Abstract: This granular material consists of a granular porous support bearing negative or positive charges, coated on its surface with a first layer of impregnation with a hydrophilic polymer bearing charges opposite to those of the support, the quantity of said charges present on said polymer being substantially equal to that of the charges present at the surface of the support; and another layer, bound to the first by irreversible chemical coupling, of another hydrophilic polymer which is functional, namely bearing groups endowing said functional hydrophilic polymer with a specific but reversible affinity for at least one biological substance. Among the applications of this material, there are mentioned the separation and purification of antithrombin III and coagulation factors (factors II, VII, VIII, IX, X), and separation of activated coagulation factors (activated factor II, activated factor IX, activated factor X) in solutions containing said non-activated factors.

Abstract: An affinity support having an improved capacity for binding target compounds. The support includes an immobilized modified ligand of increased molecular weight. The molecular weight of the ligand is increased via the action of condensation reagents or crosslinkers prior to immobilization. The affinity support is useful in affinity separations of proteins and other biomolecules from complex, biologically-derived fluids.

Abstract: A fusion protein that can function as a removable label is prepared containing a polypetide such as an enzyme and an amino acid sequence having a substrate binding region of a polysaccharidase such as cellulase that has essentially no polysaccharidase activity. By contacting the fusion protein with a .beta.-1,4 glycan matrix such as cellulose, the substrate binding region binds to the matrix to immobilize the polypeptide. The polypetide or fusion protein can be removed from the matrix with a protease capable of cleaving a specific protease cleavage site, or with a solution having a low ionic strength or a high pH. The fusion protein can be prepared by recombinant DNA technology.

Abstract: The present invention provides a process for immobilizing a protein or protein containing substance. The material to be immobilized is aggregated, contacted in a liquid with a hydrophilic solid phase and the solid phase, after contact has taken place, is dried. The present invention is also concerned with the solid phase prepared by this process and with the use thereof for analytical determination.

Abstract: The present invention relates to compositions of water dispersible and water soluble carbohydrate polymers and biologically active macromolecules of growth hormones, somatomedins, growth factors, and other biologically active fragments which are suitable for parenteral administration. The present invention also relates to a method for increasing and for maintaining increased levels of growth hormone in the blood of treated animals for extended periods of time, increasing weight gains in animals, and increasing milk production of lactating animals by the administration of the compositions of the invention.

Abstract: A modified solid carrier is used to covalently immobilize biomolecules such as proteins. The carrier is based on well-known matrix materials modified to have covalently bound functional groups of formula I ##STR1## that are suitable for covalent immobilization, where A is a spacer group; X is O, S, or NH and n is 0 or 1. The modified solid carrier is prepared by reacting ammonia with glycidyl groups of a carrier to form .alpha.-hydroxy-.beta.-amino groups, reacting these groups with 2,4,6-trichloro-s-triazine to form an N-triazinyl group-containing carrier, reacting this carrier with ammonia and reacting the resultant carrier with 2,4,6-trichloro-s-triazine.

Abstract: This invention relates to an improved cellulose chromatography support and, in particular, to substantially spherical, high density cellulose particles. This invention also relates to a method of making these spherical, high density cellulose particles and, in particular, to a method for forming spherical cellulose from a high molecular weight viscose in a stable emulsion of a liquid carrier and emulsifying agents.

Abstract: A process for covalently bonding biopolymer, such as protein, to an organic polymer surface coated with hydrophilic nonionic polymer having groups reactive with the biopolymer and having a cloud point in the reaction medium that is at least 5.degree. C. above the temperature at which the coated organic polymer surface is to be used, which comprises reacting biopolymer with the surface in an aqueous reaction medium, at a temperature not less than 5.degree. C. below the cloud point; but not above a temperature at which the biopolymer is deleteriously affected, and preferably not above about 100.degree. C., the product comprises a biopolymer immobilized on a hydrophilic solid surface having a nonionic polymer and a hydrophilic layer, coupled thereto via biopolymer-reactive groups of the nonionic polymer, and accordingly has low spontaneous adsorption of proteins and other biopolymers through electrostatic attraction and/or hydrophobic interaction.

