Abstract: Methods for treating and/or protecting against acute liver failure and other hepatotoxicities in an individual employ a combination of a first active agent comprising N-acetylcysteine and a second active agent comprising a manganese complex selected from the group consisting of (i) a calcium manganese mixed metal complex of N,N?-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N?-diacetic acid (DPDP) having a molar ratio of calcium to manganese in a range of from 1 to 10, or a pharmaceutically acceptable salt thereof, (ii) a mixture of manganese DPDP (MnDPDP), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing DPDP compound, or (iii) a mixture of manganese pyridoxyl ethylenediamine (MnPLED), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing pyridoxyl ethylenediamine (PLED) compound.

Abstract: Methods, formulations and kits for treating and/or protecting against acute liver failure and other hepatotoxicities in an individual employ a combination of a first active agent which replenishes, or decreases a loss of, functional glutathione in the individual, and a second active agent comprising a manganese complex selected from the group consisting of (i) a calcium manganese mixed metal complex of N,N?-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N?-diacetic acid (DPDP) having a molar ratio of calcium to manganese in a range of from 1 to 10, or a pharmaceutically acceptable salt thereof, (ii) a mixture of manganese DPDP (MnDPDP), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing DPDP compound, or (iii) a mixture of manganese pyridoxyl ethylenediamine (MnPLED), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing pyridoxyl ethylenediamine (PLED) compound.

Abstract: Methods, formulations and kits for treating and/or protecting against acute liver failure and other hepatotoxicities in an individual employ a combination of a first active agent which replenishes, or decreases a loss of, functional glutathione in the individual, and a second active agent comprising a manganese complex selected from the group consisting of (i) a calcium manganese mixed metal complex of N,N?-bis-(pyridoxal-5-phosphate)-ethylenediamine-N,N?-diacetic acid (DPDP) having a molar ratio of calcium to manganese in a range of from 1 to 10, or a pharmaceutically acceptable salt thereof, (ii) a mixture of manganese DPDP (MnDPDP), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing DPDP compound, or (iii) a mixture of manganese pyridoxyl ethylenediamine (MnPLED), or a pharmaceutically acceptable salt thereof, and a non-manganese-containing pyridoxyl ethylenediamine (PLED) compound.

Abstract: The invention relates to a system and method for the stable storage of sensitive biological or chemical target substance, in a bound form on certain capture media. The method comprised providing a sample containing the target substance in a suitable buffer; combining the sample with a capture media to effect reversible binding of the target substance to the capture media; and storing the capture media with the target substance at between about ?20 and 20° C.; and recovering the target substance from the capture media. The target substance recovered maintains the desired activity. Also provides are methods for reducing aggregates in the sensitive biological or chemical target substance.

Abstract: There is a recognized need for novel, more simplified, approaches to isolation of plasma from whole blood, as well as a need to isolate cell-free plasma fractions containing different plasma proteins. Methods are divulged for use of aqueous phase systems, formed in blood or blood containing solutions via addition of a single polymer at relatively low concentration, to effect isolation (clarification) of plasma proteins from blood cells. Methods are also divulged to replace widely used Cohn-type plasma protein fractionation which is based on sequential addition of up to 40% (v/v) ethanol and other precipitants, with simple sequential addition of a polyacid. The latter results in isolation of plasma protein fractions (i.e. fibrinogen, immunoglobulin, albumin) in sequence similar to that obtained with Cohn Fractionation and therefore may be suitable for use to reduce solvent use and solvent-related process complications in existing plasma protein purification processes.

Abstract: The present invention relates to a process of enriching one target compound from a liquid, which process comprises at least one step of isolation performed by differentially partitioning between two aqueous phases. In the present invention the phases are formed by adding a thermally responsive, self-associating (i.e. clouding) hydrophilic polymer, and if needed some additional salts, to an aqueous biotechnical solution (such as a fermentation sample or bioseparation process stream) under thermal and other conditions where the solution separates into a one polymer, two-phase system with one phase enriched in the polymer. The target compound is to be found in the phase not enriched in the polymer, while a significant though varying percentage of contaminants may differentially partition to the phase interface or the polymer enriched phase.

