Abstract: The present invention describes a mutant human tissue factor protein which binds functional Factor VII/VIIa but is substantially free of functional procoagulant cofactor activity, and compositions containing the mutant protein. Also disclosed are methods for using the mutant human tissue factor proteins, and recombinant DNA vectors for expressing the protein.

Abstract: A composition which, upon reacting with thrombin, functions as a fibrin sealant and is characterized as being free of detectable levels of lipid enveloped virus activity, free of prothrombin complex and active thrombin, and contains no protease inhibitors or other non-human proteins. Also, described is a method for producing the composition.

Abstract: A method of improving the therapeutic activity of von Willebrand Factor obtained from materials comprising on Willebrand Factor comprising incubating said Factor at a temperature of about 20.degree. C. to about 55.degree. C. for about 1 to about 30 hours, most preferably at from about 45.degree. C. to about 55.degree. C. for about 1 to about 5 hours.

Abstract: A method for treating urinary incontinence consisting of injecting human fibrin glue at or near the bladder neck until the urethral outflow resistance is restored. Human fibrin glue is the reaction product of human fibrinogen and thrombin in the presence of calcium chloride as catalyst.

Abstract: The invention relates to a stable preparation which comprises a protein that is bound in and/or on lipid vesicles and that was treated for the inactivation of potentially present viruses. Further, the invention relates to methods for the production of a stable preparation for the treatment of blood coagulation disorders, wherein a protein is bound in and/or on lipid vesicles, and the method comprises a step in which the protein lipid complex is subjected to a treatment for the inactivation of potentially present viruses.

Abstract: A description is given of the possibility of using transglutaminases in a process for the preparation of an immunosuppressant. Additionally described is a pharmaceutical containing a transglutaminase and a plasminogen activator inhibitor.

Abstract: Peptide ligands which bind to von Willebrand Factor (vWF) are disclosed. These peptides are selected from the group consisting of RLHSFY, RLKSFY, RLNSFY, RLQSFY, RFRSFY, RIRSFY, RVRSFY, RYRSFY, RLRSFY, HLRSFY, and KLRSFY. The preferred peptide ligand has the sequence RVRSFY. A method of using the disclosed peptides to purify vWF comprises binding the peptides to a support, then passing a solution containing vWF over the supports under condition such that the vWF will selectively bind to the peptides, and then eluting the vWF.

Abstract: The present invention is a method of using the BK enhances in tandem with a eukaryotic promoter to promote transcription of DNA that encodes a useful substance. The method of the present invention requires the presence of the E1A gene product for maximum expression of the useful substance. The present invention also comprises a number of useful expression vectors that comprise the BK enhancer in tandem with the adenovirus 2 late promoter positioned to drive expression of a variety of proteins, such as protein C, chloramphenicol acetyltransferase, and tissue plasminogen activator. The present invention further comprises a method for increasing the activity of the BK enhancer involving placement of the BK enhancer immediately upstream of the eukaryotic promoter used in tandem with the BK enhancer to drive expression of a useful substance. Furthermore, the present invention also comprises a method for coamplification of genes in primate cells.

Abstract: This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imagifig a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides.

Abstract: An 18 kDa protein, denominated FDF-3, has been isolated from cultures of human fibroblasts and has been found to potentiate the growth- and differentiation-promoting activities of certain cytokines toward hematopoietic progenitor cells. The amino acid sequence of the FDF-3 protein, shown in SEQ ID NO: 14, corresponds to the sequence of a C-terminal domain of human fibronectin. The protein is useful in combination with IL-3, G-CSF, GM-CSF, or SCF (stem cell factor) in the expansion of hematopoietic cell populations in vitro or in therapeutic methods to promote recovery from leukopenia or myelosuppresion in vivo.

Abstract: The present invention contemplates methods of decontaminating human fluids prior to processing in the clinical laboratory. The techniques handle large volumes of human serum without impairing the testing results. Novel compounds for photodecontaminating biological material are also contemplated which are compatible with clinical testing, in that they do not interfere with serum analytes.

