Abstract: Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.

Abstract: Novel polypeptides derived from human fibronectin, and fusion proteins containing those peptide sequences are described which define a receptor binding site on fibronectin that binds to the platelet receptor glycoprotein GPIIb-IIIa expressed by cells. The receptor binding site of human fibronectin includes at least fibronectin amino acid residues 1410-1436. The polypeptides facilitate attachment of cells to substrates either alone or in conjunction with RGD-containing peptides. Vectors preparing the fusion proteins and antibodies are also described. Methods for promoting cell attachment and for inhibiting cell adhesion are also described.

Abstract: Methods are disclosed for producing thrombin. The protein is produced from host cells transformed or transfected with DNA construct(s) containing information necessary to direct the expression of thrombin precursors. The DNA constructs generally include the following operably linked elements: a transcriptional promoter, DNA sequence encoding a gla-domainless prothrombin, and a transcriptional terminator. Thrombin precursors produced from transformed or transfected host cells are activated either in vivo or in vitro.

Abstract: The present invention relates to a biological support for cell cultures formed by the coagulated mixture of a concentrate of plasma proteins and thrombin.The protein concentrate is obtained by precipitating fresh plasma with ethanol and contains balanced proportions of fibrinogen, Factor XIII and fibronectin. The thrombin concentration is adjusted to obtain the desired consistency of the support coagulated in the form of a film.The biological support is preferably used for preparing a culture of keratinocytes, recovering them in the form of a reconstituted tissue and transporting same. The reconstituted tissue is thus particularly suitable for use as a graft.

Abstract: The present invention contemplates therapeutic compositions containing a D.sub.30 homolog capable of binding to the Mac-1 receptor D.sub.30 binding site and inhibiting fibrinogen binding to the Mac-1 receptor via the D.sub.30 binding site, Methods of inhibiting Mac-1 receptor binding to any Mac-1 ligand and methods of inhibiting Mac-1 receptor mediated inflammation within a patient by administering a D.sub.

Abstract: A protein having human plasmin inhibiting activity, substantially equivalent reactivity with human plasmin to a human .alpha..sub.2 -plasmin inhibitor derived from plasma, a binding ability to human fibrin about 1/4 to about 1/3 of that of the human .alpha..sub.2 -plasmin inhibitor derived from plasma, and a molecular weight of about 50,000 to about 77,000.

Abstract: A method for at least partially separating vitamin K-dependent blood clotting factors from a mixture containing at least one such factor, e.g. a prothrombin complex concentrate, which comprises adsorption of said mixture on to a chelate of a polyvalent metal immobilized on an inert support, e.g. Cu.sup.2 + -primed Chelating Sepharose, followed by elution to yield one or more fractions enriched in respect of one of said factors.

Abstract: A dry reagent consisting essentially of (a) a protein having thrombin activity, (b) at least one additive selected from the group consisting of amino acid, a salt thereof and saccharide and optionally (c) magnetic particles, and a method of assaying fibrinogen in an assay sample using the above dry reagent. The dry reagent obviates the time required for preparing a reagent and warming an assay sample, and permits facile fibrinogen assay by only diluting an assay sample. The fibrinogen assay range being broad, the dry reagent substantially obviates the procedure of remeasuring plasma having a fibrinogen concentration outside the assay range of a liquid reagent. The assay result by the dry reagent and that by a liquid reagent well correlate with each other as compared with the result by any known thrombin-containing dry reagent, and the assay by the dry reagent can be performed with good reproducibility in achievement and reliability in measurement.

Abstract: Oxidized derivatives of-fibrin and fibrin or fibrinogen degradation products or partial sequences, process for their preparation and their use as medicaments, for diagnosis or as an affinity agent are described.

Abstract: Cryoprecipitated mammalian plasma proteins with associated glycoproteins, polysaccharides, and numerous other macromolecular entities are transferred directly in the course of controlled thawing and centrifuging from native plasma phase across the boundary layer into a pre-prepared substrate transfer medium at sustained solidus--liquidus equilibrium regulated to residual icing from about 5 weight percent to about 95 weight percent to produce cryoprecipitates with enhanced productivity and enhanced qualifications for in vivo tissue bonding applications.

