a polystyrene-polydivinylbenzene copolymer claim 32 , or a insoluble aliphatic polyacrylic ester.34. The process according to claim 31 , wherein the solid support is a porous ...

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12-03-2015 дата публикации

Protein purification

Номер: US20150072918A1
Принадлежит: Genentech Inc

A method for purifying a polypeptide by ion exchange chromatography is described in which a gradient wash is used to resolve a polypeptide of interest from one or more contaminants.

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24-03-2022 дата публикации

TRANSITION ANALYSIS METHOD FOR CHROMATOGRAPHY COLUMN QUALIFICATION

Номер: US20220089716A1
Автор: Randolph Paul
Принадлежит:

The present disclosure is directed to a method of operating a chromatography column. This method involves collecting column outlet signal and accumulated flow parameters at two or more intervals of at least one mobile phase transition front during operation of the chromatography column comprising column packing. A model gamma cumulative distribution curve is determined based on the collected column outlet signal and accumulated flow parameters for the at least one mobile phase transition front. The height equivalent theoretical plate (HETP) value is calculated for the at least one mobile phase transition front using parameters of the model gamma cumulative distribution curve and the quality of the chromatography column packing is assessed based on the calculated HETP value. If during routine column monitoring, an adverse trend in HETP is observed or the control limits are exceeded, the eluate product quality, column process performance, and/or impurity removal data should be evaluated to ensure product quality for the identified batch. Should any of the product quality or column performance fail the criteria set, appropriate corrective action, such as conditioning, repacking or replacing the column, and qualification should be performed prior to release for further use. 117-. (canceled)19. The system of claim 18 , wherein the chromatography column is conditioned claim 18 , replaced claim 18 , or repacked based on said assessing.20. The system of claim 18 ,wherein the detector is configured to collect column outlet signals and accumulated flow parameters at two or more intervals of a corresponding mobile phase transition front during one or more subsequent uses of the chromatography column packing;wherein the computing device comprises processor and a non-transitory computer-readable medium with instructions stored thereon, which, when executed by the processor, perform steps comprising:a) said determining and said calculating using the column outlet signal and ...

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16-03-2017 дата публикации

METHOD FOR PREPARING FUNCTIONALIZED POLYMERS FROM POLYMER ALCOHOLS

Номер: US20170073468A1
Принадлежит:

The present invention provides, among other things, compounds that include a water-soluble and non-peptidic polymer as well as a maleimidyl group. The compounds are useful as, among other things, polymeric reagents. 1. A method for forming a functionalized polymer , comprising:(a) providing a water-soluble and non-peptidic polymer comprising two hydroxyl groups;(b) reacting the water-soluble and non-peptidic polymer comprising two hydroxyl groups, in one or more reaction steps, with one or more functionalizing reagents to effect the introduction of a functional group, Y, to form a mixture comprising (i) unsubstituted water soluble and non-peptidic polymer from step (a), (ii) a monosubstituted polymer comprising a single Y group, and (iii) a disubstituted polymer comprising two Y groups, under conditions effective to form no more than about 45 percent of the disubstituted polymer; and(c) purifying the mixture from step (b) to provide a monosubstituted polymer substantially free from the unsubstituted and disubstituted polymer species.2. The method of claim 1 , wherein said water-soluble and non-peptidic polymer is linear or branched.3. The method of claim 1 , wherein said water-soluble and non-peptidic polymer is selected from the group consisting of poly(alkylene glycol) claim 1 , poly(olefinic alcohol) claim 1 , poly(vinylpyrrolidone) claim 1 , poly(hydroxyalkylmethacrylamide) claim 1 , poly(hydroxyalkylmethacrylate) claim 1 , poly(saccharide) claim 1 , poly(α-hydroxy acid) claim 1 , poly(vinyl alcohol) claim 1 , polyphosphazene claim 1 , polyoxazoline claim 1 , poly(N-acryloylmorpholine) claim 1 , and copolymers claim 1 , terpolymers claim 1 , and mixtures thereof.4. The method of claim 1 , wherein said water-soluble and non-peptidic polymer is a diol.5. The method of claim 4 , wherein said water-soluble and non-peptidic polymer is poly(ethylene glycol).6. The method of claim 4 , wherein each of the hydroxyl groups is located at a terminus of the polymer.7. The ...

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07-03-2019 дата публикации

AUTOMATED SYSTEM FOR REMOTE INLINE CONCENTRATION OF ULTRA-LOW CONCENTRATIONS IN PURE CHEMICALS

Номер: US20190072464A1
Принадлежит:

Systems and methods are described to concentrate a remote sample for analysis. A sample concentration system embodiment includes, but is not limited to, a plurality of valves including at least a first valve, a second valve, and a third valve; a plurality of columns including at least a first column and a second column, the first column fluidically coupled to the first valve, the second column fluidically coupled to the second valve; and a flow meter coupled with the third valve, the flow meter fluidically coupled with each of the first column and the second column when the plurality of valves is in a first flow path configuration to measure an amount of the liquid sample passed through the first column and the second column, wherein the plurality of valves includes a second flow path configuration and a third flow path configuration. 1. A sample concentration system for analysis of a liquid sample by an analysis system , comprising:a plurality of valves including at least a first valve, a second valve, and a third valve, the plurality of valves switchable between differing flow path configurations;a plurality of columns including at least a first column and a second column, the first column and the second column configured to retain at least one chemical of interest from a liquid sample, the first column fluidically coupled to the first valve, the second column fluidically coupled to the second valve; anda flow meter coupled with the third valve, the flow meter fluidically coupled with each of the first column and the second column when the plurality of valves is in a first flow path configuration to measure an amount of the liquid sample passed through the first column and the second column, wherein the plurality of valves includes a second flow path configuration in which the first column, the first valve, the second valve, and the third valve are in fluid communication and the second column and the flow meter are not in fluid communication with the first column, ...

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05-03-2020 дата публикации

ELECTRODES FOR SELECTIVE REMOVAL OF MULTIVALENT IONS THROUGH CAPACITIVE DEIONIZATION

Номер: US20200071200A1
Принадлежит: William Marsh Rice University

A method of forming an electrode for capacitive deionization includes depositing an slurry onto a substrate, wherein the slurry comprises a porous material, a first crosslinkable hydrophilic polymer, and a crosslinker for the first crosslinkable hydrophilic polymer; annealing the slurry deposited on the substrate to create a crosslinked porous layer on the substrate; depositing an solution comprising an ion-exchange material, a second crosslinkable hydrophilic polymer, and a crosslinker for the second crosslinkable hydrophilic polymer onto the crosslinked porous layer; and optionally annealing and/or drying the solution on the crosslinked porous layer. 1. A method of forming an electrode for capacitive deionization , comprising:depositing a slurry onto a substrate, wherein the aqueous slurry comprises a porous material, a first crosslinkable hydrophilic polymer, and a crosslinker for the first crosslinkable hydrophilic polymer;annealing the slurry deposited on the substrate to create a crosslinked porous layer on the substrate;depositing a solution comprising an ion-exchange material, a second crosslinkable hydrophilic polymer, and a crosslinker for the second crosslinkable hydrophilic polymer onto the crosslinked porous layer; andoptionally annealing and/or drying the solution on the crosslinked porous layer.2. The method of claim 1 , wherein slurry and/or the solution are aqueous.3. The method of claim 2 , wherein depositing the aqueous slurry and/or aqueous solution is performed by one of spray coating claim 2 , dip coating claim 2 , spin coating claim 2 , printing claim 2 , slurry casting claim 2 , or a flow-coating process.4. The method of claim 2 , wherein the porous material is selected from the group consisting of carbonaceous materials claim 2 , metal organic framework claim 2 , hexacyanoferrates claim 2 , carbonized biomaterials and mixtures thereof.5. The method of claim 2 , wherein the first crosslinkable hydrophilic polymer is selected from the group ...

