Abstract: A lyophilized fibrinogen is produced which is subjected to a severe terminal virucidal heat treatment in order to inactivate viruses present, while retaining desirable biological properties. In particular the lyophilized fibrinogen has a solubility in water or other aqueous solution to 40 g/l in less than 20 minutes at 20.degree. C., and a clotting time of less than 10 seconds when exposed to at least 200 U/ml thrombin. The product may be heat treated at 80.degree. C. for 72 hours up to 100.degree. C. for 10 hours depending on formulation and water content. In the production process cryoprecipitate is washed with polyethylene glycol solution at 4 to 10.degree. C. and pH 6.8 to 8 at low ionic strength, prior to two-stage freeze drying.

Abstract: Enhanced production of cryoprecipitate is produced by dehydrating an individual unit of plasma prior to a low temperature step used to produce cryoprecipitate. This dehydration is accomplished either by placing a water absorbing material within a blood bag so that plasma occupying the bag will become dehydrated or by placing the water absorbing material within a cartridge so that plasma becomes dehydrated upon flowing through the cartridge. The preferred water-absorbing material is a cross-linked chromatographic gel having pores too small to admit clotting proteins, but large enough to admit water molecules. Suitable gels are made from carbohydrates or polyacrylamide. Carbohydrate gels such as Sephadex.RTM., produced by Pharmacia-Upjohn, are particularly preferred in the present invention.

Abstract: A method of adsorbing from a solution comprising a biological sample viruses which retain their viability and infectivity. The method comprises adjusting the pH of said solution to pH 6.0 to 8.0; adding an effective amount of a water insoluble cross-linked polycarboxylic acid polymer ("WCPP") into said solution in a volume:volume ratio of WCPP to solution of 100:1 to 1:10,000 to form a WCPP-solution mixture; incubating said WCPP-solution mixture for a time sufficient to immobilize said viruses on said WCPP forming a WCPP-virus matrix; and separating said matrix from said solution. This novel method is suitable for removing, purifying, recovering and analyzing viable viruses as well as viral components such as viral proteins and nucleic acids.

Abstract: A process for the microbial production of a protein susceptible to inactivation in a fluid production medium by continuously and reversibly protecting said protein against said inactivation during the production stage, separating the protein from the production medium, deprotecting the protein, and recovering the protein product. The process is especially useful for obtaining substantially increased yields of the protein in question by continuously precipitating said protein.

Abstract: A therapeutic composition effective on contact with thrombin at a site of treatment in a patient as a tissue adhesive, hemostat or sealant, said composition comprising non-autologous, non-single donor mammalian fibrinogen that is capable of polymerizing when provided in solution at said site at a concentration of about 30 mg/ml thereof or less, to a fibrin network having therapeutically effective strength, wherein said composition contains less than about 30% (w/w), based on total protein mass present therein, of proteins other than fibrinogen, and further comprises a sufficient amount of one or more low molecular weight physiologically-compatible solutes such that said composition, if formulated as a lyophilized material, can be reconstituted therefrom at room temperature in sterile water for injection in about 30 minutes or less, at about 25 mg/ml of said fibrinogen. Additionally, methods for producing and maintaining said composition, and methods for the use thereof.

Abstract: Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2.sub.1, C2, P1.

Abstract: A cytokine composition is prepared for use in immunotherapy of various diseases. The composition is prepared by culturing leucocytes previously infected with a virus in a culture medium containing a transal composition isolated from plasma and a complex of proteinase inhibitors composition isolated from plasma, separating leucocytes from the medium, removing impurities from the medium, and recovering a cytokine composition containing the transal composition and the complex of protease inhibitors composition. The transal composition contains transferrin, albumin and a 40 kDa protein and the complex of protease inhibitors composition contains .alpha..sub.2 -macroglobulin, a 160 kDa protein, an 80-60 kDa protein and a 20 kDa protein.

Abstract: The present invention is directed to a process for recovering the antibiotics produced by fermentation of Actinoplanes sp. ATCC 33076 or a producing mutant thereof, from a fermentation broth or a process stream, which comprises extraction of the antibiotics by a non-ionic surfactant or a cationic surfactant miscible with or dispersable in water and capable of dissolving the antibiotics, formation of two phases in the first of which the antibiotic and the surfactant are present together, and separation of the antibiotic from the surfactant by addition of suitable organic solvents.

