Abstract: The invention relates to the use of glycylglycine, optionally in combination with a sugar, and/or a sugar alcohol, and/or an amino acid, as a bulking agent in freeze-drying.

Abstract: The invention is directed to novel, purified and isolated FIL-1 theta polypeptides and fragments thereof, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and uses thereof.

Abstract: Factor X analogues having a modification in the region of the natural Factor Xa activation cleavage site, said modification representing a processing site of a protease not naturally cleaving in this region of the Factor X sequence, preparations containing the Factor X analogues according to the invention, and processes for the preparation thereof are described.

Abstract: The present invention relates to novel human coagulation Factor VIIa variants having coagulant activity as well as polynucleotide constructs encoding such variants, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.

Abstract: The invention provides vitamin K-dependent polypeptides with enhanced membrane binding affinity. These polypeptides can be used to modulate clot formation in mammals. Methods of modulating clot formation in mammals are also described.

Abstract: Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.

Abstract: Proteins comprising one or more copies of von Willebrand factor type A domain play important roles in host defense mechanisms, such as immune response, inflammation, and hemostasis. Zvwf1 is a new member of this superfamily.

Abstract: Bypass activity for hemophilia A and B can be generated by natural or recombinant Factor VIIa. Factor XIIa when implanted into a guinea pig or monkey also facilitates the conversion of endogenous factor VII to VIIa, thereby providing bypass activity. Additionally, certain modified versions of Factor XII are known to be intrinsically active, with properties like Factor XIIa. Administration of unencapsulated Factor XIIa to a guinea pig causes a transient increase in plasma bypass activity. A continuous source of Factor XIIa, as provided by a gene therapy, is therapeutic for both Hemophilia A and B. There are three ways to provide for gene therapy. In each case, the gene for Factor XII (or Factor XIIa) can be introduced into the cell by the usual means, including, but not limited to, as naked DNA, as a DNA/lipid mixture, or as part of a viral vector system.

Abstract: Contaminant viruses can be efficiently removed almost without losing the activity of protein by subjecting a plasma protein composition having a high risk of viral contamination to a treatment with a porous membrane having a pore size greater than a single-particle size of the virus, particularly by subjecting a plasma protein composition to a fractionation treatment by precipitation, before the porous membrane treatment. Particularly, a fibrinogen composition substantially free of non-enveloped viruses, Parvovirus among others, can be provided. By the application of the present invention, a safe plasma protein preparation free of viruses can be conveniently provided.

Abstract: A high-purity von Willebrand factor preparation, a process for making it, and use of the preparation and compositions containing it for the treatment of disorders are disclosed.

Abstract: The present invention relates to novel human coagulation Factor VII polypeptides, Factor VII derivatives as well as polynucleotide constructs encoding such polypeptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.

Abstract: A means for stable preparing a composition, which comprises plasma component derived from human or animals, at least fibrinogen, which is blood coagulation factor, and factor V, is provided, and the composition prepared remains stable even when allowed to stand over one day or longer in a freeze-dried state, in freeze-thawed state, in a refrigerator, or under room temperature. By adding an inhibitor of Factor XIII in an effective amount for achieving the inhibitory effect, compositions comprising human or animal plasma components, at least fibrinogen and Factor V, which are blood coagulation factors, and reagents for measuring extrinsic coagulation factor for blood coagulation function comprising at least thromboplastin, Factor V and fibrinogen can be stabilized during preparation, storage and measurement.

Abstract: Peptides derived from amino acids 307 to 356 of the human blood coagulation factor Va are provided. Such peptides comprise: i) a length of between 3 and 50 amino acids, ii) a minimum of 3 contiguous amino acids from the 307-356 heavy chain region of factor Va, excluding peptide segments comprising amino acids 311 to 325 and amino acids 321 to 335, iii) optional additional amino acids at one or both ends of the contiguous amino acids such that the entire peptide is at least 60% identical to a sequence within 307 to 356 of factor Va, and iv) have an IC50 of between 50 nM to 500 &mgr;M for inhibition of prothrombinase. The present invention also provides a pharmaceutical composition comprising one or more prothrombinase-inhibiting peptide segments. The present invention also provides administration of the pharmaceutical composition to human subjects for the purpose of preventing thrombotic disorders.

Abstract: A process for producing an intravenously-administrable gamma globulin solution substantially free of contaminating viruses by fractionating an impure gamma globulin solution and then treating the purified gamma globulin, in any order, with a solvent-detergent for viral inactivation and a heat treating for viral inactivation. Thereafter, denatured impurities, residual solvent and aggregate generated by the heat treatment are removed from the gamma globulin.