Abstract: The invention relates to a method of binding biologically active organic ligands to hydroxyl groups of polymeric carriers. The method involves bringing 4-fluorobenzenesulfonyl Chloride into reactive contact with the hydroxyl groups of polymeric carriers in such a manner to form sulfonate groups in place of the hydroxyl groups. The ligand is then brought into reactive contact with the hydroxyl groups of polymeric carriers to replace the sulfonate groups reacted with the organic ligand. The polymeric carrier containing the bound ligand can be used to isolate a biologically active material from a heterogeneous solution.

Abstract: A fusion protein is prepared containing a polypeptide such as an enzyme and an amino acid sequence having a substrate binding region of a polysaccharidase such as cellulase that has essentially no polysaccharidase activity. By contacting the fusion protein with an affinity matrix containing a substrate such as cellulose for the cellulase substrate binding region, the substrate binding region binds to the affinity matrix to immobilize the polypeptide. The polypeptide can be purified by separating the fusion protein or polypeptide from the affinity matrix. The polypeptide can be separated by cleaving the protein with a Cellulomonas fimi protease.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: Methods for modifying polyhydroxylated materials by the direct covalent bonding of nucleophilic ligands to the former sites of hydroxyl groups on the material are disclosed. More specifically, methods for activating the surface of polyhydroxylated materials such as silica, which can serve as stationary phases in various chromatographic methods, are disclosed. The silica is first contacted with a reagent, e.g., a phosphorylating agent, effective to cleave the O--H bond of at least one of said hydroxyl groups and introduce through an --O-- linkage a moiety amenable to nucleophilic displacement; and the product of step (a) is then contacted with a suitable nucleophilic ligand.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: A process for surface modifying a variety of polymeric support surfaces is disclosed in which a predetermined modifying polymer is irreversibly absorbed onto essentially all the surfaces of the support polymer accessible to the modifying polymer. The modifying polymer is selected to impart the desired surface characteristics to the modified polymeric surface.

Abstract: A carrier fleece is prepared for use as reagent carrier from which reagents can be dissolved in as assay such as immunological analysis. The carrier fleece contains from 5 to 60% by weight of cellulose-containing fibers, from 40 to 95% by weight of polyester or polyamide polymer fibers or a combination thereof and from 5 to 30% by weight of the fibers of an organic binding agent which has a hydroxyl or an ester group or a combination thereof. In an immunological analysis, the carrier fleece is impregnated with an immunologically active agent such as a beta-galactosidase conjugate and then introduced into a solution of a sample containing an immunologically active substance to be analyzed. The immunologically active agent is eluted into the sample solution and the presence of the immunologically active substance in the sample is determined.

Abstract: Biological materials such as enzymes, proteins and peptides are encapsulated by forming a mixture of the material and an aqueous non-ionic polymer solution, spraying the mixture into a circulating water-immiscible nonsolvent for the polymer at a temperature sufficient to freeze the beads and drying the frozen beads to remove essentially all unbound water such as to provide a water content of about 1-2 weight percent. Suitable non-ionic polymers are poly(vinyl alcohol), polyvinylpyrollidone, dextran and derivatized cellulose. A densification agent such as alumina may be present in the polymer solution to enhance specific gravity of the beads formed. Encapsulated material such as microbes produced by this process provide useful agricultural agents which can be delivered to the market in a dormant state and suitable for delivery to soil or plant leaves. The beads can be applied dry, via a planting or an insecticide box, or wet via a spray nozzle.

Abstract: Thromboresistant materials are disclosed comprising hirudin or hirudin derivatives covalently linked to support materials such that the resultant composition has substantially the same biological activity as hirudin. Methods for making such compositions are also disclosed.

Abstract: Homogeneous cyclophilin, a soluble binding protein, having a specific binding activity of above 50 ug cyclosporin A per mg protein and a molecular weight of about 17,600 daltons, reversibly binds immunosuppressants or antibodies thereto such as cyclosporin or anti-cyclophilin. It is isolated from the cytosol of several different mammalian tissues and can be used in various diagnostic and purifications procedures.

Abstract: The present invention provides a process for the production of a polysaccharide matrix to which haptens are covalently bound, wherein polysaccharide-containing material is rendered alkaline, dried to a water content of less than 5% and then reacted in an anhydrous medium with a hapten containing at least one activated functional group.The present invention also provides a device for carrying out this process, which comprises a winding core (3) in a container (1) for a reaction solution which has a tube (11), provided on its wall with a plurality of openings (7) and closed on one end (9), for the reception of a winding (13) of the material to be treated and two axial end walls (15, 17) for sealing off the axial ends of the winding (13) and feeds the reaction solution from the container (1) into the other end (21) of the tube (11) by means of a circulating pump cycle (19).