Abstract: There is provided water insoluble cross-linked polyhydroxy polycarboxylic acid having at least two strands each having a strand skeleton of the formula: ##STR1## wherein one carbonyl group of at least one maleoyl moiety thereof in each strand is covalently linked to a--HN.[(H).sub.p (CH).sub.z.(OH).sub.m ].NH-- moietyto provide the presence therein of at least one cross linking moiety of the formula: ##STR2## wherein R is hydrogen or lower alkylene or lower alkoxy of 1-4 carbon atoms, or phenyl, z is an integer of 1-4, p is 0 or an integer up to z-1, m is 1 or an integer up to z, wherein the ratio of cross-links to poly (alkylene carbonic acid) strands is between about 1 and about 200 to 2. There is disclosed a method of making such polyhydroxy polycarboxylic acid as well as methods of utilizing same to remove proteins from aqueous media containing same to provide a matrix.

Abstract: A composition and method for separating red blood cells from whole blood comprising a rouleaux-forming aggregator and an enhancer for enhancing the settling rate. The enhancer is a material which alters directly or indirectly the properties of the red blood cell and may alter the structure and/or reactivity of the aggregator, without adversely affecting the morphology and function of white blood cells. In most instances, the red blood cell enhancers of the invention are osmotic agents. Such agents create a hypertonic solution while not entering the cells themselves. Preferably the enhancer is a salt of oxalic acid, a salt of malonic acid, mannitol or sucrose. Potassium oxalate is most preferred. High molecular weight substances which are large enough to form molecular bridges between red blood cells form the aggregators used in the invention.

Abstract: A method for recovering hepatitis B surface antigen protein from transformed yeast cells including the steps of (i) obtaining an aqueous homogenate of the yeast cells; (ii) enriching the hepatitis B surface antigen protein in the homogenate with a protein-aggregating reagent to form a precipitate which contains hepatitis B surface antigen protein; (iii) dissolving the precipitate in a buffer to form a suspension; and (iv) post-homogenizing the suspension to obtain a 10% to 50% increase in yield of the hepatitis B surface antigen protein as calculated based on a yield achieved without performing the post-homogenizing step.

Abstract: There is provided water insoluble cross-linked polyhydroxy polycarboxylic acid having at least two strands each having a strand skeleton of the formula: ##STR1## wherein one carbonyl group of at least one maleoyl moiety thereof in each strand is covalently linked to a--HN.[(H).sub.p (CH).sub.z.(OH).sub.m ].NH-- moietyto provide the presence therein of at least one cross linking moiety of the formula: ##STR2## wherein R is hydrogen or lower alkylene or lower alkoxy of 1-4 carbon atoms, or phenyl, z is an integer of 1-4, p is 0 or an integer up to z-1, m is 1 or an integer up to z, wherein the ratio of cross-links to poly (alkylene carbonic acid) strands is between about 1 and about 200 to 2. There is disclosed a method of making such polyhydroxy polycarboxylic acid as well as methods of utilizing same to remove proteins from aqueous media containing same to provide a matrix.

Abstract: Disclosed is a primary chromatographic support containing an immobilized flocculating agent for use as a separation media for a secondary support consisting of microparticles used in affinity separation and heterogeneous immunoassays. In a specific embodiment, a flocculating agent such as polyethyleneimine is immobilized on a chromatographic resin packed in a column. The column so formed is then used to trap microparticles having an affinity ligand or binder for the ligand affixed thereon. Such microparticles are used as a solid support for the affinity reaction involved in a variety of immunoassay formats.

Abstract: A process for producing an oxidized lignosulfonate composition comprising admixing a lignosulfonate and nitric acid such that the amount of acid comprises from about 35% to about 100% by weight of dry solids of the lignosulfonate, and reacting said mixture for a time sufficient to form the oxidized lignosulfonate composition.

Abstract: A composition and method for separating red blood cells from whole blood including a rouleaux-forming aggregator and an enhancer for enhancing the settling rate. The enhancer is a material which alters directly or indirectly the properties of the red blood cell and may alter the structure and/or reactivity of the aggregator, without adversely affecting the morphology and function of white blood cells. In most instances, the red blood cell enhancers of the invention are osmotic agents. Such agents create a hypertonic solution while not entering the cells themselves. Preferably the enhancer is a salt of oxalic acid, a salt of malonic acid, mannitol or sucrose. Potassium oxalate is most preferred. High molecular weight substances which are large enough to form molecular bridges between red blood cells form the aggregators used in the invention.