Abstract: Drugs in which peptides having affinity specific for phospholipids, preferably those which are contained in the constituents of lipid bilayers forming the surface layers of cells and of which the proportion in the outer part of each lipid bilayer increases when the cell is not normal, for example, in the case where it is damaged, denatured or activated, and biologically active substances bind to each other, deoxyribonucleic acid (DNA) which codes for the amino acid sequence of the drug in the case where the biologically active substance is a peptide, and processes for producing such drugs. The drugs and novel peptides are useful as preventives and therapeutics of diseases involving coagulopathy, inflammations and immune response.

Abstract: Methods for detecting human factor VIII or factor VIII-like polypeptides in and isolating it from solutions such as blood or conditioned media are disclosed, together with reagents suitable for the purpose comprising binding moieties that recognize human factor VIII and/or a factor VIII-like polypeptide and form a binding complex therewith. Preferred polypeptide binding moieties are particularly disclosed.

Abstract: The present invention provides new compositions and methods to induce therapeutic angiogenesis locally utilizing a collagen binding domain to target an angiogenesis modulating agents. Fusion polypeptides containing a collagen binding domain linked to an angiogenesis modulating agent are provided, as are nucleic acid sequences encoding the fusion polypeptides. Also included are methods for locally altering circulation by administering a fusion polypeptide consisting of a collagen binding domain linked to an angiogenesis modulating agent, or by administering a nucleic acid sequences encoding the fusion polypeptide. Tissue grafts in which isolated tissue is treated with a fusion polypeptide consisting of a collagen binding domain linked to an angiogenesis modulating agent, or with a nucleic acid sequences encoding the fusion polypeptide are also provided, as are methods of making the grafts.

Abstract: Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5′-untranslated and 3′-untranslated region, which is substituted with a 5-′ and 3′- end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

Abstract: The present invention provides preparations of Factor VIIa polypeptides or Factor VIIa-related polypeptides that exhibit predetermined glycoform patterns. The preparations of the invention exhibit improved functional properties and are useful for treating Factor VII-mediated conditions.

Abstract: In accordance with the present invention a novel fibrin polymer structure is disclosed. The novel fibrin polymer structure useful, for example, as a surgical sealant, is comprised of a plurality of discrete, droplets of polymerizing or polymerized fibrin each encapsulated by a “skin” of fibrin polymer. These fibrin-skin encapsulated droplets are applied so as to be built up one upon the other, layer by layer, to form an integral sealant structure. The cumulative effect of the encapsulating skins of those droplets which form the sealant surface is a surface skin which unexpectedly resists cell penetration but enhances cell migration across the surface. The sealant structure of the present invention can be prepared by spray delivery of fibrin polymer forming materials wherein the time required for the materials to commence polymerizing after mixing is less than or equal to the transit time of said materials from the applicator tip to the target surface.

Abstract: The complete sequence of the canine von Willebrand Factor cDNA and deduced amino acid sequence is provided. The mutation which causes von Willebrand's Disease in Scottish Terriers, Doberman pinschers, Shetland sheepdogs, Manchester terriers and Poodles are also provided. Methods for detecting carriers of the defective vWF gene are also provided.

Abstract: Modifications of vitamin K-dependent polypeptides that lead to enhanced protein function on a weight or molar basis and/or increase of protein lifetime in the circulation are described. Both objectives are important for using vitamin K-dependent polypeptides for pro- and anti-coagulation therapies, as well as for other uses in the circulation.

Abstract: A DNA construct is disclosed which encodes a fusion protein comprising an amino acid sequence of a blood clotting factor like Factor IX and an amino acid sequence of the cytoplasmic domain of P-Selectin. Such construct may be used for the somatic gene therapy of patients suffering from a defiency of a blood coagulation factor.

Abstract: There is disclosed a method of recovering factor VIII/vWF-complex which is characterized in that factor VIII/vWF-complex from a protein solution is bound to a cation exchanger and is recovered by step-wise elution of factor VIII/vWF-complex, which particularly contains high-molecular vWF multimers, as well as a factor VIII/vWF-complex obtainable by means of cation exchange chromatography.

Abstract: The invention relates to a method of removing endotoxin from preparations of alpha-1-acid glycoprotein (orosomucoid) by contact with a finely divided non-toxic resin such as fumed silica. The invention also relates to a purification process for alpha-1-acid glycoprotein which includes this deprogenation step, and to the depyrogenated product and its clinical uses.

Abstract: The present invention relates to a process for increasing the FVII sensitivity of a thromboplastin reagent by means of heat treatment.

