Abstract: A new 3',5'-dinucleoside phosphate, the pharmaceutically acceptable salts thereof and intermediates therefor. The 3',5'-dinucleoside phosphate of 5,6-dichloro-1-.beta.-D-ribofuranosyl-1-benzimidazole and namely 5,6-dichloro-1-.beta.-D-ribofuranosyl-1-benzimidazole-3'-yl-5,6-dichloro-1 -.beta.-D-ribofuranosyl-1-benzimidazole-5'-yl-phosphate possesses potent inducing activity for the cellular synthesis of interferons and in particular .beta.-interferon. The compound is also markedly effective to induce antiviral levels of interferon and possesses significant interferon potentiation properties. The invention also contemplates methods for the preparation of the new compounds and for using the new 3',5'-dinucleoside phosphate.

Abstract: A method for the extraction of intact recombinant human immune interferon with guanidine-HCl is disclosed. This method permits the purification to homogenity of intact recombinant human immune interferon.

Abstract: Process for preparing a continuous and spontaneous human-interferon-producing lymphoblastoid cell line which involves (a) transforming human lymphocytes isolated from a human infant from birth up to about 2 years or an aborted human fetus, the transforming being carried out with Epstein Barr Virus and (b) selecting from the resulting transformed cell lines a cell line producing more than 1000 units of interferon per milliliter when cultivated at a cell density of 10.sup.6 cells per milliliter in the absence of any interferon inducer.

Abstract: Interferon glycoprotein isolates of heterologous species origin are subjected to treatment in a digestive environment and non-species-specific biologically active fractions thereof are administered, preferably through digestive tract tissue, to the circulatory system of mammals, including humans, to secure antiviral, antiproliferative (e.g., antineoplastic) and immunomodulatory (e.g., immunopotentiating) effects ordinarily associated only with parenteral administration of homologous species interferon.

Abstract: An improved process for recovering and purifying .beta.-HIFN from transformed bacterial comprising concentrating the bacteria; disrupting the cell wall and solubilizing the .beta.-HIFN into an aqueous medium with an appropriate solubilizing agent; extracting the .beta.-HIFN from the aqueous medium with 2-butanol, 2-methyl-2-butanol or mixtures thereof; precipitating and isolating the .beta.-HIFN from the alcohol phase; purifying the .beta.-HIFN by chromatography and diafiltering the .beta.-HIFN against distilled water or aqueous solutions of ethanol or glycerol at a pH of about 12; and therapeutic formulations and compositions of .beta.-HIFN within SDS levels therein reduced to less than 10 p.p.m.

Abstract: A method for stimulating the production of human IFN-.gamma. in a culture of cells is disclosed. In this method, an effective amount of a diterpene compound is added to a culture of IFN-.gamma. producing cells.

Abstract: Prophylaxis or treatment of interferon-sensitive diseases in a human is effected by the rectal or urogenital administration to a human of a liquid pharmaceutical composition of native human interferon (Types I and II), said liquid pharmaceutical composition not being clinically appropriate for intravenous or intramuscular injection.

Abstract: Disclosed herein are methods and means of microbially preparing novel human hybrid leukocyte interferons, useful in the treatment of viral and neoplastic diseases, by DNA recombination of parental interferon genes, taking advantage of common restriction endonuclease cleavage sites therein and in carrier expression plasmids.

Abstract: A method is described for reducing the level of low density lipoproteins in the serum of a patient by administering to the patient human fibroblast interferon.

Abstract: A process for recovering IFN-.beta. from transformed bacteria comprising: disrupting the cell membranes of the bacteria; solubilizing the IFN-.beta. from the disruptate into an aqueous medium with a solubilizing agent such as sodium dodecyl sulfate; extracting the IFN-.beta. from the aqueous medium with 2-butanol, 2-methyl-butanol, or mixtures thereof under conditions that maintain phase separation between the aqueous meduim and the extractant; and isolating the IFN-.beta. from the extractant such as by precipitating the IFN-.beta. from an aqeous buffer mixture of the extractant by lowering the pH thereof.