Abstract: Several poly(ethylene glycol) mixed carbonates and their preparation are closed. These carbonates are synthesized by conversion of polyethylene glycol first to the chloroformate then by reaction with the hydroxyl group of N-hydroxybenzotriazole or 2-hydroxypyrimidine or N-hydroxy-2-pyrrolidinone. These mixed carbonate analogs smoothly react with amino groups in aminoglycans and protein and amino containing surfaces to form stable, hydrolysis resistant carbamate linkages.

Abstract: An improved assay for determining sensitivity to activated protein C in test samples has been developed to ensure rapid and accurate evaluations. This assay is based on measuring the conversion, by activated factor VIII within a test sample, of added factor X to an activated form. The activated protein C sensitivity of the test sample is determined by the relative inhibition of factor X conversion as compared to a control. A test sample that has decreased sensitivity to activated protein C will show relatively low inhibition, and vice versa.

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 immunoadsorbent comprising a monoclonal antibody, and the active, highly purified and concentrated vitamin K-dependent protein produced by the method.

Abstract: A method for the separation of vitamin K-dependent proteins from non-vitamin K-dependent accompanying proteins is described wherein the method is characterized in that at least anion exchange chromatography and optionally affinity chromatography is carried out as well. The method is suitable especially for the purification of Factor II, VII, IX, X as well as Protein S, Protein C and Protein Z. With the aid of the method according to the invention a vitamin K-dependent protein is obtained which is present at a purity of 95%.

Abstract: A prothrombin time reagent is disclosed for use in a prothrombin time test. The reagent utilizes recombinant human tissue factor, phospholipids of a natural or synthetic origin, a buffer composition and calcium ion. Stabilizers and salts may also be utilized in the reagent. In addition, a method for creating lipid micelles containing tissue factor is also disclosed.

Abstract: Conjugates containing a substance with coagulant activity, such as recombinant Factor IX, non-antigenic polymers, such as poly(ethylene glycol), are disclosed. Also disclosed are methods of forming the novel conjugates of this invention.

Abstract: Functional human factor VIII produced recombinantly is used in the treatment of human beings diagnosed to be deficient in factor VIII coagulant activity. Also provided are DNA isolates and expression vehicles encoding functional human factor VIII, as well as transformed host cells and processes for producing human factor VIII by use of recombinant DNA technology.

Abstract: Pharmaceutical compositions comprising active, highly purified, and concentrated Factor IX proteins are provided. The Factor IX proteins are recovered from plasma or recombinant cell culture sources by a process involving immunoaffinity chromatography conducted in the presence of a chelating agent and in the absence of an exogenous non-chelating protease inhibitor.

Abstract: The use of human Protein C for the prevention and treatment of deposition or aggregation of thrombocytes, microparticles of thrombocytes, and leucocytes is described. In addition, an improved method for the extra-corporeal treatment of body fluids is disclosed.

Abstract: Highly purified factor XIII and methods of purifying factor XIII are disclosed. Factor XIII is purified from a biological fluid, such as a cell lysate. The methods provide factor XIII compositions that are greater than 99% pure with respect to contaminating proteins. The methods further provide factor XIII compositions wherein 1% or less of the factor XIII is activated factor XIII.

Abstract: The present invention relates to a virus-safe blood coagulation factor XIII preparation, which is obtained by heating an aqueous solution containing the blood coagulation factor XIII having a specific activity of at least 2 U/mg of total protein, wherein the solution containing less than 10% of known stabilizers selected from the group consisting of sugars, polyols, amino acids, peptides and carboxylic acids, as well as less than 0.5 mol ammonium sulfate per liter, wherein the heating is effected for a period of time sufficient to inactivate infectious agents, preferably for a period of time of from 30 min to 100 h.