Abstract: A process for the microbial production of a protein susceptible to inactivation in a fluid production medium by continuously and reversibly protecting said protein against said inactivation during the production stage, separating the protein from the production medium, deprotecting the protein, and recovering the protein product. The process is especially useful for obtaining substantially increased yields of the protein in question by continuously precipitating said protein.

Abstract: A therapeutic composition effective on contact with thrombin at a site of treatment in a patient as a tissue adhesive, hemostat or sealant, said composition comprising non-autologous, non-single donor mammalian fibrinogen that is capable of polymerizing when provided in solution at said site at a concentration of about 30 mg/ml thereof or less, to a fibrin network having therapeutically effective strength, wherein said composition contains less than about 30% (w/w), based on total protein mass present therein, of proteins other than fibrinogen, and further comprises a sufficient amount of one or more low molecular weight physiologically-compatible solutes such that said composition, if formulated as a lyophilized material, can be reconstituted therefrom at room temperature in sterile water for injection in about 30 minutes or less, at about 25 mg/ml of said fibrinogen. Additionally, methods for producing and maintaining said composition, and methods for the use thereof.

Abstract: The invention relates to polymer conjugates which are reversibly precipitable from aqueous solution and are composed of a carrier polymer which is soluble in aqueous medium and of a catalytically active compound which is chemically bonded thereto. The invention also relates to a process for the preparation of polymer conjugates of this type, and to the use thereof in homogeneous catalysis, especially biocatalysis.

Abstract: There is provided water insoluble cross-linked polyhydroxy polycarboxylic acid having at least two strands each having a strand skeleton of the formula: ##STR1## wherein one carbonyl group of at least one maleoyl moiety thereof in each strand is covalently linked to a--HN.[(H).sub.p (CH).sub.z.(OH).sub.m ].NH-- moietyto provide the presence therein of at least one cross linking moiety of the formula: ##STR2## wherein R is hydrogen or lower alkylene or lower alkoxy of 1-4 carbon atoms, or phenyl, z is an integer of 1-4, p is 0 or an integer up to z-1, m is 1 or an integer up to z, wherein the ratio of cross-links to poly (alkylene carbonic acid) strands is between about 1 and about 200 to 2. There is disclosed a method of making such polyhydroxy polycarboxylic acid as well as methods of utilizing same to remove proteins from aqueous media containing same to provide a matrix.

Abstract: The present invention provides a process for preparing a carbohydrate-binding lectin derivative for use as immune modulators or immunoconjugates. The polymer-lectin conjugate produced in accordance with the process is polyethylene glycol Ricinus communis agglutinin I (PEG-RCAI). The lectin is coupled to the polymer by activating the polymer with a coupling agent such as 1,1-carbonyldiimidazole. The polymer-lectin conjugate is biologically active, biocompatible and is expected to be substantially non-immunogenic.

Abstract: New protein hydrolyzates are produced by treating an aqueous solution of a protein hydrolyzate with an adsorptive resin functional to remove from the protein hydrolyzate bitter taste components, color and odor components and aromatic amino acids. The treated protein hydrolyzate solutions can be concentrated and dried if desired to powder form.

Abstract: Methods for purifying factor XIII from a biological fluid are provided. The methods comprise precipitation of factor XIII by adjusting the pH of the biological fluid to 5.5 to 6.5 and recovering the precipitated factor XIII.

Abstract: An intravenously administrable polyclonal immunoglobulin preparation for the treatment and prophylaxis of bacterial infections containing at least 50% by weight of IgM in terms of the total content of immunoglobulin, exhibiting a low anticomplementary activity, being stable in aqueous solution, and being free of viruses. It can also consist of or also contain a mixture of several monoclonal IgM antibodies. The source material for its manufacture is an immunoglobulin-containing fraction of human, animal, or bacterial provenance. The fraction is treated with an anion exchanger that is eluted with a saline or pH gradient and the eluate is optionally subjected to gel filtration, treated before or after the chromatography with .beta.-propiolactone and PEG 4000, and optionally heated. Treatment with .beta.-propiolactone and ultraviolet light, treatment with solvents and detergents, or pasteurization can also be conducted. Proteins, sugars, or mixtures of amino acids are optionally added to the preparation.