Abstract: Disclosed is a process for the purification of crude immune interferon to a near homogeneous preparation which comprises: (a) adsorbing the crude interferon onto a column containing Controlled Pore Glass beads and eluting with ammonium sulfate, (b) adsorbing the interferon containing eluant onto a column containing either Concanavalin A-Sepharose, lentil lectin-Sepharose or pea lectin-agarose and eluting with a buffer containing a sugar, (c) adsorbing the interferon containing eluant onto a column containing Heparin-Sepharose or Procian Red-agarose and eluting with a high salt content buffer, (d) adsorbing the interferon containing eluant onto a cationic exchange resin column and eluting with a salt buffer and (e) treating the interferon containing eluant in a gel-filtration column equilibrated in high salt to obtain a solution of immune interferon that is nearly homogeneous.

Abstract: In producing interferon by treating animal cells proliferated on a microcarrier with an interferon inducer, the cells on the microcarrier are treated with a negatively charged water-soluble macromolecular material.

Abstract: A process is described for the selective recovery and/or concentration of a protein or a class of proteins from fermentation broth employing a combination of desalting and pH adjustment thereby causing the initial precipitation of unwanted proteins, again subjecting the resulting supernatant to another set of pH adjustment and desalting to cause the protein of interest to precipitate thereby obtaining a highly enriched fraction of the selected protein. Such a process will find use in the specific recovery of genetically engineered proteins from fermentation broths, e.g. interferon, insulin, growth hormone, etc.

Abstract: A monoclonal antibody is described characterized by its specificity to interferon-.alpha. (leukocyke interferon). Preferably the antibody has specificity to human interferon-.alpha.. The monoclonal antibody is secreted by a hybrid cell formed by the fusion of lymphocyte cells derived from an animal immunized with interferon-.alpha., with mycloma cells. The antibody has applications in the purification of interferon. It may be covalently attached to a solid support and used as an immunoadsorbent. Purifications of up to 5000 fold may be obtained in a single pass through an immunoadsorption column of this type. An immunoradiometric assay for interferon-.alpha. is also described.

Abstract: This invention affords a filtration method and apparatus for extracting cell produced antiviral substances (CPAS) from a production broth using cross-flow membrane filtration. The broth is perfused into a first filtration cell and caused to cross-flow across an ultrafiltration membrane in the cell, permitting a first filtrate to pass through the membrane consisting essentially of CPAS and some molecular species and retaining in a first ex-filtrate all remaining portions of the broth.

Abstract: The present invention relates to processes for inserting DNA into eucaryotic cells, particularly DNA which includes a gene or genes coding for desired proteinaceous materials for which no selective criteria exist. The insertion of such DNA molecules is accomplished by cotransforming eucaryotic cells with such DNA together with a second DNA which corresponds to a gene coding for a selectable marker.The invention further relates to processes for inserting into eucaryotic cells a multiplicity of DNA molecules including genes coding for desired proteinaceous materials by cotransformation with the desired genes and with amplifiable genes for a dominant selectable marker in the presence of successively higher amounts of an inhibitor.

Abstract: A process is disclosed for producing human immune interferon with cell cultures of human peripheral blood leukocytes modulated with Mezerein or 12,13 phorbol dibutyrate and induced with Staphylococcal aureus enterotoxin B. After cultures are incubated for 3 to 7 days crude interferon on the order of 10.sup.3 units of interferon/ml. is produced.

Abstract: A process is disclosed for producing human immune interferon with cell cultures of human peripheral blood leukocytes modulated with Mezerein or 12, 13 phorbol dibutyrate and induced with the calcium ionophore A-23187. After cultures are incubated for 12 hours to about 7 days, crude interferon on the order of 10.sup.3 units of interferon/ml. is produced.

Abstract: Human fibroblast interferon may be purified to a high degree by using a simple two-step purification method comprising (a) subjecting an aqueous interferon solution to chromatography on porous glass beads, and (b) subjecting the resulting aqueous interferon solution to chromatography on immobilized zinc chelate. Overall recoveries of about 45-76% of the initial interferon activity may be achieved and the end product will be free of any skin reactive agents.