Abstract: A coagulation active complex of Factor VIII fragments is produced by causing coagulation inactive FVIII heavy chain to react with coagulation inactive FVIII light chain in the presence of a complex forming agent. Thus, FVIII-HC and FVIII-LC are converted to coagulation active FVIII complex in the presence of divalent metal ions, such as Mn.sup.2+, Ca.sup.2+ or C.sup.2+, or a component of the pro-thrombin complex.

Abstract: Blood loss in a patient undergoing surgery, particularly thoracic or abdominal surgery, is reduced by administration of factor XIII. The factor XIII may be administered in combination with aprotinin.

Abstract: A process for producing a highly purified preparation of an inhibited form of an activated blood factor entails providing a partially purified preparation containing the blood factor of interest, treating the partially purified preparation to convert the blood factor to an inhibited activated form in a single step, and then purifying the resulting inhibited activated blood factor.

Abstract: A method of making a platelet releasate product is disclosed involving performing an assay on a platelet releasate sample for a component of the releasate and forming platelet releasate product by comparing the assay results to a predetermined range of amounts of the component to be contained in the product. A method of treatment of tissue is disclosed involving the topical application of such product.

Abstract: Processes for reactivating membrane proteins are disclosed.

Abstract: Peptides which inhibit the binding of yon 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 virus-inactivated Factor-Xa preparation with at least 100 units coagulation factor activity per mg protein is described, wherein this preparation is produced by activation of a corresponding starting material and subsequent treatment for the inactivation of infectious agents, particularly viruses. By incubation, the preparation obtained in this manner is transformed into a stable beta-Factor Xa preparation. In addition, the use of the present preparation for the treatment of hemophilia A inhibitor patients is disclosed.

Abstract: A process for producing a highly purified preparation of an inhibited form of an activated blood factor entails providing a partially purified preparation containing the blood factor of interest, treating the partially purified preparation to convert the blood factor to an inhibited activated form in a single step, and then purifying the resulting inhibited activated blood factor.

Abstract: The present invention relates to a method and therapeutic composition for the treatment of myocardial infarction comprising administration of a tissue factor protein antagonist and a thrombolytic agent.

Abstract: DNA enclosing a tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.blll.sub.a inhibitor.

Abstract: A process for producing a highly purified preparation of an inhibited form of an activated blood factor entails providing a partially purified preparation containing the blood factor of interest, treating the partially purified preparation to convert the blood factor to an inhibited activated form in a single step, and then purifying the resulting inhibited activated blood factor.

Abstract: Chimeric blood coagulation proteins are disclosed. The proteins are (i) coagulation factor V in which at least one A3, C1 or C2 domain exon thereof is replaced with the homologous exon of coagulation factor VIII; or (ii) coagulation factor VIII in which at least one A3, C1 or C2 domain exon thereof is replaced with the homologous exon of coagulation factor V. The chimeric proteins are useful for diagnostic purposes in epitope mapping and for therapeutic purposes in facilitating blood coagulations in patients in need of such treatment.

Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilic conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.

Abstract: A test article for determining coagulation capability in a blood sample comprises a porous membrane having a coagulation initiator and substrate impregnated therein. The pore dimensions and composition of the membrane may be selected so that only blood plasma can pass into the interior of the membrane, where coagulation is initiated. Alternatively, the substrate may be selected to have an emission and/or excitation wavelength which is not absorbed by hemoglobin. The substrate is activated by a component of the coagulation pathway, typically thrombin, and produces a detectable signal upon activation. By utilizing membrane matrix materials which are substantially free from interference with the coagulation pathway, accurate results can be achieved.

Abstract: Stabilized and activated Factor VIII is used as a therapeutic agent to treat patients with a Factor VIII deficiency. This includes hemophilia A patients as well as patients with Factor VIII inhibitors which block the hemostatic activity of Factor VIII. The stabilized and activated Factor VIII is also prepared in a therapeutic composition with a therapeutically acceptable adjuvant.

Abstract: The invention relates to a method for determining platelet aggregation in the presence of an inhibitor of fibrin aggregation, which prevents the formation of an interfering fibrin clot, and to a diagnostic aid for determining the platelet aggregation-inhibiting action of thrombin inhibitors.