Abstract: For the quantitative selective removal or/and preparative isolation of tumour necrosis factor (TNF) or/and lipopolysaccharides from aqueous liquids, in particular blood, plasma or serum, the aqueous liquid is passed over an adsorption material which consists of a porous supporting material to which functional groups made of synthetic or/and semisynthetic or/and natural polyanion chains and namely in a linear or branched form, are covalently bound and if desired, the molecules chromatographically separated in this way are eluted from the adsorption material using a saline solution.

Abstract: A reagent blood coagulation that causes an increase in turbidity changes when added to a plasma sample containing a substance activating coagulation factor activating such as tissue thromboplastin, phospholipid and thrombin, calcium ion, and molecular substance such as high molecular vinyl and a high molecular polysaccharide. By adding a molecular substance to the reagent, the turbidity change due to blood coagulation is increased, and hence the changing quantity of transmitted light or scattered light increases, thereby making it possible to achieve a more accurate detection. Besides, by adjusting the electric conductivity, pH and osmotic pressure to proper values, the turbidity change due to blood coagulation may be further amplified.

Abstract: The present invention relates to a process of making a concentrate of coagulation proteins starting with whole human or animal plasma. This concentrate is used as a biological adhesive when extemporaneously mixed to thrombin. The concentrated proteins include mostly fibrinogen, fibrin stabilizing factor (factor XIII) and fibronectin. The claimed process has the advantage of being short of execution while providing an excellent yield of coagulable proteins. No protease inhibitor has to be added during the process. The process involves steps of separation by "salting-out" in presence of amino-6 hexanoic acid which prevents co-precipitation of plasminogen with the desired coagulable proteins. The proteins so obtained are very stable after reconstitution in water for at least 24 hours at room or body temperature. After mixing with thrombin and calcium, the adhesive shows excellent strength and biocompatibility.

Abstract: Oxidized derivatives of fibrin and fibrin or fibrinogen degradation products or partial sequences, process for their preparation and their use as medicaments, for diagnosis or as an affinity agent are described.

Abstract: Secretory immunoglobulin A preparations substantially not containing virus are produced by a process wherein secretory immunoglobulin A which might be contaminated with viruses is (1) heated about 60.degree. C. for about 10 hours, or (2) subjected to the reaction with tri-n-butyl phosphate and a surfactant and the heating as mentioned above, as liquidized form in an aqueous medium, and then polymerized matters are precipitated from the resulting solution by adding polyethyleneglycol thereto.

Abstract: The present invention relates to methods for the isolation and purification of immunoglobulins or fragments thereof or other biologically active factors from non-immune or immune egg yolk, by extracting the yolk with a composition containing one or more medium-chain fatty acids. The present methods provide egg immunoglobulin of high purity and high yield.

Abstract: Peptides comprising fibrin-specific epitopic sequences are used to prepare hybridoma cell lines producing antifibrin-specific monoclonal antibodies substantially devoid of fibrinogen-cross-reactivity obtained by somatic cell fusion. The antibodies are useful for the in vivo and in vitro detection of thrombi and fibrin deposits.

Abstract: This invention provides enzyme conjugates, antigens, antibodies and diagnostic test kits used in an enzyme-linked immunosorbent assay method for determining the presence and concentration of imidazolinone compounds.

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: A method of preparing fibrinogen concentrate from blood plasma by cooling said plasma from a temperature above 0.degree. C. to a first temperature between -10.degree. C. and -40.degree. C., thawing the solid material thus obtained to a temperature near the freezing point of water and subsequently physically separating the solid matter and the liquid main fraction of the plasma, viz. water, whereby the thawing is effected in steps from the first temperature to a conditioning temperature between -5.degree. C. and -1.degree. C., after which the size of the solid material is reduced and the reduced material is brought to a temperature at which the main fraction of the plasma, viz. water, becomes liquid and the solubility of fibrinogen in said fluid is as low as possible, after which fluid is separated from the fibrinogen concentrate. The invention also relates to a device for carrying out this method.