Abstract: A method for enhancing the production of interferon from normal human diploid fibroblast cells is disclosed. In this method, a distinct interferon-production phase is established in which the temperature is initially elevated for a brief period followed by a reduction in temperature for the balance of the interferon-production phase.

Abstract: A process for recovering interferon which comprises contacting a solution containing an interferon produced by the induced cells of human origin with a water-insolubilized sulfated polysaccharide to allow the interferon to be adsorbed on the water-insolubilized sulfated polysaccharide and then selectively eluting the interferon with an aqueous solution of an inorganic salt.

Abstract: Anchorage-dependent cells are grown in agitated microcarrier suspension in which the cells and microcarriers are aggregated by periodically providing a temporary residence of said microcarriers and cells outside the main cell culture reactor agitation zone and in a separate compartment wherein they are subjected to a gentle tumbling action within a confined space having substantially the same environmental conditions as in the main cell culture reactor.

Abstract: The present invention relates to a process which is easily applicable for industrial production of mouse interferon.Particularly, the present invention relates to a process based on the discovery that a large amount and high activity of mouse interferon is obtained by transplanting established mouse tumor cells to other warm-blooded animal body or inoculating the cells in a culture medium charged in a filter-membrane-interposed diffusion chamber which is designed and fitted up to or in the animal body so that its nutrient body fluid feeds the cells, multiplying the transplanted or inoculated cells in the warm-blooded animal body or the diffusion chamber utilizing said body fluid, and exposing the multiplied cells to the action of interferon inducer in vitro or in vivo.

Abstract: A process for recovering interferon which comprises contacting a solution containing an interferon produced by the induced cells of human origin with a water-insolubilized sulfated polysaccharide to allow the interferon to be adsorbed on the water-insolubilized sulfated polysaccharide and then selectively eluting the interferon with an aqueous solution of an inorganic salt.

Abstract: In the method of the present invention for production of interferon from propagating tissue culture cells, a propagating apparatus is utilized having a plurality of spaced-apart parallel flat plates. Monolayers of the tissue cells are grown on these plates and the apparatus is adapted for the introduction of gas and/or liquid mediums between the plates. In carrying out the method of the present invention the culture medium which nourishes the propagating cell tissues is exposed to a gas phase for oxygenating and adjusting the pH of the medium, while maintaining the culture medium and the propagated cells in a static and undisturbed condition.

Abstract: The present invention relates to an assay for the quantitative determination of interferon which comprises extracting a cell previously exposed to said interferon with an extractant, and determining in such extract the quantity of an enzyme the content of which in said cell is a function of the quantity of interferon to which said cell had been previously exposed and to a kit for carrying out such assay.

Abstract: The present invention relates to a process for preparing a large amount of human interferon from human leukocytes. More precisely, the invention is based on the finding that the induced interferon activity can be easily increased by exposing human leukocyte suspension to both Type I and Type II interferon inducers. Thus the induced interferon activity is enhanced about 2-20-fold or higher than those attained with either Type I interferon inducer or Type II interferon inducer.

Abstract: A method for preparing interferon in which MRC-5 cells are induced for 2 to 3 hours with an interferon-inducing medium containing from 0.1 to 50 mg 1.sup.-1 of a ds-RNA, 100 mg 1.sup.-1 of DEAE-Dextran and 250 m.M of sucrose.Other sugars which can be used include glucose, galactose, fructose, mannose and maltose, and a preferred ds-RNA is naturally occurring ds-RNA isolated from P. chrysogenum.

Abstract: An improved process for purifying proteins, particularly proteins having molecular weights in excess of 12,000 involves novel applications of high performance liquid chromatography on a preparative scale to provide homogeneous end product in excellent yield. In an embodiment of the process, human interferon is produced as a homogeneous protein.