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05-03-2020 дата публикации

PROCESS AND SYSTEM FOR OBTAINING BOTULINUM NEUROTOXIN

Номер: US20200071686A1
Принадлежит:

Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use. 1. A substantially animal product free (APF) process utilizing chromatography for obtaining a biologically active botulinum neurotoxin , the process comprising the following steps:(a) providing a substantially APF fermentation medium;{'i': 'Clostridium botulinum', '(b) fermenting bacteria in the fermentation medium, and;'}(c) recovering the biologically active botulinum neurotoxin from the fermentation medium by contacting the fermentation medium with an anion exchange chromatography media followed by contacting an eluent from the anion exchange chromatography medium with a cation exchange chromatography, thereby obtaining the biologically active botulinum neurotoxin from the substantially APF chromatography process.2. The process of claim 1 , wherein the botulinum neurotoxin obtained comprises one part or less residual nucleic acid per million of the botulinum neurotoxin obtained.3. The process of claim 1 , wherein the process is carried out in one week or less.4. A biologically active botulinum neurotoxin obtained by the process of .5. A substantially APF chromatographic process for obtaining a biologically active botulinum neurotoxin type A complex claim 1 , the process comprising the following sequential steps:{'i': 'Clostridium botulinum', '(a) culturing bacteria in a substantially APF culture medium;'}{'i': 'Clostridium botulinum', '(b) fermenting bacteria from the culture medium in about 2 L to about 75 L of a substantially APF fermentation medium, wherein at least one of the culture medium and the fermentation medium includes a vegetable protein;'}(c) harvesting the fermentation medium by removing cellular debris present in the fermentation medium;(d) concentrating the harvested fermentation medium by filtration;(e) diluting the concentrated fermentation medium by adding a buffer;(f) a first ...

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18-03-2021 дата публикации

AAV VECTOR COLUMN PURIFICATION METHODS

Номер: US20210079422A1
Автор: Oh YoungHoon, QU Guang
Принадлежит: SPARK THERAPEUTICS, INC.

Described and provided herein are purification, production and manufacturing methods for recombinant adeno-associated viral (rAAV) vector particles. Purification, production and manufacturing methods set forth herein, for example, include at least 2 column chromatography steps. Column chromatography steps include, for example, cation exchange chromatography, anion exchange chromatography, size exclusion chromatography and/or AAV affinity chromatography alone or in combination and in any order. 1. A method for purifying recombinant adeno-associated viral (rAAV) vector particles said method comprising the steps of:(a) harvesting cells and/or cell culture supernatant comprising rAAV vector particles to produce a harvest;(b) optionally concentrating said harvest produced in step (a) to produce a concentrated harvest;(c) lysing said harvest produced in step (a) or said concentrated harvest produced in step (b) to produce a lysate;(d) treating the lysate produced in step (c) to reduce contaminating nucleic acid in the lysate thereby producing a nucleic acid reduced lysate;(e) optionally filtering said nucleic acid reduced lysate produced in step (d) to produce a clarified lysate, and optionally diluting said clarified lysate to produce a diluted clarified lysate;(f) subjecting said nucleic acid reduced lysate in in step (d), clarified lysate in step (e) or diluted clarified lysate produced in step (e) to cation exchange column chromatography to produce a column eluate comprised of rAAV vector particles thereby separating rAAV vector particles from protein impurities or other production/process related impurities, and optionally diluting said column eluate to produce a diluted column eluate;(g) subjecting said column eluate or said diluted column eluate produced in step (f) to anion exchange chromatography to produce a second column eluate comprised of rAAV vector particles thereby separating rAAV vector particles from protein impurities or production/process related ...

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22-03-2018 дата публикации

METHODS FOR PURIFYING HETERODIMERIC MULTISPECIFIC ANTIBODIES FROM PARENTAL HOMODIMERIC ANTIBODY SPECIES

Номер: US20180079797A1
Принадлежит:

Methods for purifying multispecific antibodies on interest (MAIs) that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), from compositions comprising the MAI and parental homodimeric antibody species are provided, as well as reagents which may be used to practice such methods. 1. A method of purifying a multispecific antibody of interest (MAI) , wherein the MAI comprises a heterodimer comprising a first heavy chain polypeptide comprising a first heavy chain (HC) variable region and a second heavy chain polypeptide comprising a second HC variable region , wherein the first and the second variable regions have different antigen specificities and different isoelectric points , the method comprising:i) obtaining a composition comprising the MAI, a first parental homodimeric antibody species comprising either at least one copy of the first heavy chain polypeptide or at least two copies of the first heavy chain polypeptide, and a second parental homodimeric antibody species comprising either at least one copy of the second heavy chain polypeptide or at least two copies of the second heavy chain polypeptide; andii) performing chromatography whereby the MAI is separated from the first and the second parental homodimeric antibody species;thereby purifying the MAI.2. The method of claim 1 , wherein the performing step ii) comprises:a. contacting the composition with a chromatographic material forming a composition-chromatographic material complex; andb. performing an elution step wherein the chromatographic material-composition complex is contacted with a sample of eluant that is capable of eluting the MAI and parental homodimeric antibody species in a pH-dependent manner.3. The method of claim 2 , wherein the eluant comprises at least two buffering agents that each have a different negative log acid dissociation constant (pKa).4. The method according to or claim 2 , further comprising preparing or equilibrating ...

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24-03-2016 дата публикации

METHOD FOR PURIFYING ANTIBODY PROTEIN

Номер: US20160083419A1
Принадлежит: ASAHI KASEI MEDICAL CO., LTD.

A method for purifying a biologically active substance from a solution mixture containing impurities and the biologically active substance, in which an ion exchange chromatography carrier comprising a matrix and a copolymer containing at least N-isopropylacrylamide as a monomer unit and immobilized to a surface of the matrix is used, and the solution mixture is allowed to flow through a container storing the carrier at a uniform temperature, thereby recovering the biologically active substance. 1. A method for purifying a biologically active substance from a solution mixture containing impurities and the biologically active substance , whereinan ion exchange chromatography carrier having a matrix and a copolymer containing at least N-isopropylacrylamide as a monomer unit and immobilized to a surface of the matrix is used, andthe solution mixture is allowed to flow through a container storing the carrier at a uniform temperature, thereby recovering the biologically active substance.2. A method for purifying a biologically active substance from a solution mixture containing impurities and the biologically active substance , whereinat least one temperature responsive ion exchange chromatography carrier is used, andthe solution mixture is allowed to flow through a container storing the carrier at a uniform temperature, thereby recovering the biologically active substance.3. A method for removing impurities from a solution mixture containing the impurities and a biologically active substance , whereinan ion exchange chromatography carrier having a matrix and a copolymer containing at least N-isopropylacrylamide as a monomer unit and immobilized to a surface of the matrix is used, andthe solution mixture is allowed to flow through a container storing the carrier at a uniform temperature, thereby removing the impurities.4. A method for removing impurities from a solution mixture containing the impurities and a biologically active substance , whereinat least one temperature ...