Abstract: This present invention is directed to an artificial functional polypeptide represented by the following structural formula [I]:X--(Y)m--Z [I]wherein X represents a polypeptide having cell-adhesive activity like that of human FN, Y represents a spacer, Z represents a polypeptide having fibroblast growth promoting activity like that of FGF, and m is 1 or 0. This polypeptide is particularly useful for pharmaceutical purposes.

Abstract: Processes for stabilizing active PAI-1 protein comprising combining active PAI-1 protein with an aqueous buffer having an ionic strength of at least about 5 millisiemens and a sugar selected from the group consisting of monosaccharides and disaccharides, and/or subjecting the active PAI-1 protein to lyophilization, are disclosed. Also described are compositions, including pharmaceutical compositions and kits, which include the stabilized active PAI-1 protein, and therapeutic processes employing the same in the treatment of fibrinolysis.

Abstract: The present invention relates to a process of making a concentrate of coagulation proteins starting with whole human or animal plasma. This concentrate is used as a biological adhesive when extemporaneously mixed to thrombin. The concentrated proteins include mostly fibrinogen, fibrin stabilizing factor (factor XIII) and fibronectin. The claimed process has the advantage of being short of execution while providing an excellent yield of coagulable proteins. No protease inhibitor has to be added during the process. The process involves steps of acidic precipitation in presence of amino-6 hexanoic acid which prevents co-precipitation of plasminogen with the desired coagulable proteins. The proteins so obtained are very stable after reconstitution in water for at least 24 hours at room or body temperature. After mixing with thrombin, the adhesive shows excellent strength and biocompatibility.

Abstract: The present invention describes APC polypeptides and anti-peptide antibodies capable of inhibiting activated Protein C anticoagulant activity. The polypeptide and antibody are useful in diagnostic methods and systems for measuring APC in vascular fluid samples. In addition, the polypeptide and anti-peptide antibody are useful in therapeutic methods for inhibiting APC in a human patient.

Abstract: The invention provides a thrombin coagulable protein concentrate,, the preparation thereof and the therapeutic use thereof. This concentrate has a fibrinogen content greater than 70% and a sufficient amount of endogenous Factor XIII. It may be solubilized at ambient temperature. Its preparation comprises at least one cold precipitation step with dilute ethanol and uses total plasma as a starting product. The concentrate of the invention makes it possible more particularly to obtain an injectable fibrinogen and a biological glue of high quality.

Abstract: The present invention relates to a method of purifying native, intact fibrinogen from a liquid sample containing contaminants having molecular weights higher and/or lower than that of the fibrinogen. The method comprises subjecting the sample to filtration using one or more filters having a molecular weight cut-off such that the native, intact fibrinogen is separated from the contaminants.

Abstract: Disclosed is a method for the in vivo lysis of a thrombus in a host by administration of a conjugate consisting of a monoclonal antibody specific for fibrin coupled to a plasminogen activator such as tissue plasminogen activator, urokinase or streptokinase.

Abstract: The invention relates to an anti-HIV agent comprising as an effective component a plasma protein of which the polarity of the amino group of the amino acid residue constituting the plasma protein is chemically modified into a negative moiety by a carboxylic acid, for example, by maleic anhydride or succinic anhydride. Plasma proteins modified with dicarboxylic anhydride, which are the effective components of the anti-HIV agent of this invention, inhibit the formation of large cells in mixed culturing of HIV infected cells and non-infected cells as well as the direct infection of helper T cells with HIV.

Abstract: The invention relates to a process for separating proteins from a fraction of human or animal plasma.According to this process, a solubilized fraction of cryoprecipitated plasma is subjected to a single stage of chromatography on a moderately ionic anion exchange resin permitting hydrophobic interactions to take place, which does not adsorb certain proteins and fixes others, which are then eluted by increasing the ionic strength of the buffer by the addition of NaCl.The process according to the invention makes it possible, in particular, to obtain a Factor VIII concentrate of high purity that can be used for the treatment of haemophilia A. The process also makes it possible to obtain concentrates of fibrinogen, Von Willebrand's factor and fibronectin.