Abstract: A method for detecting the onset or presence of Lyme disease in a mammal, which comprises isolating a biological sample from the mammal, isolating from said biological sample any circulating immune complexes suspected to contain antibody reactive to Borrelia burgdorferi, dissociating the immune complexes so isolated, and examining the dissociated immune complexes for the presence of antibody. The present method offers a simple and reliable means for detecting Borrelia antibodies. Test kits and related methodology are also disclosed.

Abstract: A multi-step process for purifying an immune serum globulin fraction from a crude plasma protein fraction involves precipitating non-serum globulin proteins from an aqueous suspension of the crude plasma protein fraction using a protein precipitant, adding a virus-inactivating agent to the clarified immune serum globulin-containing liquid, absorbing the immune serum globulins onto a cation exchange resin and washing non-serum globulin contaminants from the resin, subjecting the eluate to ultrafiltration to concentrate the immune serum globulins and separate them from low molecular weight species, contacting the concentrate with an anion exchange resin to absorb non-serum globulin contaminants, passing the imune-serum globulins through the anion exchange resin under conditions that leave non-serum globulin contaminants bound to the resin, and subjecting the filtrate to a molecular washing step to produce a purified immune serum globulin fraction.

Abstract: An essentially pure and stablized antibody preparation comprising IgM antibodies having a purity greater than about 98% by weight and a nucleic acid content of less than about 200 pg per mg IgM. In one embodiment IgM antibodies from a monoclonal source are subjected to ion exchange and size exclusion chromatography at an alkaline pH to yield a purified IgM having a nucleic acid content of less than 10 pg/mg IgM, preferably less than about 4 pg/mg IgM. A highly purified and stabilized preparation of anti Pseudomonas aeruginosa antibodies is disclosed. The removal of nucleic acids is assured by subjecting the antibody source to at least one and preferably two low pH precipitation steps. In a very preferred embodiment, ion exchange and/or size exclusion chromatography is used to remove any residual nucleic acids.

Abstract: This invention provides a crystalline form of recombinant human granulocyte-macrophage colony-stimulating factor (r-h-GM-CSF) and methods for making such crystals.

Abstract: A method for recovering a recombinant protein from a protein solution containing high molecular weight containing proteins by directly adding amine or quaternary ammonium compounds to the solution in amounts sufficient to selectively precipitate the high molecular weight protein contaminants.The high molecular weight precipitates are removed and the solution is further processed to remove low molecular weight contaminating proteins and other non-protein contaminants. The recombinant protein is subsequently recovered and further processed to produce a protein composition suitable for its intended use.

Abstract: An aqueous two-phase protein partitioning system is disclosed which employs polyvinylpyrrolidone as the upper phase and maltodextrin as the lower phase and provides a low-cost system for protein partitioning. The system can also be employed with the amion derivatives of chlorotriazine dyes, which bind in a noncovalent manner with the PVP and serve as a ligand for the proteins to be separated.

Abstract: A method for recovering a recombinant protein from a protein solution containing high molecular weight contaminating proteins by directly adding a flocculant to the solution in amounts sufficient to selectively precipitate the high molecular weight protein contaminants is disclosed.The high molecular weight precipitates are removed and the solution is further processed to remove low molecular weight contaminating proteins and other non-protein contaminants. The recombinant protein is subsequently recovered and further processed to produce a protein composition suitable for its intended use.

Abstract: This invention relates to a process for continuously fractionating plant, animal or human proteins by selective precipitation of the proteins resulting from placing a solution of proteins in contact with a precipitating agent constituted by a fatty acid of 6 to 14 carbon atoms, such as caprylic acid, is characterized in that respective deliveries of fatty acid and of the protein solution are continuously placed in contact in a mixing chamber of small volume with respect to the deliveries, creating a strong stirring in this mixing chamber; the individual deliveries of fatty acid and of protein solution are adjusted to controlled pH and temperature so as to maintain their ratio equal to a predetermined value; the mixture is then allowed to evolve during a phase of maturation so as to form a suspension; this suspension is separated into a liquid part from which are extracted the proteins having remained soluble, and a solid part containing proteins of different nature; and the parameters intervening in the proce

Abstract: A protein called PA binding protein has been isolated which binds specifically and reversibly to tissue plasminogen activator. The protein is characterized by a molecular mass of about 100,000 daltons, and electrophoretic mobility in agarose at pH 8.6 equal to that of plasma .beta.-globulins and an isoelectric point of 6.5 to 7.0. The protein is thermostable up to at least 56.degree. C. and is cleared from the circulation with a half life on the order of days.