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31-03-2022 дата публикации

Regional decoagulation system for extracorporeal blood-circulation circuit

Номер: US20220096723A1

A system is described for the regional decoagulation of the blood in an extracorporeal circulation circuit comprising means for infusion of a solution of a citrate or citric acid on the main circuit, which are set upstream of the first filtration unit; for infusion of a solution for electrolyte restoration on the main circuit, which are set downstream of the filtration unit and a secondary circuit for recirculation of the plasma water obtained by the filtration unit. The secondary circuit comprises: a first cartridge comprising an anion-exchange resin charged with chlorine ions; a second cartridge comprising a cation-exchange resin charged with sodium and potassium ions, which is set downstream of the first cartridge and means for removal of a first fraction of the plasma water obtained by the filtration unit.

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31-03-2022 дата публикации

PROCESS FOR REMOVING LEAD IONS FROM BOLDILY FLUIDS USING METALLATE ION EXCHANGE COMPOSITIONS

Номер: US20220097019A1
Принадлежит:

A process for removing Pb toxins from bodily fluids is disclosed. The process involves contacting the bodily fluid with an ion exchange composition to remove the metal toxins in the bodily fluid, including blood and gastrointestinal fluid. Alternatively, blood can be contacted with a dialysis solution which is then contacted with the ion exchange composition. The ion exchange compositions are represented by the following empirical formula: 2. The process of wherein the bodily fluid is selected from the group consisting of whole blood claim 1 , blood plasma claim 1 , or other component of blood claim 1 , gastrointestinal fluids claim 1 , dialysate fluids claim 1 , gastrointestinal fluids and dialysate solution containing blood claim 1 , blood plasma claim 1 , other component of blood or gastrointestinal fluids.3. The process of where the ion-exchanger has the phamacosiderite topology.4. The process of where the ion-exchanger has the sitinakite topology.5. The process of where the ion-exchanger is an intergrowth of the phamacosiderite and sitinakite topologies.6. The process of where the ion-exchanger is a composite comprised of a mixture of the phamacosiderite claim 1 , sitinakite claim 1 , pharmacosiderite-sitinakite intergrowth topologies in any combination.7. The process of where a=1.8. The process of where A is hydronium (H).9. The process of where A is calcium.10. The process of where A is sodium.11. The process of where A is a mixture of hydronium (H) claim 1 , calcium and sodium.12. The process of wherein said ion exchanger is formed into a shaped article to be ingested orally claim 1 , followed by ion exchange between said ion exchanger and said Pb toxins contained in a gastrointestinal fluid in a mammal's intestines and then by excretion of said ion exchanger containing said toxins.14. The composition of wherein said bodily fluid is whole blood claim 13 , blood plasma claim 13 , other blood component or gastrointestinal fluid.16. The apparatus of wherein ...

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25-03-2021 дата публикации

CHROMATOGRAPHY RESIN HAVING AN ANIONIC EXCHANGE-HYDROPHOBIC MIXED MODE LIGAND

Номер: US20210086165A1
Принадлежит:

Chromatography resins having mixed mode ligands and methods of using such resins are provided. 125-. (canceled)32. The chromatography resin of claim 26 , wherein R-Rare each independently hydrogen claim 26 , Cor Calkyl.33. The chromatography resin of claim 32 , wherein R-Rare each independently hydrogen or —CH.34. The chromatography resin of claim 26 , wherein Xis selected from the group consisting of —O—CH— claim 26 , —O—CH—CH— claim 26 , —O—CH—CH—CH— claim 26 , —O—CH—CH—CH—CH— claim 26 , and —O—CH—CH(CH—OH)—(O—CH—CH(OH)—CH)—.35. The chromatography resin of claim 26 , wherein Ar is unsubstituted.36. The chromatography resin of claim 26 , wherein if Ar is phenyl claim 26 , chromatography matrix-(X)-L- is at a para or meta position relative to (X)—Y.37. The chromatography resin of claim 26 , wherein chromatography matrix-(X)-L-Ar—(X)—Y is any one of the structures in the right-most column of Table 1.38. The chromatography resin of claim 26 , wherein the anionic salt is hydrochloride or sulfate.39. A chromatography resin prepared by reacting any one of the ligands of Table 1 with a chromatography matrix by any one of reductive amination claim 26 , epoxide chemistry claim 26 , or azalactone chemistry.40. The chromatography resin of claim 39 , wherein the chromatography matrix comprises an aldehyde group and any one of the ligands of Table 1 is reacted with the chromatography matrix by reductive amination.41. The chromatography resin of claim 39 , wherein the chromatography matrix comprises an epoxide group and any one of the ligands of Table 1 is reacted with the chromatography matrix by epoxide chemistry.42. The chromatography resin of claim 39 , wherein prior to reacting the chromatography matrix with the ligand the chromatography matrix is reacted with allylglydicylether and bromine; 1 claim 39 ,4-butanedioldiglycidyl; or epichlorohydrin.43. The chromatography resin of claim 42 , wherein the chromatography matrix comprises an —OH group and it is reacted with ...

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29-03-2018 дата публикации

Chromatography Media And Method

Номер: US20180085743A1
Принадлежит: EMD Millipore Corp

Adsorptive media for chromatography, particularly ion-exchange chromatography, derived from a shaped fiber. In certain embodiments, the functionalized shaped fiber presents a fibrillated or ridged structure which greatly increases the surface area of the fibers when compared to ordinary fibers. Also disclosed herein is a method to add surface pendant functional groups that provides cation-exchange or anion-exchange functionality to the high surface area fibers. This pendant functionality is useful for the ion-exchange chromatographic purification of biomolecules, such as monoclonal antibodies (mAbs).

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31-03-2016 дата публикации

ION-EXCHANGER

Номер: US20160089618A1
Принадлежит: ROKI CO., LTD.