Abstract: The subject of the invention is an elastin-based product consisting of an adduct containing elastin and at least one protein which can be coagulated and/or activated by thrombin.

Abstract: A bifunctional ligand to compositions produced by reaction of the ligand with compounds containing an amino, thiolate or alcholate group, especially proteins, to chelates produced by complexing ligands with metal such as technetium and rhenium and to diagnostic and therapeutic uses of the complexes.

Abstract: The invention relates to an anti-HIV agent comprising as an effective component a plasma protein of which the polarity of the amino group of the amino acid residue constituting the plasma protein is chemically modified into a negative moiety by a carboxylic acid, for example, by maleic anhydride or succinic anhydride.Plasma proteins modified with dicarboxylic anhydride, which are the effective components of the anti-HIV agent of this invention, inhibit the formation of large cells in mixed culturing of HIV infected cells and non-infected cells as well as the direct infection of helper T cells with HIV. They are very safe compounds and are expected to be applicable to the treatment of HIV infected patients.

Abstract: Pharmaceutically active conjugates comprising a pharmaceutically active substance for treating a disorder of the body that involves a specified body tissue conjugated directly or indirectly with at least one fragment of an adhesive glycoprotein such as fibronectin, the said glycoprotein fragment(s) having improved binding specificity compared with the parent protein for the said body tissue.

Abstract: A method of producing a virus-inactivated protein-containing composition from a protein-containing composition which may be contaminated with virus. The method according to the present invention permits production of pharmaceutically safer virus-inactivated protein preparations without spoiling the protein activity.

Abstract: A method of fractionating plasma protein which comprises treating a plasma protein-containing material in the following sequence of steps, provided that steps (ii) through (v) may be performed in an optional order: (i) freeze-thaw treatment, (ii) treatment at 5 to 10% ethanol concentration, (iii) treatment with an anion exchanger, (iv) affinity chromatography with immobilized lysine, (v) affinity chromatography with immobilized heparin, (vi) treatment at 18 to 30% ethanol concentration, (vii) treatment at 35 to 45% ethanol concentration.

Abstract: A dentifrice composition useful in inhibiting caries and ginivitis comprising a caries and gingivitis inhibiting amount of a material selected from the group consisting of a water soluble salt of a whole caseinate, a water soluble salt of alpha.sub.s -caseinate, a water soluble salt of beta-casinate and a digest of a whole caseinate, alpha.sub.s -caseinate or beta-caseinate and mixtures thereof is disclosed.

Abstract: Antibodies are provided which are directed against a sequence of amino acids corresponding to amino acids from the sequence 311-379 in particular 311-336 of the .gamma.-chain of fibrinogen. These novel antibodies react specifically with fibrin, both type I and type II. They are effective in detecting, preventing and treating blood clot formation.

Abstract: An aqueous solution containing fibrinogen is heated in the presence of at least a sugar, an amino acid and a magnesium salt to thereby inactivate virus(es) possibly contaminating said fibrinogen. According to this process, the inactivation of the contaminating viruses can be achieved while maintaining the activity of the fibrinogen. Thus a highly safe fibrinogen preparation of excellent qualities can be prepared on an industrial scale.

Abstract: Disclosed is a soluble, biocompatible, pharmacological agent for inhibiting thrombin generation and thrombus formation, and methods for producing the same. The pharmacological agent or conjugate includes a soluble, biocompatible carrier and a thrombogenesis inhibitor immobilized thereto via the carrier which binds the inhibitor. The thrombogenesis inhibitor is hirudin, or an active analog or active fragment thereof. The thrombogenesis inhibitor may be bound to the carrier via a bifunctional cross-linking reagent.

Abstract: A method of and apparatus for separating proteins adsorbed by ion-exchange gels, especially anion-exchanging gels includes at least one chromatographic column in which the protein-carrying gel is charged and is subjected to a gradient-elution with a buffer solution as eluant whose property is changed with time by gradually changing the ionic strength and maintaining a substantially constant pH value or by gradually changing the pH value and maintaining substantially a constant ionic strength. The obtained eluate is then fractionated into its various components.