Abstract: Compositions and devices are provided for the specific removal of components of plasma in efficient and economical ways. The devices provide for a tortuous path of the plasma through a high surface material to which is bound a binding compound for removal of the fluid component. The devices find particular application with plasma, in diagnosis, therapy, and for production of specific physiologically active materials.

Abstract: A composite containing DEAE-cellulose agglomerated with a hydrophobic polymer is treated with tap water, deionized water or a dilute salt solution at a temperature of at least 60.degree. C. for a time sufficient to increase adsorption capacity for charged macromolecules by at least about 30%. Treatment is preferably at a temperature of about 80.degree. to about 100.degree. C. for a time period of about one-half hour to about 5 hours. The macromolecule is preferably a protein such as the enzyme, glucose isomerase.

Abstract: Disclosed herein are a novel group of compounds, termed Recognins, and particularly Recognin M and Recognin L produced, respectively, from artificial mammary and lymphoma cancer cells. The Recognins are useful for diagnostic purposes.

Abstract: A solution of an active protein substance and an inactive protein substance is reacted with a cross-linking agent, optionally in the presence of an inert carrier, under cross-linking conditions to produce articles comprising both active and inactive protein substances. The active protein substance comprises up to about 20 percent, e.g. from 1 to 20 percent by weight, based on the final weight of the total protein substance, whereas the cross-linking agent comprises from 0.5 to 8 percent by weight, based on the weight of the total treated mixture. The obtained articles are in the form of a solution or a suspension in aqueous medium, in the form of a film, in the form of a membrane, in the form of a fabric, in the form of a porous material, or in the form of a mass, such as granules, pills or tablets.

Abstract: The present invention involves a method for producing a substrate useful in a system for the detection of antibodies directed against platelet antigens. This method comprises several steps. A platelet sample of interest is initially treated with an aqueous solution comprising a dialyzable nonionic detergent. This initial treatment is under conditions to solubilize platelet components and produce a platelet lysate. Such conditions may involve treatment of a platelet sample with an aqueous solution comprising nonionic detergent at a concentration between about 0.2% and about 0.5%. Platelet antigens are most preferably solubilized for about 30 min and at about 0.degree. C. in an aqueous solution comprising about 1 mg dialyzable nonionic detergent per mg platelet protein.The partially purified platelet antigens resulting from these manipulations are then preferably affixed to a solid matrix.

Abstract: A regenerable support matrix useful for immobilization of biologically active materials is prepared by coating a core support with a cellulose ester, removing ester groups by hydrolysis to produce hydroxyl groups and converting the hydroxyl groups to dialkylaminoalkyl ether groups. The support matrix can immobilize biologically active proteinaceous materials with a net negative charge by adsorption. The support matrix is readily regenerated when an immobilized biologically active material becomes inactive by washing the support with a base or salt solution and adsorbing additional biologically active material to the support. Multiple cycles of immobilization and regeneration are possible without significant deleterious affects.

Abstract: Methods and materials are described for the preparation of novel immobilized membrane compositions. The described compositions are useful for evaluating membrane association charcteristics of chemical compounds, and as a chromatographic support material for separation/purification of biomolecules and particularly those expressed by genetically transformed cells as novel hybrid proteins having covalently bound membrane-binding peptides. Novel phospholipid carboxylates are useful intermediates for the preparation of chromatography supports having surfaces formed as covalently bound artificial membranes which simulate natural cellular membranes. The immobilized membrane compositions are adapted for use in chromatographic systems to study interactions of biologically active substances with membranes in vitro.