An ion-exchanger includes a case member provided with a cooling liquid flow-in pipe through which cooling liquid is introduced and a cooling liquid discharge pipe through which the cooling liquid is discharged, a cartridge member to be detachably accommodated in the case member, and a number of ion-exchange resin particles sealed within the cartridge member. The cartridge member is provided with an engaging portion detachably engaging with an end portion of the case member, and the case member is provided with an engagement portion to be engaged with the engaging portion provided for the cartridge member. 1. An ion-exchanger comprising:a case member provided with a cooling liquid flow-in portion through which cooling liquid is introduced and a cooling liquid discharge portion through which the cooling liquid is discharged;a cartridge member to be detachably accommodated in the case member; anda number of ion-exchange resin particles sealed within the cartridge member,wherein the cartridge member is provided with an engaging portion detachably engaging with an end portion of the case member, and the case member is provided with an engagement portion to be engaged with the engaging portion.2. The ion-exchanger according to claim 1 , wherein the engagement portion to be engaged with the engaging portion is composed of a groove having a vertical groove portion extending in an axial direction of the case member and an outer peripheral groove portion extending in a circumferential direction of the case member from one end of the vertical groove portion.3. The ion-exchanger according to claim 1 , wherein the cartridge member is provided with a bottomed cylindrical cartridge body in which a number of ion-exchange resin particles are sealed and a closing member integrally welded to the cartridge body and formed with the engaging portion.4. The ion-exchanger according to claim 3 , wherein the closing member is formed with an oblique surface to a surface facing the ion- ...

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29-03-2018 дата публикации

PREPARATION AND SEPARATION OF A DI-CARBOXYLIC ACID-CONTAINING MIXTURE

Номер: US20180086688A1
Принадлежит: RENNOVIA INC.

Processes for separating a di-carboxylic acid or salt thereof from a mixture containing the di-carboxylic acid or salt thereof and one or more other components are provided. Also separation media useful for these separation processes is provided. In particular, processes for preparing an aldaric acid are described, such as glucaric acid from glucose, which includes separating the aldaric acid from the reaction product. Also, various glucaric acid products are described. 1. A glucaric acid product comprising:from about 20 wt. % to about 65 wt. % glucaric acid and lactones thereof,from about 25 wt. % to about 70 wt. % gluconic acid and lactones thereof,from about 1 wt. % to about 20 wt. % guluronic acid and lactones thereof,less than about 10 wt. % of one or more ketogluconic acids and lactones thereof,{'sub': 2', '5, 'one or more C-Cdi-acids and/or lactones thereof, and'}less than about 5 wt. % glucose, wherein each weight percent is based on the dissolved solids content of the glucaric acid product.2. The glucaric acid product of wherein the concentration of guluronic acid and lactones thereof is from about 5 wt. % to about 15 wt. % based on the dissolved solids content.3. The glucaric acid product of wherein the concentration of glucaric acid and lactones thereof is from about 40 wt. % to about 60 wt. % of the dissolved solids contents.4. The glucaric acid product of wherein the concentration of gluconic acid and lactones thereof is from about 25 wt. % to about 45 wt. % of the dissolved solids contents5. The glucaric acid product of wherein the concentration of the ketogluconic acids and lactones thereof is from about 1 wt. % to about 10 wt. % of the dissolved solids contents and wherein the ketogluconic acids are 2-ketogluconic acid claim 1 , 3-ketogluconic acid claim 1 , 4-ketogluconic acid claim 1 , and 5-ketogluconic acid.6. (canceled)7. The glucaric acid product of wherein the concentration of the one or more C-Cdi-acids and lactones thereof is from about 1 wt ...

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21-03-2019 дата публикации

REMOVAL OF LEAKED AFFINITY PURIFICATION LIGAND

Номер: US20190085021A1
Принадлежит: Amgen Inc.

The invention provides for the removal of a large fraction of contaminants from protein preparations while maintaining a high level of recovery using tentacle anion exchange matrix chromatography medium. Using the methods of the invention, leached affinity chromatography contaminants can be removed from recombinant protein preparations. 1. A method for purifying a recombinant protein from a sample containing the recombinant protein and a second protein that binds to the protein , comprising subjecting the sample to a tentacle anion exchange matrix chromatography medium under conditions whereby the recombinant protein binds to the tentacle anion exchange matrix chromatography medium , followed by eluting the recombinant protein bound to the chromatography medium in an eluant , whereby at least 85% of the recombinant protein is recovered in the eluant and at least 75% of the second protein is removed from the eluant.2. The method of claim 1 , wherein the tentacle anion exchange matrix chromatography medium contains a strong anion functional group.3. The method of claim 2 , wherein the strong anion functional group is trimethyl-ammoniumethyl (TMAE).4. The method of claim 1 , wherein the resin substrate of the tentacle anion exchange matrix chromatography medium is a methacrylate polymeric resin or a polyvinylstyrene polymeric resin.5. The method of claim 1 , wherein the chromatography medium is Fractogel® EMD TMAE HiCap.6. The method of claim 1 , wherein the recombinant protein contains a C2/C3 region of an antibody.7. The method of claim 6 , wherein the second protein is Protein A or Protein G.8. The method of claim 1 , wherein the sample is obtained from affinity purification of the protein over a Protein A chromatography medium.9. The method of claim 6 , wherein the recombinant protein is an antibody or an Fc fusion protein.10. The method of claim 9 , wherein the recombinant protein is a tumor necrosis factor receptor Fc fusion protein.11. The method of claim 10 , ...

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19-03-2020 дата публикации

PROTEIN COMPLEX BY USE OF A SPECIFIC SITE OF AN IMMUNOGLOBULIN FRAGMENT FOR LINKAGE

Номер: US20200085913A1
Принадлежит: HANMI PHARM. CO., LTD

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs. 1. A protein complex comprising a physiologically active polypeptide linked to an immunoglobulin Fc region via a non-peptidyl polymer , wherein the non-peptidyl polymer is site-specifically linked to a N-terminus of the immunoglobulin Fc region ,wherein the physiologically active polypeptide is granulocyte colony-stimulating factor derivative in which the amino acids at positions 17 and 65 of the native G-CSF is substituted with serine.2. The protein complex of claim 1 , wherein both ends of the non-peptidyl polymer is respectively linked to the physiologically active polypeptide and the immunoglobulin Fc region through reactive groups by a covalent bond.3. The protein complex of claim 1 , (a) wherein the immunoglobulin Fc region is aglycosylated;(b) wherein the immunoglobulin Fc region consists of one to four domains selected from the group consisting of CH1, CH2, CH3, and CH4 domains;(c) wherein the immunoglobulin Fc region further comprises a hinge region; or(d) wherein the immunoglobulin Fc region is an immunoglobulin Fc fragment derived from IgG, IgA, IgD, IgE, or IgM.4. The protein complex of claim 3 , (a) wherein each domain of the immunoglobulin Fc fragment is a hybrid of ...

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05-05-2022 дата публикации

PURIFICATION PLATFORMS FOR OBTAINING PHARMACEUTICAL COMPOSITIONS HAVING A REDUCED HYDROLYTIC ENZYME ACTIVITY RATE

Номер: US20220135620A1
Принадлежит:

The present disclosure provides purification platforms comprising a depth filter step and/or a hydrophobic interaction chromatography (HIC) step and/or a MM-HIC/IEX chromatography step, and are useful for providing a method of reducing a hydrolytic enzyme activity rate of a composition obtained from said purification platforms. Also disclosed herein are methods of using the purification platforms described herein and compositions obtained therefrom, such as pharmaceutical compositions.

