Abstract: Methods are provided for measuring the procoagulant activity of platelets in blood by means of a chromogenic assay which is specific for procoagulant phospholipids. These methods include the determination of the resting activity and/or excitability of platelets, which determines the threshold at which activating clotting factors (circulating in blood) are dangerous. Also methods are provided for screening drugs for their potential inhibitory effect on the activation of platelets.

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: Peptides which inhibit the binding of von Willebrand Factor to Factor VIII. Monoclonal antibodies capable of specifically binding to the region of von Willebrand Factor containing the Factor VIII binding domain. Improved methods of preparing Factor VIII.

Abstract: Novel soluble oxidation resistant thrombomodulin analogs are produced for various therapeutic and other uses, such as in thrombotic and vascular disease therapies. These analogs exhibit the characteristic therapeutic properties of native thrombomodulin, yet they are soluble and are not inactivated after they have been exposed to oxidants. Some of the analogs disclosed are multifunctional fusion proteins having both antithrombotic activity and some additional bioactivity.

Abstract: A process for preparing a thromboplastin extract including extracting a powdered thromboplastin source in an aqueous solution having a metal ion chelator, and separating the powder in solution into sedimented powder and supernatant thromboplastin extract is disclosed. The supernatant thromboplastin extract is mixed with calcium ions, and may be mixed with one or more of a stabilizer and a preservative, to prepare thromboplastin reagent.

Abstract: The invention relates to synthetic peptides which contain certain partial sequences from factor VIIa, the synthesis thereof and the use of these peptides for immunizing an animal and for purifying specific antibodies against the said peptides, to antibodies against these peptides and the use of these antibodies and peptides in therapy and diagnosis.

Abstract: The invention relates to a human Factor XI concentrate having high specific activity prepared using a process comprising a filtration-adsorption step and a single step of chromatography on cation exchange resin.The concentrate obtained is perfectly suitable for therapeutic use in replacement therapy in cases of Factor XI deficiency.

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: A method for isolating Factor VIII from other proteins dissolved in blood plasma is disclosed, wherein plasma is subjected to gel filtration under group separation conditions giving a fraction containing Factor VIII in very high yield and almost free of other proteins.

Abstract: The subject invention concerns novel methods and compositions for thrombolytic therapy. More specifically, a receptor with high affinity for plasmin has been characterized, purified, cloned, and expressed. This receptor can be used in combination therapies where it is administered prior to, concurrently with, or after a plasminogen activator. Also, this receptor can be bound to plasmin and administered to humans or animals in need of fibrinolytic activity. Additionally, the invention pertains to a novel immobilized form of plasmin which advantageously accumulates at the point where antifibrinolytic activity is needed.

Abstract: A method for determination of biological activity of AT III which comprises mixing a specimen, AT III free-extrinsic coagulation factor-containing plasma, heparin and a prothrombin time-measuring reagent or a factor X-activating reagent and then measuring a coagulation time, and a reagent and plasma to be used therefor.

Abstract: The present invention describes a process for activating Factor II to Factor II.sub.a by incubating Factor II in the presence of Factor V, Factor X.sub.a, phospholipids, and calcium ions. Each of the factors is prepared from a single impure protein fraction which includes Factors II, V and X. The Factor II, V and X purification procedure comprises the steps of DEAE ligand chromatography and precipitation by the addition of barium chloride. Factor V is recovered from the barium chloride supernatant, and Factors II and X are contained in the barium chloride precipitate. The barium chloride precipitate is dissolved in an aqueous solution and is applied to a chromatographic resin coupled with a ligand which binds Factor X and Factor II weakly or not at all. Factor II is recovered from the fraction, which remains unbound or weakly bound to the Factor X binding ligand. Factor X.sub.

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: Polypeptides which are derived from the Arg-Gly-Asp (RGD) binding portion of an Integrin beta subunit are disclosed as are their use for modulation of Integrin ligand binding. Anti-peptide antibodies, hybridomas secreting these antibodies, as well as methods of making and using such antibodies, and recombinant DNA molecules that define the structural gene coding for the polypeptides are also contemplated as within the scope of the present invention.