Abstract: This invention provides a selective cellular fibronectin (cFN) adsorbent utilizing a nonwoven cellulose sulfate fabric and a method for fractional purification of FN which comprises contacting an FN matter containing both plasma fibronectin (pFN) and cellular fibronectin (cFN) with the nonwoven cellulose sulfate fabric to separate pFN and cFN from each other. By the fractional purification method of the invention, cFN and pFN can be fractionated in an expedient manner and with high efficiency and both pFN and cFN can be recovered in high purity and good yield.

Abstract: Therapeutic agent for threatened abortion which contains human blood coagulation factor XIII as the active ingredient. Human blood coagulation factor XIII administered to patients with threatened abortion successfully treats the disease, and its effects are marked.

Abstract: The present invention relates to a process for producing recombinant desulphatohirudin by means of culturing microorganisms.Concerning the codon usage of microorganisms the synthesized nucleotide sequences were joined downstream of and in reading frame with isolated promoters and signal sequences, subsequently the expression/secretion cassettes comprising the foregoing elements were inserted into plasmid DNAs allowing the cultivation of cells under selective culture conditions. E. coli, Saccharomyces and Streptomyces species were transformed with the said recombinant plasmids to biosynthesize the thrombin inhibitor desulphatohirudin HV-1 which was then isolated and identified.The thus-produced desulphatohirudin can be used to inhibit blood coagulation.

Abstract: This invention relates to methods of removing undesired antibodies from blood-derived compositions containing both the antibodies and coagulation factors, such that the coagulation factors are substantially retained in the composition. The undesired antibodies may be blood group antibodies. This invention also relates to compositions in which undesired antibodies have been removed and desired coagulation factors are retained. This invention further relates to methods of inactivating virus and removing undesired antibodies from blood-derived compositions containing virus, antibodies and coagulation factors without removing coagulation factors therefrom, and to the resulting compositions.

Abstract: There is disclosed the use of prothrombin fragments, preferably of human prothrombin fragments, having a thrombin-like activity, in particular of meizothrombin, meizo thrombin (desF1), or mixtures thereof, for diagnostic purposes for assaying thrombin substrates as well as a reagent containing these prothrombin fragments.

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: Assay methods for diagnosing blood clotting disorders are described. The assays use data bases for pooled normal plasma (PNP) and plasma from healthy volunteers, males and females ages 18 to 64 years. Charting on a comparative basis of patient plasma and PNP allows the results to be interpreted by reference to the data base. Simple, rapid, inexpensive and highly sensitive and specific assays devised for diagnosing blood clotting disorders are described.

Abstract: The present invention relates to a novel DNA sequence coding for factor IX or a similar protein, corresponding to a prosequence and to mature factor IX or the mature similar protein. According to the invention, position (-3) in the prosequence is occupied by a codon coding for valine, arginine, lysine, threonine or serine, and/or the first codon of the sequence coding for the mature protein codes for an alanine.

Abstract: Soluble azoles in aqueous solutions can be used as virucidal agents for biologically active protein preparations.

Abstract: A thromboplastin extract including an aqueous thromboplastin extract of a powdered thromboplastin source including a metal ion chelator. A thromboplastin reagent for use in blood coagulation tests, the thromboplastin reagent includes the extract and calcium ions, and may include one or more of a stabilizer and a preservative.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. 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 Prothrombin Time (PT) is used as a screening test for blood coagulation factor deficiencies and for monitoring oral anti-coagulant therapy using coumadin. Thromboplastin reagents activate the extrinsic pathway of coagulation and are the basis for the Prothrombin Time (PT) test. This invention describes the use of barium sulfate and chaotropic agents, and nonionic detergents, for the extraction of sensitive thromboplastin reagents from tissue. Extraction with sodium thiocyanate alone also greatly enhances thromboplastin sensitivity. This invention should be useful for all thromboplastins and will improve their sensitivity for all PT-based tests and specific assays.

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.