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07-04-2016 дата публикации

Reduction of Endotoxin in Polysialic Acids

Номер: US20160096905A1
Принадлежит: Lipoxen Technologies Limited

The present invention relates to process for reducing the endotoxin content of a sample of fermentation broth containing polysialic acid and endotoxin comprising the sequential steps: (i) adding to the sample a base having a pKa of at least 12 to form a basic solution having a pH of at least 12, incubating the solution for a pre-determined time at a pre-determined temperature; and (ii) recovery of PSA, suitably by (iii) passing the sample through an anion-exchange column whereby polysialic acid is absorbed on the ion exchange resin; (iv) washing the column with one washing buffer, whereby polysialic acid remains absorbed on the ion exchange resin; and (v) eluting the polysialic acid from the column using an elution buffer to provide a product solution of polysialic acid having reduced endotoxin content. 1. A method for reducing the content of an endotoxin in a sample including a polysialic acid (PSA) and the endotoxin , the method comprising:a) adding a base having a pKa of at least 12 to the sample to form a solution having a pH of at least 12; wherein the PSA in the sample has a weight average molecular weight of up to about 100 kDa;b) incubating the sample for a time period ranging from 5 minutes to 24 hours;c) passing the sample through an anion-exchange column;d) washing the column with a wash buffer; ande) recovering the PSA from the anion exchange column, wherein the recovered PSA sample has a reduced endotoxin content.2. The method of claim 1 , wherein the base has a pKa of at least 13 and/or the pH of the formed solution is 13.3. The method of claim 2 , wherein the base has a pKa of at least 14 and/or the pH of the formed solution is 14.4. The method of claim 1 , wherein the time period ranges from 30 minutes to about 6 hours.5. The method of claim 4 , wherein the time period is about 2 hours.6. The method of claim 1 , wherein the PSA includes a poly(2 claim 1 ,8-linked sialic acid) claim 1 , a poly(2 claim 1 ,9-linked sialic acid) claim 1 , an alternating ...

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05-04-2018 дата публикации

MATERIALS AND METHODS FOR THE SELECTIVE RECOVERY OF MONOVALENT PRODUCTS FROM AQUEOUS SOLUTIONS USING CONTINUOUS ION EXCHANGE

Номер: US20180093202A1
Автор: Conradie Alex
Принадлежит:

This document describes a process for the high purity and high concentration recovery of monovalent products via continuous ion exchange from aqueous solution for further downstream purification. 1. A method of recovering at least one monovalent product from an aqueous solution using continuous ion exchange comprising:a. adsorbing at least one monovalent product on an ion exchange resin at a pH of approximately the logarithm of a first acid dissociation constant of the at least one monovalent product;b. eluting the at least one monovalent product from the ion exchange resin; andc. charging adsorbent sites on the ion exchange resin with a sufficient amount of protons or proton donors to provide buffering capacity towards the pH of approximately the logarithm of the at least one monovalent product's first acid dissociation constant.2. The method of claim 1 , wherein the at least one monovalent product is chosen from fatty acids claim 1 , monoamines claim 1 , and amino acids.3. The method of claim 2 , wherein the monoamines comprise at least one of 4-aminobutyrate claim 2 , 5-aminopentanoate claim 2 , 6-aminohexanoate claim 2 , and 7-aminoheptanoate.4. The method of claim 1 , wherein the at least one monovalent product is eluted from the ion exchange resin with a solution comprising at least one compound chosen from ammonia claim 1 , ammonium carbonate claim 1 , and ammonium bicarbonate.5. The method of claim 1 , comprising charging the adsorbent site on the ion exchange resin with an acidic solution.6. The method of claim 5 , wherein the acidic solution comprises sulphuric acid.7. The method of claim 1 , comprising charging the adsorbent sites on the ion exchange resin with an ammonium bicarbonate solution.8. The method of claim 1 , further comprising at least one wash step after at least one of steps (a) claim 1 , (b) claim 1 , and (c).9. The method of claim 8 , wherein the at least one wash step comprises washing the ion exchange resin with an aqueous solution.10. ...

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07-04-2016 дата публикации

PROCESS AND SYSTEM FOR OBTAINING BOTULINUM NEUROTOXIN

Номер: US20160097045A1
Принадлежит:

Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use. 1. A substantially animal product free (APF) process utilizing chromatography for obtaining a botulinum neurotoxin , the process comprising the following steps:(a) providing a substantially APF fermentation medium;(b) fermenting clostridium botulinum bacteria in the fermentation medium, wherein the clostridium botulinum bacteria produce a botulinum neurotoxin, and;(c) sequentially contacting a plurality of chromatography resins with an aqueous medium containing the botulinum neurotoxin, wherein the plurality of chromatography resins comprise an ion exchange resin, a hydrophobic interaction resin, a gel filtration resin, or combinations thereof; thereby obtaining the botulinum neurotoxin from the substantially APF chromatography process.2. The process of claim 1 , wherein the ion exchange resin comprises an anion exchange resin claim 1 , a cation exchange resin claim 1 , or combinations thereof.3. The process of claim 1 , wherein the ion exchange resin is an anion exchange resin.4. The process of claim 1 , wherein the ion exchange resin is a cation exchange resin.5. The process of claim 1 , wherein the fermentation medium comprises no more than about 5% w/v of a vegetable-derived protein product claim 1 , no more than about 2% w/v of a yeast extract and no more than about 2% w/v glucose claim 1 , and wherein the pH level of the fermentation medium is from about pH 6.5 to about pH 8.0 at the commencement of the fermenting step.6. The process of claim 1 , wherein the fermenting step is carried out for about 60 to 80 hours and until an optical density of the fermentation medium at about 890 nm decreases to between about 0.05 AU to about 0.7 AU.7. The process of claim 1 , wherein the botulinum neurotoxin obtained comprises one ng or less than one ng of residual nucleic acid for each mg of the botulinum ...

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05-04-2018 дата публикации

FUNCTIONALIZED POLYOLEFIN CAPILLARIES FOR OPEN TUBULAR ION CHROMATOGRAPHY

Номер: US20180093262A1
Принадлежит:

Open tubular capillary columns for liquid and ion chromatography, based upon an ionically impermeable polyolefin capillary having a bore with a sulfonate-group- or amine-group-functionalized internal surface. The capillary columns may include a coating of ion exchanging nanoparticles electrostatically bound to the functionalized internal surface. The capillary columns may be made by exposing the interior surface to a sulfonating reagent comprising chlorosulfonic acid (ClSOH), preferably from 85 wt % to 95 wt % chlorosulfonic acid at a process temperature of 20 to 25° C. The interior surface may be subsequently exposed to an asymmetrical diamine to form a sulfonic mid-linkage to the diamine, i.e., to form a sulfonamide-linked, amine-group-functionalized internal surface. The coating may be provided by subsequently exposing the interior surface to an aqueous suspension of ion exchanging nanoparticles to electrostatically bond the ion exchanging nanoparticles to the functionalized internal surface. 1. An open tubular capillary column for liquid and ion chromatography , the column comprising:an ionically impermeable polyolefin capillary;the capillary having a bore with a sulfonate-group-functionalized internal surface.2. The open tubular capillary column of claim 1 , wherein the sulfonate-group-functionalized internal surface provides a sulfonate-group associated cation exchange capacity of at most 9 peq/mm.3. The open tubular capillary column of claim 2 , wherein the sulfonate-group-functionalized internal surface provides a sulfonate-group associated cation exchange capacity of at least 0.5 peq/mm.4. The open tubular capillary column of claim 1 , wherein the sulfonate-group-functionalized internal surface provides a sulfonate-group associated cation exchange capacity of at most 300 peq/mm.5. The open tubular capillary column of claim 1 , wherein the bore further includes a coating of anion exchanging nanoparticles electrostatically bound to the sulfonate-group- ...