Abstract: This invention relates to a novel glycoprotein with anticoagulant activity in human urine, a process for its preparation and a pharmaceutical composition comprising the said glycoprotein for the prevention and/or treatment of diseases related to the disorders in the blood coagulation system.

Abstract: An improved method for producing Factor VIII:c is disclosed. The method involves culturing mammalian cells which contain DNA encoding Factor VIII:c and which are capable of expressing Factor VIII:c. In accordance with this invention the cells are cultured in a medium containing an effective amount of a Factor VIII:c-stabilizing substance comprising (a) von Willebrand Factor (VWF), (b) a phospholipid or phospholipid mixture, or a mixture of (a) and (b).

Abstract: The present invention relates to a method for preparing activated protein C (APC) from a sample containing the said activated protein C, characterized in that the activated protein C is bound to insolubilized aprotinin and then in that, after washing of the said activated protein C/aprotinin complex with a buffered saline solution, the said activated protein C is collected by elution with an acidic aqueous solution or a solution containing a chaotropic agent.The invention also relates to the activated protein C thereby obtained according to the method described above.

Abstract: A method of inhibiting angiogenesis and preparations for use therein are disclosed. The preparations comprise human thrombospondin in trimer or monomer form or a fragment thereof capable of inhibiting vascularization. The method and preparations are especially applicable to the treatment of solid tumors including skin cancers for controlling tumor neovascularization and thereby arresting tumor enlargement.

Abstract: A method for treating patients suffering from bleeding disorders not caused by clotting factor defects or clotting factor inhibitors, as well as a novel composition for use in treating bleeding disorders as disclosed. The method includes administering to a patient a composition comprising an effective haemostatic amount of factor VIIa, and is particularly effective in treating patients suffering from thrombocytopenia and von Willebrand's disease, as well as other platelet disorders. A composition suitable for use in treating such bleeding disorders comprises purified factor VIIa in a concentration of at least 25 .mu.g/ ml.

Abstract: The blood-clotting protein, factor IX, is synthesized in the bod in liver cells, where it undergoes three distinct types of post-translational modification before it is secreted into the bloodstream as a 415 amino acid long protein. It is therefore a difficult protein to produce by recombinant DNA technology in a highly biologically active form. Nevertheless, such a result has been achieved by the present invention in which typically factor IX cDNA in a plasmid is linearized and inserted into an expression vector having a promoter sequence of SV40 early gene, an SV40 polyadenylation sequence, the TK/NEO selectable marker and an ampicillin resistance gene. Mammalian cells such as from a dog kidney or rat liver are transfected by the calcium phosphate precipitation method.

Abstract: Modified HV1-type hirudinin which valine at the N-terminal end of the HV1-type hirudin and aspartic acid at the 5th residue of the N-terminal end were replaced with alanine and glutamic acid, respectively. A secretion plasmid into which a DNA sequence coding for a precursor with an addition of a secretion signal of neutral protease of Bacillus amyloliquefaciens at the N-terminal end of this modified HV1-type hirudin is integrated is introduced into bacteria of the genus Bacillus and the precursor is expressed intracellularly. The modified HV1-type hirudin can be efficiently secreted extracellularly while maintaining its high thrombin inhibiting activity.

Abstract: An agent for the therapy of diabetic gangrene is described containing blood coagulation factor XIII as the active ingredient.

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: Compositions, and methods of use thereof, for the inhibition of tumor growth and killing of tumors having extensive microcirculation wherein the active agent is a compound blocking the Protein C system, preferably anti-Protein C antibody, anti-Protein S antibody, and C4b binding protein. In the most preferred embodiment, the Protein C blocking compound is provided in combination with a cytokine such as tumor necrosis factor (TNF), gamma interferon, interleukin-1, interleukin-2 and granulocyte-macrophage colony stimulating factor. Examples are provided demonstrating the administration of the Protein C blocking compound, alone or in combination with TNF, to dogs having canine veneral tumors, or fibrosarcoma, and an adenocarcinoma, and pigs with melanoma followed by significant tumor reduction.