Abstract: A polysaccharide derivative having the structure Sacch--O--Z--Ar--CH.dbd.N--Y or ##STR1## where Sacch--O-- represents a polysaccharide molecule; Z is --(CH.sub.2).sub.n -- or ##STR2## Ar is a divalent aromatic group; Y is (a) a monovalent group derived from a water-soluble substituted or unsubstituted aromatic compound containing only one free primary amine group, or (b) a monovalent group derived from a water-soluble substituted or unsubstituted aliphatic or cycloaliphatic compound containing only one primary amine group, or (c) a multivalent group derived from a water-soluble protein containing more than one primary amine group; n is one or greater; and m is zero or greater, is prepared by first modifying the polysaccharide with a reagent to introduce free aromatic aldehyde groups and then reacting with a suitable amine-containing reagent. The siloxane-containing starch derivatives are useful in glass forming size compositions.

Abstract: A membrane mimetic structure having a hydrophilic outer portion and a hydrophobic inner portion is covalently bound to a surface having reactive functional groups. The membrane mimetic structure consists essentially of adjacent amphiphilic molecules independently covalently bound to the surface. The structures can be applied to surfaces and should find application in a wide variety of disciplines requiring surfaces exhibiting properties of biological membranes.

Abstract: A component for the rapid detection of anti-Treponema pallidum antibodies adapted for use as a selective foundation material in standard immunoassays is provided. The component comprises a quantity of fibronectin insolubilized to a solid matrix. The fibronectin component provides a foundation material for the selective binding of antigenic outer membrane proteins extracted from Treponema pallidum. Incorporation of the insolubilized fibronectin component bound to the antigenic outer membrane proteins extracted from Treponema pallidum into a standard immunoassay test pack provides an immunological assay for the presence of respective complementary anti-Treponema pallidum antibody in a biological sample.

Abstract: A biological composition comprises a solid phase support matrix or marker molecule bound to protein, typically a glycoprotein such as an immunoglobulin through a linking group, spacer arm, and hydrazone group. The linking group is conveniently an ether linkage, while the spacer arm is a linear chain including six atoms, where at least one of the atoms is a tertiary amine which is protonated at a pH below about 8. The hydrazone is formed by reacting the solid phase or marker molecule having the linking arm and the spacer arm including a terminal hydrazide group with a glycoprotein oxidized to include a terminal aldehyde group. Immunological reagents prepared by linking an immunoglobulin (IgG) through a carbohydrate on the Fc or hinge regions have been found to provide very high binding capacity approaching the theoretical bivalent limit of two moles of bound antigen for every mole of bound immunoglobulin.

Abstract: The invention relates to compositions comprising adducts of activated polysaccharides with biologically active growth hormones, somatomedins, growth factors and biologically active fragments. The invention also relates to a method for increasing and maintaining increased levels of these biologically active molecules in the blood of treated animals for extended periods of time, increasing weight gains in animals, and increasing milk production of lactating animals by the administration of a composition of the invention.

Abstract: The invention relates to a new method of immunological analysis for serum amyloid A protein (SAA) and serum amyloid P-component (SAP), kits therefor and a method of purification of SAA and SAP. These methods are based on the efficient binding of SAP to a plastic surface and to carriers bearing nitrated phenyl groups in the presence of calcium and related bivalent ions, and of SAA to a plastic surface and to carriers bearing nitrated phenyl groups with or without calcium ions. The method of immunological analysis allows for rapid and reliable screening of serum samples with a high sensitivity. SAA and SAP play a key role in the diagnosis and management of inflammatory diseases.

Abstract: A novel process for the isolation and purification of vancomycin class antibiotics which utilized affinity chromatography by the formation of a sorption complex between the antibiotic and an immobilizing ligand selected from -D-alanyl-D-alanine or -X-D-alanyl-D-alanine, wherein X is an amino acid radical and the novel affinity chromatography sorbent employed therein are disclosed.

Abstract: A support composition based on triazine derivatives is prepared having high binding capacity. The support composition contains a polymer compound having no triazine groups, a polymer compound with 4,6-dihalogen-1,3,5-triazine groups, a 2,4,6-trihalogen-1,3,5-triazine filler component and an alkali metal halogenide filler component. The support is useful in molecular biology particularly for the fixing of biomacromolecules and for clinical and analytical detection of immunologically significant factors or organic or inorganic components of liquids.

Abstract: A product, Astrocytin, derived from brain cancer cells growing in vivo, and the method of preparing same. Astrocytin may be complexed with an inert carrier, such as bromoacetyl cellulose, and employed in tests for brain tumors. The antibody to Astrocytin is also prepared. A complex of Astrocytin and an inert carrier may be further complexed to anti-Astrocytin.