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12-05-2022 дата публикации

REMOVAL OF LEAKED AFFINITY PURIFICATION LIGAND

Номер: US20220144886A1
Принадлежит: Amgen Inc.

The invention provides for the removal of a large fraction of contaminants from protein preparations while maintaining a high level of recovery using tentacle anion exchange matrix chromatography medium. Using the methods of the invention, leached affinity chromatography contaminants can be removed from recombinant protein preparations. 120-. (canceled)21. A method for purifying an antibody from a sample containing the antibody and a second protein that binds to the antibody , comprising subjecting the sample to a tentacle anion exchange matrix chromatography medium under conditions whereby the antibody binds to the tentacle anion exchange matrix chromatography medium , followed by eluting the antibody bound to the chromatography medium in an eluant , whereby at least 85% of the antibody is recovered in the eluant and at least 75% of the second protein is removed from the eluant , wherein the second protein is Protein A or Protein G.22. The method of claim 21 , wherein the antibody is a humanized antibody or human antibody.23. The method of claim 21 , wherein the antibody is adalimumab claim 21 , bevacizumab claim 21 , infliximab claim 21 , abciximab claim 21 , alemtuzumab claim 21 , bapineuzumab claim 21 , basiliximab claim 21 , belimumab claim 21 , briakinumab claim 21 , canakinumab claim 21 , certolizumab pegol claim 21 , cetuximab claim 21 , conatumumab claim 21 , denosumab claim 21 , eculizumab claim 21 , gemtuzumab ozogamicin claim 21 , golimumab claim 21 , ibritumomab tiuxetan claim 21 , labetuzumab claim 21 , mapatumumab claim 21 , matuzumab claim 21 , mepolizumab claim 21 , motavizumab claim 21 , muromonab-CD3 claim 21 , natalizumab claim 21 , nimotuzumab claim 21 , ofatumumab claim 21 , omalizumab claim 21 , oregovomab claim 21 , palivizumab claim 21 , panitumumab claim 21 , pemtumomab claim 21 , pertuzumab claim 21 , ranibizumab claim 21 , rituximab claim 21 , rovelizumab claim 21 , tocilizumab claim 21 , tositumomab claim 21 , trastuzumab claim 21 , ...

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12-05-2022 дата публикации

PROCESS AND SYSTEM FOR OBTAINING BOTULINUM NEUROTOXIN

Номер: US20220145279A1
Принадлежит:

Rapid, animal protein free, chromatographic processes and systems for obtaining high potency, high yield botulinum neurotoxin for research, therapeutic and cosmetic use. 112-. (canceled)13Clostridial botulinum. A substantially animal product free (APF) process for purifying and obtaining approximately 150 kDa serotype A (BoNT/A) in a clarified culture comprising BoNT/A complex and at least one impurity protein , said process comprising:(a) directly loading an anion exchange chromatography column with the clarified culture to afford a first purified sample;(b) contacting the first purified sample with a cation exchange chromatography column to afford a second purified sample;(c) contacting the second purified sample with an aqueous solution having a pH between about 7.0 and about 8.0 to provide a third purified sample comprising dissociated approximately 150 kDa BoNT/A;(d) contacting the third purified sample with one or more additional chromatography columns selected from an ion exchange chromatography column, a gel filtration chromatography column, or an affinity column; and(e) recovering the dissociated approximately 150 kDa BoNT/A.14. The method of claim 13 , wherein the clarified culture has been prepared without an acid precipitation step.15. The method of claim 13 , wherein the one or more additional chromatography columns comprise a third chromatography column and a fourth chromatography column.16. The method of claim 15 , wherein the third chromatography column is a subsequent cation exchange chromatography column.17. The method of claim 15 , wherein the fourth chromatography column is a gel filtration chromatography column.18. The method of claim 13 , wherein step (a) further comprises contacting the clarified culture with a first buffer on the anion exchange chromatography column.19. The method of claim 18 , wherein the first buffer is phosphate buffer.20. The method of claim 18 , wherein the first buffer has a pH of about 6.5.21. The method of claim 13 , ...

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03-07-2014 дата публикации

GRAFT COPOLYMER FOR CATION-EXCHANGE CHROMATOGRAPHY

Номер: US20140183136A1
Автор: GRAALFS Heiner

The invention relates to chromatographic separating materials having improved binding capacity for biological constituents in cell culture supernatants, or animal or human body fluids, in particular for monoclonal antibodies. The present invention likewise relates to the preparation of separating materials of this type, and to the use thereof, in particular for the removal of charged biopolymers from corresponding liquids. 1. Separating materials for ion exchange chromatography based on hydroxyl-containing base supports , to the surfaces of which copolymers are covalently bonded , whereina) the base support contains aliphatic hydroxyl groups,b) the covalently bonded copolymers are bonded to the support via a terminal monomer unit,c) the copolymers comprise at least two different monomer unitsd) the monomer units are linked in a linear manner,e) the copolymer comprises at least one monomer unit which carries a negative charge in the form of a sulfonic acid or carboxylic acid and in addition contains ester or amide groups and alkyl and/or alkylene groups and in total a maximum of 8 C atoms, but no aryl groups, orwhich carries a negative charge in the form of a sulfonic acid or carboxylic acid and in addition contains alkyl and/or alkylene groups, but no aryl groups,f) the copolymer comprises at least one monomer unit which carries, as hydrophobic group, a straight-chain or branched alkyl having 4 to 18 C atoms or corresponding aryl groups and contains ester or amide groups, andg) the ratio of the monomer units having a negative charge to the monomer units containing a hydrophobic group is in a range between 99:1 to 10:90.5. Separating material according to claim 1 , whereina) the copolymer comprises 2-acrylamido-2-methylpropanesulfonic acid or/and 2-acrylamidoethanesulfonic acid as monomer unit having a negative charge,b) the ratio of the monomer units having a negative charge to the monomer units containing a hydrophobic phenyl, benzyl or phenylethyl group is in a ...