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: An anticoagulant composition containing an effective amount of factor Xa having the active serine site inactivated that functions rapidly and effectively in vivo to suppress coagulation. In a preferred embodiment, Factor Xa, a serine esterase that forms a complex with Factor Va, Ca++, and phospholipid to catalyze prothrombin activation, is first inactivated with an active site inhibitor, such as dansyl-glu- gly-arg-chloromethyl ketone, to form inactivated factor Xa. In another embodiment, Factor Xa is expressed from a gene sequence wherein the portion encoding the active serine region is modified. The inactivated protein retains the ability to bind to endogenous factor Va in vivo, and has a half-life of approximately ten hours. Administration of inactive factor Xa to the blood of a patient results in the formation of inactive factor Xa-Va complexes in vivo, thereby inhibiting coagulation.

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: There is provided in accordance with the practice of this invention, a process for separating Factor VIII complex from an impure protein fraction containing Factor VIII complex. An aqueous solution of the impure protein fraction containing Factor VIII complex is applied to a heparin coupled chromatographic medium to bind the Factor VIII complex to the medium. The Factor VIII is then recovered from the heparin coupled chromatographic medium by elution with an aqueous CaCl.sub.2 solution.

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: 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: The separation material for separating and recovering a blood coagulation factor comprises a porous matrix having linked thereon one or more ligands each consisting of a radical exhibiting an affinity for the blood coagulation factor to be recovered, said matrix having a specific surface area of at least 1.5 m.sup.2 per milliliter of the separation material with respect to pores having diameters of at least 0.1 .mu.m and being derived from a porous particulate material having an exclusion limit molecular weight of at least 1.5.times.1.sup.6 as determined with polyethylene glycol. The separation material is prepared by the process steps of subjecting a porous particulate material having an exclusion limit molecular weight of at least 1.5.times.10.sup.

Abstract: A method for determination of biological activity of AT III by measuring coagulating time of blood plasma comprises mixing a specimen having AT III free-extrinsic coagulation factor-containing plasma, heparin and a prothrombin time-measuring reagent or a factor X-activating reagent and then measuring the coagulation time, and a reagent and plasma to be used therefor.

Abstract: The invention relates to a new active substance--amblyommin--for anticoagulant therapy and to a process for the isolation thereof from hard ticks. The isolated protein having a thrombin-inhibitory action has a molecular weight of 20000 to 30000 dalton, an isoelectric point between 5.05 and 5.65 and the partial amino acid sequencesIle-Leu-Phe-Thr-Gln-Gly-Asn-X-Gly-Glu-Leu-Glu-Asn-X-Phe-Glu-,Lys-Ile-Leu-Phe-X-Gln-Gly- andAla-Ser-Tyr-Ile-Val-X-Ser-Glu-Ser-Ile-Gln-Ile-Leu-X-Leu-Ser-Glu-Gly-Ile-in which each radical X can be identical or different and each represents a naturally occurring amino acid.

Abstract: An agent for the therapy of hemophilia A which is resistant to treatment with factor VIII is described, and is obtainable by maintaining a mixture of factor VIII, antithrombin III, a phospholipid and calcium ions in an aqueous solution at a temperature of from 1.degree. to 45.degree. C. for at least one minute, adding factor IX, and maintaining the solution at a temperature offrom 1.degree. to 45.degree. C. until addition of a sample of this solution to an inhibitor plasma results in a partial thromboplastin time (PTT) of 15 to 30 seconds, where appropriate adding a polyol and, where appropriate, an amino acid, and, where appropriate, drying the solution.

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 method for the separation of blood into the components thereof, characterized by subjecting the blood to strong centrifugation thereby separating said blood into an upper layer (A) of platelet-deficient blood plasma an intermediate layer (B) of a mixture of platelets and white blood corpuscles, and a lower layer (C) of a red blood corpuscle concentrate, adjusting the hematocrit value of said red blood corpuscle concentrate of (C) to not more than 80% by diluting said red blood corpuscle concentrate with part of said platelet-deficient blood plasma of (A), and subjecting said mixture of (B) to weak centrifugation thereby separating said mixture into a lower layer of white blood corpuscles and an upper layer of a platelet concentrate, and if desired, subjecting the remaining platelet-deficient blood plasma to the treatments of freezing, thawing, and centrifugation thereby separating said platelet-deficient blood plasma into cryoprecipitate and cryoprecipitate-deficient blood plasma, and apparatus therefor.