Abstract: A polypeptide having the cell-spreading activity of human fibronectin. Methods of preparing the polypeptide are described.

Abstract: A method of preparing a sterile and stable plasma-protein solution containing fibrinogen and Factor XIII from human blood plasma which has been stabilized with citrate, comprising treating the plasma with .beta.-propiolactone and irradiating it with ultraviolet light, removing the Factors II, VII, IX and X by adsorption onto anion exchangers that adsorb proteins, precipitating the companion proteins out by adding ethanol until the solution has a final concentration of about 9% by volume at -3.degree. C., centrifuging the precipitate off, dissolving the precipitate in a citrate buffer at a pH of about 6.35 and a temperature of about 37.degree. C., adjusting the protein level of the solution to about 13.3 g/l with sodium citrate solution, adding ethanol, a glycine citrate buffer, and a solution of sodium citrate to precipitate out the companion proteins, adding ethanol to the remaining solution until the solution has a final concentration of about 9% by volume at -3.degree. C.

Abstract: Factor VIII concentrate, or Factor IX concentrate, or fibrinogen concentrate, or other clotting-factor product, is subjected to a sequence of heating steps to reduce the infectivity of a virus (such as hepatitis- or AIDS-causing virus), if present. The heating is performed while the concentrate is lyophilized (or dried by another process). The heating steps in the sequence are for two or more different times, and at two or more different temperatures. After the heating sequence, the concentrate is reconstituted for use. This sequential method contemplates greater inactivation of different viral forms, or reduction of the heating required, or both. Reduction of heating requirements may appear as reduced overall heating time, or reduced aggregate power consumption, or both. Advantages include heightened quality-control assurance level. Also possibly, the invention offers some potential for preparation of vaccines against the virus, if sufficient quantity of the virus is present in the concentrate.

Abstract: Antibodies are provided, which are directed against a sequence of amino acids corresponding to amino acids from the sequence 111-207, in particular 148-161, of the A.alpha.-chain of fibrinogen. These novel antibodies react specifically with fibrin, both type I and type II, and not with fibrinogen. They are effective in detecting, preventing and treating blood clot formation.

Abstract: A compound of the formula II: ##STR1## wherein n is an integer of 2 to 10, A' is a bivalent linking group formed by reacting both the reactive groups of a cross linking reagent, andB is a residue of a polypeptide compound, and physiologically acceptable salts thereof are disclosed. Such compound is useful as a non-radioactive carrier for radioactive metal elements.

Abstract: The present invention relates to a chemical product usable as a non-radioactive carrier which comprises (1) a unit of a polyformyl compound having at least three formyl groups per molecule, (2) at least two units of an amino group-containing chelating compound bonded to the polyformyl compound by a methyleneimine linkage (--CH.dbd.N--) or a methyleneamine linkage (--CH.sub.2 NH--) between a formyl group in the polyformy compound and an amino group in the chelating compound, optionally followed by reduction, (3) at least one unit of an amino group-containing physiologically active substance bonded to the polyformyl compound by a methyleneimine linkage or a methyleneamine linkage between a formyl group in the polyformyl compound and the amino group in the physiologically active substance, optionally followed by reduction.

Abstract: Soluble, intermediate length alcohols (C.sub.4 -C.sub.10) in aqueous solutions at low pH (4.0-7.0) can be used as virucidal agents for therapeutic biologically active protein preparations. Treatment with the alcohols is especially useful for proteins having activity not adversely affected by low pH.

Abstract: A polypeptide having the cell-spreading activity of human fibronectin. Methods of preparing the polypeptide are described.

Abstract: A method and therapeutic composition for the treatment of bleeding disorders, for example those characterized by a tendency toward hemorrhage or a hypercoagulative state, by the administration of tissue factor protein or antagonists thereof.

Abstract: New fragments of the Factor VIII procoagulant protein (Factor VIIIC) are disclosed. These fragments have an Mr value of 88,000 d or 49,000 d or extend from amino acid residues 1974 to 2332 or 2052 to 2332. These fragments have use in the treatment of patients who have developed antibodies which inhibit Factor VIII.