Abstract: A method for purifying a biologically active ligate. In this method, a ligand bonded to a first phase and having a specific affinity for the ligate is provided. The ligate is provided with a second phase. The first and second phases are then contacted together under conditions in which the ligand and ligate form a complex bonded to the first phase, with the ligand and ligate held together only by one or more non-covalent pressure sensitive bonds. At least a part of the second phase is then separated from the first phase to provide a purified first phase, and the purified first phase subjected to a pressure of at least 300 atmospheres under conditions sufficient to cause release of the ligate from the complex, but not sufficient to cause significant release of the ligand from the first phase. These conditions do not irreversibly cause biological activity of the ligate to be significantly reduced.

Abstract: A liquid phase containing preS2+S antigen is separated into two phases after which the desired antigen is concentrated, washed and adsorbed and desorbed from a fumed silica to produce a product that is purified and concentrated in antigen:protein ratio and that is suitable for final purification.

Abstract: A method for the solubilization and recovery of insoluble parasite protective antigenic factors associated with parasite material comprising solubilizing the antigenic factors with a non-ionic detergent and separating the solubilized material from undispersed residual material. The purified protective antigenic factors are useful as vaccines, particularly against malaria, and as diagnostic agents.

Abstract: Method and composition for providing a non-toxic, sterile, virally inactivated human transferrin preparation for use in cell culture systems. The method comprises saturation of the transferrin with an excess of iron, removal of free iron radicals and unwanted proteins, and pasteurization of the iron-bound transferrin substantially free of iron radicals.

Abstract: There is disclosed a method for separating alpha-1-proteinase inhibitor (also known as alpha-1 antitrypsin) from an aqueous solution of plasma proteins, especially from Cohn Effluent II & III and Cohn Effluent I. The method includes the steps of first treating the aqueous solution to lower the concentration of salts therein and, optionally, its alcohol content, contacting the resulting solution with an anion exchange resin having selective affinity for alpha-1-proteinase inhibitor to selectively bind the alpha-1-proteinase inhibitor and allow unwanted plasma proteins to elute through the resin, displacing the alpha-1-proteinase inhibitor from the resin and recovering the same.

Abstract: There is disclosed an improved method for separating and recovering proteins, particularly therapeutically active proteins, from an aqueous system also containing a component having the ability to create two liquid phases by use of salt partitioning technology. By the addition of water soluble inorganic salts to an aqueous system containing one or more therapeutically active proteins or nucleic acids, especially an aqueous system obtained from fractionation of a blood plasma fraction or from a tissue culture fluid resulting from a biotechnology production operation such as recombinant DNA and monoclonal antibody technologies, the aqueous system may be separated into two or more liquid phases. Such separated phases may be selectively enriched in components of the original aqueous system having differing solubility in the so-separated liquid phases.

Abstract: The process is applicable to the supernatant of engineered yeast cells disrupted in the presence of a non-ionic detergent: it comprises the precipitation of contaminants by polyethylene glycol and the treatment cation or, after eventual ultrafiltration, with ammonium sulfate.

Abstract: A process for the purification of proteins from a fluid medium wherein said proteins have an isoelectric pH higher than the pH of said fluid medium, said process comprising passing the liquid medium over acidic polysaccharide gel particles of at least 0.5 mm in the shortest dimension, and recovering the desired proteins from the gel particles by elution with an aqueous salt solution having ions concentration of at least 5 grams per liter.

Abstract: There are disclosed a process for enhancing the immunogenicity of a lipid membrane based immunogen comprising flash heating it at a membrane concentrations sufficient under the conditions of flash heating to result in melting of membranes and fusing the melted membranes into novel morphologic forms and a proteinaceous mass comprising particles of HBsAg, said particles including particles of HBsAg in morphologic form not found in nature, said HBsAg contains particles being filaments, branched filaments, closed circular or closed circular branched filaments.