Abstract: There is a recognized need for novel, more simplified, approaches to isolation of plasma from whole blood, as well as a need to isolate cell-free plasma fractions containing different plasma proteins. Methods are divulged for use of aqueous phase systems, formed in blood or blood containing solutions via addition of a single polymer at relatively low concentration, to effect isolation (clarification) of plasma proteins from blood cells. Methods are also divulged to replace widely used Cohn-type plasma protein fractionation which is based on sequential addition of up to 40% (v/v) ethanol and other precipitants, with simple sequential addition of a polyacid. The latter results in isolation of plasma protein fractions (i.e. fibrinogen, immunoglobulin, albumin) in sequence similar to that obtained with Cohn Fractionation and therefore may be suitable for use to reduce solvent use and solvent-related process complications in existing plasma protein purification processes.

Abstract: The invention relates to a system and method for the stable storage of sensitive biological or chemical target substance, in a bound form on certain capture media. The method comprised providing a sample containing the target substance in a suitable buffer; combining the sample with a capture media to effect reversible binding of the target substance to the capture media; and storing the capture media with the target substance at between about ?20 and 20° C.; and recovering the target substance from the capture media. The target substance recovered maintains the desired activity. Also provides are methods for reducing aggregates in the sensitive biological or chemical target substance.

Abstract: The present invention relates to a liquid mixture comprising a first polymer, which is a poly(acid), a second polymer, which is a poly(ether), and at least one salt, wherein the molecular weight of the poly(acid) is in the range of 1000-100,000 Da. The second polymer is selected to be capable of forming immiscible aqueous phases in the presence of the poly(acid) and salt. The poly(acid) may be selected from the group consisting of poly(acrylic acid) and poly(methacrylic acid), and the second synthetic polymer may comprise ethylene oxide. The invention may be used for separation of biomolecules, cells or particles.

Abstract: The present invention relates to a method for cell expansion. In the method, preferably a cell culture product is used, such as a microcarrier, or other adherent cell culture surface, comprising degradable polysaccharide, preferably starch, modified with small molecular weight cell-binding ligands. This allows recovery (detachment) of adhered cells to be aided by degradation of the culture surface with enzymatic agents, such as amylase. The method for cell expansion comprises the following steps: a) adding cells, culture medium and cell culture surface comprising a degradable polysaccharide with guanidine group containing ligands to a bioreactor; b) expanding said cells by adherent cell culture; and c) aiding the detachment of said cells by exposing them to a polysaccharidase to degrade the culturing surface.

Abstract: The present invention relates to liquid clarification. More closely, the invention relates to beverage clarification, such as reduction of colloidal (not microbial) haze-causing substances in beer or related beverages such as wine, juices, flavorings etc. The method of the invention uses a hydrophilic surface for adsorption of haze-forming substances by hydrogen bonding interaction properties between the surface and the haze-forming substances.

Abstract: The present invention relates to methods of isolating biomolecules. More particularly, the invention relates to methods for isolating antibodies (mAbs) and related proteins including antibody fragments (Fabs) under conditions where they are positive and relatively hydrophobic and will react with negatively charged polymer to form polymer-protein complexes which precipitate. The isolation can be accomplished using inexpensive and biocompatible negatively charged polymers such as polyacrylic acid or carboxymethyldextran polymers of various molecular weights as precipitant. It occurs at relatively high concentrations of polymer (e.g. 10%) and high salt concentration (>50 mM) and conductivity (e.g. >10 mS/cm) over wide range of pH.

Abstract: The present invention relates to a process of enriching one target compound from a liquid, which process comprises at least one step of isolation performed by differentially partitioning between two aqueous phases. In the present invention the phases are formed by adding a thermally responsive, self-associating (i.e. clouding) hydrophilic polymer, and if needed some additional salts, to an aqueous biotechnical solution (such as a fermentation sample or bioseparation process stream) under thermal and other conditions where the solution separates into a one polymer, two-phase system with one phase enriched in the polymer. The target compound is to be found in the phase not enriched in the polymer, while a significant though varying percentage of contaminants may differentially partition to the phase interface or the polymer enriched phase.