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19-04-2018 дата публикации

LIQUID TREATMENT APPARATUS WITH REPLACEABLE TREATMENT CARTRIDGE AND CARTRIDGE CONNECTION SYSTEM

Номер: US20180104627A1
Автор: ZÖLLER Jochen
Принадлежит:

A device for forming a liquid treatment apparatus includes a main part; and a receiving part including a cavity for receiving a connecting head of a replaceable liquid treatment cartridge having at least one port in liquid communication with an interior of the liquid treatment cartridge such that the at least one port(s) of the connecting head are in sealed liquid communication with corresponding ports of the receiving part. The receiving part is journalled for movement between a first and a second position with respect to the main part whilst the connecting head is inserted in the cavity. The head is insertable into and retractable from the cavity in the first position. The liquid treatment cartridge is lockable to the device by at least moving the receiving part with the inserted connecting head into the second position. 1. Device for forming a liquid treatment apparatus , including:a main part; and{'b': 6', '6, 'a receiving part (; ′) including a cavity for receiving a connecting head of a replaceable liquid treatment cartridge having at least one port in liquid communication with an interior of the liquid treatment cartridge such that the at least one port(s) of the connecting head are in sealed liquid communication with corresponding ports of the receiving part,'}wherein the receiving part is journalled for movement between a first and a second position with respect to the main part whilst the connecting head is inserted in the cavity,wherein the connecting head is insertable into and re-tractable from the cavity in the first position,wherein the liquid treatment cartridge is lockable to the device by at least moving the receiving part with the inserted connecting head into the second position, andwherein the movement includes a component corresponding to an intrinsic rotation in a plane parallel to a direction of insertion,characterised in thatthe movement further includes at least a component corresponding to a displacement of the receiving part relative to ...

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20-04-2017 дата публикации

ION EXCHANGE CHROMATOGRAPHY WITH IMPROVED SELECTIVITY FOR THE SEPARATION OF POLYPEPTIDE MONOMERS, AGGREGATES AND FRAGMENTS BY MODULATION OF THE MOBILE PHASE

Номер: US20170107249A1
Автор: NEUMANN SEBASTIAN
Принадлежит: Hoffmann-La Roche Inc.

Herein is reported a method for producing a polypeptide in monomeric form comprising the following step: recovering the polypeptide in monomeric form from an ion exchange chromatography material by applying a solution comprising a non-ionic polymer and an additive. 19.-. (canceled)10. A method for producing an antibody of the IgG class in monomeric form comprising the following steps:applying a first solution that optionally comprises poly (ethylene glycol) and glycine to a cation exchange chromatographic material thereby equilibrating the material,applying the solution comprising the antibody of the IgG class to the equilibrated chromatography material and thereby loading the chromatography material,producing the antibody of the IgG class in monomeric form by applying a solution to the chromatographic material comprising poly (ethylene glycol) and glycine, and thereby desorbing/eluting the antibody of the IgG class in monomeric form from the chromatographic material,whereby the poly (ethylene glycol) polymer has a concentration of about 0% to about 10% by weight.11. A method for producing an antibody of the IgG class preparation with reduced host cell protein content comprising the following steps:applying a first solution that optionally comprises poly (ethylene glycol) and glycine to a cation exchange chromatographic material and thereby equilibrating the material,applying the solution comprising the antibody of the IgG class to the equilibrated chromatography material and thereby loading the chromatography material,producing the antibody of the IgG class with reduced host cell protein content by applying a solution to the chromatographic material comprising poly (ethylene glycol) and glycine and thereby desorbing/eluting the antibody of the IgG class from the chromatographic material,whereby the poly (ethylene glycol) has a concentration of about 0% to about 10% by weight.12. The method of claim 10 , wherein the poly (ethylene glycol) has a concentration of ...

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02-04-2020 дата публикации

METHOD AND APPARATUS FOR CHROMATOGRAPHIC PURIFICATION

Номер: US20200101399A1
Автор: Skudas Romas
Принадлежит: Merck Patent GmBH

A method and an apparatus suitable for a continuous chromatography process which only needs three separation columns, and a two-step process containing two chromatographic steps, in which the first chromatographic step (capture) is performed alternating and sequentially on two separation columns, the second chromatographic step (polishing) is performed, also sequentially, on the third column. 1. An apparatus comprising{'b': 1', '2', '1', '2', '1', '2, 'two separation units A and A both having the same chromatography matrix and a separation unit B having a chromatography matrix which differs from the chromatography matrix of separation units A and A, all separation units having a fluid inlet and a fluid outlet, whereby there is at least fluid connection between the fluid outlet of separation unit A and the fluid inlet of separation unit B and fluid connection between the fluid outlet of separation unit A and the fluid inlet of separation unit B'}{'b': 1', '2', '1', '2, 'at least one valve in the fluid connection between separation units A and A and separation unit B that allows to switch between fluid communication between the outlet of separation unit A and the fluid inlet of separation unit B and fluid communication between the outlet of separation unit A and the fluid inlet of separation unit B,'}at least two buffer reservoirs and at least two pumps{'b': 1', '2, 'a reservoir containing sample solution that is in fluid connection with the inlets of separation units A and A'}212. Apparatus according to claim 1 , characterized in that the separation units A and A have an affinity chromatography claim 1 , a cation exchange claim 1 , a mixed mode cation exchange or an anion exchange chromatography matrix.3. Apparatus according to claim 1 , characterized in that the separation unit B has a cation exchange claim 1 , a mixed mode anion exchange or an anion exchange chromatography matrix.412. Apparatus according to claim 1 , characterized in that the separation units A and ...

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29-04-2021 дата публикации

METHODS OF PRODUCING ANTI-C5 ANTIBODIES

Номер: US20210122806A1
Принадлежит:

The present application relates to a method of producing an anti-C5 antibody (ravulizumab). wherein the method comprises: —culturing mammalian cells comprising a nucleic acid encoding the anti-C5 antibody in a cell culture production medium—Performing two or more steps selected from the group consisting of: a recovery step; purification by Protein A affinity chromatography, a low pH viral inactivation step; Purification by cation exchange chromatography; Purification by anion exchange chromatography; a virus reduction filtration step; and a concentration and diafiltration step 2. A method of producing an anti-C5 antibody , wherein the method comprises:a. culturing mammalian cells comprising a nucleic acid encoding the anti-C5 antibody in a cell culture production medium, such that the anti-C5 antibody is produced in said cell culture production medium;b. a recovery step;c. purification by Protein A affinity chromatography;d. a low pH viral inactivation step;e. purification by cation exchange chromatography;f. purification by anion exchange chromatography;g. a virus reduction filtration step; andh. a concentration and diafiltration step.3. The method of or , wherein the anti-C5 antibody:(a) comprises the heavy chain variable region set forth in SEQ ID NO:12 and the light chain variable region set forth in SEQ ID NO:8;(b) comprises a heavy chain constant region set forth in SEQ ID NO:13;(c) comprises a heavy chain polypeptide comprising the amino acid sequence set forth in SEQ ID NO:14 and a light chain polypeptide comprising the amino acid sequence set forth in SEQ ID NO:11;(d) binds to human C5 at pH 7.4 and 25° C. with an affinity dissociation constant (KD) that is in the range 0.1 nM≤KD≤1 nM;(e) binds to human C5 at pH 6.0 and 25° C. with a KD≥10 nM; and/or(f) is ravulizumab.48-. (canceled)9. The method of or , wherein the recovery step comprises filtering cell culture production medium through a depth filter.10. The method of claim 9 , wherein the depth filter is ...

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20-04-2017 дата публикации

MASS SPECTROMETRY METHOD FOR ORGANIC ACID, ANALYTICAL COLUMN AND ANALYTICAL DEVICE

Номер: US20170108474A1
Принадлежит: SHOWA DENKO K.K.