Abstract: Provided by the present invention are novel compositions and methods for obtaining concentrated preparations of factor IX and formulations of factor IX suitable for storage and administration.

Abstract: A non-naturally occuring Factor IX protein having an amino acid substitution at amino acid position 338 is provided. Preferred substitutions include the substitution of analanine, leucine, or valine for the arginine at amino acid position 338. Factor IX of the present invention is non-naturally occuring (e.g., does not contain only an arginine to proline substitution at amino acid position 338). Factor IX proteins of the invention are useful for facilitating blood clotting in subjects in need thereof, such as subjects afflicted with hemophilia B. Pharmaceutical formulations comprising Factor IX of the invention are provided, along with nucleic acids encoding the same and vectors containing such nucleic acids.

Abstract: There are disclosed a stable factor VIII/vWF-complex, particularly comprising high-molecular vWF multimers, being free from low-molecular vWF molecules and from proteolytic vWF degradation products, as well as a method of producing this complex.

Abstract: The application relates to a method for determining the anticoagulatory potential of a sample by adding thrombomodulin and thromboplastin in a coagulation test.

Abstract: The present invention relates to a process for increasing the FVII sensitivity of a thromboplastin reagent by means of heat treatment.

Abstract: Proteins comprising one or more copies of von Willebrand factor type A domain play important roles in host defense mechanisms, such as immune response, inflammation, and hemostasis. Zvwf1 is a new member of this superfamily.

Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.

Abstract: The invention relates to a pharmaceutical composition comprising Factor VIIa for subcutan, intramuscular or interdermal administration. Factor VIIa administered subcutanously, intramuscularly or intradermally shows a sufficient transport into the bloodstream in biologically active form and in adequate concentrations, and favorable pharmacokinetic properties.

Abstract: The present invention relates to novel compounds and pharmaceutical composition, their preparation, and their use, having a antithrombotic effect through reversible inhibition of activated blood coagulation factor VIIa “FVIIa”.

Abstract: The present invention relates to biologically active peptides which specifically inhibit the Factor IX-dependent pathway of blood coagulation. These peptides are based on a specific motif which represents a sequence of Factor VIII (amino acid 1811-1818) involved in binding to activated Factor IX as well as to the intact Factor IX zymogen. Binding of said peptides to Factor IX or activated derivatives thereof effectively inhibits complex assembly with Factor VIII. These peptides thereby specifically interfere in the Factor IX-dependent pathway of thrombin formation, while leaving other haemostatic pathways unaffected. By virtue of this unique specificity, the peptides of this invention are particularly useful in novel pharmaceutical compositions for the treatment of thrombotic disorders.

Abstract: The invention relates to a non-glycosylated protein with enzymatic and serin protease activity, the zymogenous form thereof comprising the following domains of a protease of the factor IX family: (a) a catalytic domain, N-terminal bonded with (b) a zymogenous activation domain, N terminal bonded with (c) a EGF1 and/or EGF2 domain. Said protein can be used in a same way as the natural serine proteases of the factor IX family.

Abstract: A fibrinogen solution which is suitable for use in a tissue adhesive and can be stored at temperatures between +4° C. and +25° C. for at least four weeks without loss of its ability to function, in particular without significant change in consistency and coagulation properties, and a process for the preparation thereof.

Abstract: Methods for detecting human factor VIII or factor VIII-like polypeptides in and isolating it from solutions such as blood or conditioned media are disclosed, together with reagents suitable for the purpose comprising binding moieties that recognize human factor VIII and/or a factor VIII-like polypeptide and form a binding complex therewith. Preferred polypeptide binding moieties are particularly disclosed.

Abstract: Novel fibrin monomer compositions which are solutions including additional coharvested components, such as prothrombin and Factor XIII, are useful in fibrin sealant applications. Preferably, the compositions are autologous to the patient receiving the sealant and these compositions may also include coharvested plasminogen, Factor X, antithrombin III and/or fibronectin.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: A method of isolating a protein from a mixture containing the protein, the method including providing an antibody immobilized on a solid support, which antibody is reactive with the protein complexed with a ligand and substantially unreactive with the protein not complexed with the ligand; contacting the mixture, in the presence of the ligand, with the immobilized antibody to bind the protein, complexed with the ligand, to the immobilized antibody to form an immune complex; and contacting the immune complex with a compound having a binding affinity for the ligand higher than the binding affinity of the protein for the ligand, to release the protein from the immobilized antibody.