Abstract: The present invention relates to processes which are easily applicable for industrial production of Type II interferon and Type II interferon-containing agents.Particularly, the present processes are based on the invention that a large amount of high-titred Type II interferon is easily obtainable by transplanting established human cells in other warm-blooded animal body or inoculating the cells in a culture medium charged in a filter-membrane-interposed diffusion chamber which is designed and fitted in or to the animal body so that the cells can grow on its nutrient body fluid, multiplying the transplanted or inoculated cells in the warm-blooded animal body or the diffusion chamber utilizing the body fluid, then exposing the multiplied cells to the action of a Type II interferon inducer in vivo or in vitro to induce Type II interferon, and purifying and separating the induced Type II interferon.

Abstract: Therapeutic induction of interferon production in living animal cells is effected by subjecting such cells to the species-specific interferon inducing effect of an organogermanium compound having the formula:(GeCH.sub.2 CH.sub.2 COX).sub.2 O.sub.3wherein X is --OH, --NH.sub.2 or --O--alkyl.

Abstract: Human interferons produced in the absence of added serum or sera can be purified to greater than 95% protein purity by adsorption on immobilized Cibacron Blue F3G-A and eluting the interferon adsorbed on the Cibacron Blue F3G-A with ethylene glycol in an aqueous buffer solution. The purified interferon in solution can be converted to interferon of uniform molecular weight by heating the interferon solution in the presence of an organic thiol compound.

Abstract: The present invention relates to processes for an easily applicable industrial production of interferon and the possibilities of the products for preventing and treating interferonsensitive diseases.The process easily produces a large amount of interferon and transplanting established human cells to other warm-blooded animals or inoculating the cells in a diffusion chamber and multiplying the cells therein while allowing the animals to supply the cells with their nutrient body fluids, then exposing in vivo or in vitro the resultant cells to the action of interferon inducer. The present invention is also based on the discovery that the interferon obtained by the present method is an effective and superior preparation for preventing and treating interferon-sensitive diseases.

Abstract: This invention is directed to a process of producing interferon which comprises incubating permanent cell lines of lymphoblast origin or human fibroblast cells with interferon inducers and stimulator substances and recovering the interferon produced.

Abstract: Method for preparing interferon, mRNA for interferon, and competent recombinant DNA containing dsDNA and cDNA from mRNA coding for mammalian interferon. The method employs crossing a mutant mammalian cell which is semiconstitutive for interferon with a cell derived from the same or different mammal having wild type gene(s) for interferon and for the regulation of interferon synthesis and desirably having phenotypic properties allowing for selection of the hybrid cells. The desired hybrid clones are then induced to produce IF mRNA, wherein the amounts of mRNA for interferon are greatly enhanced over the amounts normally obtained from wild type cell strains. The mRNA is employed to produce cDNA which codes for the mammalian interferon. The single stranded cDNA is employed as a template to prepare dsDNA which is then combined with a replicon recognized by a microorganism host to provide a recombinant DNA.

Abstract: A rapid cytopathic effect inhibition assay for interferon is disclosed. The assay can be completed in about 16 hours or less, allowing its use to assist in clinical diagnosis of viral infections and also, in monitoring the production and purification of interferon whether leukocyte or fibroblast.

Abstract: Process for the production of human TAF in vitro comprising growing the human osteosarcoma cell line MG-63 in agitated, liquid suspension of nutrient culture medium at about 35.degree.-38.degree. C. for a sufficient time to elaborate TAF and recovering the resulting TAF from the cells or cell product.

Abstract: Process for the production of human TAF in vitro comprising growing the human Burkitt lymphoma cell line Raji in agitated, liquid suspension of nutrient culture medium at about 35.degree.-38.degree. C. for a sufficient time to elaborate TAF and recovering the resulting TAF from the cells or cell product.

Abstract: The invention provides structurally modified interferons, processes for producing such and a method of purification of interferons and structurally modified interferons. The modified interferons are useful as anti-viral agents.

Abstract: KS-substance was obtained as raw material from the cultured mycelium of Daedalea dickinsii KSDD 6 (FERM-P No. 3993), Lentinus edodes KSLE 7 (FERM-P No. 3994) or Lentinus edodes KSLE 28 (FERM-P No. 4196), and by refining this substance a novel substance KS-2-A was obtained. This substance KS-2-A and also the KS-substance as the raw material both enhance the host defense function of the living body.