A mass spectrometry method by a liquid chromatograph-mass spectrometer that can detect an organic acid with high sensitivity by retaining, separating and eluting the organic acid without adding any nonvolatile substance to a mobile phase and without receiving any restriction of a ratio of a water-soluble organic solvent, and an analytical column are provided. The mass spectrometry method is a mass spectrometry method for an organic acid by a liquid chromatograph-mass spectrometer, wherein a column packed with a hydrophilic polymer having an anion-exchange group is used, and as a mobile phase, a water-soluble organic solvent-water mixed solution is used. The analytical column is a column for liquid chromatography for an organic acid, in which a polyether ether ketone (PEEK) resin housing for liquid chromatography is packed with a hydrophilic polymer having an anion-exchange group. 1. A mass spectrometry method for an organic acid by liquid chromatography-mass spectrometry using a liquid chromatograph-mass spectrometer , wherein a column using , as a packing material , a hydrophilic polymer having an anion-exchange group is used , and as a mobile phase , a water-soluble organic solvent-water mixed solution is used.2. The mass spectrometry method for an organic acid as claimed in claim 1 , wherein a base material of the hydrophilic polymer having an anion-exchange group is polyvinyl alcohol.3. The mass spectrometry method for an organic acid as claimed in claim 1 , wherein the anion-exchange group of the hydrophilic polymer having an anion-exchange group is a quaternary ammonium group claim 1 , and the content of the quaternary ammonium group is 0.01 to 0.1 meq based on 1 g of the hydrophilic polymer.4. The mass spectrometry method for an organic acid as claimed in claim 1 , wherein the water-soluble organic solvent-water mixed solution is a solution containing the water-soluble organic solvent in an amount of 50 to 95% in terms of volume ratio.5. The mass spectrometry ...

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02-04-2020 дата публикации

ULTRACLEAN AUTOSAMPLER WITH SYRINGE DELIVERY FOR MASS SPECTROMETRY

Номер: US20200103077A1
Принадлежит:

A system can include a valve assembly including a first valve and a second valve in fluid communication with the first valve. The valve assembly can be configured to deliver one or more of a sample, a chemical (e.g., an acid, a base, an organic chemical, etc.), and a standard via flow of a working fluid facilitated by one or more syringe pumps. Further, the one or more of the sample, the chemical, and the standard can maintain a physical separation from the one or more syringe pumps during delivery of the one or more of the sample, the chemical, and the standard. 120.-. (canceled)21. A system comprising:a first valve switchable between a first operating position and a second operating position;a first fluid holding line coupled to the first valve;a second fluid holding line coupled to the first valve;a second valve in fluid communication with the first valve, the second valve switchable between a first operating position and a second operating position;a first fluid line coupled between the first valve and the second valve;a second fluid line coupled between first valve and the second valve; anda plurality of syringe pumps including at least a first syringe pump and a second syringe pump,wherein the first syringe pump is in fluid communication with the first fluid holding line when each of the first valve and the second valve is in the second operating position, the first syringe pump is not in fluid communication with the first fluid holding line when the first valve is in the first operating position, the second syringe pump is in fluid communication with the second fluid holding line when each of the first valve and the second valve is in the second operating position, and the second syringe pump is not in fluid communication with the second fluid holding line when the first valve is in the first operating position, andwherein each of the first syringe pump and the second syringe pump is in fluid communication with a source of working fluid when the second valve ...

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10-07-2014 дата публикации

CHROMATOGRAPHIC MEDIA

Номер: US20140194543A1
Принадлежит:

This invention concerns the preparation and use of novel polymeric chromatographic media and preferably mixed mode polymeric chromatographic media. In accordance with the present invention, polymeric media is prepared using polymeric particles derivatized with polyethyleneimine, and preferably such polyethyleneimine derivatized polymeric particles further functionalized with appropriate reactants. The polymeric chromatographic media is especially useful for bioseparations. 1. Chromatographic media comprising polymeric resin particles derivatized with polyethyleneimine on the surface of the polymer.2. Chromatographic media according to wherein the polymeric particles comprise polymers selected from the group consisting of cellulose claim 1 , agarose claim 1 , epoxidized or halogenated polystyrenes claim 1 , epoxidized or halogenated polyacrylates or polymethacrylates claim 1 , and epoxidized or halogenated polydivinylbenzenes.3. Chromatographic media according to wherein the polymeric particles comprise polymers selected from the group consisting of epoxidized or halogenated polystyrenes claim 2 , epoxidized or halogenated polyacrylates or polymethacrylates claim 2 , and epoxidized or halogenated polydivinylbenzenes.4. Chromatographic media according to wherein the polymeric resin particles derivatized with polyethyleneimine on the surface of the polymer are functionalized by reaction of a functionalization reagent with terminal amino groups of the polyethyneneimine on the surface of the polymeric resin.5. Chromatographic media according to wherein the polymeric resin particles derivatized with polyethyleneimine on the surface of the polymer are functionalized by reaction of a functionalization reagent with terminal amino groups of the polyethyneneimine on the surface of the polymeric resin.6. Chromatographic media according to wherein the functionalization agent is selected from the group consisting of: acid anhydrides claim 4 , sulfonation agents claim 4 , alkyl ...

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02-04-2020 дата публикации

Highly sensitive emitter for strontium isotope analysis of picogram-level samples by thermal ionization mass spectrometry

Номер: US20200105514A1
Автор: Li Chaofeng
Принадлежит:

A method for strontium isotope analysis of picogram-level samples using highly sensitive silicotungstic acid emitter is presented by a thermal ionization mass spectrometry. The emitter has merits of extremely high sensitivity, low cost, simple operation, etc. It is an important innovation of the strontium isotope analysis of the picogram-level samples. Compared with a sample consumption of 1-50 ng of conventional emitter, the present invention only needs 30-200 pg to obtain satisfying measurement accuracy. The present invention greatly improves test sensitivity, and has broad application prospects in future. 1. A method for strontium isotope analysis of a picogram-level sample , comprising a step of: using silicotungstic acid and phosphoric acid as a highly sensitive emitter for a thermal ionization mass spectrometry.2. The method claim 1 , as recited in claim 1 , specifically comprising steps of:I) loading the phosphoric acid onto a Re filament with high purity; after the phosphoric acid is evaporated to dryness, loading a silicotungstic acid emitter onto the Re filament with the high-purity; after the silicotungstic acid emitter is evaporated to dryness, loading the sample onto the Re filament and evaporating to dryness; increasing a filament current until the Re filament turns dark red for 4-6 seconds, then tuning the filament current to zero; andII) measuring the sample by the thermal ionization mass spectrometer.3. The method claim 1 , as recited in claim 1 , wherein a method for preparing and purifying the silicotungstic acid comprises steps of:1) weighing silicotungstic acid powder into a Teflon® vial, and adding high-purity water to dissolve the silicotungstic acid powder;2) prewashing an AG50W-X12 cation resin column with 30 mL 6M hydrochloric acid and 20 mL deionized water in turn; and{'sup': '87', '3) passing silicotungstic acid solution through the AG50 cation resin column containing 1.5 mL of AG50W-X12 resin; wherein a trace amount of strontium and ...

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