Abstract: A method of enrichment of coagulation Factors II, VII, IX and X in preparations obtained from plasma, plasma fractions, or other liquids containing the factors, by adsorbing the factor or factors onto a polymeric matrix that carries an .alpha.-hydroxylamine group, and eluting the factors. When the chromatography conditions are appropriate, it is also easy to prepare a highly concentrated Factor IX preparation with a purity of more than 10 U per mg of protein.

Abstract: This invention discloses proteins which inhibit the coagulation of the blood, processes for preparing these proteins, and the use thereof.

Abstract: This invention discloses proteins which inhibit the coagulation of the blood, processes for preparing these proteins, and the use thereof.

Abstract: A method of isolating blood-clotting Factor IX. A solution containing the Factor IX is adsorbed onto an adsorbent carrying .alpha.-hydroxylamine groups, and the factor is eluted. The Factor IX from the eluate is adsorbed onto a matrix carrying sulfated carbohydrates, with the conductivity adjusted to 13-17 mS/cm, and eluted with a salt gradient. The pure Factor IX is concentrated and freeze-dried.

Abstract: A method of recovering active, highly purified and concentrated vitamin K-dependent proteins from plasma, concentrate or mixtures of proteins produced by recombinant DNA technology using an immuno adsorbent comprising a monoclonal antibody.

Abstract: The present invention is directed to immunochemical detection procedures, e.g., using both Western blotting and direct immunoassays, for Factor V/Va and Factor V/Va fragments, which can thus be used; (a) in a predictive manner to evaluate the existence and/or extent of a thrombotic complication; (b) to monitor the efficacy of prophylaxis for a thrombotic condition; and (c) as a means to evaluate potential risk of hemorrhage during thrombolytic therapy.

Abstract: The invention relates to a method for the purification of the a subunit of factor XIII by affinity chromatography, to a therapeutic composition containing the latter, and to the use of the therapeutic composition.Factor XIII has hitherto been purified either by methods which are technically very elaborate or else by use of toxic affinity chromatography materials. The invention has the aim of providing an improved method for the purification of the a subunit of factor XIII.Factor XIII is obtained according to the invention by a method in which the a subunit of factor XIII is reversibly bound to a matrix suitable for disulfide exchange reactions and is removed from the matrix by reaction with a reducing agent. The method according to the invention makes it possible to provide the biologically active a subunit of factor XIII in high purity.

Abstract: Peptides which inhibit the binding of von Willebrand Factor to Factor VIII. Monoclonal antibodies capable of specifically binding to the region of von Willebrand Factor containing the Factor VIII binding domain. Improved methods of preparing Factor VIII.

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: A method of preparing von Willebrand Factor by disassociating it from a chaotropic agent in solution therewith and preferably treating the same under controlled temperature either in liquid or lyophilized form.

Abstract: Hybrid procoagulant proteins are disclosed which contain peptide sequences of human blood coagulation factors V and VIII. DNA molecules encoding these proteins and materials and methods for expressing them are also disclosed. Preferably, peptide sequence in the B domain of Factor VIII is replaced with peptide sequence derived from human Factor V.

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: The present invention is directed to in vitro and in vivo immunodiagnosis and immunotherapy using monoclonal antibodies reactive with difucosyl blood group antigens Y-6 and B-7-2.

Abstract: The invention relates to a fully solubilizable fibrin based composition, which is characterized by the combination that the fibrin is desAA-fibrin or desAA-fibrin from which the C-terminal portions of the .alpha.-chains have been removed by enzymatic digestion, and that the solubilizing agent is a tetrapeptide containing the amino acid sequence -L-prolyl-L-arginyl-, preferably glycyl-L-prolyl-L-arginyl-L-prolin.The full solubility of the fibrin makes possible new uses within the area of determination of important fibrinolytical parameters, and the invention also relates to three such important alternative uses. A first use according to the invention is the use of the composition in connection with detection or quantification of the activity of the enzyme tissue plasminogen activator.