Abstract: An adhesive for tissue capable of uniformly forming a high concentration of fibrin so as to provide a high closing effect is disclosed. The adhesive for tissue comprises a fibrinogen solution and a thrombin solution which solutions are separated from each other. The adhesive is to be mixed and spray coated together with a sterile gas and has a volume ratio of the fibrinogen solution to the thrombin solution of about 2:1 to 10:1. This adhesive is to be sprayed together with a sterile gas for the adhesion or closing of living tissue of a human being or animal.

Abstract: The invention relates to a process for preparing factor V-deficient plasma, in particular a factor V-deficient plasma from a starting plasma using antibodies, and a deficient plasma which is obtained in this way.

Abstract: The present invention provides an antibody which specifically reacts with an epitope of a polypeptide comprising the amino acid sequence X-Y-CYS GLN GLU GLU GLU CYS PRO ASP PRO TYR LEU CYS SER PRO VAL THR ASN ARG CYS GLU CYS THR PRO VAL LEU CYS ARG MET TYR CYS LYS PHE TRP ALA LYS ASP GLU LYS GLY CYS GLU ILE CYS LYS CYS GLU GLU LEU CYS GLN ASN GLN ASN CYS THR LYS ASP MET LEU CYS SER SER VAL THR ASN ARG CYS ASP CYS GLN ASP PHE LYS CYS PRO GLN SER TYR CYS-Z (SEQ. ID NO. 1) wherein X is MET or absent; Y is 0-28 amino acids of the sequence LYS MET CYS TRP ASN LYS GLY CYS PRO CYS GLY GLN ARG CYS ASN LEU HIS ARG ASN GLU CYS GLU VAL ILE ALA GLU ASN ILE GLU, (SEQ. ID NO. 2) with the proviso that if part of the sequence is present, it is a carboxy-terminal part of the sequence including the carboxy-terminal GLU and wherein Val may be preceded by Gly; and Z is absent or all or a part of the sequence Pro110-Lys156 shown in FIG. 7 (SEQ. ID NO.

Abstract: A method of treatment for human patients with an acquired hypercoagulable state or acquired protein C deficiency associated with sepsis, purpura fulminans, meningococcal sepsis, bone marrow and other transplantations, severe burns, pregnancy, major surgery, severe trauma, or ARDS, which comprises administering activated protein C providing a highly selective therapeutic agent with a low potential for causing bleeding complications.

Abstract: The present invention relates to a Chlamydia pneumoniae antigen comprising protein derived from the outer membrane of Chlamydia pneumoniae, a method for producing a Chlamydia pneumoniae antigen which comprises solubilizing the cytosol and the cytoplasmic membrane of Chlamydia pneumoniae elementary body with an ionic detergent, and then removing the solubilized portion to obtain the residue, a method for measuring an anti-Chlamydia pneumoniae antibody which comprises using the Chlamydia pneumoniae antigen, and a reagent for measuring anti-Chlamydia pneumoniae antibody, said reagent comprising the Chlamydia pneumoniae antigen.In accordance with the present invention, there are provided a Chlamydia pneumoniae antigen which has a high species-specificity, very few clinically problematic false negatives, and few false positives, a method for producing said antigen, a method for measuring an anti-Chlamydia pneumoniae antibody, and a reagent for measuring an anti-Chlamydia pneumoniae antibody.

Abstract: A method and device for activating and applying a solution of fibrinogen to form fibrin glue at a desired site. The method includes contacting the solution of fibrinogen with immobilized thrombin under conditions that result in a solution of polymerizable fibrin and delivering the activated solution to the desired site. The device includes a housing having a compartment for a solution of fibrinogen, a container for immobilized thrombin, a structure following the solution of fibrinogen to be brought into contact with the immobilized thrombin under conditions which permit the activation of the fibrinogen to polymerizable fibrin, and a structure allowing for delivery of the activated solution to the desired site.

Abstract: A process for determining glycosaminoglycans in antithrombin III (ATIII)-containing solutions by increasing the ionic strength of the AT III-containing solution until the interaction between AT III and glycosaminoglycans is prevented, removing the AT III which has been released from the glycosaminoglycans from the solution, and desalting and determining the glycosaminoglycan which has remained in the solution.

Abstract: The invention relates to new prothrombin mutants or derivatives thereof which comprise one or more changes in their protein sequence as compared to natural protein, are either inactive or have an activity of approximately 10% at the most, preferably approximately 0.25% at the most, of the natural protein and which have a binding capacity relative to natural ligands (natural or synthetic anticoagulants) substantially corresponding to that of the natural protein. Furthermore, the use of mutated prothrombin mutants or derivatives, respectively, as pharmaceutical preparations is described.