Abstract: The present invention relates to a method of isolating at least one plasmid from other components of a liquid, which method comprises the steps of providing a separation matrix comprised of one or more porous carriers, which carrier(s) present anion exchange groups on external surfaces as well as pore surfaces and a pore size distribution that does not allow access of plasmids to pore surfaces; contacting said matrix with the liquid to allow adsorption of the plasmids to ligands present on the separation matrix; contacting an eluent with the separation matrix to release the plasmids and recovering plasmids from a fraction of said eluent. Thus, the present method allows the plasmids to adsorb to the external surfaces of the matrix, while other components such as RNA is adsorbed onto the pore surfaces. In one embodiment, the matrix presents a DNA exclusion limit of at least about 270 base pairs; such as at least about 1,000 base pairs.

Abstract: The present invention relates to a separation matrix comprised of a support to the surfaces of which polymer chains have been coupled, wherein each polymer chain presents recurring proton-donating groups and at least the surface of the support is substantially hydrophilic. In the most advantageous embodiment, the support is porous cross-linked agarose, the polymers are poly(acrylic acid) and the proton-donating groups are carboxyl groups. The matrix is useful e.g. to remove PEG from pegylated and/or native compounds in a liquid. Accordingly, the invention also encompasses a method, such as a chromatographic method, wherein the separation matrix according to the invention is used, for example as a pre-treatment of a reaction mixture that comprises unreacted PEG, pegylated proteins and native proteins.

Abstract: A microfluidic device comprising a set of one or more, preferably more than 5, covered microchannel structures manufactured in the surface of a planar substrate. The device is characterized in that a part surface of at least one of the microchannel structures has a coat exposing a non-ionic hydrophilic polymer. The non-ionic hydrophilic polymer is preferably attached covalently directly to the part surface or to a polymer skeleton that is attached to the surface.

Abstract: The present invention relates to liquid clarification and stabilization. More closely, the invention relates to both clarification by removal of suspended particles, as well as stabilization against formation of non-microbial haze via reduction of haze forming substances in various liquids. The haze forming substances are proteins and polyphenol tannins which occur in various plant related fluids such as beer wine, juices, flavorings, plant extracts, and even bioprocess streams. The method of the invention accomplishes both size based removal of colloidal non-haze related particles as well as adsorption based removal of haze forming substances without a need for added flocculants. The to method of the invention utilizes hydrophilic surfaces for adsorption of haze forming substances with such surfaces presented by materials arranged in manner so that size based exclusion of suspended particles is also achieved.

Abstract: The present invention relates to multifunctional protein production tags comprising at least 4, preferably 4-8 amino acids, for optimising expression of proteins and purification thereof by various multi-step processes including chromatographic or filtration, as well as batch unit operations. The tags include sequences of multiple defined purposes which are not generated in defined linear sequence regions related to one purpose but as integrated sequences often overlapping each other, i.e. the defined purposes are not discrete separate units on the tag but rather heterogeneously distributed in the tag. The invention also relates to an expression vector encoding the multipurpose tag and a method for protein purification, comprising expressing a protein in the expression vector and purifying the protein in several steps using functionalities of the multipurpose tag.

Abstract: The present invention relates to a liquid mixture comprising a first polymer, which is a poly(acid), a second polymer, which is a poly(ether), and at least one salt, wherein the molecular weight of the poly(acid) is in the range of 1000-100,000 Da. The second polymer is selected to be capable of forming immiscible aqueous phases in the presence of the poly(acid) and salt. The poly(acid) may be selected from the group consisting of poly(acrylic acid) and poly(methacrylic acid), and the second synthetic polymer may comprise ethylene oxide. The invention may be used for separation of biomolecules, cells or particles.

Abstract: The present invention relates to a process of isolating one or more target compounds, wherein the clarification of feed is performed using partitioning in a multiphase system comprising a first polymer, which is a synthetic poly(acid), a second synthetic polymer, which is a poly(ether), and at least one salt, which clarification is followed by at least one step of affinity chromatography. The molecular weight of the poly(acid) may be in the range of 1000-100,000 Da. The target compound is preferably a biomolecule, such as a monoclonal antibody.